Papers - SHIRAISHI Yasuyuki

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

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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

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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.

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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

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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

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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.

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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

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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

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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.

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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

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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.

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