著者
Hiroyuki Tsutsui Hiroshi Ito Masafumi Kitakaze Issei Komuro Toyoaki Murohara Tohru Izumi Kenji Sunagawa Yoshio Yasumura Masafumi Yano Kazuhiro Yamamoto Tsutomu Yoshikawa Takayoshi Tsutamoto Junwei Zhang Akifumi Okayama Yoshihiko Ichikawa Kazuhiro Kanmuri Masunori Matsuzaki for the J-EMPHASIS-HF Study Group
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-0323, (Released:2017-08-19)
参考文献数
19
被引用文献数
23

Background:The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction (HFrEF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. However, similar efficacy and safety have not been established in Japanese patients. We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter, randomized, double-blind placebo-controlled outcome study (ClinicalTrials.gov Identifier: NCT01115855). The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of <1 for the hazard ratio.Methods and Results:HFrEF patients with NYHA functional class II–IV and an EF ≤35% received eplerenone (n=111) or placebo (n=110) on top of standard therapy for at least 12 months. The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF. The primary endpoint occurred in 29.7% of patients in the eplerenone group vs. 32.7% in the placebo group [hazard ratio=0.85 (95% CI: 0.53–1.36)]. Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone. A total of 17 patients (15.3%) in the eplerenone group and 10 patients (9.1%) in the placebo group died. Adverse events, including hyperkalemia, were similar between the groups.Conclusions:Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study.
著者
Hiroyuki Tsutsui Hiroshi Ito Masafumi Kitakaze Issei Komuro Toyoaki Murohara Tohru Izumi Kenji Sunagawa Yoshio Yasumura Masafumi Yano Kazuhiro Yamamoto Tsutomu Yoshikawa Takayoshi Tsutamoto Junwei Zhang Akifumi Okayama Yoshihiko Ichikawa Kazuhiro Kanmuri Masunori Matsuzaki for the J-EMPHASIS-HF Study Group
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.1, pp.148-158, 2017-12-25 (Released:2017-12-25)
参考文献数
19
被引用文献数
23

Background:The mineralocorticoid receptor antagonist eplerenone improved clinical outcomes among patients with heart failure with reduced ejection faction (HFrEF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. However, similar efficacy and safety have not been established in Japanese patients. We evaluated the efficacy and safety of eplerenone in patients with HFrEF in a multicenter, randomized, double-blind placebo-controlled outcome study (ClinicalTrials.gov Identifier: NCT01115855). The aim of the study was to evaluate efficacy predefined as consistency of the primary endpoint with that of EMPHASIS-HF at a point estimate of <1 for the hazard ratio.Methods and Results:HFrEF patients with NYHA functional class II–IV and an EF ≤35% received eplerenone (n=111) or placebo (n=110) on top of standard therapy for at least 12 months. The primary endpoint was a composite of death from cardiovascular causes or hospitalization for HF. The primary endpoint occurred in 29.7% of patients in the eplerenone group vs. 32.7% in the placebo group [hazard ratio=0.85 (95% CI: 0.53–1.36)]. Hospitalization for any cause and changes in plasma BNP and LVEF were favorable with eplerenone. A total of 17 patients (15.3%) in the eplerenone group and 10 patients (9.1%) in the placebo group died. Adverse events, including hyperkalemia, were similar between the groups.Conclusions:Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF study.
著者
Taro Temma Toshiyuki Nagai Masaya Watanabe Rui Kamada Yumi Takahashi Hikaru Hagiwara Taro Koya Motoki Nakao Kazunori Omote Kiwamu Kamiya Hiroyuki Iwano Kazuhiro Yamamoto Tsutomu Yoshikawa Yoshihiko Saito Toshihisa Anzai
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-19-0963, (Released:2020-02-01)
参考文献数
31
被引用文献数
9

Background:Atrial fibrillation (AF) is an important prognostic determinant in heart failure (HF) with preserved ejection fraction (HFpEF). However, it is unclear which HFpEF phenotypes are affected by AF in terms of long-term clinical outcomes because HFpEF is a heterogeneous syndrome with comorbidities such as coronary artery disease (CAD). In this study we determined the differential prognostic significance of AF in HFpEF patients according to CAD status.Methods and Results:Data for 408 hospitalized HFpEF patients enrolled in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Nationwide Multicenter Registry were analyzed. Patients were divided into 4 groups according to the presence of AF and CAD. The primary outcome was the composite of all-cause death and HF rehospitalization. The incidence of adverse events was higher in the AF–non-CAD than non-AF–non-CAD group (P=0.004). On multivariable Cox regression analysis with prespecified confounders, AF–non-CAD was significantly associated with an increased risk of adverse events than non-AF–non-CAD (adjusted HR, 1.91; 95% CI: 1.02–3.92) regardless of the type of AF. In contrast, risk was comparable between the AF–CAD and non-AF–CAD groups (adjusted HR, 1.24; 95% CI: 0.64–2.47).Conclusions:In HFpEF patients without CAD, AF was independently related to adverse events, indicating that intensive management of AF would have more beneficial effects particularly in HFpEF patients without CAD.
著者
Jin Komuro Yuji Nagatomo Keitaro Mahara Mitsuaki Isobe Ayumi Goda Yasumori Sujino Atsushi Mizuno Yasuyuki Shiraishi Takashi Kohno Shun Kohsaka Tsutomu Yoshikawa West Tokyo Heart Failure (WET-HF) Registry Investigators
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.1, no.4, pp.162-170, 2019-04-10 (Released:2019-04-10)
参考文献数
31
被引用文献数
8

Background: The concept of Clinical Scenario (CS) classification has been widely utilized to aid in choosing appropriate management strategies for acute decompensated heart failure (ADHF). Methods and Results: The West Tokyo-Heart Failure (WET-HF) Registry is a multicenter, prospective cohort registry enrolling consecutive hospitalized ADHF patients. Based on systolic blood pressure (SBP) at admission, 4,000 patients enrolled between 2006 and 2017 were classified into 3 groups: CS1, SBP ≥140 mmHg; CS2, 100≤SBP<140 mmHg; and CS3, SBP <100 mmHg. The CS1 group had a high rate of fluid retention such as leg edema, and the largest reduction in body weight at discharge. In-hospital diuretics use was the most frequent in CS1. Although the primary endpoint of long-term all-cause death and/or ADHF re-hospitalization was more common in more advanced CS, there was no significant difference between the 3 CS groups in patients with HF with preserved ejection fraction (HFpEF; P=0.10). Although more advanced CS was associated with larger left ventricular (LV) chamber size in HF with reduced EF (HFrEF), it was associated with smaller LV size in HFpEF. Conclusions: The long-term prognostic value of CS classification was limited in HFpEF. Whereas CS was closely associated with degree of LV remodeling in HFrEF, a smaller LV chamber might be associated with a lower cardiovascular functional reserve in HFpEF.
著者
Yuji Nagatomo Tsutomu Yoshikawa Hiroshi Okamoto Akira Kitabatake Masatsugu Hori on behalf of J-CHF Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-0442, (Released:2017-09-07)
参考文献数
33
被引用文献数
18

Background:Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (β=0.13, P=0.047) and BNP (β=−0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2at baseline was not associated with differential response to carvedilol therapy. During 3.8±1.4 years follow-up, group [A] had a higher incidence of the composite endpoint of death, hospitalization for cardiovascular causes including HF compared with [N] (P=0.006). Baseline Hb was an independent predictor of the composite endpoint (hazard ratio 0.86, P=0.04), whereas baseline eGFR was not.Conclusions:Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.
著者
Takanori Ohata Nozomi Niimi Yasuyuki Shiraishi Fumiko Nakatsu Ichiro Umemura Takashi Kohno Yuji Nagatomo Makoto Takei Tomohiko Ono Munehisa Sakamoto Shintaro Nakano Keiichi Fukuda Shun Kohsaka Tsutomu Yoshikawa
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-23-0356, (Released:2023-10-31)
参考文献数
43
被引用文献数
1

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.
著者
Yuji Nagatomo Tsutomu Yoshikawa Hiroshi Okamoto Akira Kitabatake Masatsugu Hori on behalf of J-CHF Investigators
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.2, no.3, pp.143-151, 2020-03-10 (Released:2020-03-10)
参考文献数
27
被引用文献数
1

Background:Heart rate (HR) reduction by β-blocker might not benefit patients with heart failure and reduced ejection fraction (HFrEF) with atrial fibrillation (AF).Methods and Results:The J-CHF study was a prospective randomized multicenter trial that assigned 360 HFrEF patients to a 2.5 mg/5 mg/20 mg target dose of carvedilol. Carvedilol was uptitrated over 8 weeks and then the dose was fixed. Of 321 patients available for analysis, AF was identified in 65 (20%). Using the median absolute change in HR at 32 weeks (∆HR), the subjects were further divided into group A (∆HR >−6 beats/min) and B (∆HR ≤−6 beats/min). Both in sinus rhythm (SR) and AF, baseline characteristics and achieved carvedilol dose were similar between groups A and B. In SR, the time-dependent change in left ventricular EF (LVEF) and LV end-diastolic dimension (LVEDD) over 56 weeks was more favorable in B compared with A (∆LVEF, P=0.036; ∆LVEDD, P=0.047), and ∆HR was independently associated with ∆LVEF (P=0.040). Group B had a lower rate of the primary endpoint, defined as a composite of death and hospitalization due to cardiovascular causes including acute decompensated HF at 3 years (P=0.002). ∆HR was an independent predictor of the primary endpoint (P=0.01), but this was not observed in AF.Conclusions:Response to the carvedilol HR reduction might differ in HFrEF between SR and AF.
著者
Kyohei Marume Seiji Takashio Toshiyuki Nagai Kenichi Tsujita Yoshihiko Saito Tsutomu Yoshikawa Toshihisa Anzai
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-18-0639, (Released:2018-11-09)
参考文献数
50
被引用文献数
24

Background:Statins might be associated with improved survival in patients with heart failure with preserved ejection fraction (HFpEF). The effect of statins in HFpEF without coronary artery disease (CAD), however, remains unclear.Methods and Results:From the JASPER registry, a multicenter, observational, prospective cohort with Japanese patients aged ≥20 years requiring hospitalization with acute HF and LVEF ≥50%, 414 patients without CAD were selected for outcome analysis. Based on prescription of statins at admission, we divided patients into the statin group (n=81) or no statin group (n=333). We followed them for 25 months. The association between statin use and primary (all-cause mortality) and secondary (non-cardiac death, cardiac death, or rehospitalization for HF) endpoints was assessed in the entire cohort and in a propensity score-matched cohort. In the propensity score-matched cohort, 3-year mortality was lower in the statin group (HR, 0.21; 95% CI: 0.06–0.72; P=0.014). The statin group had a significantly lower incidence of non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001), but not cardiac death (P=0.593). The beneficial effect of statins on mortality did not have any significant interaction with cholesterol level or HF severity.Conclusions:Statin use has a beneficial effect on mortality in HFpEF without CAD. The present findings should be tested in an adequately powered randomized clinical trial.