Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

Division display >> ／ All the affair displays 1 - 155 of about 155

JCS/JHFS 2025 Guideline on Diagnosis and Treatment of Heart Failure

Kitai T, Kohsaka S, Kato T, Kato E, Sato K, Teramoto K, Yaku H, Akiyama E, Ando M, Izumi C, Ide T, Iwasaki YK, Ohno Y, Okumura T, Ozasa N, Kaji S, Kashimura T, Kitaoka H, Kinugasa Y, Kinugawa S, Toda K, Nagai T, Nakamura M, Hikoso S, Minamisawa M, Wakasa S, Anchi Y, Oishi S, Okada A, Obokata M, Kagiyama N, Kato NP, Kohno T, Sato T, Shiraishi Y, Tamaki Y, Tamura Y, Nagao K, Nagatomo Y, Nakamura N, Nochioka K, Nomura A, Nomura S, Horiuchi Y, Mizuno A, Murai R, Inomata T, Kuwahara K, Sakata Y, Tsutsui H, Kinugawa K, Japanese Circulation Society and the Japanese Heart Failure Society Joint Working Group

Circulation Journal : Official journal of the Japanese Circulation Society 2025.03

Research paper (scientific journal), ISSN 1346-9843

Access to Document (DOI)

Residual Pulmonary Hypertension and Clinical Outcomes in Acute Decompensated Heart Failure Patients Stratified by Left Ventricular Ejection Fraction

Tanaka DT, Shiraishi Y, Kang R, Kohno T, Shoji S, Okuyama T, Oi Y, Goda A, Nakamaru R, Nagatomo Y, Kitamura M, Sakamoto M, Nomoto M, Mizuno A, Nagoshi T, Kohsaka S, Yoshikawa T.

European Journal of Heart Failure 2025.06

Research paper (scientific journal), Joint Work, Accepted

Hospital Variability in the Use of Vasoactive Agents in Patients Hospitalized for Acute Decompensated Heart Failure for Clinical Phenotypes

Shiraishi Y, Niimi N, Kohsaka S, Harada K, Kohno T, Takei M, Jimba T, Nakano H, Matsuda J, Shindo A, Kitano D, Tsukamoto S, Koba S, Yamamoto T, Takayama M

Circulation: Cardiovascular Quality and Outcomes 18 ( 3 ) e011270 2024.12

Research paper (scientific journal), Lead author, Accepted, ISSN 19417713

BACKGROUND: The absence of practice standards in vasoactive agent usage for acute decompensated heart failure has resulted in significant treatment variability across hospitals, potentially affecting patient outcomes. This study aimed to assess temporal trends and institutional differences in vasodilator and inotrope/vasopressor utilization among patients with acute decompensated heart failure, considering their clinical phenotypes. METHODS: Data were extracted from a government-funded multicenter registry covering the Tokyo metropolitan area, comprising consecutive patients hospitalized in intensive/cardiovascular care units with a primary diagnosis of acute decompensated heart failure between January 2013 and December 2021. Clinical phenotypes, that is, pulmonary congestion or tissue hypoperfusion, were defined through a comprehensive assessment of clinical signs and symptoms, vital signs, and laboratory findings. We assessed the frequency and temporal trends in phenotype-based drug utilization of vasoactive agents and investigated institutional characteristics associated with adopting the phenotype-based approach using generalized linear mixed-effects models, with random intercepts to account for hospital-level variability. RESULTS: Among 37 293 patients (median age, 80 years; 43.7% female), 88.6% and 21.2% had pulmonary congestion and tissue hypoperfusion status, respectively. Throughout the study period, both overall and phenotype-based vasodilator utilizations showed significant declines, with overall usage dropping from 61.4% in 2013 to 48.6% in 2021 (Ptrend<0.001). Conversely, no temporal changes were observed in overall inotrope/vasopressor utilization from 24.6% in 2013 to 25.8% in 2021 or the proportion of phenotype-based utilization. Notably, there was considerable variability in phenotype-based drug utilization among hospitals, with a median ranging from 48.3% to 77.8%. In multivariable-adjusted models, a higher number of board-certified cardiologists were significantly associated with lower rates of phenotype-based vasodilator utilization and reduced inappropriate inotrope/vasopressor utilization, while tertiary care hospitals were linked to more appropriate inotrope/vasopressor utilization. CONCLUSIONS: Substantial variability existed among hospitals in phenotype-based drug utilization of vasoactive agents for patients with acute decompensated heart failure, highlighting the need for standardized treatment protocols.

Access to Document (DOI)

Improved prediction of sudden cardiac death in patients with heart failure through digital processing of electrocardiography.

Shiraishi Y, Goto S, Niimi N, Katsumata Y, Goda A, Takei M, Saji M, Sano M, Fukuda K, Kohno T, Yoshikawa T, Kohsaka S

EP Europace : Journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 25 ( 3 ) 922 - 930 2023.01

Research paper (scientific journal), Lead author, Corresponding author, Accepted, ISSN 1099-5129

Aims: Available predictive models for sudden cardiac death (SCD) in heart failure (HF) patients remain suboptimal. We assessed whether the electrocardiography (ECG)-based artificial intelligence (AI) could better predict SCD, and also whether the combination of the ECG-AI index and conventional predictors of SCD would improve the SCD stratification among HF patients.

Methods and results: In a prospective observational study, 4 tertiary care hospitals in Tokyo enrolled 2559 patients hospitalized for HF who were successfully discharged after acute decompensation. The ECG data during the index hospitalization were extracted from the hospitals' electronic medical record systems. The association of the ECG-AI index and SCD was evaluated with adjustment for left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class, and competing risk of non-SCD. The ECG-AI index plus classical predictive guidelines (i.e. LVEF ≤35%, NYHA Class II and III) significantly improved the discriminative value of SCD [receiver operating characteristic area under the curve (ROC-AUC), 0.66 vs. 0.59; P = 0.017; Delong's test] with good calibration (P = 0.11; Hosmer-Lemeshow test) and improved net reclassification [36%; 95% confidence interval (CI), 9-64%; P = 0.009]. The Fine-Gray model considering the competing risk of non-SCD demonstrated that the ECG-AI index was independently associated with SCD (adjusted sub-distributional hazard ratio, 1.25; 95% CI, 1.04-1.49; P = 0.015). An increased proportional risk of SCD vs. non-SCD with an increasing ECG-AI index was also observed (low, 16.7%; intermediate, 18.5%; high, 28.7%; P for trend = 0.023). Similar findings were observed in patients aged ≤75 years with a non-ischaemic aetiology and an LVEF of >35%.

Conclusion: To improve risk stratification of SCD, ECG-based AI may provide additional values in the management of patients with HF.

Access to Document (DOI)

Catheter ablation for patients with atrial fibrillation and heart failure with reduced and preserved ejection fraction: insights from the KiCS-AF multicentre cohort study

Shiraishi Y, Kohsaka S, Ikemura N, Kimura T, Katsumata Y, Tanimoto K, Suzuki M, Ueda I, Fukuda K, Takatsuki S

EP Europace : Journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 25 ( 1 ) 83 - 91 2022.06

Research paper (scientific journal), Lead author, Accepted, ISSN 1099-5129

Aims: The usefulness of catheter ablation (CA) for atrial fibrillation (AF) across a broad spectrum of heart failure (HF) patients remains to be established. We assessed the association of CA with both health-related quality of life (QoL) and cardiovascular events among HF patients with reduced and preserved left ventricular ejection fraction (LVEF) in an 'all-comer' outpatient-based AF registry.

Methods and results: Of 3303 patients with AF consecutively enrolled in a retrospective multicentre registry that mandated the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire at registration and 1-year follow-up, we extracted data from 530 patients complicating clinical HF. The association between CA and both 1-year change in AFEQT Overall Summary (AFEQT-OS) scores and 2-year composite clinical outcomes (including all-cause death, stroke, and HF hospitalization) was assessed by multivariable analyses. The median duration of AF was 108 days (52-218 days), and 83.4% had LVEF >35%. Overall, 75 patients (14.2%) underwent CA for AF within 1-year after registration. At 1-year follow-up, 67.2% in the ablation group showed clinically meaningful improvements of ≥ 5 points in AFEQT-OS score than 47.8% in the non-ablation group {adjusted odds ratio, 2.03 [95% confidence interval (CI): 1.13-3.64], P = 0.017}. Furthermore, the composite endpoint of all-cause death, stroke, and HF hospitalization occurred less frequently in the ablation group than the non-ablation group [adjusted hazard ratio, 0.27 (95% CI: 0.09-0.86), P = 0.027].

Conclusion: Among AF-HF patients, CA was associated with improved QoL and lower risk of cardiovascular events against drug therapy alone, even for patients with mildly reduced and preserved LVEF.

Access to Document (DOI)

Electronic Patient-Reported Outcome System Implementation in Outpatient Cardiovascular Care: A Randomized Clinical Trial.

Yamashita S, Katsumata Y, Kohsaka S, Kitakata H, Shiraishi Y, Yamaoka K, Muramoto Y, Ono T, Shoji S, Yagyu K, Oginosawa Y, Kataoka M, Hashimoto M, Ko SBH, Kitagawa Y, Jinzaki M

JAMA network open 8 ( 1 ) e2454084 2025.01

Importance: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance. Objective: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice. Design, Setting, and Participants: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan. During phase 1 (conducted from December 2021 to March 2022), this ePRO monitoring system was developed at a single outpatient center using feedback from patients and physicians. Eligible patients were older than 18 years with a clinical diagnosis of heart failure (HF), atrial fibrillation (AF), or coronary artery disease (CAD). Participants were randomly assigned 1:1 to either the ePRO or control group. Statistical analysis was based on the intention-to-treat approach. Intervention: Patients in the ePRO group were asked to complete the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT), or Seattle Angina Questionnaire (SAQ) on smart tablets before their clinical examination. Results were reviewed by physicians at each outpatient visit. The control group received usual care consisting of medication management, lifestyle modification, and invasive procedures in accordance with clinical guidelines. Both groups had 5 monthly outpatient visits. Main Outcomes and Measures: Patient satisfaction, quality of information (QOI) provided by physicians, and disease knowledge were assessed using questionnaires (eg, Patient Satisfaction Questionnaire [PSQ]; score range: 5-25, with higher scores indicating greater patient satisfaction) at baseline and the fifth visit, over approximately 4 months. Results: Of the 50 patients included, 48 (median [SD] age, 71.0 [62.3-75.0] years; 28 males [58.3%]) completed follow-up. The prevalence was 56.2% (n = 27) for HF, 75.0% (n = 36) for AF, and 10.4% (n = 5) for CAD. The distribution of PRO measures used was 21 patients (43.8%) for KCCQ-12, 24 (50.0%) for AFEQT, and 3 (6.2%) for SAQ. Compared with the control group, the ePRO group showed significant improvements in mean (SD) PSQ score (0.16 [2.06] vs 1.61 [1.75]; P = .01) and QOI score regarding treatment (-0.12 [0.53] vs 0.35 [0.71]; P = .01). The ePRO group exhibited a greater increase in the PSQ score regarding communication (-0.12 [0.53] vs 0.43 [0.90]; P = .01). Conclusions and Relevance: In this randomized clinical trial, implementation of the ePRO monitoring system significantly enhanced patient-physician communication and the clarity of physicians' explanations about treatment. These findings suggest that the ePRO monitoring system is capable of supporting patient-centered cardiovascular care. Trial Registration: University Hospital Medical Information Network Identifier: UMIN000049251.

Access to Document (DOI)

Revised Definition of Pulmonary Hypertension Subtypes Enhances Prognostic Stratification in Hospitalized Heart Failure Patients.

Fukushi K, Goda A, Kohno T, Takeuchi S, Nakamaru R, Shiraishi Y, Shoji S, Tanaka TD, Nagatomo Y, Kitamura M, Sakamoto M, Nomoto M, Mizuno A, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2025.06

Research paper (scientific journal), Accepted, ISSN 1053-2498

Access to Document (DOI)

Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001)

Katsumata Y, Muramoto Y, Ishida N, Takemura R, Nagashima K, Ikoma T, Kawamatsu N, Araki M, Goda A, Okawara H, Sawada T, Ichihara Y, Hattori O, Yamaoka K, Seki Y, Ryuzaki T, Ikura H, Nakashima D, Nagura T, Nakamura M, Sato K, Shiraishi Y

Scientific Reports 14 ( 1 ) 18985 2024.12

Research paper (scientific journal), Last author, Accepted

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

Access to Document (DOI)

Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients

Shiraishi Y, Ikemura N, Urashima M, Kohno T, Nakano S, Tanaka T, Nagatomo Y, Ikoma T, Ono T, Numasawa Y, Sakamoto M, Nishikawa K, Takei M, Hakuno D, Nakamaru R, Ueda I, Kohsaka S

BMJ open (BMJ Open) 14 ( 2 ) e076519 2024.02

Research paper (scientific journal), Lead author, Accepted

Introduction The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. Methods and analysis In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. Ethics and dissemination The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. Trial registration number UMIN000045229

Access to Document (DOI)

Time to intravenous diuretic administration in patients hospitalized with heart failure: An observational study.

Shiraishi Y, Kurita Y, Mori H, Ooishi K, Matsukawa M

ESC Heart Failure 11 ( 6 ) 4061 - 4070 2024.08

Research paper (scientific journal), Lead author, Corresponding author, Accepted

Aims: To help establish optimized treatment strategies for congestion in patients with acute heart failure, this study aimed to provide a detailed summary of real-world diuretic use in hospitalized patients with heart failure requiring urgent therapy in Japan. Methods and results: This observational study used a Japanese medical records database to extract data of patients admitted to hospital with a heart failure diagnosis and an intravenous diuretic prescription from the day before admission to 2 days after. Time from hospital visit to first dose, second dose, and maximum dose of intravenous diuretics were determined. Patients were grouped according to whether they received diuretic modification, defined as an intravenous diuretic dose increase or concomitant use of other diuretics. Results: Overall, 1577 patients were included in the study (without diuretic modification, n = 1140 [72.3%]; with diuretic modification, n = 437 [27.7%]). The study population was 49.5% female (n = 780) and the mean age ± standard deviation was 80.1 ± 12.7 years. Intravenous diuretic treatment was received within 1 h of their hospital visit in 43.5% of patients (686/1577) and ≤2 h in 16.4% of patients (258/1577). Among 437 patients with an inadequate response following their first dose, 42.1% received an intravenous dose titration, 56.5% received combination diuretics, and 1.4% received both. Over half of the patients (59.0% [258/437]) with diuretic modification received it after the first 24 h of the hospital visit. The median time from hospital visit to first dose titration was similar to time to first combination diuretic use (18.6 h and 17.0 h, respectively). The mean ± standard deviation duration of intravenous diuretic use was significantly longer for patients with versus without diuretic modification (6.3 ± 5.2 vs. 3.7 ± 3.2 days), and a significantly greater proportion of patients (44.6% [195/437] vs. 35.0% [399/1140]) received repeated intravenous diuretic administration. Other characteristics/outcomes of intravenous diuretic use were similar with versus without diuretic modification, including in-hospital death (15.6% [68/437] vs. 13.9% [159/1140]) and mean ± standard deviation length of hospitalization (21.9 ± 14.7 days vs. 22.1 ± 21.2 days). Conclusions: In Japan, real-world patterns of intravenous diuretic administration for patients with heart failure remains far from the time-sensitive approach recommended in Japanese, European, and United States guidelines.

Access to Document (DOI)

Visually assessing work performance using a smartwatch via day-to-day fluctuations in heart rate variability.

Okawara H, Shiraishi Y, Sato K, Nakamura M, Katsumata Y

Digital health (Digital Health) 10 20552076241239240 2024.01

ISSN 2055-2076

Objective: To optimize workplace health promotion, a simple method for quantifying allostatic load response is needed. This study examines the feasibility of optimizing objective anxiety and presenteeism monitoring using daily smartwatch-measured ultra-short heart rate variability (HRV). Methods: Office workers without diagnosed disease prospectively performed 30 s HRV self-measurement each morning for two months and responded to the State-Trait Anxiety Inventory (STAI) and Work Limitation Questionnaire (WLQ). Logistic regression analysis examined daily HRV parameters in the high-trait anxiety group (HTA, STAI ≥ 40) using mean and variance HRV, age, self-reported gender, and body mass index (BMI). The ideal cutoff value enabled comparison of WLQ using the Mann–Whitney U test. Heart rate variability data were collected for 279 participants (male ratio, 83.9%; age, 42 ± 10 years) who completed questionnaires and monitored HRV for 30+ days. Results: Compared to the low-trait anxiety group, HTA exhibited higher variance of the log-transformed coefficient of component variance of high-frequency component (LnccvHF) and low-frequency per HF (Lnccv L/H), in addition to differences in the means of these HRV parameters. In addition to BMI (odds ratio [OR] = 0.92, p = 0.02) and mean LnccvL/H (OR = 10.75, p < 0.01), the variance of Lnccv L/H was an independent predictor of HTA (OR = 2.39E + 8, p = 0.011). The daily Lnccv L/H dispersion group had a lower WLQ productivity loss score (p = 0.02, r = 0.17). Conclusions: By focusing on HRV dispersion status, this simple and instantly applicable daily HRV monitoring system enables optimized quantitative monitoring of anxiety and productivity.

Access to Document (DOI)

Timing of Worsening Renal Function in Patients Hospitalized for Heart Failure Exacerbation Who Were Being Treated With Intravenous Diuretic Therapy.

Shiraishi Y, Kurita Y, Mori H, Oishi K, Matsukawa M

Circulation Journal 88 ( 5 ) 680 - 691 2023.12

Research paper (scientific journal), Lead author, Corresponding author, Accepted, ISSN 1346-9843

BACKGROUND: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan.Methods and Results: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001). CONCLUSIONS: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.

Access to Document (DOI)

Temporal Trends in Heart Failure Management and Outcomes: Insights From a Japanese Multicenter Registry of Tertiary Care Centers.

Nakamaru R, Kohsaka S, Shiraishi Y, Kohno T, Goda A, Nagatomo Y, Kitamura M, Nakano S, Takei M, Mizuno A, Yoshikawa T

Journal of the American Heart Association (Journal of the American Heart Association) 12 ( 21 ) e031179 2023.11

BACKGROUND: The management of heart failure (HF) has markedly changed, due to changes in demographics and the emer-gence of novel pharmacotherapies. However, detailed analyses on the temporal trends in characteristics and outcomes among patients with HF are scarcely available. This study aimed to assess the temporal trends over 11 years in clinical management and outcomes in patients with HF. METHODS AND RESULTS: We analyzed data from a multicenter registry of hospitalized patients with acute HF, including 6877 patients registered from 2011 to 2021. Age-adjusted mortality was calculated using standardized mortality ratios. During the study period, mean age increased from 75.2 years in 2011 to 2012 to 76.4 years in 2020 to 2021 (P for trend <0.001). The proportion of HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction <40%) remained constant (from 43.4% to 42.7%, P for trend=0.38). The median duration of hospital stays (from 15 to 17 days, P for trend<0.001) had increased. As for the implementation of guideline-directed medical therapy, the use of mineralocorticoid receptor antagonist at discharge increased in patients with HFrEF (from 44.3% to 60.2%, P for trend<0.001). There was also an increase in the use of sodium-glucose cotransporter-2 inhibitors following their approval for use. The age-adjusted 1-year mortality decreased in patients with HFrEF (from 18.0% to 9.3%, P for trend<0.001) but not in patients with non-HFrEF (left ventricular ejection fraction ≥40%; from 9.2% to 9.5%, P for trend=0.79). CONCLUSIONS: Hospitalized patients with HF have been aging over the past decade. Their long-term outcomes after discharge have improved predominantly because of decreased mortality in patients with HFrEF.

Access to Document (DOI)

Initiation and Up-Titration of Guideline-Based Medications in Hospitalized Acute Heart Failure Patients　- A Report From the West Tokyo Heart Failure Registry.

Ohata T, Niimi N, Shiraishi Y, Nakatsu F, Umemura I, Kohno T, Nagatomo Y, Takei M, Ono T, Sakamoto M, Nakano S, Fukuda K, Kohsaka S, Yoshikawa T

Circulation journal : official journal of the Japanese Circulation Society (Circulation journal : official journal of the Japanese Circulation Society) 88 ( 1 ) 22 - 30 2023.10

ISSN 1346-9843

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (β-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Access to Document (DOI)

Cardiac sarcoidosis preceded by sick sinus syndrome presenting as biventricular involvement and intracardiac giant thrombus: a case report.

Hirai A, Shiraishi Y, Fukuda K, Fujita J

European heart journal. Case reports (European Heart Journal - Case Reports) 7 ( 9 ) ytad435 2023.09

Background: Sarcoidosis is a granulomatous disorder characterized by the formation of non-necrotizing granulomas in various organs. Cardiac sarcoidosis presents with various clinical, anatomical, and electrophysiological manifestations. As cardiac involvement is related to adverse outcomes, the early diagnosis of cardiac sarcoidosis is crucial and sometimes challenging. Case summary: A 65-year-old woman was initially treated for sick sinus syndrome (SSS) with normal cardiac function. Cardiac conduction defects and biventricular dysfunction continued to progress over a short clinical course, and the patient was eventually referred to our hospital for further investigation and treatment of cardiogenic shock due to pacemaker pacing failure. An echocardiography revealed a large thrombus formation in the right ventricle and atrium. An urgent thrombectomy was performed, and myocardial biopsy confirmed the diagnosis of cardiac sarcoidosis. Steroid pulse therapy was initiated and was effective in treating the cardiogenic shock. One year after discharge, the patient manifested with sustained ventricular tachycardia and ultimately died of severe cardiac pump failure. On autopsy, diffuse fibrotic tissues were noted in both ventricles and atria. Discussion: While conduction abnormalities, such as right bundle brunch block and atrioventricular block, are common clinical manifestations, SSS is rarely reported as a primary manifestation of cardiac sarcoidosis. Thus, clinicians should ensure that sufficient investigations are carried out when diagnosing idiopathic SSS.

Access to Document (DOI)

Real-Time Estimation of Anaerobic Threshold during Exercise Using Electrocardiogram in Heart Failure Patients

Ryuzaki T, Shiraishi Y, Miura K, Ikura H, Seki Y, Azuma K, Sato K, Fukuda K, Katsumata Y

Journal of Clinical Medicine (Journal of Clinical Medicine) 12 ( 16 ) 2023.08

Research paper (scientific journal), Corresponding author, Accepted, ISSN 2077-0383

Exercise therapy at the aerobic level is highly recommended to improve clinical outcomes in patients with heart failure, in which cardiopulmonary exercise testing (CPX) is required to determine anaerobic thresholds (ATs) but is not available everywhere. This study aimed to validate a method to estimate the AT using heart rate variability (HRV) analysis from electrocardiography data in patients with heart failure. Between 2014 and 2019, 67 patients with symptomatic heart failure underwent CPXs in a single university hospital. During the CPX, RR intervals was measured continuously and the HRV threshold (HRVT), defined as the inflection point of <5 ms2 of a high-frequency component (HFC) using the power spectrum analysis, was determined. Patients were divided into two groups according to the mean HFC at rest (high-HFC group, n = 34 and low-HFC group, n = 33). The high-HFC group showed good correlation between the VO2 at AT and HRVT (r = 0.63, p < 0.001) and strong agreement (mean difference, −0.38 mL/kg, p = 0.571). The low-HFC group also showed modest correlation (r = 0.41, p = 0.017) but poor agreement (mean differences, 3.75 mL/kg, p < 0.001). In conclusion, the HRVT obtained from electrocardiography may be a useful indicator for estimating AT in patients with heart failure.

Access to Document (DOI)

Association of Pre-Hospital Precipitating Factors with Short- and Long-term Outcomes of Acute Heart Failure Patients: A Report from the WET-HF2 Registry

Kawakubo-Ichihara Y, Shiraishi Y, Kohsaka S, Nakano S, Yuji Nagatomo Y, Ono T, Takei M, Sakamoto M, Mizuno A, Kitamura M, Niimi N, Kohno T, Yoshikawa T

International Journal of Cardiology (International Journal of Cardiology) 389 131161 2023.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 01675273

Background: Interest in clinical course preceding heart failure (HF) exacerbation has grown, with a greater emphasis placed on patients' clinical factors including precipitant factor (PF). Large-scale studies with precise PF documentation and temporal-outcome variation remain limited. Methods: We reviewed prospectively collected 2412 consecutive patient-level records from a multicenter Japanese registry of hospitalized patients with HF (West Tokyo Heart Failure2 Registry: 2018–2020). Patients were categorized based on PFs: behavioral (i.e., poor adherence to physical activity, medicine, or diet regimen), treatment-required (i.e., anemia, arrhythmia, ischemia, infection, thyroid dysfunction or other conditions as suggested exacerbating factors), and no-PF. The composite outcomes of HF rehospitalization and death within 1 year after discharge and HF rehospitalization were individually assessed. Results: Median patient age was 78 years (interquartile range: 68–85 years), and 1468 (61%) patients had documented PFs, of which 356 (15%) were considered behavioral. The behavioral PF group were younger, more male and had past HF hospitalization history compared to those in the other groups (all p < 0.05). Although risk of in-hospital death was lower in the behavioral PF group, their risk of composite outcome was not significantly different from the treatment-required group (hazard ratio [HR] 1.19 [95% confidence interval {CI} 0.93–1.51]) and the no-PF group (HR 1.28 [95%CI 1.00–1.64]). Furthermore, the risk of HF rehospitalization was higher in the behavioral PF group than in the other two groups (HR 1.40 [95%CI 1.07–1.83] and HR 1.39 [95%CI 1.06–1.83], respectively). Conclusion: Despite a better in-hospital prognosis, patients with behavioral PFs were at significantly higher risk of HF rehospitalization.

Access to Document (DOI)

Real-World Intravenous Diuretic Use to Treat Congestion in Patients With Heart Failure　- An Observational Study Using a Research Database.

Shiraishi Y, Kurita Y, Matsukawa M, Mori H

Circulation reports 5 ( 2 ) 27 - 37 2023.02

Access to Document (DOI)

Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.

Nakamaru R, Shiraishi Y, Niimi N, Kohno T, Nagatomo Y, Takei M, Ikoma T, Nishikawa K, Sakamoto M, Nakano S, Kohsaka S, Yoshikawa T

Journal of the American Heart Association 12 ( 3 ) e027689 2023.01

Research paper (scientific journal), Accepted

Background The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). Conclusions In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.

Access to Document (DOI)

Treatment patterns and trajectories in patients after acute heart failure hospitalization

Nakamaru R, Shiraishi Y, Kohno T, Nagatomo Y, Akiyama H, Motoya Y, Fukui M, Yajima T, Yoshikawa T, Kohsaka S

ESC Heart Failure (ESC Heart Failure) 11 ( 2 ) 692 - 701 2023

Research paper (scientific journal), Accepted

Aims: The trajectories of systolic function after admission for acute heart failure (HF) and their effect on clinical outcomes have not been fully elucidated. We aimed to assess changes in left ventricular ejection fraction (LVEF) between the index and 1 year after discharge and to examine their prognostic implications. Methods and results: We extracted data from a prospective multicentre registry of patients hospitalized for acute HF and identified 1636 patients with LVEF data at admission and 1 year after discharge. We categorized them into five groups based on LVEF changes: HF with unchanged-preserved EF [HFunc-pEF (EF ≥ 50%); N = 527, 32.2%], unchanged-mildly reduced EF [HFunc-mrEF (EF 41–49%); N = 86, 5.3%], unchanged-reduced EF [HFunc-rEF (EF ≤ 40%); N = 377, 23.0%], worsened EF (HFworEF; N = 83, 5.1%), and improved EF (HFimpEF; N = 563, 34.4%). We then evaluated the subsequent composite outcome of cardiovascular death and HF readmission. During 1 year after discharge, 53% of patients with HF with reduced EF and 67% of those with HF with mildly reduced EF (HFmrEF) transitioned to other categories, whereas 92% of those with HF with preserved EF (HFpEF) remained within the same category. Patients with HFimpEF were more likely to be younger and had relatively preserved renal function, whereas those with HFworEF were the oldest and had more comorbidities among the five groups. After multivariable adjustment, patients with HFimpEF and HFunc-pEF had a lower risk for composite outcomes when referenced to patients with HFunc-rEF [hazard ratio (95% confidence interval), P-value: 0.28 (0.16–0.49), P < 0.001, and 0.40 (0.25–0.63), P < 0.001, respectively]. Conversely, patients with HFunc-mrEF and HFworEF had a comparable risk [0.44 (0.18–1.07), P = 0.07, and 0.63 (0.29–1.39), P = 0.26, respectively]. Conclusions: A substantial number of patients with HF experienced transitions to other categories after discharge. Notably, patients with decreased EF experienced a worse prognosis, even with slight decreases (e.g. HFpEF transitioning to HFmrEF). These findings emphasize the significance of longitudinal assessments of systolic function to better manage patients following acute decompensation.

Access to Document (DOI)

Time Trend in Incidence of Sudden Cardiac Death After Percutaneous Coronary Intervention from 2009 to 2017 (from the Japanese Multicenter Registry).

Nakamaru R, Shiraishi Y, Niimi N, Ueda I, Ikemura N, Suzuki M, Noma S, Inohara T, Numasawa Y, Fukuda K, Kohsaka S

The American Journal of Cardiology 188 44 - 51 2022.12

Research paper (scientific journal), Accepted, ISSN 0002-9149

The advances in the integrated management of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) have reduced subsequent cardiovascular events. Nonetheless, sudden cardiac death (SCD) remains a major concern. Therefore, we aimed to investigate the time trend in SCD incidence after PCI and to identify the clinical factors contributing to SCD. From a prospective, multicenter cohort registry in Japan, 8,723 consecutive patients with coronary artery disease undergoing PCI between 2009 and 2017 were included. We evaluated the SCD incidence 2 years after PCI; all death events were adjudicated, and SCD was defined as unexpected death without a noncardiovascular cause in a previously stable patient within 24 hours from the onset. The Fine and Gray method was used to identify the factors associated with SCD. Overall, the mean age of the patients was 68.3 ± 11.3 years, and 1,173 patients (13.4%) had heart failure (HF). During the study period, the use of second-generation drug-eluting stents increased. The 2-year cumulative incidence of all-cause mortality and SCD was 4.29% and 0.45%, respectively. All-cause mortality remained stable during the study period (p for trend = 0.98), whereas the crude incidence of SCD tended to decrease over the study period (p for trend = 0.052). HF was the strongest predictor associated with the risk of SCD (crude incidence [vs non-HF] 2.13% vs 0.19%; p <0.001). In conclusion, the incidence of SCD after PCI decreased over the last decade, albeit the high incidence of SCD among patients with HF remains concerning.

Access to Document (DOI)

Cardiovascular vs. non-cardiovascular deaths after heart failure hospitalization in young, older, and very old patients.

Nakamaru R, Shiraishi Y, Sandhu AT, Heidenreich PA, Shoji S, Kohno T, Takei M, Nagatomo Y, Nakano S, Kohsaka S, Yoshikawa T

ESC Heart Failure (ESC Heart Failure) 10 ( 1 ) 673 - 684 2022.11

Research paper (scientific journal), Accepted

Aims: The long-term outcome in patients with heart failure (HF) after hospitalization may vary substantially depending on their age and left ventricular ejection fraction (LVEF). We aimed to assess the relative rates of cardiovascular death (CVD) and non-CVD based on the age and how the rates differ under the updated LVEF classification system. Methods and results: Consecutively registered hospitalized patients with HF (N = 3558; 39.7% women with a mean age of 73.9 ± 13.3 years) were followed for a median of 2 (interquartile range, 0.8–3.1) years. The CVDs and non-CVDs were evaluated based on age [young (<65 years), older (65–84 years), and very old (≥85 years)] and LVEF classification [HF with preserved EF (HFpEF; LVEF ≥50%) and non-HFpEF (LVEF <50%)]. The adverse clinical events were adjudicated independently by a central committee. Overall, 1505 (42.3%) had HFpEF [young: n = 182 (12.1%), older: n = 894 (59.4%), very old: n = 429 (28.5%)], and 2053 (57.7%) had non-HFpEF [young: n = 575 (28.0%), older: n = 1159 (56.5%), very old: n = 319 (15.5%)]. During the follow-up, the crude incidence of all-cause death was higher in non-HFpEF than in HFpEF across all age groups (non-HFpEF vs. HFpEF, young: 10.4% vs. 5.5%, log-rank P = 0.10; older: 26.6% vs. 20.9%, log-rank P = 0.002; very old: 36.7% vs. 31.7%, log-rank P = 0.043). CVDs accounted for more than half of all deaths in non-HFpEF (young 65.0%, older 64.2%, and very old 55.6%), whereas the proportion of CVDs remained less than half in HFpEF (young 50.0%, older 41.2%, very old 38.2%). HF readmission was associated with subsequent all-cause death in non-HFpEF [hazard ratio (HR): 1.72, 95% confidence interval (CI): 1.41–2.09, P < 0.001], but not in HFpEF (HR: 1.12, 95% CI: 0.87–1.43, P = 0.39). Conclusions: The probability of a non-CVD increases in both LVEF categories with advancing age, but that it is greater in the HFpEF category. The findings indicate that mitigating CV-related outcomes alone may be insufficient for treating HF in older population, particularly in the HFpEF category.

Access to Document (DOI)

Use of short-acting vs. long-acting loop diuretics after heart failure hospitalization

Imaeda S, Shiraishi Y, Kohsaka S, Niimi N, Goda A, Nagatomo Y, Takei M, Saji M, Nakano S, Kohno T, Fukuda K, Yoshikawa T

ESC Heart Failure (ESC Heart Failure) 9 ( 5 ) 2967 - 2977 2022.06

Research paper (scientific journal), Lead author, Accepted

Aims: Furosemide, a short-acting loop diuretic (SD), is the dominant agent prescribed for heart failure (HF) in clinical practice. However, accumulating data suggests that long-acting loop diuretics (LD), such as torsemide or azosemide, might have more favourable pharmacological profiles. This study aimed to investigate the relationship between the type of loop diuretics and long-term outcomes among patients hospitalized for acute HF enrolled in a contemporary multicentre registry. Methods and results: Within the West Tokyo Heart Failure Registry from 2006 to 2017, a total of 2680 patients (60.1% men with a median age of 77 years) were analysed. The patients were characterized by the type of diuretics used at the time of discharge; 2073 (77.4%) used SD, and 607 (22.6%) used LD. The primary endpoint was composite of all-cause death or HF re-admission after discharge, and the secondary endpoints were all-cause death and HF re-admission, respectively. During the median follow-up period of 2.1 years, 639 patients died [n = 519 (25.0%) in the SD group; n = 120 (19.8%) in the LD group], and 868 patients were readmitted for HF [n = 697 (33.6%) in the SD group; n = 171 (28.2%) in the LD group]. After multivariable adjustment, the LD group had lower risk for the composite outcome [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.66–0.96; P = 0.017], including all-cause death (HR; 0.73; 95% CI; 0.54–0.99; P = 0.044) and HF re-admission (HR, 0.81; 95% CI, 0.66–0.99; P = 0.038), than the SD group. Propensity score matching yielded estimates that were consistent with those of the multivariable analyses, with sub-group analyses demonstrating that use of LD was associated with favourable outcomes predominantly in younger patients with reduced ejection fraction. Conclusions: LD was associated with lower risk of long-term outcomes in patients with HF and a recent episode of acute decompensation.

Access to Document (DOI)

Potential association with malnutrition and allocation of combination medical therapies in hospitalized heart failure patients with reduced ejection fraction.

Kawakubo Y, Shiraishi Y, Kohsaka S, Kohno T, Goda A, Nagatomo Y, Nishihata Y, Saji M, Takei M, Ikegami Y, Niimi N, Sandhu ATS, Nakano S, Yoshikawa T, Fukuda K, West Tokyo Heart Failure Registry.

Scientific Reports 12 ( 1 ) 8318 2022.05

Research paper (scientific journal), Accepted

Malnutrition is common in patients with heart failure with reduced ejection fraction (HFrEF) and may influence the long-term prognosis and allocation of combination medical therapy. We reviewed 1231 consecutive patient-level records from a multicenter Japanese registry of hospitalized HFrEF patients. Nutritional status was assessed using geriatric nutritional risk index (GNRI). Combination medical therapy were categorized based on the use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists. The composite outcome of all-cause death and HF rehospitalization was assessed. The mean age was 72.0 ± 14.2 years and 42.6% patients were malnourished (GNRI < 92). At discharge, 43.6% and 33.4% of patients were receiving two and three agents, respectively. Malnourished patients had lower rates of combination medical therapy use. The standardized GNRI score was independently associated with the occurrence of adverse events (hazard ratio [HR]: 0.88, 95% confidence interval [CI] 0.79–0.98). Regardless of the GNRI score, referenced to patients receiving single agent, risk of adverse events were lower with those receiving three (HR: 0.70, 95% CI 0.55–0.91) or two agents (HR: 0.70, 95% CI 0.56–0.89). Malnutrition assessed by GNRI score predicts long-term adverse outcomes among hospitalized HFrEF patients. However, its prognosis may be modified with combination medical therapy.

Access to Document (DOI)

Machine learning models for prediction of adverse events after percutaneous coronary intervention

Niimi N., Shiraishi Y., Sawano M., Ikemura N., Inohara T., Ueda I., Fukuda K., Kohsaka S.

Scientific Reports (Scientific Reports) 12 ( 1 ) 6262 2022.04

An accurate prediction of major adverse events after percutaneous coronary intervention (PCI) improves clinical decisions and specific interventions. To determine whether machine learning (ML) techniques predict peri-PCI adverse events [acute kidney injury (AKI), bleeding, and in-hospital mortality] with better discrimination or calibration than the National Cardiovascular Data Registry (NCDR-CathPCI) risk scores, we developed logistic regression and gradient descent boosting (XGBoost) models for each outcome using data from a prospective, all-comer, multicenter registry that enrolled consecutive coronary artery disease patients undergoing PCI in Japan between 2008 and 2020. The NCDR-CathPCI risk scores demonstrated good discrimination for each outcome (C-statistics of 0.82, 0.76, and 0.95 for AKI, bleeding, and in-hospital mortality) with considerable calibration. Compared with the NCDR-CathPCI risk scores, the XGBoost models modestly improved discrimination for AKI and bleeding (C-statistics of 0.84 in AKI, and 0.79 in bleeding) but not for in-hospital mortality (C-statistics of 0.96). The calibration plot demonstrated that the XGBoost model overestimated the risk for in-hospital mortality in low-risk patients. All of the original NCDR-CathPCI risk scores for adverse periprocedural events showed adequate discrimination and calibration within our cohort. When using the ML-based technique, however, the improvement in the overall risk prediction was minimal.

Access to Document (DOI)

Temporal trends in tolvaptan use after revision of national heart failure guidelines in Japan

Yamazaki Y, Shiraishi Y, Kohsaka S, Nagatomo Y, Fukuda K, Kohno T, Yoshikawa T

Scientific Reports 11 ( 1 ) 19360 2021.12

Research paper (scientific journal), Accepted

Within no definite diuretic protocol for acute heart failure (AHF) patients and its variation in regional clinical guidelines, the latest national guidelines in Japan commends use of tolvaptan in diuretic-resistant patients. This study aimed to examine trends in tolvaptan usage and associated outcomes of AHF patients requiring hospitalization. Between April, 2018 and October, 2019, 1343 consecutive AHF patients (median 78 [69–85] year-old) were enrolled in a prospective, multicenter registry in Japan. Trends over time in tolvaptan usage, along with the severity of heart failure status based on the Get With The Guideline-Heart Failure [GWTG-HF] risk score, and in-hospital outcomes were investigated. During the study period, tolvaptan usage has increased from 13.0 to 28.7% over time (p for trend = 0.07), and 49.4% started tolvaptan within 3 days after admission. The GWTG-HF risk score in the tolvaptan group has significantly decreased over time, while that in the non-tolvaptan group has unchanged. There were no differences in the in-hospital mortality rate between the patients with and without tolvaptan (6.7% vs. 5.8%). After revision of the Japanese clinical practice guidelines for AHF in March 2018, tolvaptan usage for AHF patients has steadily increased. However, in-hospital outcomes including mortality do not seem to be affected.

Access to Document (DOI)

Assessment of physical activity using waist-worn accelerometers in hospitalized heart failure patients and its relationship with Kansas City Cardiomyopathy Questionnaire

Shiraishi Y, Niimi N, Goda A, Takei M, Kimura T, Kohno T, Kawana M, Fukuda K, Kohsaka S

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 18 ) 2021.09

Research paper (scientific journal), Lead author, Corresponding author, Accepted, ISSN 2077-0383

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-re-ported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomy-opathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %seden-tary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p < 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sed-entary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.

Access to Document (DOI)

Transcatheter Mitral Valve Repair Effective and Safe Refractory Eclipsed Mitral Regurgitation-Induced Cardiogenic Shock: A Case Report

Umei T.C, Shiraishi Y, Tsuruta H, Hayashida K, Imaeda S, Ryuzaki T, Myojin S, Kobari Y, Saito T, Yoshijima N, Itabashi Y, Kishino Y, Katsumata Y, Yuasa S, Fukuda K

Circulation: Cardiovascular Imaging 14 ( 7 ) 681 - 684 2021.06

Research paper (scientific journal), Corresponding author, Accepted

Access to Document (DOI)

Abnormal liver function tests and long-term outcomes in patients discharged after acute heart failure

Miyama H, Shiraishi Y, Kohsaka S, Goda A, Nishihata Y, Nagatomo Y, Takei M, Fukuda K, Kohno T, Yoshikawa T

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 8 ) 2021.04

Research paper (scientific journal), Accepted, ISSN 2077-0383

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years; men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed; borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes.

Access to Document (DOI)

Time-sensitive approach in the management of acute heart failure

Shiraishi Y, Kawana M, Nakata J, Sato N, Fukuda K, Kohsaka S

ESC Heart Failure 8 ( 1 ) 204 - 221 2021.02

Research paper (scientific journal), Lead author, Accepted

Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is ‘time sensitive’ and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the ‘time-sensitive’ approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.

Access to Document (DOI)

Derivation and Validation of Clinical Prediction Models for Rapid Risk Stratification for Time-Sensitive Management for Acute Heart Failure

Shiraishi Y, Kohsaka S, Abe T, Nagai T, Goda A, Nishihata Y, Nagatomo Y, Saji M, Toyosaki Y, Takei M, Kitai T, Kohno T, Fukuda K, Matsue Y, Anzai T, Yoshikawa T

Journal of Clinical Medicine (Journal of Clinical Medicine) 9 ( 11 ) 1 - 13 2020.10

Research paper (scientific journal), Lead author, Accepted, ISSN 2077-0383

Early and rapid risk stratification of patients with acute heart failure (AHF) is crucial for appropriate patient triage and outcome improvements. We aimed to develop an easy-to-use, in-hospital mortality risk prediction tool based on data collected from AHF patients at their initial presentation. Consecutive patients’ data pertaining to 2006-2017 were extracted from the West Tokyo Heart Failure (WET-HF) and National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registries (n = 4351). Risk model development involved stepwise logistic regression analysis and prospective validation using data pertaining to 2014-2015 in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure Syndrome (REALITY-AHF) (n = 1682). The final model included data describing six in-hospital mortality risk predictors, namely, age, systolic blood pressure, blood urea nitrogen, serum sodium, albumin, and natriuretic peptide (SOB-ASAP score), available at the time of initial triage. The model showed excellent discrimination (c-statistic = 0.82) and good agreement between predicted and observed mortality rates. The model enabled the stratification of the mortality rates across sixths (from 14.5% to <1%). When assigned a point for each associated factor, the integer score’s discrimination was similar (c-statistic = 0.82) with good calibration across the patients with various risk profiles. The models’ performance was retained in the independent validation dataset. Promptly determining in-hospital mortality risks is achievable in the first few hours of presentation; they correlate strongly with mortality among AHF patients, potentially facilitating clinical decision-making.

PDF1

Access to Document (DOI)

Natriuretic Peptide Measurement is Key to a Solution in the Clinical Trial and Clinical Practice

Momoi M, Shiraishi Y, Kohsaka S, Fukuda K, Yoshikawa T

JACC Heart Failure 8 ( 9 ) 782 - 783 2020.09

ISSN 2213-1779

Access to Document (DOI)

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Shiraishi Y, Amiya E, Hatano M, Katsuki T, Bujo C, Tsuji M, Nitta D, Maki H, Ishida J, Kagami Y, Endo M, Kimura M, Ando M, Shimada S, Kinoshita O, Ono M, Komuro I

ESC Heart Failure 7 ( 4 ) 1842 - 1849 2020.05

Research paper (scientific journal), Lead author, Accepted

Aims: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7–96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9–83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. Conclusions: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

PDF2

Access to Document (DOI)

Benefit and harm of intravenous vasodilators across the clinical profile spectrum in acute cardiogenic pulmonary oedema patients

Shiraishi Y, Kohsaka S, Katsuki T, Harada K, Miyazaki T, Miyamoto T, Matsushita K, Iida K, Takei M, Yamamoto Y, Shindo A, Kitano D, Nagatomo Y, Jimba T, Yamamoto T, Nagao K, Takayama M, for Tokyo CCU Network Scientific Committee.

European Heart Journal: Acute Cardiovascular Care 9 ( 5 ) 2048872619891075 - 458 2020.01

Research paper (scientific journal), Lead author, Accepted, ISSN 2048-8726

Access to Document (DOI)

Discrepancy between patient-reported quality of life and the prognostic assessment of Japanese patients hospitalized with acute heart failure

Shoji S., Shiraishi Y., Sawano M., Katsumata Y., Yuasa S., Kohno T., Fukuda K., Spertus J., Kohsaka S.

Heart and Vessels (Heart and Vessels) 34 ( 9 ) 1464 - 1470 2019.09

Research paper (scientific journal), Accepted, ISSN 09108327

© 2019, Springer Japan KK, part of Springer Nature. Patient-reported quality of life (PRQL) is a primary therapeutic target for patients with chronic heart failure (HF) and is associated with long-term prognosis. However, its utility in hospitalized HF (HHF) patients in the acute setting remains unclear. We aimed to assess the utility of PRQL (the Kansas City Cardiomyopathy Questionnaire [KCCQ]) in HHF patients and its association with long-term prognosis as well as with the clinical risk score (Get With The Guidelines-Heart Failure [GWTG-HF] risk score). PRQL was evaluated using the KCCQ in consecutive 114 HHF patients. Its association with the composite outcome of all-cause mortality or HF readmission within the first year after discharge was analyzed. Furthermore, its distribution by the clinical risk score (GWTG-HF) was evaluated using Pearson’s correlation coefficient. The median KCCQ was 34.9, but was widely distributed (interquartile range 23.7–56.8). After adjustment for known prognostic indicators, the KCCQ was not an independent predictor of the composite outcome within the first year (group with high vs. low KCCQ scores: hazard ratio, 0.67; 95% confidence interval 0.26–1.71). There was no significant correlation between the KCCQ and the GWTG-HF risk score. In conclusion, PRQL during the acute phase of HF was significantly impaired and also varied widely, irrespective of patient characteristics or severity. PRQL assessment and risk prediction for HHF patients in the acute setting seemed to provide two distinct types of information for health care providers.

Access to Document (DOI)

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients

Shiraishi Y, Kohsaka S, Nagai T, Goda A, Mizuno A, Nagatomo Y, Sujino Y, Fukuoka R, Sawano M, Kohno T, Fukuda K, Anzai T, Shadman R, Dardas T, Levy W, Yoshikawa T

Journal of Cardiac Failure 25 ( 7 ) 561 - 567 2019.07

Research paper (scientific journal), Lead author, Accepted, ISSN 10719164

© 2018 Elsevier Inc. Background: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. Methods and Results: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = −0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = −0.04) but not for HFpEF patients. Conclusions: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.

Access to Document (DOI)

Staged transcatheter closure for atrial septal defect and patent ductus arteriosus: A case report

Soma Y., Shiraishi Y., Kanazawa H., Fukuda K.

European Heart Journal - Case Reports (European Heart Journal - Case Reports) 3 ( 2 ) 2019

Research paper (scientific journal), Corresponding author, Accepted

© The Author(s) 2019. Background Atrial septal defect (ASD) and patent ductus arteriosus (PDA) are both common congenital heart diseases, but the combination of these two cardiac defects is extremely rare, and the therapeutic strategy is controversial. Case summary We treated an adult patient with combined ASD and PDA, and safely attained a successful outcome with two-stage transcatheter closure, which is PDA closure preceding ASD closure, to prevent serious complications. Discussion Transcatheter closure of one of the defects is now widely accepted as an alternative to surgical closure. In addition, adults with both ASD and PDA are better suited for transcatheter closure than surgical closure. One of the reasons is the difficulty to ligate the ductus arteriosus of an adult patient due to its friability and calcification. Meanwhile, simultaneous combined transcatheter closure of ASD and PDA can result in serious complications, such as thrombocytopenia and haemolysis, whose mechanism is considered to be the destruction of platelets and red blood cells by the residual shunt through implanted devices. Additionally, antiplatelet therapy that prevents device-related thrombus formation after ASD closure can possibly exacerbate thrombocytopenia and haemolysis. Therefore, the staged strategy is reasonable from the perspectives of antiplatelet therapy and haemodynamic changes.

Access to Document (DOI)

Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide

Shiraishi Y, Nagai T, Kohsaka S, Goda A, Nagatomo Y, Mizuno A, Kohno T, Rigby A, Fukuda K, Yoshikawa T, Clark A, Cleland J

Clinical Research in Cardiology 107 ( 12 ) 1103 - 1110 2018.12

Research paper (scientific journal), Lead author, Accepted, ISSN 18610684

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Methods: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Results: Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years; p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m 2 ; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. Conclusions: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan.

Access to Document (DOI)

9-year Trend in the Management of Acute Heart Failure in Japan: A Report from the National Consortium of Acute Heart Failure Registries

Shiraishi Y., Kohsaka S., Sato N., Takano T., Kitai T., Yoshikawa T., Matsue Y.

Journal of the American Heart Association (Journal of the American Heart Association) 7 ( 18 ) e008687 2018.09

Research paper (scientific journal), Lead author, Accepted

© 2018 The Authors. Background-—Acute heart failure (AHF) is a heterogeneous condition, and its characteristics and management patterns differ by region. Furthermore, limited evidence is available on AHF outside of Western countries. A project by the National Consortium of Acute Heart Failure Registries was designed to evaluate the trends over time in patient backgrounds, in-hospital management patterns, and long-term outcomes of patients with AHF over 9 years in Japan. Methods and Results-—Between 2007 and 2015, registry data for patients with AHF were collected from 3 large-scale quality AHF registries (ATTEND/WET-HF/REALITY-AHF). Predefined end points were trends over time in age, sex, and clinical outcomes, including short- and long-term mortality and readmission for heart failure. The final data set consisted of 9075 patients with AHF. No significant differences in patient backgrounds and laboratory findings (eg, anemia or renal function) were observed, with the exception of patient age; mean age became substantially higher over 9 years (71.6–77.0 years; P for trend, <0.001). On the contrary, length of hospital stay became shorter (mean, 26–16 days). These changes were not associated with in-hospital mortality (4.7–7.5%) or 30-day heart failure readmission rate (4.8–5.4%), as well as 1-year mortality and heart failure readmission rate (20.1– 23.3% and 23.6–26.2%, respectively). Conclusions-—Length of hospital stay in patients with AHF shortened over the 9-year period despite the increasing age of the patients. However, short- and long-term outcomes do not seem to be affected; continuous efforts to monitor clinical outcomes in patients with AHF are needed.

Access to Document (DOI)

Impact of Triggering Events on Outcomes of Acute Heart Failure

Shiraishi Y, Kohsaka S, Abe T, Harada K, Miyazaki T, Miyamoto T, Iida K, Tanimoto S, Yagawa M, Takei M, Nagatomo Y, Hosoda T, Yamamoto T, Nagao K, Takayama M

American Journal of Medicine 131 ( 2 ) 156 - 164.e2 2018.02

Research paper (scientific journal), Lead author, Accepted, ISSN 00029343

Background: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. Methods: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. Results: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P =.0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. Conclusion: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

Access to Document (DOI)

Real-time analysis of the heart rate variability during incremental exercise for the detection of the ventilatory threshold

Shiraishi Y, Katsumata Y, Sadahiro T, Azuma K, Akita K, Isobe S, Yashima F, Miyamoto K, Nishiyama T, Tamura Y, Kimura T, Nishiyama N, Aizawa Y, Fukuda K, Takatsuki S

Journal of the American Heart Association 7 ( 1 ) 2018.01

Research paper (scientific journal), Lead author, Accepted

Background: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). Methods and Results: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P > 0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P > 0.05). Conclusions: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

Access to Document (DOI)

Degree of dyspnoea in patients with non-ST-elevation acute coronary syndrome: A report from Japanese multicenter registry.

Shiraishi Y, Kohsaka S, Ueda I, Inohara T, Sawano M, Numasawa Y, Hayashida K, Maekawa Y, Momiyama Y, Fukuda K

International Journal of Clinical Practice 70 ( 12 ) 978 - 987 2016.12

Research paper (scientific journal), Lead author, Accepted, ISSN 1368-5031

Access to Document (DOI)

Correlation of Pre- and In-Hospital Systolic Blood Pressure in Acute Heart Failure Patients and the Prognostic Implications　- Report From the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

Shiraishi Y, Kohsaka S, Harada K, Miyamoto T, Tanimoto S, Iida K, Sakai T, Miyazaki T, Yagawa M, Matsushita K, Furihata S, Sato N, Fukuda K, Yamamoto T, Nagao K, Takayama M, Tokyo CCU Network Scientific Committee.

Circulation Journal 80 ( 12 ) 2473 - 2481 2016.11

Research paper (scientific journal), Lead author, Accepted, ISSN 1346-9843

Access to Document (DOI)

Endomyocardial fibrosis: missing tricuspid valve and Fontan-like circulation.

Shiraishi Y, Kohno T, Fujii-Nishimura Y, Shimoda M, Ikeda Y, Nakajima K, Nishiyama T, Nishiyama N, Murata M, Maekawa Y, Sano M, Fukuda K

Heart and Vessels 31 ( 9 ) 1579 - 82 2016.09

Research paper (scientific journal), Lead author, Accepted, ISSN 0910-8327

Access to Document (DOI)

Validation of the Seattle Heart Failure Model in Japanese heart failure patients.

Shiraishi Y, Sawano M, Kohno T, Nishiyama T, Maekawa Y, Sano M, Fukuda K, Kohsaka S

International Journal of Cardiology 203 87 - 9 2016.01

Research paper (scientific journal), Lead author, Accepted, ISSN 0167-5273

Access to Document (DOI)

Validation of the Get With The Guideline-Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level.

Shiraishi Y, Kohsaka S, Abe T, Mizuno A, Goda A, Izumi Y, Yagawa M, Akita K, Sawano M, Inohara T, Takei M, Kohno T, Higuchi S, Yamazoe M, Mahara K, Fukuda K, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

American Heart Journal 171 ( 1 ) 33 - 9 2016.01

Research paper (scientific journal), Lead author, Accepted, ISSN 0002-8703

Access to Document (DOI)

Thrombus in acute aortic dissection with atrial fibrillation: a treatment dilemma.

Shiraishi Y, Kohno T, Egashira T, Maekawa Y, Yamada Y, Yoshitake A, Shimizu H, Sano M, Jinzaki M, Fukuda K

American Journal of Emergency Medicine 33 ( 2 ) 308.e3 - 4 2015.02

Research paper (scientific journal), Lead author, Accepted, ISSN 0735-6757

Access to Document (DOI)

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database.

Shiraishi Y, Kohsaka S, Harada K, Sakai T, Takagi A, Miyamoto T, Iida K, Tanimoto S, Fukuda K, Nagao K, Sato N, Takayama M, Scientific Committee of Tokyo CCU Network.

PloS One 10 ( 11 ) e0142017 2015

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Comments on "the role of the emergency department in acute heart failure clinical trials-Enriching patient identification and enrollment" by Collins et al.

Shiraishi Y, Kohsaka S, Sakai T, Harada K, Sato N, Takagi A, Miyamoto T, Fukuda K, Nagao K, Takayama M

American Heart Journal 166 ( 6 ) e45 - 6 2013.12

Research paper (scientific journal), Lead author, Accepted, ISSN 0002-8703

Access to Document (DOI)

Primary aldosteronism associated with a giant coronary aneurysm after drug-eluting stent implantation.

Shiraishi Y, Tanaka H, Hayashi T, Inui Y, Takayama E, Ikegami Y, Fuse J, Sakamoto M, Chong T, Momiyama Y

Journal of Cardiology Cases 7 ( 1 ) e11 - e14 2013.01

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Association of Tricuspid Regurgitation With Mortality in Heart Failure With Left-Sided Heart Disease

Kitamura M., Amami K., Yaguchi T., Okabe K., Shiraishi Y., Nakamaru R., Nagatomo Y., Goda A., Nomoto M., Mizuno A., Sakamoto M., Ichihara Y.K., Kohno T., Kohsaka S., Yoshikawa T.

Jacc Advances 4 ( 6P1 ) 101832 2025.06

Background: Left-sided heart disease is the leading etiology of tricuspid regurgitation (TR) in heart failure (HF); however, the association between different HF phenotypes and the adverse effects of TR remains unclear. Objectives: The authors aimed to elucidate the association between TR and outcomes across the subtypes of left-sided heart disease in patients hospitalized for HF. Methods: We analyzed data from the multicenter West Tokyo Heart Failure registry between January 2006 and December 2021. Moderate or severe mitral or aortic valve disease was defined as left-sided valve dysfunction (LVD). Patients with congenital heart disease, secondary cardiomyopathy, systemic conditions related to HF, or those with incomplete datasets were excluded. Using a multivariable Cox hazard model, the survival effect of TR on mortality in patients with LVD was examined. Results: Overall, 3,040 presented with LVD (median age, 80 years; 45.9% female), and 2,438 had no LVD (median age, 74 years; 27.8% female). The prevalence of moderate and severe TR was 27.6% and 6.5% in patients with LVD and 9.2% and 1.5% in those without LVD, respectively. The adjusted HRs of moderate and severe TR for mortality were 1.25 (95% CI: 1.03-1.52) and 1.72 (95% CI: 1.30-2.29) in those with LVD, respectively, and 2.15 (95% CI: 1.62-2.84) and 3.09 (95% CI: 1.87-5.09) in those without LVD, respectively. Significant interactions between the subtypes were observed (P = 0.005). Conclusions: TR severity stratified mortality after acute decompensated HF better in patients without LVD than in those with LVD.

Access to Document (DOI)

Exercise hemodynamic evaluation in the management of dasatinib-related pulmonary arterial hypertension: a case report.

Yamashita S, Hiraide T, Shiraishi Y, Katsumata Y, Kataoka M, Fukui S, Kawakami M, Yuasa S, Okamoto S, Fukuda K, Ieda M

Journal of medical case reports 19 ( 1 ) 209 2025.05

Background: Dasatinib-related pulmonary arterial hypertension is a rare complication of chronic therapy for hematological malignancies. Pulmonary hypertension often persists despite drug discontinuation and might require vasodilators. Normalizing pulmonary hemodynamics and avoiding the long-term use of vasodilators is challenging. Case presentation: Patient was a 55-year-old Japanese man complaining of progressive dyspnea on effort and fatigue. He had a history of hypertension and chronic myeloid leukemia treated with dasatinib. He was diagnosed with dasatinib-related pulmonary arterial hypertension by a right heart catheterization at rest, demonstrating a mean pulmonary artery pressure of 31 mmHg and a normal pulmonary arterial wedge pressure of 6 mmHg. Symptoms and hemodynamics significantly improved after the discontinuation of dasatinib and the initiation of upfront combination therapy of vasodilators. An exercise right heart catheterization, performed more than 2 years after the initiation of vasodilators, showed a mean pulmonary artery pressure of 15 mmHg at rest and 29 mmHg at peak exercise (normal reference value, < 30 mmHg), suggesting normal pulmonary microcirculation. On the basis of these findings, pulmonary vasodilators were discontinued. Notably, a repeat exercise right heart catheterization demonstrated preserved pulmonary microcirculation, and the patient has remained asymptomatic for more than 2 years after discontinuing pulmonary-arterial-hypertension-targeted therapy. Conclusions: The evaluation of pulmonary microcirculation by exercise right heart catheterization can be useful for withdrawing pulmonary vasodilators safely in the management of patients with dasatinib-related pulmonary arterial hypertension.

Access to Document (DOI)

Contemporary clinical characteristics and management patterns in hypertrophic cardiomyopathy: insights from baseline enrolment data in a nationwide prospective Japanese registry.

Kubo T, Sugiura K, Tokita Y, Takano H, Takamisawa I, Takayama M, Doi YL, Minami Y, Shirotani S, Ebato M, Tsujiuchi M, Nabeta T, Inomata T, Kato T, Okamoto R, Dohi K, Takei Y, Chikamori T, Watanabe E, Furugen A, Doi H, Akita K, Maekawa Y, Ogimoto A, Tada N, Yokota T, Ikeda S, Yamaguchi O, Izumiya Y, Shibata A, Takashio S, Tsujita K, Maejima Y, Fujino N, Nomura A, Akasaki Y, Higuchi K, Fujita S, Hoshiga M, Shiraishi Y, Ieda M, Miyamoto Y, Kitaoka H

Heart (British Cardiac Society) 2025.03

ISSN 1355-6037

Background The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan. Methods This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis. Results The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy. Conclusions As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.

Access to Document (DOI)

Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.

Miura Y, Higuchi S, Kohno T, Shiraishi Y, Kitamura M, Nagatomo Y, Kawakubo Ichihara Y, Mizuno A, Nakano S, Soejima K, Goda A, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure (WET-HF) Registry Investigators

International journal of obesity (2005) 49 ( 5 ) 888 - 895 2025.01

ISSN 0307-0565

Background: Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia. Methods: A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20–25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated. Results: This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90–0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30–2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34–2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61–8.08; p = 0.002). Conclusions: BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox. (Figure presented.)

Access to Document (DOI)

Rapid Reversal of Pulmonary Hypertension by High-Dose Thiamine Supplementation: A Case Report

Moriizumi T., Hiraide T., Momoi M., Shinya Y., Kishino Y., Shiraishi Y., Iai W., Matsumura K., Kohsaka S., Ieda M.

CJC Open 6 ( 12 ) 1534 - 1537 2024.12

Access to Document (DOI)

COVID-19パンデミックが急性心不全診療における呼吸器管理に与える影響

中野宏己, 山下淳, 河野隆志, 北野大輔, 木庭新治, 白石泰之, 進藤彰人, 神馬崇宏, 武井眞, 塚本茂人, 松下健一, 松田淳也, 原田和昌, 香坂俊, 長尾建, 山本剛, 高山守正, 東京都CCUネットワーク学術委員会

ICUとCCU (医学図書出版(株)) 48 ( 別冊 ) S43 - S46 2024.12

ISSN 0389-1194

【背景】COVID-19パンデミック下では急性心不全患者における非侵襲的陽圧換気(NPPV)の使用制限が予想され,患者予後への悪影響が懸念される。【方法】多施設共同前向きコホートである東京都CCUネットワークに登録された急性心不全患者を対象にCOVID-19流行前の2019年に登録された5,233人とCOVID-19パンデミック下2020年に登録された4,499人の2群間で比較検討した。【結果】COVID-19流行前後でNPPVの使用率は有意に減少し(41.4% vs.32.3%,P<0.001),気管挿管の施行率は上昇した(4.2% vs.6.9%,P<0.001)。一方で患者背景や院内死亡率に有意差を認めなかった(9.5% vs.9.3%,P=0.842)。気管挿管を施行された患者はCOVID-19流行前と比較してCOVID-19パンデミック下では若年で搬送時血圧が高い患者に使用され(145±44 vs.136±43,P=0.021),院内死亡率は低かった(18.3% vs.26.4%,P=0.028)。【結論】COVID-19パンデミック下における急性心不全診療において全体の予後への悪影響は認めなかったが,NPPV使用率が減少し,気管挿管施行率が上昇した。エアロゾル拡散が制御できるNPPV方法の導入が望まれる。(著者抄録)

Pulmonary arterial hypertension therapies in patients with obesity hypoventilation syndrome: a case series.

Daigo K, Hiraide T, Momoi M, Shinya Y, Katsumata Y, Kishino Y, Shiraishi Y, Nishiyama T, Kohsaka S, Ieda M

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 21 ( 4 ) 723 - 732 2024.11

ISSN 1550-9389

Obesity hypoventilation syndrome is caused by complex interactions between multiple pathological processes, including diminished respiratory drive and sleep-related breathing alterations, leading to structural and functional respiratory impairment and ultimately, pulmonary hypertension. Because pulmonary hypertension is closely associated with obesity hypoventilation syndrome, thoroughly evaluating its etiology is essential, and individualized treatments must be considered. We describe 2 patients with obesity hypoventilation syndrome exhibiting severe pulmonary hypertension with pulmonary vascular resistance exceeding 5 Wood units; both were classified as Group 1 pulmonary hypertension, ie, pulmonary arterial hypertension. Initially admitted to our hospital complaining of dyspnea, both patients commenced pulmonary arterial hypertension therapies in addition to positive airway pressure therapy and diuretics, improving their hemodynamic status, dyspnea, and exercise capacity, and finally enabling their discharge. These findings suggest that pulmonary arterial hypertension can coexist with obesity hypoventilation syndrome, and pulmonary arterial hypertension therapies, introduced with careful consideration, may provide substantial benefits for select patients.

Access to Document (DOI)

Post-Discharge Self-Care Confidence and Performance Levels in Hospitalized Heart Failure Patients.

Himeno Y, Kitakata H, Kohno T, Hashimoto S, Fujisawa D, Shiraishi Y, Nakano N, Hiraide T, Kishino Y, Katsumata Y, Yuasa S, Kohsaka S, Ieda M

Journal of cardiac failure 2024.11

ISSN 1071-9164

Background: Multidisciplinary self-care education plays a critical role in ensuring the high-quality transitional care of patients hospitalized due to heart failure (HF). However, whether confidence concerning self-care during their index hospitalizations would influence their post-discharge self-care performances and long-term outcomes remains uncertain. Methods: We conducted an assessment of 100 consecutive patients with HF who completed self-care questionnaires both during their hospitalizations and 1 year after discharge. Among these patients hospitalized due to HF, self-care confidence was assessed immediately after they completed their pre-discharge education program. One year after the index hospitalization, we evaluated self-care performance by using the European Heart Failure Self-care Behavior Scale. Logistic regression analysis was employed to identify determinants of poor self-care behavior 1 year after the hospitalization. Additionally, the Cox proportional hazards model with adjustment for the Seattle Heart Failure Model was applied to assess their association with 2-year mortality and readmission risk. Results: The enrolled patients predominantly had HF with reduced ejection fraction (43.0%), and approximately half of the patients had experienced a previous hospitalization due to HF (47.0%). The 3 worst-performing aspects of post-discharge self-care behavior (among the 12 items) were appropriate consultation for fatigue (40.0%), weight gain (52.0%) and application of regular exercise (57.0%). After adjustment, low self-care confidence during the index hospitalization was associated with poor post-discharge self-care performance (OR: 1.11, CI: 1.00–1.21). Poor post-discharge self-care behavior was not associated with worse prognoses over a 2-year follow-up (hazard ratio [HR]: 1.82, CI: 0.85–3.86); however, the association was significant in patients with reduced ejection fraction (HR: 4.04, CI: 1.17–13.89) and previous HF hospitalization (HR: 3.66, CI: 1.46–9.13). Conclusions: Post-discharge self-care performance was associated with self-care confidence during the index HF hospitalization. Effective measures that improve pre-discharge confidence levels in self-care should be considered to enhance the quality of transitional care.

Access to Document (DOI)

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.

Takeuchi S, Kohno T, Goda A, Shiraishi Y, Kitamura M, Nagatomo Y, Takei M, Nomoto M, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators

International journal of cardiology (International Journal of Cardiology) 409 132190 2024.05

ISSN 0167-5273

Background: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. Methods: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30–60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30–44, 45–59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41–49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. Results: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74–86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43–0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. Conclusions: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Access to Document (DOI)

Supra-normal and mildly reduced ejection fraction in women -An overlooked vulnerable subpopulation in heart failure.

Kawai A, Nagatomo Y, Yukino-Iwashita M, Ikegami Y, Takei M, Goda A, Kohno T, Mizuno A, Kitamura M, Nakano S, Sakamoto M, Shiraishi Y, Kohsaka S, Adachi T, Yoshikawa T, as WET-HF investigators

International journal of cardiology (International Journal of Cardiology) 409 132166 2024.05

ISSN 0167-5273

Background: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. Methods: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. Results: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and β-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037). Conclusions: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management.

Access to Document (DOI)

Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging　- A Prospective Multicenter Study.

Kato S, Kitai T, Utsunomiya D, Azuma M, Fukui K, Hagiwara E, Ogura T, Ishibashi Y, Okada T, Kitakata H, Shiraishi Y, Torii S, Ohashi K, Takamatsu K, Yokoyama A, Hirata KI, Matsue Y, Node K

Circulation journal : official journal of the Japanese Circulation Society 88 ( 9 ) 1450 - 1458 2024.03

ISSN 1346-9843

Background: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR). Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. Conclusions: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

Access to Document (DOI)

Prognostic effect of a vasopressin V<inf>2</inf> receptor antagonist in acute congestive heart failure patients with hypoperfusion, the wet–cold pattern

Matsushita K., Harada K., Miyamoto T., Iida K., Yamamoto Y., Shiraishi Y., Nagatomo Y., Yoshino H., Yamamoto T., Nagao K., Takayama M.

European Journal of Clinical Pharmacology 80 ( 11 ) 1795 - 1805 2024

ISSN 00316970

Purpose: This study investigated whether the oral vasopressin V2 receptor antagonist tolvaptan has beneficial effects on mortality in real-world congestive heart failure (CHF) patients with hypoperfusion (i.e. the wet–cold pattern), from the viewpoint of cardiorenal syndrome. Methods: Data on 5511 consecutive CHF patients were extracted from the Tokyo CCU Network data registry. Congestion and hypoperfusion were defined by Nohria–Stevenson clinical profiles at the time of hospitalization. Propensity scores for tolvaptan use were calculated for each patient and used to assemble two matched cohorts of patients receiving tolvaptan or not in the CHF with and without hypoperfusion groups. Results: Of the entire study cohort, 1073 patients (19%) had CHF with hypoperfusion (i.e. the wet–cold pattern). In-hospital mortality was significantly higher for CHF patients with than without hypoperfusion (log-rank, P < 0.001). The rate of tolvaptan use did not differ significantly between CHF patients with and without hypoperfusion (15% vs. 14%, respectively; P = 0.7848). In the propensity-matched CHF with hypoperfusion cohort, there was a significant association between the use of tolvaptan and a reduction in in-hospital mortality (log-rank, P = 0.0052). Conversely, in the matched CHF without hypoperfusion cohort, tolvaptan use was not associated with in-hospital mortality (log-rank, P = 0.4417). Conclusion: There was a significant association between the use of tolvaptan and a reduction in in-hospital mortality in CHF patients with, but not without, hypoperfusion. These findings hint at possible individualized therapies for patients with CHF.

Access to Document (DOI)

Effect of basic activities of daily living independence on home discharge and long-term outcomes in patients hospitalized with heart failure

Izumi K., Kohno T., Goda A., Takeuchi S., Shiraishi Y., Higuchi S., Nakamaru R., Nagatomo Y., Kitamura M., Takei M., Sakamoto M., Mizuno A., Nomoto M., Soejima K., Kohsaka S., Yoshikawa T.

Heart and Vessels 40 ( 6 ) 471 - 483 2024

ISSN 09108327

Patients hospitalized for heart failure (HF) experience impairments in functional status, primarily affecting basic activities of daily living (ADL). We investigated the independent effect of functional status for ADL on patient-centered outcomes (i.e., home discharge) and conventional clinical outcomes in HF. We analyzed 2936 consecutive hospitalized patients with HF from a prospective multicenter registry. The functional status of ADL was assessed before discharge by using the Barthel index (BI). Patients were categorized into the lower BI group (≤85; the lowest tertile) and higher BI group (>85). We evaluated the risk-adjusted association between BI and non-home discharge, as well as the two-year all-cause mortality. Exploratory subgroups included patients categorized by age, sex, HF hospitalization, left ventricular ejection fraction, body mass index, and estimated glomerular filtration rate (eGFR). Of the participants (age: 79 [69–85] years; 41.1% women), 86.3% were discharged home. A lower BI was independently associated with non-home discharge (OR: 5.12, 95% CI 3.86–6.80) and higher all-cause mortality rates (HR: 1.96, 95% CI 1.58–2.45). Two-year cardiac and non-cardiac mortality rates were higher in the lower BI group; however, the proportion of cardiac causes in two-year deaths did not differ between the lower and higher BI groups (48.8% vs. 49.5%, P = 0.891). Subgroup analyses consistently demonstrated an association between two-year mortality and lower BI; however, this association was stronger among patients with a higher eGFR (P-value for interaction = 0.004). A lower BI was independently associated with non-home discharge and higher mortality rates because of cardiac- and non-cardiac-related causes in hospitalized patients with HF.

Access to Document (DOI)

Discontinuation of Oral Anticoagulants in Atrial Fibrillation Patients: Impact of Treatment Strategy and on Patients' Health Status.

Nakamaru R, Ikemura N, Kimura T, Katsumata Y, Sherrod CF, Miyama H, Shiraishi Y, Kanki H, Negishi K, Ueda I, Fukuda K, Takatsuki S, Kohsaka S

Journal of clinical medicine (Journal of Clinical Medicine) 12 ( 24 ) 2023.12

ISSN 2077-0383

Aims: The discontinuation of oral anticoagulants (OACs) remains as a significant concern in the management of atrial fibrillation (AF). The discontinuation rate may vary depending on management strategy, and physicians may also discontinue OACs due to concerns about patient satisfaction with their care. We aimed to assess the incidence of OAC discontinuation and its relationship to patients’ health in an outpatient AF registry. Methods and Results: From a multicenter registry for newly recognized AF patients (n = 3313), we extracted 1647 (49.7%) patients with OACs and a CHA2DS2-Vasc score of ≥2. Discontinuation was defined as sustained cessation of OACs within a 1-year follow-up. We examined predictors associated with discontinuation and its relations to health status defined by the AFEQT questionnaire. Of the 1647 patients, 385 (23.6%) discontinued OACs after 1 year, with discontinuation rates varying across treatment strategies (15.3% for catheter ablation, 4.9% for rhythm control with antiarrhythmic drugs, and 3.0% for rate control). Successful rhythm control was associated with discontinuation in the catheter ablation (OR 6.61, 95% CI 3.00–14.6, p < 0.001) and antiarrhythmic drugs (OR 6.47, 95% CI 2.62–15.9, p < 0.001) groups, whereas the incidence of bleeding events within 1 year was associated with discontinuation in the rate control group. One-year AFEQT scores did not significantly differ between patients who discontinued OACs and those who did not in each treatment strategy group. Conclusions: OAC discontinuation was common among AF patients with significant stroke risk but varied depending on the chosen treatment strategy. This study also found no significant association between OAC discontinuation and patients’ health status.

Access to Document (DOI)

バルーン肺動脈形成術後の急性肺血栓塞栓症に対して抗凝固療法の変更が有効であった慢性血栓塞栓性肺高血圧症の1例

梅井智彦, 岸野喜一, 川上崇史, 平出貴裕, 白石泰之, 猪原拓, 湯浅慎介, 福田恵一

心臓 ((公財)日本心臓財団) 55 ( 7 ) 743 - 748 2023.07

ISSN 0586-4488

症例は65歳男性で、労作時呼吸困難を主訴とした。リバーロキサバンによる抗凝固療法中の慢性血栓塞栓性肺高血圧症に対し、バルーン肺動脈形成(BPA)目的で入院した。BPA治療後、労作時息切れ症の改善を認めたが、2ヵ月後に再増悪を認めた。肺動脈造影では左A10に血栓を疑う造影欠損を認め、肺高血圧症も認めた。吸引とバルーン拡張を繰り返したが、造影欠損の完全な消失は得られなかった。赤色血栓が吸引されたため、亜急性期新鮮血栓を疑い、ヘパリン持続静注治療後にワルファリンに切り替えた。肺高血圧症にはリオシグアトを導入した。血栓は完全に消失し、血流も良好で、労作時息切れ症状も改善した。現在まで再燃なく経過良好である。

Perspectives of hospitalized heart failure patients: preferred and perceived participation roles in treatment decisions.

Sekine O, Kitakata H, Kohsaka S, Fujisawa D, Nakano N, Shiraishi Y, Kishino Y, Katsumata Y, Yuasa S, Fukuda K, Kohno T

Heart and vessels (Heart and Vessels) 38 ( 10 ) 1244 - 1255 2023.06

ISSN 0910-8327

Shared decision-making (SDM) is a pivotal process in seeking optimal individual treatment and incorporating clinical evidence and patients’ autonomous preferences. However, patients’ actual attitudes toward participation in decision-making for state-of-the-art heart failure (HF) treatment remain unclear. We conducted a questionnaire-based survey distributed by nurses and physicians specializing in HF care to assess patients’ preferred and perceived participation roles in treatment decision-making during the index hospitalization, rated on five scales (from extremely passive to purely autonomous attitudes). Simultaneously, we investigated the important factors underlying treatment decision-making from the perspective of hospitalized HF patients. Of the 202 patients who were approached by our multidisciplinary HF team between 2017 and 2020, 166 (82.2%) completed the survey. Logistic regression analyses were conducted to identify the clinical determinants of patients who reported that they left all decisions to physicians (i.e., extremely passive attitude). Of the 166 participants (male 67.5%, median age 73 years), 32.5% preferred an extremely passive attitude, while 61.4% reported that they actually chose an extremely passive attitude. A sole determinant of choosing an extremely passive decision-making role was lower educational status (odds ratio: 2.11, 95% confidence interval 1.11–4.00). The most important factor underlying the decision-making was “Physician recommendation” (89.2%). Notably, less than 50% considered “In alignment with my values and preferences” as an important factor underlying treatment decision-making. The majority of HF patients reported that they chose an extremely passive approach, and patients prioritized physician recommendation over their own values and preferences. Graphical abstract: [Figure not available: see fulltext.].

Access to Document (DOI)

Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry.

Niimi N, Kohsaka S, Shiraishi Y, Takei M, Kohno T, Nakano S, Nagatomo Y, Sakamoto M, Saji M, Ikemura N, Inohara T, Ueda I, Fukuda K, Yoshikawa T

Clinical research in cardiology : official journal of the German Cardiac Society (Clinical Research in Cardiology) 112 ( 8 ) 1108 - 1118 2023.04

ISSN 1861-0684

Background: Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods. Methods: A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year. Results: At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: ‘no physical congestions’ (N = 251); ‘congestion without JVD’ (N = 1415); and ‘congestion with JVD’ (N = 1495). Patients in ‘no physical congestion’ were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in ‘congestion without JVD’, and ‘congestion with JVD’ were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in ‘no physical congestion,’ ‘congestion without JVD,’ and ‘congestion with JVD’, respectively), the patients in ‘congestion with JVD’ were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26–2.55 when ‘no physical congestion’ was a reference). Conclusions: Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes.

Access to Document (DOI)

Geriatric Nutritional Risk Index at Hospital Admission or Discharge in Patients with Acute Decompensated Heart Failure.

Ono M, Mizuno A, Kohsaka S, Shiraishi Y, Kohno T, Nagatomo Y, Goda A, Nakano S, Komiyama N, Yoshikawa T

Journal of clinical medicine (Journal of Clinical Medicine) 12 ( 5 ) 2023.02

ISSN 2077-0383

Geriatric Nutritional Risk Index (GNRI) is known both as a reliable indicator of nutritional status and a predictor of long-term survival among patients with acute decompensated heart failure (ADHF). However, the optimal timing to evaluate GNRI during hospitalization remains unclear. In the present study, we retrospectively analyzed patients hospitalized with ADHF in the West Tokyo Heart Failure (WET-HF) registry. GNRI was assessed at hospital admission (a-GNRI) and discharge (d-GNRI). Out of 1474 patients included in the present study, 568 (40.1%) and 796 (57.2%) patients had lower GNRI (<92) at hospital admission and discharge, respectively. After the follow-up (median 616 days), 290 patients died. The multivariable analysis showed that all-cause mortality was independently associated with d-GNRI (per 1 unit decrease, adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.09, p < 0.001), but not with a-GNRI (aHR: 0.99, 95% CI: 0.97–1.01, p = 0.341). The predictability of GNRI for long-term survival was more pronounced when evaluated at hospital discharge than at hospital admission (area under the curve 0.699 vs. 0.629, DeLong’s test p < 0.001). Our study suggested that GNRI should be evaluated at hospital discharge, regardless of the assessment at hospital admission, to predict the long-term prognosis for patients hospitalized with ADHF.

Access to Document (DOI)

Standard modifiable cardiovascular risk factors in patients with acute coronary syndrome: A report from multicenter percutaneous coronary intervention registry

Iwata J., Inohara T., Shiraishi Y., Nakamaru R., Niimi N., Ueda I., Suzuki M., Noma S., Numasawa Y., Fukuda K., Kohsaka S.

Journal of Cardiology (Journal of Cardiology) 81 ( 6 ) 571 - 576 2023

ISSN 09145087

Background: High mortality in patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors [SMuRFs (e.g. diabetes, hypertension, smoking, and dyslipidemia)] has been reported. However, details regarding their acute presentation and reasons for the excess risk remain unclear. Method: Patient-level data were extracted from a multicenter procedure-based registry (KiCS-PCI). We analyzed consecutive patients with ACS who underwent de novo percutaneous coronary intervention (PCI) between 2009 and 2020. The primary outcome of interest was the in-hospital mortality. Results: Among the 10,523 patients with ACS, 7775 met the inclusion criteria. Patients without SMuRFs who underwent PCI [n = 529 (6.8 %)] were older [median 71 (IQR: 63–79) vs. 68 (59–76) years, p < 0.001] and more often presented with cardiogenic shock or cardiopulmonary arrest (14.6 % vs. 8.6 %, p < 0.001; 12.7 % vs. 5.3 %, p < 0.001, respectively). In patients with ST-elevation myocardial infarction (STEMI), median door-to-balloon time was significantly longer in SMuRF-less patients (90 min vs 82 min). In-hospital death was significantly higher in SMuRF-less patients [10.2 % vs. 4.1 %, p < 0.001, adjusted odds ratio, 1.81 (95%CI, 1.26–2.59); p = 0.001], whereas the rate of procedural complications showed no significant difference. When stratified by the ACS presentation pattern, the findings were consistent, although the association between SMuRF-less and the increased risk of in-hospital mortality was not statistically significant in patients with non-ST-elevation- (NSTE)-ACS. Conclusions: SMuRF-less ACS patients frequently presented with cardiopulmonary arrest and/or cardiogenic shock, leading to high in-hospital mortality. When stratified by the ACS presentation pattern, the association of SMuRF-less and the increased risk of mortality was more prominent in STEMI patients and it was not statistically significant in NSTE-ACS patients. Almost half of these patients had amendable left main trunk or left anterior descending artery disease and treating clinicians should be aware of this paradox to avoid the delay in treatment.

Access to Document (DOI)

Forecasting the Acute Heart Failure Admissions: Development of Deep Learning Prediction Model Incorporating the Climate Information

Jimba T., Kodera S., Kohsaka S., Otsuka T., Harada K., Shindo A., Shiraishi Y., Kohno T., Takei M., Nakano H., Matsuda J., Yamamoto T., Nagao K., Takayama M.

Journal of Cardiac Failure (Journal of Cardiac Failure) 30 ( 2 ) 404 - 409 2023

ISSN 10719164

Background: Climate is known to influence the incidence of cardiovascular events. However, their prediction with traditional statistical models remains imprecise. Methods and Results: We analyzed 27,799 acute heart failure (AHF) admissions within the Tokyo CCU Network Database from January 2014 to December 2019. High-risk AHF (HR-AHF) day was defined as a day with the upper 10th percentile of AHF admission volume. Deep neural network (DNN) and traditional regression models were developed using the admissions in 2014–2018 and tested in 2019. Explanatory variables included 17 meteorological parameters. Shapley additive explanations were used to evaluate their importance. The median number of incidences of AHF was 12 (9–16) per day in 2014–2018 and 11 (9–15) per day in 2019. The predicted AHF admissions correlated well with the observed numbers (DNN: R2 = 0.413, linear regression: R2 = 0.387). The DNN model was superior in predicting HR-AHF days compared with the logistic regression model [c-statistics: 0.888 (95% CI: 0.818–0.958) vs 0.827 (95% CI: 0.745–0.910): P = .0013]. Notably, the strongest predictive variable was the 7-day moving average of the lowest ambient temperatures. Conclusions: The DNN model had good prediction ability for incident AHF using climate information. Forecasting AHF admissions could be useful for the effective management of AHF.

Access to Document (DOI)

Real-time analysis of heart rate variability during aerobic exercise in patients with cardiovascular disease

Ikura H., Katsumata Y., Seki Y., Ryuzaki T., Shiraishi Y., Miura K., Sato K., Fukuda K.

IJC Heart and Vasculature (IJC Heart and Vasculature) 43 101147 2022.12

ISSN 23529067

Background: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient's medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise. Methods: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO2) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland–Altman method was used to confirm similarity. Results: VO2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO2: r = 0.647, HR: r = 0.534). The Bland–Altman plot revealed no bias between the mean values (e.g., 19 min; VO2: −0.22 mL/kg/min; HR: −0.07/min). Conclusion: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

Access to Document (DOI)

Association of Potassium Level at Discharge with Long-Term Mortality in Hospitalized Patients with Heart Failure

Miura Y., Higuchi S., Kohno T., Shiraishi Y., Kitamura M., Nagatomo Y., Takei M., Nakano S., Goda A., Soejima K., Kohsaka S., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 11 ( 24 ) 2022.12

ISSN 2077-0383

Dyskalemia (hypokalemia and hyperkalemia) is a common comorbidity of heart failure (HF). Although dyskalemia is associated with poor prognosis, different prognostic impacts of hypo- and hyperkalemia remain vastly unclear. This study investigated the association of dyskalemia with prognosis in HF patients, especially the mode of death and left ventricular ejection fraction (LVEF). The multicenter study included 3398 patients hospitalized for HF. Patients were divided into three groups based on serum potassium levels at discharge: hypokalemia (<3.5 mEq/L; n = 115 (3.4%)), normokalemia (3.5–5.0 mEq/L; n = 2960 (87.1%)), and hyperkalemia (≥5.0 mEq/L; n = 323 (9.5%)). Two-year all-cause, cardiac, and non-cardiac mortality was evaluated. Association of serum potassium with two-year mortality demonstrated a U-shaped curve, with a worse prognosis for patients with hypokalemia. All-cause mortality at two-years did not differ among the three groups. Hypokalemia was associated with 2-year cardiac death (adjusted hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20–5.64) in HF with reduced ejection fraction (HFrEF; LVEF < 40%), but not in non-HFrEF. Regardless of LVEF, hyperkalemia was not independently associated with any mortality. Hypokalemia was independently associated with cardiac death, particularly in HFrEF patients. Such an association was not observed in hyperkalemia regardless of LVEF.

Access to Document (DOI)

画像情報と深層学習を応用した心疾患患者の予後予測

白石泰之

上原記念生命科学財団研究報告集 ((公財)上原記念生命科学財団) 36 1 - 6 2022.12

Social Isolation and Implementation of Advanced Care Planning Among Hospitalized Patients With Heart Failure

Kitakata H., Kohno T., Kohsaka S., Fujisawa D., Nakano N., Sekine O., Shiraishi Y., Kishino Y., Katsumata Y., Yuasa S., Fukuda K.

Journal of the American Heart Association (Journal of the American Heart Association) 11 ( 21 ) e026645 2022.11

Background The implementation of advance care planning (ACP) in heart failure management is insufficient. Social isolation (SI) could be a barrier to ACP initiation, albeit the relationship between SI and patients' preference for ACP or end-of-life care remains unknown. Methods and Results We conducted a questionnaire survey, including assessments of SI using the 6-item Lubben Social Network Scale as well as patients' perspectives on ACP and end-of-life care. Of the 160 patients approached by our multidisciplinary heart failure team during admission, 120 patients (75.0%) completed the survey (median age, 73.0 years; men, 74.2%). A Cox proportional hazard model was constructed to elucidate the short-term (180-day) prognostic impact of SI. Overall, 28.3% of participants were at high risk for SI (6-item Lubben Social Network Scale score <12). High-risk patients had more negative attitudes toward ACP than those without (61.8% versus 80.2%; P=0.035). The actual performance of ACP conversation in patients with and without high risk were 20.6% and 30.2%, respectively. Regarding preference in end-of-life care, "Saying what one wants to tell loved ones" (73.5% versus 90.6%; P=0.016) and "Spending enough time with family" (58.8% versus 77.9%; P=0.035) were less important in high-risk patients. High risk for SI was associated with higher 180-day risk-adjusted all-cause mortality (hazard ratio, 7.89 [95% CI, 1.53-40.75]). Conclusions In hospitalized patients with heart failure, high risk for SI was frequently observed. High-risk patients were associated with a negative attitude toward ACP, despite higher mortality. Further research is required to establish an ideal approach to provide ACP in socially vulnerable patients.

Access to Document (DOI)

Low blood pressure and guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Izumi K, Kohno T, Goda A, Takeuchi S, Shiraishi Y, Saji M, Nagatomo Y, Tanaka TD, Takei M, Nakano S, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology (International Journal of Cardiology) 370 255 - 262 2022.10

ISSN 0167-5273

Background: Patients with heart failure (HF) presenting with low blood pressure (BP) have been underrepresented in large-scale clinical trials. We investigated the characteristics and implementation of conventional guideline-directed medical therapy (GDMT; renin-angiotensin system inhibitors and β-blockers) in patients with low BP hospitalized for HF with systolic dysfunction. Methods: Conventional GDMT was evaluated by discharge BP among 2043 consecutive patients with HF and left ventricular ejection fraction (LVEF) < 50% in the WET-HF registry. Among the 708 (34.7%) patients with lower discharge BP (≤ 100 mmHg; the lower tertiles), exploratory subgroups included patients with previous HF hospitalization, inotrope use, New York Heart Association (NYHA) III–IV class, and lower estimated glomerular filtration rate (eGFR) and LVEF (lower than median value). We evaluated the risk-adjusted association between GDMT implementation and 2-year adverse events (all-cause mortality or HF rehospitalization). Results: Among the 2043 patients (age 74 [63–82] years), the median systolic BP was 108 (98–120) mmHg. Among patients with lower BP, GDMT prescription rate was 62.7%, and GDMT use was associated with decreased adverse events (HR:0.74, 95%CI:0.58–0.94). GDMT prescription rates were lower among higher-NYHA class and lower-eGFR subgroups compared with their reference subgroups, and directionally similar outcomes were noted in all subgroups (favoring GDMT use); however, this association was somewhat attenuated in the lower-eGFR group (HR:0.87, 95%CI:0.64–1.17). Conclusions: Conventional GDMT use was associated with decreased adverse outcomes in most patients with HF compounded by systolic dysfunction and low BP, albeit caution is warranted in patients with renal dysfunction.

Access to Document (DOI)

Malnutrition in real-world patients hospitalized for heart failure with preserved ejection fraction and its potential impact on generalizability of EMPEROR-Preserved trial.

Takeuchi S, Kohno T, Goda A, Shiraishi Y, Saji M, Nagatomo Y, Tanaka TD, Takei M, Nakano S, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology (International Journal of Cardiology) 370 263 - 270 2022.10

ISSN 0167-5273

Background: Despite the benefits of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin, its suitability for patients with heart failure (HF) in the real-world setting remains unclear. Considering the unique pharmacological profile of SGLT2i (e.g., glucose excretion leading to calorie loss) and increasingly aging patients with HF, applicability of trials' finding in patients with malnutrition is important. Methods: We examined 1633 consecutive patients with a preserved left ventricular ejection fraction (LVEF; >40%) enrolled in a multicenter-based acute HF registry. After applying the EMPEROR-Preserved eligibility criteria, we compared the baseline characteristics of trial-eligible and actual trial participants, and patients with and without malnutrition among the trial-eligible group. Malnutrition was assessed by the geriatric nutritional risk index (GNRI). The trial-eligible patients were divided into high (GNRI≥92) and low (GNRI<92) nutritional groups, and a composite endpoint comprising all-cause death and HF rehospitalization was evaluated. Results: Majority (70.2%) of the analyzed patients were eligible for the EMPEROR-Preserved trial (age: 77 ± 12 years and body mass index [BMI]: 22.0 ± 4.1 kg/m2), but were older and had lower BMIs than the actual trial participants. Notably, 51.9% of the eligible patients were at high risk for malnutrition and had a higher rate of the composite endpoint than non-malnourished counterparts (HR 1.27, 95%CI 1.04–1.56, P = 0.020). The difference in outcomes was predominantly due to mortality from non-cardiac causes. Conclusions: Mostly patients with HF in a real-world setting met the EMPEROR-Preserved criteria; however, approximately half were at high risk for malnutrition with poorer outcomes owing to non-cardiac-related causes.

Access to Document (DOI)

Confidence in self-care after heart failure hospitalization.

Hashimoto S, Kitakata H, Kohsaka S, Fujisawa D, Shiraishi Y, Nakano N, Sekine O, Kishino Y, Katsumata Y, Yuasa S, Fukuda K, Kohno T

Journal of cardiology (Journal of Cardiology) 81 ( 1 ) 42 - 48 2022.10

ISSN 0914-5087

Background: Understanding patient perspectives of self-care is critical for improving multidisciplinary education programs and adherence to such programs. However, perspectives of self-care for patients with heart failure (HF) as well as the association between patient perspectives and patient-physician communication remain unclear. Methods: Confidence levels regarding self-care behaviors (eight lifestyle behaviors and four consulting behaviors) and self-monitoring were assessed using a self-administered questionnaire survey, which was directly distributed by dedicated physicians and nurses to consecutive patients hospitalized with HF in a tertiary-level hospital. Patient-physician communication was evaluated according to the quality of physician-provided information regarding “treatment and treatment choices” and “prognosis” using the Prognosis and Treatment Perception Questionnaire. Out of 202 patients, 187 (92.6 %) agreed to participate, and 176 completed the survey [valid response rate, 87.1 %; male, 67.0 %; median age, 73 (63–81) years]. Multivariate logistic regression analyses were conducted to predict low confidence in self-care (score in the lowest quartile). Results: High confidence (confident or completely confident >75 % of patients) was observed for all self-care behavior categories except low-salt diet (63.1 %), regular exercise (63.1 %), and flu vaccination (65.9 %). Lower confidence in self-care behavior was associated with low quality of patient-physician communication. With regard to self-monitoring, 62.5 % of patients were not confident in distinguishing worsening symptoms of HF from other diseases; non-confidence was also associated with low quality of patient-physician communication. Conclusions: Hospitalized patients with HF had low confidence regarding regular exercise, salt restriction, and flu vaccination. The results also suggest patient-physician communication affects patient confidence.

Access to Document (DOI)

Association between class of foundational medication for heart failure and prognosis in heart failure with reduced/mildly reduced ejection fraction.

Ito M, Maeda D, Matsue Y, Shiraishi Y, Dotare T, Sunayama T, Nogi K, Takei M, Ueda T, Nogi M, Ishihara S, Nakada Y, Kawakami R, Kagiyama N, Kitai T, Oishi S, Akiyama E, Suzuki S, Yamamoto M, Kida K, Okumura T, Nagatomo Y, Kohno T, Nakano S, Kohsaka S, Yoshikawa T, Saito Y, Minamino T

Scientific reports (Scientific Reports) 12 ( 1 ) 16611 2022.10

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF.

Access to Document (DOI)

Divergent effect of blood glucose dysregulation on long-term clinical outcome in acute decompensated heart failure: A reappraisal in contemporary practice.

Chishiki T, Nagatomo Y, Saji M, Takei M, Goda A, Kohno T, Nakano S, Nishihata Y, Ikegami Y, Shiraishi Y, Kohsaka S, Adachi T, Yoshikawa T, for WET-HF Investigators.

International journal of cardiology (International Journal of Cardiology) 365 91 - 99 2022.07

ISSN 0167-5273

Background: The prognostic implication of elevated or decreased blood glucose (BG) level in acute decompensated heart failure (ADHF) has been still controversial. Indices of stress hyperglycemia, expressed by the ratio of BG and chronic BG control, has been reported to be associated with poor outcome in different disease population. We sought to assess BG at admission and %ΔBG, an index of BG deviation from estimated average BG calculated from glycated hemoglobin (HbA1c), on the long-term outcome in ADHF patients. Methods and results: The West Tokyo Heart Failure (WET-HF) Registry is a prospective multicenter registry enrolling consecutive hospitalized ADHF patients. Among the patients (N = 3078, 77 [67–84] years, male 59%), BG at admission discriminated the long-term (1000 days) incidence of ADHF rehospitalization, but not cardiac death. BG at admission showed a U-shape relationship with the long-term incidence of ADHF rehospitalization after adjustment for covariates. Especially, in patients with HbA1c ≥ 6.5%, the lowest quartile showed the highest risk of ADHF rehospitalization. On the contrary, %ΔBG showed U-shape relationship with the long-term incidence of cardiac death after discharge, rather than ADHF rehospitalization after adjustment for covariates. In addition, elevated %ΔBG was associated with the long-term risk of sudden cardiac death (SCD) even after adjustment for covariates. Conclusions: For ADHF patients, BG at admission and %ΔBG might be a simple, useful tool for predicting and stratifying long-term risk of cardiac events. Especially, elevated %ΔBG might be an important in predicting hard events such as cardiac death or SCD.

Access to Document (DOI)

Association of ambient temperature and acute heart failure with preserved and reduced ejection fraction.

Jimba T, Kohsaka S, Yamasaki M, Otsuka T, Harada K, Shiraishi Y, Koba S, Takei M, Kohno T, Matsushita K, Miyazaki T, Kodera S, Tsukamoto S, Iida K, Shindo A, Kitano D, Yamamoto T, Nagao K, Takayama M, Tokyo CCU Network Scientific Committee.

ESC heart failure (ESC Heart Failure) 9 ( 5 ) 2899 - 2908 2022.06

Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5–13.3°C; IQR3 13.3–19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2 = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per −1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140–100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per −1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

Access to Document (DOI)

Multimorbidity, guideline-directed medical therapies, and associated outcomes among hospitalized heart failure patients.

Takeuchi S, Kohno T, Goda A, Shiraishi Y, Kawana M, Saji M, Nagatomo Y, Nishihata Y, Takei M, Nakano S, Soejima K, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

ESC heart failure (ESC Heart Failure) 9 ( 4 ) 2500 - 2510 2022.05

Aims: Multimorbidity is common among heart failure (HF) patients and may attenuate guideline-directed medical therapy (GDMT). Multimorbid patients are under-represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes. Methods and results: We examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (<50%) in a multicentre registry (West Tokyo HF Registry: WET-HF). Ten comorbid conditions in the WET-HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0–2: n = 451; 3–4: n = 787; and ≥5: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all-cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3–4: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13–1.77, P = 0.003; ≥5: HR 2.12, 95%CI 1.69–2.65, P < 0.001; and reference: 0–2] and lower GDMT prescription rate (0–2: 69.2%; 3–4: 57.7%; and ≥5: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0–2: HR 0.53, 95%CI 0.35–0.78; P = 0.001; 3–4: HR 0.82, 95%CI 0.65–1.04, P = 0.095; and ≥5: HR 0.81, 95%CI 0.65–1.00, P = 0.053; P for interaction = 0.156). Conclusions: Comorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients.

Access to Document (DOI)

Regional variations in the process of care for patients undergoing percutaneous coronary intervention in Japan

Shoji S., Yamaji K., Sandhu A.T., Ikemura N., Shiraishi Y., Inohara T., Heidenreich P.A., Amano T., Ikari Y., Kohsaka S.

The Lancet Regional Health - Western Pacific (The Lancet Regional Health - Western Pacific) 22 100425 2022.05

Background: Measuring the quality of care has been central for improving the outcomes of patients undergoing percutaneous coronary intervention (PCI). This study described the performance rates and regional variations in quality metrics for PCI using a representative national Japanese registry. Methods: Overall, 760,854 patients across 714 institutions (2016–2018) were analysed. Quality metrics included preprocedural antiplatelet therapy use, door-to-balloon time ≤90 min for ST-elevation myocardial infarction, transradial approach, and preprocedural noninvasive stress testing for elective cases in 47 Japanese prefectures. Coronary computed tomography angiography (CCTA) and fractional flow reserve (FFR) were also evaluated. Factors associated with preprocedural testing rates were evaluated using multivariable linear regression. Findings: Rates of preprocedural antiplatelet therapy use were high with low variations (96·4% [94·7–97·2%]), but there was still substantial room for improvement in the rates of door-to-balloon time (74·7% [71·2–78·9%]) and transradial approach use (70·9% [65·1–73·4%]). Rates of preprocedural noninvasive stress testing were low with substantial variation (36·6% [27·1–49·7%]). Additionally, we found substantial variations in CCTA (50·0% [39·5–55·1%]) and FFR measurement (15·7% [113·–18·3%]) rates. The number of scintigraphy scanners/ prefecture was associated with the performance of noninvasive stress testing (13·4% [95% CI, 2·45–24·4%] increase for every 1/100,000 population increase in scanners). Interpretations: We observed substantial regional variation in the use of preprocedural testing, and its performance was directly related to nuclear-scanner availability. These findings suggest the need for targeted efforts in improving testing rates, whether by optimising resource allocation or additional education or feedback mechanisms. Funding: This study was funded by the Japan Society for the Promotion of Science (Grant Nos. 20H03915, 16H05215, 16KK0186, and 20K22883) and by the Ministry of Health, Labor and Welfare Grants-in-Aid for Scientific Research Program (Grant No. 21FA1015). The J-PCI registry is led and supported by the Japanese Association of Cardiovascular Intervention and Therapeutics.

Access to Document (DOI)

Conventional medical therapy in heart failure patients eligible for the PARADIGM-HF, DAPA-HF, and SHIFT trials.

Shoji S, Kohsaka S, Shiraishi Y, Kohno T, Sawano M, Ikemura N, Niimi N, Nagatomo Y, Tanaka TD, Takei M, Ono T, Sakamoto M, Nakano S, Nakamura I, Inoue S, Fukuda K, Yoshikawa T

International journal of cardiology (International Journal of Cardiology) 359 76 - 83 2022.04

ISSN 0167-5273

Background: Recent trials on novel heart failure (HF) treatments (angiotensin receptor-neprilysin inhibitor, sodium-glucose cotransporter 2 inhibitor, and ivabradine) emphasize the use of conventional medical therapy (angiotensin-converting enzyme inhibitors, beta-blockers [BB], and mineral corticosteroid receptor antagonists). We aimed to evaluate the prescription rate of conventional medical therapy and its association with long-term outcomes in patients eligible for recent trials. Methods: We examined 1295 consecutive patients with HF with reduced ejection fraction (HFrEF) from a multicenter registry (WET-HF registry). We assessed conventional medical therapy implementation among patients meeting the PARADIGM-HF/DAPA-HF and SHIFT enrollment criteria. We also examined the association between conventional medical therapy use and long-term outcomes within each enrollment criterion. Results: Overall, 62.2% and 35.3% of HFrEF patients met the enrollment criteria of the PARADIGM-HF/DAPA-HF and SHIFT trials. Only 33.9% and 31.9% received full conventional medical therapy within each patient subset. Notably, 84.2% of patients who met the SHIFT enrollment criteria were on BB, and only 23.0% and 4.4% were on ≥50% or the full recommended dose, respectively. Implementation of full conventional medical therapy use was associated with lower 2-year mortality and HF readmission rates in the PARADIGM-HF/ DAPA-HF eligible group (HR 0.68, 95% CI 0.50–0.92). The use of BB at ≥50% of the recommended dose was associated with lower 2-year mortality and HF readmission rates in the SHIFT-eligible group (HR 0.50, 95% CI 0.30–0.84). Conclusions: Conventional medical therapy was underutilized among patients eligible for novel trials within a Japanese HF registry. Further efforts to optimize conventional medical therapy are needed.

Access to Document (DOI)

Personalized Target Heart Rate for Patients with Heart Failure and Reduced Ejection Fraction

Yumita Y., Nagatomo Y., Takei M., Saji M., Goda A., Kohno T., Nakano S., Nishihata Y., Ikegami Y., Shiraishi Y., Kohsaka S., Adachi T., Yoshikawa T.

Journal of Personalized Medicine (Journal of Personalized Medicine) 12 ( 1 ) 2022.01

ISSN 2075-4426

The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (∆HR) from −10 to ±0 was associated with a lower risk of primary endpoint and ∆HR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies.

Access to Document (DOI)

Sex differences in sleep and psychological disturbances among patients admitted for cardiovascular diseases

Jono Y., Kohno T., Kohsaka S., Kitakata H., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

Sleep and Breathing (Sleep and Breathing) 26 ( 4 ) 1 - 9 2022

ISSN 15209512

Background: Understanding sex differences is critical for improving outcomes in patients with cardiovascular conditions. Sleep and psychological disturbances contribute to the development and progression of cardiovascular diseases, and important sex differences persist in their incidence and association with clinical outcomes. Methods: Sex-based variation in sleep and psychological disturbances were assessed in consecutive patients with cardiovascular diseases in a single university hospital. The prevalence of insomnia, sleep disordered breathing (SDB), anxiety, and depression was assessed using the Pittsburgh Sleep Quality Index (PSQI), nocturnal pulse oximeter, and the Hospital Anxiety and Depression Scale (HADS). The effect of sex on the prevalence of sleep and psychological disturbances as well as their associations was quantified using multivariate logistic regression models. Results: Among 1,233 patients (mean age 63.6 years, 25% women), women were significantly less likely than men to experience SDB (17.5% vs 31.5%, p < 0.001), but more likely to report an increased burden of insomnia (54.7% vs 43.3%, p = 0.001) and depression (23.9% vs 16.7%, p = 0.004). Insomnia was associated with depression, which was more remarkable among women (p value for interaction: 0.039). SDB was associated with anxiety among women but not men (p value for interaction: 0.003). There was no significant difference in the prevalence of anxiety between women and men. Conclusions: Among patients with cardiovascular disease, women reported an increased burden of insomnia and depression compared to men. The association between sleep and psychological disturbances may be more pronounced in women, suggesting that cardiologists should increase efforts for identification of such comorbidities and administer corresponding treatment, especially in women.

Access to Document (DOI)

Impact of Left Ventricular Chamber Size on Outcome in Heart Failure with Preserved Ejection Fraction

Ogawa S., Nagatomo Y., Takei M., Saji M., Goda A., Kohno T., Nakano S., Nishihata Y., Ikegami Y., Shoji S., Shiraishi Y., Kohsaka S., Yoshikawa T.

International Heart Journal (International Heart Journal) 63 ( 1 ) 62 - 72 2022

ISSN 13492365

Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heteroge-neity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thor-oughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF. A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm. Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e’, and tricuspid regurgitation pressure gradient and greater severity of mitral regur-gitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009). In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

Access to Document (DOI)

Recurrence of myopericarditis following mRNA COVID-19 vaccination in a male adolescent.

Umei TC, Kishino Y, Shiraishi Y, Inohara T, Yuasa S, Fukuda K

CJC open (CJC Open) 4 ( 3 ) 350 - 352 2021.12

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease has spread worldwide, resulting in health and economic crises. Vaccination against SARS-CoV-2 infection is considered a valid prevention measure to control this pandemic. There have been reports of cases of myopericarditis following mRNA COVID-19 vaccination. We present a case of a 20-year-old man with recurrent myopericarditis following an initial episode of influenza virus–induced myopericarditis and after a second dose of the mRNA-1273 Moderna COVID-19 vaccine. Careful attention should be paid to patients with a history of myocarditis following COVID-19 vaccination.

Access to Document (DOI)

A novel device for detecting anaerobic threshold using sweat lactate during exercise

Seki Y., Nakashima D., Shiraishi Y., Ryuzaki T., Ikura H., Miura K., Suzuki M., Watanabe T., Nagura T., Matsumato M., Nakamura M., Sato K., Fukuda K., Katsumata Y.

Scientific Reports (Scientific Reports) 11 ( 1 ) 4929 2021.12

The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland–Altman plot described no bias between the mean values (mean differences: − 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.

Access to Document (DOI)

Preferences on advance care planning and end-of-life care in patients hospitalized for heart failure

Kitakata H., Kohno T., Kohsaka S., Fujisawa D., Nakano N., Shiraishi Y., Katsumata Y., Nagatomo Y., Yuasa S., Fukuda K.

ESC Heart Failure (ESC Heart Failure) 8 ( 6 ) 5102 - 5111 2021.12

Aims: Early engagement in advance care planning (ACP) is recommended in heart failure (HF) management. We investigated the preferences of patients with HF regarding ACP and end-of-life (EOL) care, including their desired timing of ACP initiation. Methods and results: Data were collected using a 92-item questionnaire survey, which was directly distributed to hospitalized patients by dedicated physicians and nurses in a university hospital setting. One-hundred eighty-seven patients agreed to participate (response rate: 92.6%), and 171 completed the survey [valid response rate: 84.7%; men: 67.3%; median age: 73.0 (63.0–81.0) years]. Logistic regression analyses were conducted to identify the predictors of positive attitudes towards ACP. Most recognized ACP as important for their care (n = 127, 74.3%), 48.1% stated that ACP should be initiated after repeated HF hospitalizations in the past year, and 29.0% preferred ACP to begin during the first or second HF hospitalization. Only 21.7% of patients had previously engaged in ACP conversations during HF management. Positive attitudes towards ACP were associated with lower depressive symptoms [two-item Patient Health Questionnaire; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.61–0.92, P-value: 0.006], marriage (OR: 2.53, 95% CI: 1.25–5.12, P-value: 0.010), and a high educational level (OR: 2.66, 95% CI: 1.28–5.56, P-value: 0.009), but not with severity of HF (represented by Seattle Heart Failure Model risk score). Regarding EOL care, while ‘Saying what one wants to tell loved ones’ (83.4%), ‘Dying a natural death’ (81.8%), and ‘Being able to stay at one's favorite place’ (75.6%) were the three most important factors for patients, preferences for ‘Receiving sufficient treatment’ (56.5%) and ‘Knowing what to expect about future condition’ (50.3%) were divergent. Conclusions: Despite patients' preferences for ACP conversations, there was a discrepancy between preference and engagement in ACP among patients hospitalized for HF. Patients' preferences regarding EOL care may differ; physicians need to consider the appropriate ACP approach to align with patients' care goals.

Access to Document (DOI)

Phenomapping in patients experiencing worsening renal function during hospitalization for acute heart failure

Yagi R., Takei M., Kohsaka S., Shiraishi Y., Ikemura N., Shoji S., Niimi N., Higuchi S., Goda A., Kohno T., Nagatomo Y., Nishihata Y., Sujino Y., Saji M., Ikegami Y., Nakano S., Takahashi T., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 8 ( 6 ) 5192 - 5203 2021.12

Aims: The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. Methods and results: Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all-cause death and re-hospitalization due to heart failure, with those of a propensity score-matched, non-WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. Conclusions: Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function.

Access to Document (DOI)

Association of non-invasive positive pressure ventilation with short-term clinical outcomes in patients hospitalized for acute decompensated heart failure

Yukino M., Nagatomo Y., Goda A., Kohno T., Takei M., Nishihata Y., Saji M., Toyosaki Y., Nakano S., Ikegami Y., Shiraishi Y., Kohsaka S., Adachi T., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 21 ) 2021.11

ISSN 2077-0383

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) > 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP < 100 mmHg and CONUT score > 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use.

Access to Document (DOI)

Sudden cardiac death after acute decompensation in heart failure patients: implications of discharge haemoglobin levels

Fukuoka R., Kohsaka S., Shiraishi Y., Sawano M., Abe T., Levy W.C., Nagatomo Y., Nishihata Y., Goda A., Kohno T., Kawamura A., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 8 ( 5 ) 3917 - 3928 2021.10

Aims: Heart failure (HF) patients have a high risk of mortality due to sudden cardiac death (SCD) and non-SCD, including pump failure death (PFD). Anaemia predicts more severe symptomatic burden and higher morbidity, as noted by markedly increased hospitalizations and readmission rates, and mortality, underscoring its importance in HF management. Herein, we aimed to determine whether haemoglobin (Hb) level at discharge affects the mode of death and influences SCD risk prediction. Methods: We evaluated the data of 3020 consecutive acute HF patients from a Japanese prospective multicentre registry. Patients were divided into four groups based on discharge Hb levels. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The mode of death (SCD, PFD or other cause) was adjudicated by a central committee. Finally, we investigated whether adding Hb level to the Seattle Proportional Risk Model (SPRM; established risk score utilized to estimate ‘proportion’ of SCD among death events) would affect its performance. Results: The mean age of studied patients was 74.3 ± 12.9 years, and 59.8% were male. The mean Hb level was 12.0 ± 2.1 g/dL (61.3% of patients had anaemia defined by World Health Organization criteria). During the 2-year follow-up, 474 deaths (15.7%) occurred, including 93 SCDs (3.1%), 171 PFDs (5.7%) and 210 other deaths (7.0%; predominantly non-cardiac death). Absolute risk of PFD (P < 0.001) or other death (P < 0.001) increased along with the severity of anaemia, whereas the incidence of SCD was low but remained consistent across all four groups (P = 0.440). As a proportion of total deaths in each Hb level group, the contributions from non-SCD increased and from SCD decreased along with anaemia severity (P = 0.007). Adding Hb level to the SPRM improved the overall discrimination (c-index: 0.62 [95% confidence interval (CI) 0.56–0.69] to 0.65 [95% CI 0.59–0.71]), regardless of the baseline ejection fraction (EF) (c-index: 0.64 [95% CI 0.55–0.73] to 0.67 [95% CI 0.58–0.75] for reduced EF and 0.55 [95% CI 0.45–0.66] to 0.61 [95% CI 0.52–0.70] for preserved EF). Conclusions: The discharge Hb level provides information about both absolute and proportional risks for each mode of death in acute HF patients, and the addition of Hb level improves the performance of SPRM by identifying more non-SCD cases. Future ‘proportional’ SCD risk models should incorporate Hb level as a covariate to meet this high performance.

Access to Document (DOI)

Different impact of beta-blockers on long-term mortality in heart failure patients with and without chronic obstructive pulmonary disease

Higuchi S., Kohno T., Kohsaka S., Shiraishi Y., Takei M., Goda A., Shoji S., Nagatomo Y., Yoshikawa T.

Journal of Clinical Medicine (Journal of Clinical Medicine) 10 ( 19 ) 2021.10

ISSN 2077-0383

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction <50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044; non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.

Access to Document (DOI)

Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty

Miura K., Katsumata Y., Kawakami T., Ikura H., Ryuzaki T., Shiraishi Y., Fukui S., Kawakami M., Kohno T., Sato K., Fukuda K.

PLoS ONE (PLoS ONE) 16 ( July ) e0255180 2021.07

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (followup). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics.

Access to Document (DOI)

Psychological disturbances and their association with sleep disturbances in patients admitted for cardiovascular diseases

Matsuda R., Kohno T., Kohsaka S., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

PLoS ONE (PLoS ONE) 16 ( 1 January ) e0244484 2021.01

Copyright: © 2021 Matsuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Depression and anxiety are common mental health problems that are strongly associated with sleep disturbances, according to community-based researches. However, this association has not been investigated among patients admitted for cardiovascular diseases (CVDs). We examined the prevalence of depression and anxiety in inpatients with various CVDs and their association with sleep disturbances. Materials and methods This cross-sectional study included 1294 patients hospitalized for CVDs in a Japanese university hospital were evaluated for their mental status using the Hospital Anxiety and Depression Scale (HADS), for sleep-disordered breathing (SDB) using pulse oximetry, and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Results Patient characteristics were as below: mean age, 63.9±14.7 years; 25.7% female. Overall, 18.9% had depression (HADS-depression>8) and 17.1% had anxiety (HADS-anxiety>8). The presence of depression was associated with female sex, older age, higher plasma brain natriuretic peptide level, lower estimated glomerular filtration rate, and the prevalence of heart failure. Overall, 46.5% patients were categorized as having a poor sleep quality (PSQI>5), and 28.5% patients had SDB (3% oxygen desaturation index>15). Although depression and anxiety were not associated with SDB, they were independently associated with poor sleep quality (OR = 3.09, 95% CI 2.19–4.36; OR = 3.93, 95% CI 2.71–5.69, respectively). Conclusions Depression and anxiety were not uncommon in patients with CVDs. Poor sleep quality could be an important risk factor linked to psychological disturbances.

Access to Document (DOI)

Sleep-disordered breathing is independently associated with elevated natriuretic peptide levels in patients with cardiovascular diseases

Sugiura K., Kohno T., Kohsaka S., Shiraishi Y., Katsumata Y., Hayashida K., Yuasa S., Takatsuki S., Fukuda K.

Heart and Vessels (Heart and Vessels) 37 ( 6 ) 994 - 1002 2021

ISSN 09108327

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66 years (55–74 years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9 pg/ml (23.5–146.4 pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8 pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17–10.88; moderate: OR, 3.62; 95% CI 2.17–6.02; mild: OR, 2.22: 95% CI 1.42–3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

Access to Document (DOI)

Evidence-to-practice gap for preventing procedure-related acute kidney injury in patients undergoing percutaneous coronary intervention

Shoji S., Sawano M., Sandhu A.T., Heidenreich P.A., Shiraishi Y., Noma S., Suzuki M., Numasawa Y., Fukuda K., Kohsaka S.

Journal of the American Heart Association (Journal of the American Heart Association) 10 ( 15 ) e020047 2021

BACKGROUND: Acute kidney injury (AKI) is a common complication of percutaneous coronary intervention. This risk can be minimized with reduction of contrast volume via preprocedural risk assessment. We aimed to identify quality gaps for implementing the available risk scores introduced to facilitate more judicious use of contrast volume. METHODS AND RESULTS: We grouped 14 702 patients who underwent percutaneous coronary intervention according to the calculated NCDR (National Cardiovascular Data Registry) AKI risk score quartiles (Q1 [lowest]–Q4 [highest]). We compared the used contrast volume by the baseline renal function and NCDR AKI risk score quartiles. Factors associated with increased contrast volume usage were determined using multivariable linear regression analysis. The overall incidence of AKI was 8.9%. The used contrast volume decreased in relation to the stages of chronic kidney disease (168 mL [SD, 73.8 mL], 161 mL [SD, 75.0 mL], 140 mL [SD, 70.0 mL], and 120 mL [SD, 73.7 mL] for no, mild, moderate, and severe chronic kidney disease, respectively; P<0.001), albeit no significant correlation was observed with the calculated NCDR AKI risk quartiles. Of the variables included in the NCDR AKI risk score, anemia (7.31 mL [1.76–12.9 mL], P=0.01), heart failure on admission (10.2 mL [6.05–14.3 mL], P<0.001), acute coronary syndrome presentation (10.3 mL [7.87–12.7 mL], P<0.001), and use of an intra-aortic balloon pump (17.7 mL [3.9–31.5 mL], P=0.012) were associated with increased contrast volume. CONCLUSIONS: The contrast volume was largely determined according to the baseline renal function, not the patients’ overall AKI risk. These findings highlight the importance of comprehensive risk assessment to minimize the contrast volume used in susceptible patients.

Access to Document (DOI)

Frequent nightmares and its associations with psychological and sleep disturbances in hospitalized patients with cardiovascular diseases.

Horie H, Kohno T, Kohsaka S, Kitakata H, Shiraishi Y, Katsumata Y, Hayashida K, Yuasa S, Takatsuki S, Fukuda K

European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology (European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology) 20 ( 5 ) 421 - 427 2020.12

ISSN 1474-5151

AIMS: Frequent nightmares can pose a serious clinical problem, especially in association with sleep and psychological disturbances, in the general population. However, this association has not been investigated in inpatients with cardiovascular (CV) diseases. Furthermore, whether CV medications could induce iatrogenic nightmares remains unknown. In a cross-sectional designed study, we evaluated the prevalence and determinants of frequent nightmares and its association with sleep and psychological disturbances among hospitalized CV patients. METHODS AND RESULTS: A total of 1233 patients (mean age, 64 ± 15 years; 25.1% female) hospitalized for various CV diseases in a single university hospital were enrolled. We assessed nightmares and sleep characteristics using the Pittsburgh Sleep Quality Index (PSQI), sleep-disordered breathing (SDB) using nocturnal pulse oximetry, and psychological disturbances using Hospital Anxiety and Depression Scale (HADS). Overall, 14.8% and 3.6% of the patients had at least one nightmare per month and per week (frequent nightmares), respectively. In this cohort, 45.9% had insomnia (modified PSQI > 5), 28.0% had SDB (3% oxygen desaturation index > 15), 18.5% had depression (HADS-depression ≥ 8), and 16.9% had anxiety (HADS-anxiety ≥ 8). Frequent nightmares were not associated with CV medications and SDB but were associated with depression [odds ratio (OR) = 4.61, 95% confidence interval (CI) = 2.03-10.48], anxiety (OR = 5.32, 95% CI = 2.36-12.01), and insomnia (OR = 7.15, 95% CI = 2.41-21.22). CONCLUSIONS: Frequent nightmares were not uncommon in patients hospitalized for CV diseases. Although the cause-effect relationship is unclear, frequent nightmares were associated with psychological disturbances and insomnia, but not iatrogenic factors, among hospitalized CV patients. Cardiologists should be more conscientious to nightmare complaints with respect to screening for psychological disturbances and insomnia.

Access to Document (DOI)

Prognostic Understanding and Preference for the Communication Process with Physicians in Hospitalized Heart Failure Patients.

Kitakata H, Kohno T, Kohsaka S, Fujisawa D, Nakano N, Shiraishi Y, Katsumata Y, Yuasa S, Fukuda K

Journal of cardiac failure (Journal of Cardiac Failure) 27 ( 3 ) 318 - 326 2020.11

ISSN 1071-9164

© 2020 Elsevier Inc. Background: Heart failure (HF) is a highly prevalent, heterogeneous, and life-threatening condition. Precise prognostic understanding is essential for effective decision making, but little is known about patients’ attitudes toward prognostic communication with their physicians. Methods and Results: We conducted a questionnaire survey, consisting of patients’ prognostic understanding, preferences for information disclosure, and depressive symptoms, among hospitalized patients with HF (92 items in total). Individual 2-year survival rates were calculated using the Seattle Heart Failure Model, and its agreement level with patient self-expectations of 2-year survival were assessed. A total of 113 patients completed the survey (male 65.5%, median age 75.0 years, interquartile range 66.0–81.0 years). Compared with the Seattle Heart Failure Model prediction, patient expectation of 2-year survival was matched only in 27.8% of patients; their agreement level was low (weighted kappa = 0.11). Notably, 50.9% wished to know “more,” although 27.7% felt that they did not have an adequate prognostic discussion. Compared with the known prognostic variables (eg, age and HF severity), logistic regression analysis demonstrated that female and less depressive patients were associated with patients’ preference for “more” prognostic discussion. Conclusions: Patients’ overall prognostic understanding was suboptimal. The communication process requires further improvement for patients to accurately understand their HF prognosis and be involved in making a better informed decision.

Access to Document (DOI)

Successful Percutaneous Abscess Drainage and Irrigation for the Treatment of Infected Aortic Aneurysm Post–Thoracic Endovascular Aortic Repair

Tsuzuki I., Kishino Y., Shiraishi Y., Katsumata Y., Yuasa S., Ito N., Inoue M., Ito T., Shimizu H., Fukuda K.

CJC Open (CJC Open) 2 ( 6 ) 735 - 738 2020.11

© 2020 Canadian Cardiovascular Society Infected aortic aneurysm (IAA) is a rare, life-threatening disease with rapid progression and a high mortality rate. An 84-year-old man developed IAA caused by urosepsis owing to extended-spectrum β-lactamase–producing Escherichia coli infection. Considering surgical risk and perioperative mortality, the patient underwent computed tomography–guided percutaneous abscess drainage and continuous irrigation with optimal antibiotic therapy. We controlled his systemic inflammation without surgery; thus, he was discharged. Six months later, we confirmed that the abscess had almost disappeared in the follow-up computed tomography scan. Percutaneous abscess drainage and irrigation may be an effective therapeutic option for surgical high-risk patients with IAA.

Access to Document (DOI)

Feasibility of the deep learning method for estimating the ventilatory threshold with electrocardiography data

Miura K, Goto S, Katsumata Y, Ikura H, Shiraishi Y, Sato K, Fukuda K

NPJ digital medicine 3 ( 1 ) 141 2020.10

Access to Document (DOI)

Applicability and Eligibility of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) for Patients who Underwent Revascularization with Percutaneous Coronary Intervention.

Niimi N, Sawano M, Ikemura N, Nagai T, Nakano S, Shoji S, Shiraishi Y, Ueda I, Numasawa Y, Suzuki M, Noma S, Fukuda K, Kohsaka S

Journal of clinical medicine (Journal of Clinical Medicine) 9 ( 9 ) 1 - 14 2020.09

ISSN 2077-0383

In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, an early invasive strategy did not decrease mortality compared to a conservative strategy for stable ischemic heart disease (SIHD) patients with moderate-to-severe ischemia, and the role of revascularization would be revised. However, the applicability and potential influence of this trial in daily practice remains unclear. Our objective was to assess the eligibility and representativeness of the ISCHEMIA trial on the patients with percutaneous coronary intervention (PCI). From a multicenter registry, we extracted a consecutive 13,223 SIHD patients with PCI (baseline cohort). We applied ISCHEMIA eligibility criteria and compared the baseline characteristics between the eligible patients and the actual study participants (randomized controlled trial (RCT) patients). In 3463 patients with follow-up information (follow-up cohort), the 2 year composite of major adverse cardiac events was evaluated between the eligible patients and RCT patients, as well as eligible and non-eligible patients in the registry. In the baseline cohort, 77.3% of SIHD patients with moderate-to-severe ischemia were eligible for the ISCHEMIA. They were comparable with RCT patients for baseline characteristics and outcomes unlike the non-eligible patients. In conclusion, the trial results seem applicable for the majority of PCI patients with moderate-to-severe ischemia except for the non-eligible patients.

Access to Document (DOI)

Delay in seeking treatment before emergent heart failure readmission and its association with clinical phenotype

Takei M., Harada K., Shiraishi Y., Matsuda J., Iwasaki Y., Yamamoto Y., Matsushita K., Miyazaki T., Miyamoto T., Iida K., Tanimoto S., Nagatomo Y., Hosoda T., Kohsaka S., Yamamoto T., Nagao K., Takayama M.

Journal of Intensive Care (Journal of Intensive Care) 8 ( 1 ) 65 2020.08

ISSN 2052-0492

© 2020 The Author(s). Background: Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier. Methods: Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared. Results: Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure. Conclusions: More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.

Access to Document (DOI)

Successful Surgical Treatment Combined With Infliximab in a Patient With Acute Aortic Regurgitation Caused by Behçet Disease

Kawakubo Y., Katsumata Y., Komuro J., Shiraishi Y., Yuasa S., Itabashi Y., Kohno T., Fukuda K.

Canadian Journal of Cardiology (Canadian Journal of Cardiology) 36 ( 7 ) 1161.e3 - 1161.e5 2020.07

ISSN 0828282X

© 2020 Canadian Cardiovascular Society Standard aortic valve replacement for aortic regurgitation caused by Behçet disease (BD) is frequently complicated by postoperative recurrent prosthetic valve detachment. Tumour necrosis factor (TNF) α is known to be associated with higher inflammation activities. Therefore, the concomitant use of immunomodulatory agents with TNFα inhibitors may be the key to a better outcome. This is a case report of a 46-year-old woman with severe acute aortic regurgitation due to BD. Immunosuppressive therapy including the TNFα inhibitor infliximab, which has not been reported for perioperative use to date, resulted in the prompt remission of inflammation, leading to the success of Bentall surgery.

Access to Document (DOI)

Prognostic Implications of Early and Midrange Readmissions After Acute Heart Failure Hospitalizations: A Report From a Japanese Multicenter Registry

Kitakata H, Kohno T, Kohsaka S, Shiraishi Y, Parizo JT, Niimi N, Goda A, Nishihata Y, Heidenreich PA, Yoshikawa T

Journal of the American Heart Association (Journal of the American Heart Association) 9 ( 10 ) e014949 2020.05

Background Although 30-day readmission is thought to be an important quality indicator in patients with hospitalized heart failure, its prognostic impact and comparison of patients who were readmitted beyond 30 days has not been investigated. We assessed early (0-30 days) versus midrange (31-90 days) readmission in terms of incidence and distribution, and elucidated whether the timing of readmission could have a different prognostic significance. Methods and Results We examined patients with hospitalized heart failure registered in the WET-HF (West Tokyo Heart Failure) registry. The primary outcomes analyzed were all-cause death and HF readmission. Data of 3592 consecutive patients with hospitalized heart failure (median follow-up, 2.0 years [interquartile range, 0.8-3.1 years]; 39.6% women, mean age 73.9±13.3 years) were analyzed. Within 90 days after discharge, HF readmissions occurred in 11.1% patients. Of them, patients readmitted within 30 and 31 to 90 days after discharge accounted for 43.1% and 56.9%, respectively. Independent predictors of 30- and 90-day readmission were almost identical, and after adjustment, readmission for HF within 90 days (including both early and midrange readmission) was an independent predictor of subsequent all-cause death (hazard ratio, 2.36; P<0.001). Among 90-day readmitted patients, the time interval from discharge to readmission was not significantly associated with subsequent all-cause death. Conclusions Among patients readmitted within 90 days after index hospitalization discharge, ≈60% of readmission events occurred beyond 30 days. Patients readmitted within 90 days had a higher risk of long-term mortality, regardless of the temporal proximity of readmission to the index hospitalization.

Access to Document (DOI)

Optimal sampling in derivation studies was associated with improved discrimination in external validation for heart failure prognostic models

Iwakami N., Nagai T., Furukawa T.A., Tajika A., Onishi A., Nishimura K., Ogata S., Nakai M., Takegami M., Nakano H., Kawasaki Y., Alba A.C., Guyatt G.H., Shiraishi Y., Kohsaka S., Kohno T., Goda A., Mizuno A., Yoshikawa T., Anzai T.

Journal of Clinical Epidemiology (Journal of Clinical Epidemiology) 121 71 - 80 2020.05

ISSN 08954356

© 2020 Elsevier Inc. Objectives: The objective of the study was to identify determinants of external validity of prognostic models. Study Design and Setting: We systematically searched for studies reporting prognostic models of heart failure (HF) and examined their performance for predicting 30-day death in a cohort of consecutive 3,452 acute HF patients. We applied published critical appraisal tools and examined whether bias or other characteristics of original derivation studies determined model performance. Results: We identified 224 models from 6,354 eligible studies. The mean c-statistic in the cohort was 0.64 (standard deviation, 0.07). In univariable analyses, only optimal sampling assessed by an adequate and valid description of the sampling frame and recruitment details to collect the population of interest (total score range: 0–2, higher scores indicating lower risk of bias) was associated with high performance (standardized β = 0.25, 95% CI: 0.12 to 0.38, P < 0.001). It was still significant after adjustment for relevant study characteristics, such as data source, scale of study, stage of illness, and study year (standardized β = 0.24, 95% CI: 0.07 to 0.40, P = 0.01). Conclusion: Optimal sampling representing the gap between the population of interest and the studied population in derivation studies was a key determinant of external validity of HF prognostic models.

Access to Document (DOI)

Hospital meal intake in acute heart failure patients and its association with long-term outcomes.

Yoshida T, Shoji S, Shiraishi Y, Kawana M, Kohno T, Inoue K, Fukuda K, Heidenreich PA, Kohsaka S

Open heart (Open Heart) 7 ( 1 ) 2020.05

ISSN 2398595X

© 2020 Author(s). Background: Risk prediction for hospitalised heart failure (HF, HHF) patients remains suboptimal. We aimed to determine the prognostic value of hospital food intake (FI) immediately before discharge among HHF patients. Method: We analysed the data of 255 HHF patients extracted from the records of a single university hospital. The FI percentage of the three meals the day before hospital discharge was averaged. Patients were stratified into adequate FI (100% consumption) and inadequate FI (less than 100% consumption) groups. The primary outcome was the composite of all-cause mortality and/or HF readmission within 1 year. Results: Only 49.3% of HHF patients consumed 100% of their meals. Patients with inadequate FI were older; predominantly women; and had a lower body mass index, higher brain natriuretic peptide levels and Clinical Frailty Scale scores at discharge than those with adequate FI. Inadequate FI was significantly associated with adverse outcomes after adjustments (HR 2.00; 95% CI 1.09 to 3.67; p=0.026). The effect of interaction by ejection fraction (EF) was highly significant: HF with preserved EF (≥40%) was significantly associated with inadequate FI with adverse outcomes (HR 4.95; 95% CI 1.71 to 14.36; p=0.003) but HF with reduced EF (<40%) was not (HR 0.77; 95% CI 0.31 to 1.95; p=0.590). Conclusions: The hospital FI assessment might be a simple, useful tool for predicting and stratifying risk for HHF patients.

Access to Document (DOI)

Exploring Triaging and Short-Term Outcomes of Early Invasive Strategy in Non-ST Segment Elevation Acute Coronary Syndrome: A Report from Japanese Multicenter Registry.

Ikemura N, Shiraishi Y, Sawano M, Ueda I, Numasawa Y, Noma S, Suzuki M, Momiyama Y, Hayashida K, Yuasa S, Miyata H, Fukuda K, Kohsaka S

Journal of Clinical Medicine (Journal of Clinical Medicine) 9 ( 4 ) 2020.04

Research paper (scientific journal), Accepted, ISSN 2077-0383

This observational study aimed to examine the extent of early invasive strategy (EIS) utilization in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) according to the National Cardiovascular Data Registry (NCDR) CathPCI risk score, and its association with clinical outcomes. Using a prospective multicenter Japanese registry, 2968 patients with NSTE-ACS undergoing percutaneous coronary intervention within 72 hours of hospital arrival were analyzed. Multivariable logistic regression analyses were performed to determine predictors of EIS utilization. Additionally, adverse outcomes were compared between patients treated with and without EIS. Overall, 82.1% of the cohort (n = 2436) were treated with EIS, and the median NCDR CathPCI risk score was 22 (interquartile range: 14-32) with an expected 0.3-0.6% in-hospital mortality. Advanced age, peripheral artery disease, chronic kidney disease or patients without elevation of cardiac biomarkers were less likely to be treated with EIS. EIS utilization was not associated with a risk of in-hospital mortality; yet, it was associated with an increased risk of acute kidney injury (AKI) (adjusted odds ratio: 1.42; 95% confidence interval: 1.02-2.01) regardless of patients’ in-hospital mortality risk. Broader use of EIS utilization comes at the cost of increased AKI development risk; thus, the pre-procedural risk-benefit profile of EIS should be reassessed appropriately in patients with lower mortality risk.

Access to Document (DOI)

Prediction of sudden cardiac death in Japanese heart failure patients: international validation of the Seattle Proportional Risk Model.

Fukuoka R, Kohno T, Kohsaka S, Shiraishi Y, Sawano M, Abe T, Nagatomo Y, Goda A, Mizuno A, Fukuda K, Shadman R, Dardas TF, Levy WC, Yoshikawa T

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) 22 ( 4 ) 588 - 597 2020.04

ISSN 1099-5129

© 2020 Published on behalf of the European Society of Cardiology. All rights reserved. Aims: Heart failure (HF) is associated with an increased risk of sudden cardiac death (SCD). This study sought to demonstrate the incidence of SCD within a multicentre Japanese registry of HF patients hospitalized for acute decompensation, and externally validate the Seattle Proportional Risk Model (SPRM). Methods and results: We consecutively registered 2240 acute HF patients from academic institutions in Tokyo, Japan. The discrimination and calibration of the SPRM were assessed by the c-statistic, Hosmer-Lemeshow statistic, and visual plotting among non-survivors. Patient-level SPRM predictions and implantable cardioverter-defibrillator (ICD) benefit [ICD estimated hazard ratio (HR), derived from the Cox proportional hazards model in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)] was calculated. During the 2-year follow-up, 356 deaths (15.9%) occurred, which included 76 adjudicated SCDs (3.4%) and 280 non-SCDs (12.5%). The SPRM showed acceptable discrimination [c-index = 0.63; 95% confidence interval (CI) 0.56-0.70], similar to that of original SPRM-derivation cohort. The calibration plot showed reasonable conformance. Among HF patients with reduced ejection fraction (EF; < 40%), SPRM showed improved discrimination compared with the ICD eligibility criteria (e.g. New York Heart Association functional Class II-III with EF ≤ 35%): c-index = 0.53 (95% CI 0.42-0.63) vs. 0.65 (95% CI 0.55-0.75) for SPRM. Finally, in the subgroup of 246 patients with both EF ≤ 35% and SPRM-predicted risk of ≥ 42.0% (SCD-HeFT defined ICD benefit threshold), mean ICD estimated HR was 0.70 (30% reduction of all-cause mortality by ICD). Conclusion: The cumulative incidence of SCD was 3.4% in Japanese HF registry. The SPRM performed reasonably well in Japanese patients and may aid in improving SCD prediction.

Access to Document (DOI)

Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment

Shoji S., Sawano M., Sandhu A.T., Heidenreich P.A., Shiraishi Y., Ikemura N., Ueno K., Suzuki M., Numasawa Y., Fukuda K., Kohsaka S.

JAMA network open (JAMA network open) 3 ( 4 ) e202004 2020.04

Importance: Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear. Objective: To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019. Exposures: Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI. Main Outcomes and Measures: Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition. Results: Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7). Conclusions and Relevance: Since its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference in ischemic events between the 2 groups. These results suggest the importance of a risk assessment of bleeding prior to selecting a P2Y12 inhibitor, even for the use of a lower approved dose, when treating patients of East Asian descent.

Access to Document (DOI)

Long-Term Outcomes According to Etiology May Alter Under Different Circumstances

Shoji S, Shiraishi Y, Kohsaka S, Fukuda K, Yoshikawa T

JACC: Heart Failure 8 ( 1 ) 83 - 84 2020.01

Research paper (scientific journal), Accepted, ISSN 2213-1779

Access to Document (DOI)

Peripheral pulmonary stenosis with Noonan syndrome treated by balloon pulmonary angioplasty

Ko S., Komuro J., Katsumata Y., Shiraishi Y., Kawakami T., Yamada Y., Yuasa S., Kohno T., Kosaki K., Fukuda K.

Pulmonary Circulation (Pulmonary Circulation) 10 ( 4 ) 2045894020954310 2020

ISSN 20458932

© The Author(s) 2020. Noonan syndrome is known to have various cardiovascular defects, which include pulmonary artery stenosis. Pulmonary artery stenosis is characterized by obstruction of pulmonary artery blood flow that can cause elevated pulmonary artery pressure and ventilation-perfusion inequality, which can cause dyspnea on exertion and eventually, heart failure. Although the etiology of pulmonary artery stenosis related to congenital diseases is still unknown, balloon pulmonary angioplasty has being reported to be effective to selected patients with Alagille and Williams syndromes, but not from Noonan syndrome despite of modest prevalence of pulmonary artery stenosis. Here, we report the first Noonan syndrome patient with pulmonary artery stenosis who underwent successful balloon pulmonary angioplasty. The strategy used in balloon pulmonary angioplasty was planned with careful morphologic evaluation by computed tomographic angiography, and performed with scoring balloons in a graded approach with multiple sessions. After balloon pulmonary angioplasty, we confirmed maintained dilation of lesions and symptom alleviation, suggesting that balloon pulmonary angioplasty can be performed safely on pulmonary artery stenosis in a Noonan syndrome patient.

Access to Document (DOI)

Left Ventricular Thrombus With COVID-19 Complication in a Patient With Dilated Cardiomyopathy

Imaeda S., Kabata H., Shiraishi Y., Kamata H., Tsuruta H., Yuasa S., Ishii M., Fukuda K., Fukunaga K.

CJC Open (CJC Open) 3 ( 1 ) 124 - 126 2020

© 2020 Canadian Cardiovascular Society Thrombosis, especially venous thromboembolism, is a complication often associated with coronavirus disease 2019 (COVID-19). However, there have been relatively few reports of arterial thrombosis. Here, we describe a case of non-severe COVID-19 in a patient with dilated cardiomyopathy. After admission, symptoms, laboratory data, and imaging findings improved, but D-dimer levels gradually increased. Contrast computed tomography and echocardiography revealed a left ventricular thrombus. Anticoagulant treatment diminished the thrombus, and the patient recovered and was discharged. Although a left ventricular thrombus is a rare COVID-19 complication, performing appropriate diagnostic tests could improve COVID-19 mortality in patients with dilated cardiomyopathy.

Access to Document (DOI)

Appropriateness rating for the application of optimal medical therapy and multidisciplinary care among heart failure patients

Shoji S., Kohsaka S., Shiraishi Y., Oishi S., Kato M., Shiota S., Takada Y., Mizuno A., Yumino D., Yokoyama H., Watanabe N., Isobe M.

ESC Heart Failure (ESC Heart Failure) 8 ( 1 ) 300 - 308 2020

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology Aims: Clinical guidelines for improving the patients' quality of care vary in clinical practice, particularly in super-aging societies, like in Japan. We aimed to develop a set of appropriate-use criteria (AUC) for contemporary heart failure (HF) management to assist physicians in decision making. Methods and results: With the use of the RAND methodology, a multidisciplinary writing group developed patient-based clinical scenarios in 10 selected key topics, stratified mainly by HF stage, age, and renal function. Nine nationally recognized expert panellists independently rated the clinical scenario appropriateness twice on a scale of 1–9, as ‘appropriate’ (7–9), ‘may be appropriate’ (4–6), or ‘rarely appropriate’ (1–3). Decisions were based on clinical evidence and professional opinions in the context of available resource use and costs. An interactive round-table discussion was held between the first and second ratings; the median score of the nine experts was then assigned to an appropriate-use category. Most clinical scenarios without strong evidence were evaluated as ‘may be appropriate’. Frailty assessments in elderly patients (age ≥ 75 years), regardless of the HF stage, and advanced care planning in patients with stage C/D HF, regardless of age, were considered ‘appropriate’. For HF with reduced ejection fraction, beta-blocker administration in elderly patients (age ≥ 75 years) with heart rate < 50 b.p.m. and mineral corticosteroid receptor antagonist use in elderly patients (age ≥ 75 years) with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 were considered ‘rarely appropriate’. Conclusions: The HF management AUC provide a practical guide for physicians regarding scenarios commonly encountered in daily practice.

Access to Document (DOI)

De winter ST-T complex.

Niimi N, Ooka R, Shiraishi Y, Fukuda K

QJM : monthly journal of the Association of Physicians 2019.11

ISSN 1460-2725

Access to Document (DOI)

Length of hospital stay and its impact on subsequent early readmission in patients with acute heart failure: a report from the WET-HF Registry

Moriyama H., Kohno T., Kohsaka S., Shiraishi Y., Fukuoka R., Nagatomo Y., Goda A., Mizuno A., Fukuda K., Yoshikawa T.

Heart and Vessels (Heart and Vessels) 34 ( 11 ) 1777 - 1788 2019.11

ISSN 09108327

© 2019, Springer Japan KK, part of Springer Nature. Heart failure (HF) is characterized by frequent rehospitalization and prolonged hospital stay. Although length of stay has been used as a surrogate marker for hospital performance, its association with early rehospitalization remains unknown. We investigated their precise association using contemporary Japanese HF registry. We analyzed the 2785 acute HF patients who were registered in the West Tokyo Heart Failure registry and discharged or transferred to the recuperation facilities (mean age, 73.8 ± 13.5 years; 60.8% were men). Median length of stay was 15 days (interquartile range, 10–23 days). One-hundred and fourteen patients (4.1%) were readmitted for worsening HF within 30 days after discharge. Thirty-day risk-adjusted HF readmission after a shorter length of stay (1–12 days; the lower tertile within the cohort) was higher than those after intermediate (13–19 days; the middle tertile) [HR 1.71, 95% confidence interval (CI) 1.05–2.77]. Even after a longer length of stay, there tended to be a higher risk of 30-day HF readmission (HR 1.59, 95% CI 0.96–2.65). In conclusion, the Japanese acute HF patients had low rates of early-HF readmission after quite a long length of stay at urban tertiary care centers. Shorter length of stay was associated with increased rates of 30-day HF readmission, while longer length of stay also the same trended. Clinical Trial Registration: https://www.umin.ac.jp/icdr/index-j.html. Unique identifier: UMIN000001171.

Access to Document (DOI)

経皮的中隔心筋焼灼術施行後に左室流出路狭窄が再燃し再焼灼にて治療し得た閉塞性肥大型心筋症の1症例

松本龍門, 三山寛司, 秋田敬太郎, 白石泰之, 勝俣良紀, 板橋裕史, 荒井隆秀, 鶴田ひかる, 湯浅慎介, 河野隆志, 前川裕一郎, 村田光繁, 福田恵一

心臓 ((公財)日本心臓財団) 51 ( 10 ) 1072 - 1076 2019.10

Research paper (scientific journal), Accepted, ISSN 0586-4488

症例は84歳女性。2011年に閉塞性肥大型心筋症(HOCM)を偶発的に指摘され近医通院を開始した。その後2016年8月頃より労作時胸痛が出現し増悪傾向を認め、同年11月に当院循環器内科を紹介受診した。経胸壁心エコーにて最大圧較差119mmHgの左室潤出路狭窄を認め、シベンゾリン、ビソプロロール導入後も改善に乏しく、2017年1月に経皮的中隔心筋焼灼術(PTSMA)を施行した。心室中隔基部を灌流する合計4本の中隔枝に対しアルコール焼灼を施行し、術中にエコー上で最大圧較差19mmHgまで軽減を確認した。術後は症状も消失したため問題なく退院となったが、2ヵ月後の2017年3月頃より労作時胸痛が再燃し、心エコーで最大圧較差96mmHgと流出路狭窄の再増悪を認め、PTSMA再施行目的に同年4月に入院となった。冠動脈造影では初回治療時にアルコール焼灼した4本の中隔枝のうち最も近位部の枝に再灌流を認め、同枝に対し再度アルコール焼灼を施行した。術後心エコーで最大圧較差15mmHgまで改善を認め、症状も消失し、1年半後の現在も再燃なく経過している。今回、初回PTSMA施行後の遠隔期に有症候性の流出路狭窄が再燃し、2回目のPTSMAで治療し得た閉塞性肥大型心筋症の1例を経験したので文献的考察を交えて報告する。(著者抄録)

Heart Failure With Midrange Ejection Fraction in Patients Admitted for Acute Decompensation: A Report from the Japanese Multicenter Registry

Takei M., Kohsaka S., Shiraishi Y., Goda A., Nagatomo Y., Mizuno A., Suzino Y., Kohno T., Fukuda K., Yoshikawa T.

Journal of Cardiac Failure (Journal of Cardiac Failure) 25 ( 8 ) 666 - 673 2019.08

ISSN 10719164

© 2019 Elsevier Inc. Background: Patients having heart failure with midrange ejection fraction (HFmrEF: 40% ≤ EF < 50%) are increasingly being considered a new subset of the population with heart failure. Despite recent advances in heart-failure treatment strategies, the prognosis of these patients has not improved substantially over time. In addition, the significance of this new phenotype in hospitalized patients with acute decompensated heart failure (ADHF), another population whose prognosis has not improved, also remains poorly understood. This study aimed to describe the clinical characteristics, prognosis and treatment responses of patients with HFmrEF hospitalized for ADHF. Methods: On the basis of consecutive inpatient data from a multicenter ADHF registry, 651 of 3572 patients (17.1%) were classified as having HFmrEF. Prognostic factors predicting composite outcomes, defined as all-cause death and heart failure readmission, as well as all-cause death alone, were analyzed. Results: In the median follow-up duration of 724 days, both composite endpoints and all-cause death alone were comparable in those with heart failure with preserved ejection fraction, HFmrEF and heart failure with reduced ejection fraction. Age, anemia, hyponatremia, elevated blood urea nitrogen, chronic kidney disease, and elevated plasma brain natriuretic peptide levels were significant predictors of composite outcomes in HFmrEF. Conclusions: Roughly one-sixth of the patients with ADHF had HFmrEF. The long-term prognosis of patients with HFmrEF was not significantly different from that of patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in the population with ADHF. Risk factors for adverse outcomes in HFmrEF were also similar to those for heart failure with preserved ejection fraction and HFmrEF in the hospitalized population with ADHF.

Access to Document (DOI)

Association of renin-angiotensin system inhibitors with long-term outcomes in patients with systolic heart failure and moderate-to-severe kidney function impairment

Higuchi S., Kohsaka S., Shiraishi Y., Katsuki T., Nagatomo Y., Mizuno A., Sujino Y., Kohno T., Goda A., Yoshikawa T.

European Journal of Internal Medicine (European Journal of Internal Medicine) 62 58 - 66 2019.04

ISSN 09536205

© 2019 European Federation of Internal Medicine Purpose: Although guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) should be treated with renin-angiotensin system (RAS) inhibitors, the long-term efficacy of RAS inhibitors in HFrEF patients with moderate-to-severe chronic kidney disease (CKD) remains unclear. Methods: The present study included consecutive patients hospitalized for acute heart failure across five Japanese teaching hospitals. The impact of RAS inhibitors on 2-year all-cause mortality was evaluated in patients with an ejection fraction ≤40% and CKD, defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m 2 , at discharge. Its severity was subclassified from 3B to 5 according to eGFR. Results: Overall, 553 patients (age, 76 ± 11 years; 68% male) were included. RAS inhibitors were prescribed more frequently in 227 patients with stage 3B (71.2%) than in 107 patients with stage 4 or 5 CKD (45.7%). All-cause mortality was recorded in 119 patients (23.4%) (55 [18.5%] patients with stage 3B; 64 [30.3%] patients with stage 4 or 5 CKD), within the median follow-up period of 609 (220–983) days. After many-to-one propensity score matching (87 pairs in stage 3; 60 pairs in stage 4 or 5 CKD), those with RAS inhibitors had reduced mortality rate in stage 3B (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.19–0.83) but not in stage 4 or 5 CKD (HR, 1.08; 95% CI, 0.57–2.03). Conclusions: In HFrEF patients with CKD, RAS inhibitors are associated with reduction in mortality in stage 3B CKD, but the association is less clear in stage 4 or 5 CKD.

Access to Document (DOI)

Clinical Scenario Classification for Characterization and Outcome Prediction of Acute Decompensated Heart Failure Under Contemporary Phenotyping.

Komuro J, Nagatomo Y, Mahara K, Isobe M, Goda A, Sujino Y, Mizuno A, Shiraishi Y, Kohno T, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure (WET-HF) Registry Investigators.

Circulation reports 1 ( 4 ) 162 - 170 2019.03

Access to Document (DOI)

Different prognostic associations of beta-blockers and diuretics in heart failure with preserved ejection fraction with versus without high blood pressure

Matsushita K., Harada K., Miyazaki T., Miyamoto T., Kohsaka S., Iida K., Tanimoto S., Takei M., Hosoda T., Yamamoto Y., Shiraishi Y., Yoshino H., Yamamoto T., Nagao K., Takayama M.

Journal of hypertension (Journal of hypertension) 37 ( 3 ) 643 - 649 2019.03

ISSN 0263-6352

OBJECTIVE: No agents have been proven to improve survival in heart failure with preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF suggests it may be possible to identify specific HFpEF phenotypes that will benefit from certain treatments. This study compared the risk factors for and prognostic impacts of treatments on in-hospital mortality between HFpEF patients with (+) and without (-) high blood pressure (HBP). METHODS: Data on 2238 consecutive HFpEF patients were extracted from Tokyo CCU Network data registry and analysed. HFpEF was defined as an ejection fraction greater than or equal to 50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at admission. Potential risk factors for in-hospital mortality were selected by univariate analyses and those with P < 0.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS: In-hospital mortality was significantly lower for HFpEF + HBP than HFpEF - HBP patients (log-rank, P < 0.001). Independent risk factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio 7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in-hospital treatment without diuretics (hazard ratio 4.201) were identified as independent risk factors in HFpEF - HBP patients. CONCLUSION: There were significant differences in prognostic factors, including beta-blocker and diuretic treatments, for in-hospital mortality between HFpEF patients with and without HBP. These findings suggest possible individualized therapies for patients with HFpEF.

Access to Document (DOI)

Controlling Nutritional Status Score As a Predictive Marker for Patients With Implantable Left Ventricular Assist Device.

Saito A, Amiya E, Hatano M, Shiraishi Y, Nitta D, Minatsuki S, Maki H, Hosoya Y, Tsuji M, Bujo C, Nawata K, Kinoshita O, Kimura M, Endo M, Kagami Y, Nemoto M, Ikeda Y, Morita H, Ono M, Komuro I

ASAIO journal (American Society for Artificial Internal Organs : 1992) (ASAIO journal (American Society for Artificial Internal Organs : 1992)) 66 ( 2 ) 166 - 172 2019.02

ISSN 1058-2916

Although a correlation between the nutritional status and the prognosis of patients with heart failure has been suggested, a correlation between the nutritional status and outcomes after the left ventricular assist device (LVAD) implantation remains unclear. We aimed to investigate the efficacy of the Controlling Nutritional Status (CONUT) score (range 0-12, including serum albumin, total cholesterol, and lymphocytes) as a nutritional index in speculating the prognosis of patients undergoing LVAD implantation. We examined 63 consecutive patients who underwent the continuous-flow LVAD implantation. Using the preoperative CONUT score, patients were categorized into two groups: lower CONUT score (0-4: normal to mild malnutrition) and higher CONUT score (5-12: moderate to severe malnutrition). We compared for the backgrounds and the clinical events after LVAD implantation. The higher CONUT group exhibited a significantly higher mean right atrial pressure (10.9 ± 4.7 vs. 7.3 ± 4.1 mmHg; p = 0.0019). In that group, the mortality rate was significantly higher (25% vs. 2.6%; p = 0.0059) and the Kaplan-Meier analysis showed lower survival rate. Furthermore, more bleeding events significantly occurred in the higher CONUT group. The preoperative CONUT score may reflect systemic venous congestion and offer a useful prognostic index of clinical courses after LVAD implantation.

Access to Document (DOI)

In-hospital outcome in patients presenting with acute coronary syndrome with left main coronary artery disease: A report from Japanese prospective multicenter percutaneous coronary intervention registry

Tani H., Sawano M., Numasawa Y., Kobayashi Y., Suzuki M., Noma S., Shiraishi Y., Ueda I., Fukuda K., Kohsaka S.

Journal of Cardiology (Journal of Cardiology) 75 ( 6 ) 635 - 640 2019

ISSN 09145087

© 2019 Japanese College of Cardiology Background: Patients presenting with acute coronary syndrome (ACS) from left main (LM) disease are at a high risk for mortality despite recent advancement in devices and techniques during percutaneous coronary interventions (PCI). We aimed to evaluate patient characteristics, clinical presentations, and key clinical characteristics associated with adverse in-hospital outcomes among ACS patients undergoing LM-PCI. Methods: We retrospectively identified 280 LM-ACS patients (3.7 %) from 7608 ACS patients in the prospective multicenter Japan Cardiovascular Database-Keio Inter-Hospital Cardiovascular Studies registry from March 2009 to May 2016 and divided them into those with/without PCI/coronary artery bypass grafting. We compared baseline demographics, coronary lesion characteristics, PCI details, and short-term outcomes, including in-hospital mortality and periprocedural complications, between the two groups. Results: Among LM-ACS patients, 38.6 % presented with ST elevation myocardial infarction, 29.6 % with cardiogenic shock (CS), and 15.4 % with cardiac arrest. The observed in-hospital mortality rate was 18.9 % with presence of CS [odds ratio (OR): 10.16, 95 % confidence interval (CI): 4.51–22.91, p < 0.001] and absence of prior revascularization (de novo patients; OR: 4.31, 95 % CI: 1.43–12.94, p = 0.009) was independently associated with higher incidence of in-hospital mortality. Notably, the observed mortality rate was substantially higher among de novo patients than the predicted mortality rate with a contemporary risk model (observed: 25.1 %; predicted: 11.6 %). Conclusions: Prior revascularization act as a protective factor among LM-ACS patients in the contemporary era of PCI. Further studies to detect those at higher risk for LM coronary lesion progression are needed to fully implement these findings into clinical practice.

Access to Document (DOI)

Clinical implications of the blood urea nitrogen/creatinine ratio in heart failure are and their association with haemoconcentration

Sujino Y., Nakano S., Tanno J., Shiraishi Y., Goda A., Mizuno A., Nagatomo Y., Kohno T., Muramatsu T., Nishimura S., Kohsaka S., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 6 ( 6 ) 1274 - 1282 2019

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: The blood urea nitrogen (BUN)/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF). However, the clinical impact of a high BUN/creatinine ratio at discharge with respect to renal dysfunction, neurohormonal hyperactivity, and different responsiveness to decongestion therapy remains unclear. Herein, we examined (i) the predictive value of a high BUN/creatinine ratio at discharge and (ii) its haemoconcentration-dependent effects, in patients with ADHF. Methods and results: The West Tokyo Heart Failure registry was a multicentre, prospective cohort registry-based study that enrolled patients hospitalized with a diagnosis of ADHF. The endpoint was post-discharge all-cause death. Based on the degree of haemoconcentration, patients (n = 2090) were divided into four subcategories. In multivariate proportional hazard analyses, a higher BUN/creatinine ratio was independently associated with higher all-cause mortality in the total population and in the extreme haemodilution (ΔHaemoglobin ≤ −0.9 g/dL) and haemoconcentration (0.8 g/dL ≤ ΔHaemoglobin) subcategories, but not in the modest haemodilution/haemoconcentration subcategories. Conclusions: A higher BUN/creatinine ratio at discharge was independently associated with higher post-discharge all-cause mortality in patients with ADHF. The predictive value of a high BUN/creatinine ratio at discharge was haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution.

Access to Document (DOI)

Prognostic impact of previous hospitalization in acute heart failure patients

Akita K., Kohno T., Kohsaka S., Shiraishi Y., Nagatomo Y., Goda A., Mizuno A., Sujino Y., Fukuda K., Yoshikawa T.

Circulation Journal (Circulation Journal) 83 ( 6 ) 1261 - 1268 2019

ISSN 13469843

© 2019, Japanese Circulation Society. All rights reserved. Background: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown. Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10–2.13; HR, 1.90 95% CI, 1.47–2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01–1.85; HR, 2.83, 95% CI, 2.19–3.65, respec-tively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18–1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66–1.20). Conclusions: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.

Access to Document (DOI)

Impact of catheter-induced iatrogenic coronary artery dissection with or without postprocedural flow impairment: A report from a Japanese multicenter percutaneous coronary intervention registry

Hiraide T., Sawano M., Shiraishi Y., Ueda I., Numasawa Y., Noma S., Negishi K., Ohki T., Yuasa S., Hayashida K., Miyata H., Fukuda K., Kohsaka S.

PLoS ONE (PLoS ONE) 13 ( 9 ) e0204333 2018.09

© 2018 Hiraide et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Despite the ever-increasing complexity of percutaneous coronary intervention (PCI), the incidence, predictors, and in-hospital outcomes of catheter-induced coronary artery dissection (CICAD) is not well defined. In addition, there are little data on whether persistent coronary flow impairment after CICAD will affect clinical outcomes. We evaluated 17,225 patients from 15 participating hospitals within the Japanese PCI registry from January 2008 to March 2016. Associations between CICAD and in-hospital adverse cardiovascular events were evaluated using multivariate logistic regression. Outcomes of patients with CICAD with or without postprocedural flow impairment (TIMI flow 2 or 3, respectively) were analyzed. The population was predominantly male (79.4%; mean age, 68.2 ± 11.0 years); 35.6% underwent PCI for complex lesions (eg. chronic total occlusion or a bifurcation lesion.). CICAD occurred in 185 (1.1%), and its incidence gradually decreased (p < 0.001 for trend); postprocedural flow impairment was observed in 43 (23.2%). Female sex, complex PCI, and target lesion in proximal vessel were independent predictors (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.53–3.10; OR, 2.19; 95% CI, 1.58–3.04; and OR, 1.55; 95% CI, 1.06–2.28, respectively). CICAD was associated with an increased risk of in-hospital adverse events (composite of new-onset cardiogenic shock and new-onset heart failure) regardless of postprocedural flow impairment (OR, 10.9; 95% CI, 5.30–22.6 and OR, 2.27; 95% CI, 1.20–4.27, respectively for flow-impaired and flow-recovered CICAD). In conclusion, CICAD occurred in roughly 1% of PCI cases; female sex, complex PCI, and proximal lesion were its independent risk factors. CICAD was associated with adverse in-hospital cardiovascular events regardless of final flow status. Our data implied that the appropriate selection of PCI was necessary for women with complex lesions.

Access to Document (DOI)

Mortality after admission for heart failure in the UK compared with Japan

Nagai T., Sundaram V., Rothnie K., Quint J., Shoaib A., Shiraishi Y., Kohsaka S., Piper S., McDonagh T., Hardman S., Goda A., Mizuno A., Kohno T., Rigby A., Yoshikawa T., Clark A., Anzai T., Cleland J.

Open Heart (Open Heart) 5 ( 2 ) e000811 2018.08

ISSN 2053-3624

© Author(s) (or their employer(s)) 2018. Objective Mortality amongst patients hospitalised for heart failure (HHF) in Western and Asian countries may differ, but this has not been investigated using individual patient-level data (IPLD). We sought to remedy this through rigorous statistical analysis of HHF registries and variable selection from a systematic literature review. Methods and results IPLD from registries of HHF in Japan (n=3781) and the UK (n=894) were obtained. A systematic literature review identified 23 models for predicting outcome of HHF. Five variables appearing in 10 or more reports were strongly related to prognosis (systolic blood pressure, serum sodium concentration, age, blood urea nitrogen and creatinine). To compare mortality in the UK and Japan, variables were imputed in a propensity model using inverse probability of treatment weighting (IPTW) and IPTW with logistic regression (doubly robust IPTW). Overall, patients in the UK were sicker and in-patient and post-discharge mortalities were greater, suggesting that the threshold for hospital admission was higher. Covariate-adjusted in-hospital mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86), but 180-day postdischarge mortality was substantially higher in the UK (doubly robust IPTW OR: 2.33, 95% CI 1.58 to 3.43). Conclusions Despite robust methods to adjust for differences in patient characteristics and disease severity, HHF patients in the UK have roughly twice the mortality at 180 days compared with those in Japan. Similar analyses should be done using other data sets and in other countries to determine the consistency of these findings and identify factors that might inform healthcare policy and improve outcomes.

Access to Document (DOI)

Performance of the MAGGIC heart failure risk score and its modification with the addition of discharge natriuretic peptides

Sawano M., Shiraishi Y., Kohsaka S., Nagai T., Goda A., Mizuno A., Sujino Y., Nagatomo Y., Kohno T., Anzai T., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 5 ( 4 ) 610 - 619 2018.08

Research paper (scientific journal), Accepted

© 2018 The Authors. Aims Predictive models for heart failure patients are widely used in the clinical practice to stratify patients’ mortality and enable clinicians to tailor and intensify their approach. However, such models have not been validated internationally. In addition, biomarkers are now frequently measured to obtain prognostic information, and the implications of this practice are not known. In this study, we aimed to validate the model performance of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score in a Japanese acute heart failure registry and further explore the incremental prognostic value of discharge B-type natriuretic peptide (BNP) level. Methods and Results In this study, we evaluated the registered data of 2215 consecutive acute HF patients (with 694 119 person-years follow-up) from a prospective multicentre registry (the West Tokyo Heart Failure) conducted in Japan from April 2006 to August 2016. The mean age was 73.0 ± 13.0, and 61.2% were male. The MAGGIC score demonstrated modest discrimination (c-index = 0.71, 95% confidence interval 0.67–0.74) and good calibration (R2 value = 0.97); there was constant overestimation for 1 year mortality. However, when the BNP level was added to the original MAGGIC variables, the model demonstrated good discrimination (c-index = 0.74, 95% confidence interval 0.70–0.78) with adequate calibration (R2 value = 0.91). The modified MAGGIC BNP score was externally validated in a separate Japanese registry (NaDEF) and demonstrated moderate discrimination (c-index = 0.69, 95% confidence interval 0.65–0.73) and calibration (R2 value = 0.85). Conclusion The original MAGGIC score performed modestly in Japanese patients, but the addition of discharge BNP level enhanced model performance. The addition of objective biomarkers may result in effective modification of preexisting internationally recognized risk models and aid in multinational comparisons of heart failure patients’ outcomes.

Access to Document (DOI)

Validation of U.S. mortality prediction models for hospitalized heart failure in the United Kingdom and Japan

Nagai T., Sundaram V., Shoaib A., Shiraishi Y., Kohsaka S., Rothnie K., Piper S., McDonagh T., Hardman S., Goda A., Mizuno A., Sawano M., Rigby A., Quint J., Yoshikawa T., Clark A., Anzai T., Cleland J.

European Journal of Heart Failure (European Journal of Heart Failure) 20 ( 8 ) 1179 - 1190 2018.08

ISSN 13889842

© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology Aims: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan. Methods and results: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital (4.8% vs. 2.5%) and 180-day (20.7% vs. 9.5%) mortality. The model c-statistics for the published/derivation (range 0.70–0.76) and Japanese (range 0.75–0.77) cohorts were similar and higher than for the UK (0.62–0.75) but models consistently overestimated mortality in Japan. For in-hospital mortality, the OPTIMIZE-HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74–0.77); 0.75 (0.68–0.81); and 0.77 (0.70–0.83), respectively], and least overestimated mortality in Japan. For 180-day mortality, the c-statistics for the ASCEND-HF model were similar in published/derivation (0.70) and UK [0.69 (0.64–0.74)] cohorts but higher in Japan [0.75 (0.71–0.79)]; calibration was good in the UK but again overestimated mortality in Japan. Conclusion: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.

Access to Document (DOI)

Incidence of hospital-acquired hyponatremia by the dose and type of diuretics among patients with acute heart failure and its association with long-term outcomes

Yamazoe M., Mizuno A., Kohsaka S., Shiraishi Y., Kohno T., Goda A., Higuchi S., Yagawa M., Nagatomo Y., Yoshikawa T.

Journal of Cardiology (Journal of Cardiology) 71 ( 6 ) 550 - 556 2018.06

ISSN 09145087

© 2018 Background: Diuretics are the cornerstone therapy for acute heart failure (AHF) but can lead to various electrolyte disturbances and inversely affect the patients’ outcome. We aimed to evaluate whether (1) the dose of loop diuretics could predict hospital-acquired hyponatremia (HAH) during AHF treatment, (2) addition of thiazide diuretics could affect development of HAH, and (3) assess their impact on long-term outcomes. Methods: We analyzed the subjects enrolled in the multicenter AHF registry (WET-HF). Risk of HAH, defined as hyponatremia at discharge with normonatremia upon admission, was evaluated based on oral non-potassium-sparing diuretics via multivariate logistic regression analysis. Additionally, we performed one-to-one matched analysis based on propensity scores for thiazide diuretics use and compared long-term mortality. Results: Of total 1163 patients (mean age 72.6 ± 13.6 years, male 62.6%), 92 (7.9%) had HAH. Compared with low-dose loop diuretics users (<40 mg; without thiazide diuretics), risks for developing HAH were significantly higher in patients with thiazide diuretics, regardless of the dose of loop diuretics (OR 2.67, 95% CI 1.13–6.34 and OR 2.31, 95% CI 1.50–5.13 for low- and high-dose loop diuretics, respectively). The association was less apparent in patients without thiazide diuretics (OR 1.29, 95% CI 0.73–2.27 for high-dose loop diuretics alone). Among 206 matched patients, all-cause and cardiac mortality rate was 27% and 14% in non thiazide diuretics users and 50% and 30% in thiazide diuretics users, respectively (HR 2.46, 95% CI 1.29–4.69, p = 0.006 and HR 2.50, 95% CI 1.10–5.67, p = 0.028, respectively) during a mean 19.3 months of follow-up. Conclusions: Thiazide diuretics use, rather than loop diuretics dose, was independently associated with HAH; and mortality was higher in thiazide diuretics users even after statistical matching.

Access to Document (DOI)

Long-Term Prognostic Significance of Plasma B-Type Natriuretic Peptide Level in Patients With Acute Heart Failure With Reduced, Mid-Range, and Preserved Ejection Fractions

Hamatani Y., Nagai T., Shiraishi Y., Kohsaka S., Nakai M., Nishimura K., Kohno T., Nagatomo Y., Asaumi Y., Goda A., Mizuno A., Yasuda S., Ogawa H., Yoshikawa T., Anzai T.

American Journal of Cardiology (American Journal of Cardiology) 121 ( 6 ) 731 - 738 2018.03

ISSN 00029149

© 2017 Elsevier Inc. Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p <0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

Access to Document (DOI)

Stroke after percutaneous coronary intervention in the era of transradial intervention report from a Japanese multicenter registry

Shoji S., Kohsaka S., Kumamaru H., Sawano M., Shiraishi Y., Ueda I., Noma S., Suzuki M., Numasawa Y., Hayashida K., Yuasa S., Miyata H., Fukuda K.

Circulation: Cardiovascular Interventions (Circulation: Cardiovascular Interventions) 11 ( 12 ) e006761 2018

ISSN 19417640

© 2018 American Heart Association, Inc. BACKGROUND: Periprocedural stroke is a rare but life-threatening complication of percutaneous coronary intervention (PCI). Transradial intervention (TRI) is more beneficial than transfemoral intervention for periprocedural bleeding and acute kidney injuries, but its effect on periprocedural stroke has not been fully investigated. Our study aimed to assess risk predictors of periprocedural stroke according to PCI access site. METHODS AND RESULTS: Between 2008 and 2016, 17966 patients undergoing PCI were registered in a prospective multicenter database. Periprocedural stroke was defined as loss of neurological function caused by an ischemic or hemorrhagic event with residual symptoms lasting at least 24 hours after onset. Periprocedural stroke was observed in 42 patients (0.3%). Stroke patients were older and had a higher incidence of chronic kidney disease, peripheral artery disease, and acute coronary syndrome but were less likely to undergo TRI. Multivariable logistic regression analysis revealed TRI (odds ratio; 0.33; 95% CI, 0.16-0.71; P=0.004) was significantly associated with a lower occurrence of periprocedural stroke. Finally, propensity score-matching analysis showed that TRI was associated with a reduced risk of periprocedural stroke compared with transfemoral intervention (0.1% versus 0.4%; P=0.014). According to our sensitivity analysis, this finding was robust to the presence of an unmeasured confounder in almost all plausible scenarios. CONCLUSIONS: TRI was associated with a reduced risk of periprocedural stroke compared with transfemoral intervention. Increased TRI use may reduce overall PCI complications and should be recommended as the optimal access site for both urgent/emergent and elective PCIs.

Access to Document (DOI)

Identification of left atrial appendage thrombi in patients with persistent and long-standing persistent atrial fibrillation using intra-cardiac echocardiography and cardiac computed tomography

Ikegami Y., Tanimoto K., Inagawa K., Shiraishi Y., Fuse J., Sakamoto M., Momiyama Y., Takatsuki S.

Circulation Journal (Circulation Journal) 82 ( 1 ) 46 - 52 2018

ISSN 13469843

© 2017, Japanese Circulation Society. All rights reserved. Background: Intracardiac echocardiography (ICE) and cardiac computed tomography (CCT), in addition to standard transesophageal echocardiography (TEE), have been used to identify left atrial (LA) thrombi prior to ablation for atrial fibrillation (AF). The clinical advantages of this, however, remain unclear. This study therefore investigated the advantages of additional pre-procedural LA appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in persistent and long-standing persistent AF. Methods and Results: We analyzed data from 108 consecutive patients with persistent and long-standing persistent AF who were scheduled to undergo AF ablation. TEE was performed within 24 h prior to ablation. ICE was performed for 97 patients in whom a thrombus was not detected on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the reference for thrombus detection, the sensitivity, specificity, positive predictive value, and negative predictive value of CCT for identifying contrast defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. Conclusions: ICE combined with TEE increased the detection rate of LAA thrombi in patients with persistent and long-standing persistent AF. Moreover, CCT had high sensitivity and negative predictive value for LAA thrombus detection.

Access to Document (DOI)

Effect of Heart Failure Secondary to Ischemic Cardiomyopathy on Body Weight and Blood Pressure.

Matsushita K, Harada K, Miyazaki T, Miyamoto T, Kohsaka S, Iida K, Tanimoto S, Yagawa M, Shiraishi Y, Yoshino H, Yamamoto T, Nagao K, Takayama M

The American journal of cardiology 120 ( 9 ) 1589 - 1594 2017.11

ISSN 0002-9149

Access to Document (DOI)

Effect of Obesity on the Prognostic Impact of Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

Yagawa M, Nagatomo Y, Izumi Y, Mahara K, Tomoike H, Shiraishi Y, Kohno T, Mizuno A, Goda A, Kohsaka S, Yoshikawa T, West Tokyo Heart Failure (WET-HF) Registry Collaborative Group.

Circulation journal : official journal of the Japanese Circulation Society 81 ( 7 ) 966 - 973 2017.06

ISSN 1346-9843

Access to Document (DOI)

The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction　- First Pilot Study in Humans.

Katsumata Y, Sano F, Abe T, Tamura T, Fujisawa T, Shiraishi Y, Kohsaka S, Ueda I, Homma K, Suzuki M, Okuda S, Maekawa Y, Kobayashi E, Hori S, Sasaki J, Fukuda K, Sano M

Circulation journal : official journal of the Japanese Circulation Society 81 ( 7 ) 940 - 947 2017.06

ISSN 1346-9843

Access to Document (DOI)

Rapid Improvement of thyroid storm-related hemodynamic collapse by aggressive anti-thyroid therapy including steroid pulse: A case report.

Kiriyama H, Amiya E, Hatano M, Hosoya Y, Maki H, Nitta D, Saito A, Shiraishi Y, Minatsuki S, Sato T, Murakami H, Uehara M, Manaka K, Makita N, Watanabe M, Komuro I

Medicine 96 ( 22 ) e7053 2017.06

ISSN 0025-7974

Access to Document (DOI)

Barriers Associated With Door-to-Balloon Delay in Contemporary Japanese Practice.

Ikemura N, Sawano M, Shiraishi Y, Ueda I, Miyata H, Numasawa Y, Noma S, Suzuki M, Momiyama Y, Inohara T, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S

Circulation journal : official journal of the Japanese Circulation Society 81 ( 6 ) 815 - 822 2017.05

ISSN 1346-9843

Access to Document (DOI)

Current use of guideline-based medical therapy in elderly patients admitted with acute heart failure with reduced ejection fraction and its impact on event-free survival.

Akita K, Kohno T, Kohsaka S, Shiraishi Y, Nagatomo Y, Izumi Y, Goda A, Mizuno A, Sawano M, Inohara T, Fukuda K, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology 235 162 - 168 2017.05

ISSN 0167-5273

Access to Document (DOI)

A Novel SCN5A Mutation Found in a Familial Case of Long QT Syndrome Complicated by Severe Left Ventricular Dysfunction.

Kimura M, Kohno T, Aizawa Y, Inohara T, Shiraishi Y, Katsumata Y, Egashira T, Fukushima H, Kosaki K, Fukuda K

The Canadian journal of cardiology 33 ( 4 ) 554.e5 - 554.e7 2017.04

ISSN 0828-282X

Access to Document (DOI)

Three novel <i>BMPR2</i> mutations associated with advanced pulmonary arterial hypertension.

Hara H, Takeda N, Morita H, Hatano M, Amiya E, Maki H, Minatsuki S, Taki M, Shiraishi Y, Fujiwara T, Maemura S, Komuro I

Human genome variation 4 17010 2017

ISSN 2054-345X

Access to Document (DOI)

Increased Hematocrit During Sodium-Glucose Cotransporter 2 Inhibitor Therapy Indicates Recovery of Tubulointerstitial Function in Diabetic Kidneys.

Sano M, Takei M, Shiraishi Y, Suzuki Y

Journal of clinical medicine research 8 ( 12 ) 844 - 847 2016.12

ISSN 1918-3003

Access to Document (DOI)

Early vs. late reverse ventricular remodeling in patients with cardiomyopathy.

Banno A, Kohsaka S, Inohara T, Koide K, Shiraishi Y, Kohno T, Sano M, Yoshikawa T, Fukuda K

Journal of cardiology 68 ( 1 ) 57 - 63 2016.07

ISSN 0914-5087

Access to Document (DOI)

Enhanced oxidative stress is associated with sleep-disordered breathing and obesity in patients with heart failure.

Kondo M, Kohno T, Kohsaka S, Fukuoka R, Shiraishi Y, Sawano M, Inohara T, Sano M, Yoshikawa T, Fukuda K

International journal of cardiology 209 133 - 5 2016.04

ISSN 0167-5273

Access to Document (DOI)

Independent Prognostic Value of Single and Multiple Non-Specific 12-Lead Electrocardiographic Findings for Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

Sawano M, Kohsaka S, Okamura T, Inohara T, Sugiyama D, Shiraishi Y, Watanabe M, Nakamura Y, Higashiyama A, Kadota A, Okuda N, Murakami Y, Ohkubo T, Fujiyoshi A, Miura K, Okayama A, Ueshima H, NIPPON DATA 80/90 Research Group.

PloS one 11 ( 6 ) e0157563 2016

Access to Document (DOI)

Application of the United States acute heart failure risk prediction model in Japanese patients; analysis from a contemporary multicenter registry.

Makino J, Kohsaka S, Shiraishi Y, Inohara T, Goda A, Izumi Y, Yagawa M, Mizuno A, Fukuda K, Yoshikawa T

International journal of cardiology 195 323 - 5 2015.09

ISSN 0167-5273

Access to Document (DOI)

Effect of estimated plasma volume reduction on renal function for acute heart failure differs between patients with preserved and reduced ejection fraction.

Takei M, Kohsaka S, Shiraishi Y, Goda A, Izumi Y, Yagawa M, Mizuno A, Sawano M, Inohara T, Kohno T, Fukuda K, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

Circulation. Heart failure 8 ( 3 ) 527 - 32 2015.05

ISSN 1941-3289

Access to Document (DOI)

Seasonal changes in systemic volume overload are to be considered.

Mizuno A, Kohsaka S, Shiraishi Y, Goda A, Yoshikawa T, West of Tokyo Heart Failure Registry Investigators.

Circulation journal : official journal of the Japanese Circulation Society 79 ( 3 ) 670 2015

ISSN 1346-9843

Access to Document (DOI)

Outcomes of Percutaneous Coronary Intervention Performed With or Without Preprocedural Dual Antiplatelet Therapy.

Ikegami Y, Kohsaka S, Miyata H, Ueda I, Fuse J, Sakamoto M, Shiraishi Y, Numasawa Y, Negishi K, Nakamura I, Maekawa Y, Momiyama Y, Fukuda K

Circulation journal : official journal of the Japanese Circulation Society 79 ( 12 ) 2598 - 607 2015

ISSN 1346-9843

Access to Document (DOI)

MRI and serum high-sensitivity C reactive protein predict long-term mortality in non-ischaemic cardiomyopathy.

Sadahiro T, Kohsaka S, Okuda S, Inohara T, Shiraishi Y, Kohno T, Yoshikawa T, Fukuda K

Open heart 2 ( 1 ) e000298 2015

ISSN 2053-3624

Access to Document (DOI)

Prognostic impact of renal and hepatic dysfunction based on the MELD-XI score in patients with acute heart failure.

Inohara T, Kohsaka S, Shiraishi Y, Goda A, Sawano M, Yagawa M, Mahara K, Fukuda K, Yoshikawa T, West Tokyo Heart Failure Registry Investigators.

International journal of cardiology 176 ( 3 ) 571 - 3 2014.10

ISSN 0167-5273

Access to Document (DOI)

Myocardial delayed enhancement with dual-source CT: advantages of targeted spatial frequency filtration and image averaging over half-scan reconstruction.

Kurobe Y, Kitagawa K, Ito T, Kurita Y, Shiraishi Y, Nakamori S, Nakajima H, Nagata M, Ishida M, Dohi K, Ito M, Sakuma H

Journal of cardiovascular computed tomography 8 ( 4 ) 289 - 98 2014.07

ISSN 1934-5925

Access to Document (DOI)

Dose reduction in dynamic CT stress myocardial perfusion imaging: comparison of 80-kV/370-mAs and 100-kV/300-mAs protocols.

Fujita M, Kitagawa K, Ito T, Shiraishi Y, Kurobe Y, Nagata M, Ishida M, Sakuma H

European radiology 24 ( 3 ) 748 - 55 2014.03

ISSN 0938-7994

Access to Document (DOI)

Prognostic implication of physical signs of congestion in acute heart failure patients and its association with steady-state biomarker levels.

Negi S, Sawano M, Kohsaka S, Inohara T, Shiraishi Y, Kohno T, Maekawa Y, Sano M, Yoshikawa T, Fukuda K

PloS one 9 ( 5 ) e96325 2014

Access to Document (DOI)

脳梗塞発症予測における頭部CTとCAVI・頚動脈エコーの有用性の比較

白石泰之, 前淵大輔, 田中宏明

Japanese journal of National Medical Services 65 ( 9 ) 475 - 478 2011.09

Research paper (scientific journal), Lead author, Accepted

　 Previous page - Next page 　