Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

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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.

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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.

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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.

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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

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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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.

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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.

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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.

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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

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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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.

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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

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

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

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

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

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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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.].

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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.

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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.

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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

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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