Japanese Heart Failure Patients Research Articles

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

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

P5667Predicting sudden cardiac death in Japanese heart failure patients: International validation of the Seattle Proportional Risk Model

P5667Predicting sudden cardiac death in Japanese heart failure patients: International validation of the Seattle Proportional Risk Model

SP3-4 - Development of Prediction Models for Mortality in Japanese Heart Failure Patients

SP3-4 - Development of Prediction Models for Mortality in Japanese Heart Failure Patients

O24-5 - Validation of the Seattle Heart Failure Model in Japanese Heart Failure Patients

O24-5 - Validation of the Seattle Heart Failure Model in Japanese Heart Failure Patients

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study

BackgroundThe prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. Methods and designThis is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. ConclusionsThe design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

Prognostic Impacts of Hyponatremia, Renal Dysfunction, and High-Dose Diuretics During a 10-Year Study Period in 4,087 Japanese Heart Failure Patients.

Prognostic Impacts of Hyponatremia, Renal Dysfunction, and High-Dose Diuretics During a 10-Year Study Period in 4,087 Japanese Heart Failure Patients.

Abstract 18801: Light-intensity Physical Activity After Discharge Predicts 6-month Postdischarge Adverse Events in Older Japanese Patients With Heart Failure

Introduction: Moderate physical activity (PA) is recommended in patients with heart failure (HF). However, patient’ characteristics in those with low PA and the impact of light-intensity PA on postdischarge major adverse cardiovascular events (MACE) remain unclear in older Japanese HF patients. Methods: Thirty seven patients (Stage C/D: 76±5 yrs, 21m) who had been admitted due to HF and 23 Stage A/B patients (73±5 yrs) with risk factors were enrolled. PA was measured using the Omuron HJ350IT accelerometer from the day of discharge for 7 days. Light-intensity PA at an intensity of 1.5-3.0 metabolic equivalents (METs), moderate-intensity PA (≥3METs), and total PA were determined. At discharge, knee-extensor muscle strength, 6-min walking distance (6MWD),SF-36 score, and left ventricular (LV) structure by echocardiography were evaluated. Stage C/D patients were stratified into High-PA and Low-PA according to the median total PA value of 8.4 METs·hour/day. Stage A/B patients underwent these measurements, and values were compared. Factors related to the 6-month postdischarge MACE were assessed. Results: Stage C/D patients were anemic, took fewer steps per day, and had higher brain natriuretic peptide (BNP) than Stage A/B patients. Patients in Low-PA were less likely to engage in household work, and had shorter active time, fewer steps per day, and lower light- and moderate-intensity PA than those in High-PA. No differences were observed in 6MWD (263±110 vs. 303±77 m), knee-extensor muscle strength, BNP (405±346 vs. 267±179 pg/ml), SF-36 physical composite score, or LV ejection fraction between Low-PA and High-PA. Light-intensity and total PA, but not moderate-intensity PA, were associated with the 6-month postdischarge MACE through univariate analyses. Multivariate regression analysis showed that total PA was the independent predictor of the 6-month postdischarge MACE (odds ratio: 0.66) among functional capacity variables including 6MWD and knee-extensor muscle strength. Conclusions: Physical activity, especially at light-intensity, is inversely associated with the 6-month postdischarge MACE in older HF patients. Our results may indicate that postdischarge PA assessed by accelerometer is useful to distinguish those at high risks for MACE.

Presentations and outcomes of patients with acute decompensated heart failure admitted in the winter season

BackgroundSeasonal variations in cardiovascular disease is well recognized. However, little is known about the presentations and outcomes of Japanese heart failure (HF) patients in the winter season. Methods and resultsWe used a single hospital-based cohort from the Shinken Database 2004–2012, comprising all new patients (n=19,994) who visited the Cardiovascular Institute Hospital. A total of 375 patients who were admitted owing to acute decompensated HF were included in the analysis. Of these patients, 136 (36%) were admitted in winter. Winter was defined as the period between December and February. The HF patients admitted in winter were older, and had a higher prevalence of hypertension and diabetes mellitus than the patients admitted in other seasons. Patients with conditions categorized as clinical scenario 1 tended to be admitted more commonly in winter. HF with preserved left ventricular ejection fraction (LVEF) was more common in HF patients admitted in winter than in those admitted in other seasons. Beta-blocker use at hospital discharge was more common in the patients admitted in other seasons. Kaplan–Meier curves and log-rank test results indicated that the incidences of all-cause death, cardiovascular death, and HF admission were comparable between the patients admitted in winter and those admitted in other seasons. ConclusionsHF admission was frequently observed in the winter season and HF patients admitted in the winter season were older, and had higher prevalence of hypertension and diabetes mellitus, and preserved LVEF suggesting that we might need to pay more attention for elderly patients with hypertension, diabetes mellitus, and HF with preserved LVEF to decrease HF admissions in the winter season.

Results of the prospective multicenter Japanese bridge to transplant study with a continuous-flow left ventricular assist device

Continuous-flow left ventricular assist devices (LVADs) are becoming the standard of care for patients with refractory end-stage heart failure. We present the outcomes of patients enrolled in a prospective multicenter clinical study in Japan using the HeartMate II continuous-flow LVAD for bridge to transplantation. The study evaluated 6 inotrope-dependent heart failure patients failing on medical management (3 males and 3 females, age 44.7 ± 15.8 years, BSA 1.58 ± 0.17 m(2)) implanted with the HMII LVAD at 5 Japanese centers. Functional status, adverse events and outcomes were determined for the first 6 months with follow-up at 2 years. After implant, functional improvement was evident in 6-min walk distance which increased from 268 ± 92 m at baseline to 399 ± 105 m at 6 months, and 100% of patients were in NYHA class I or II at 6 months compared to 0% at baseline. Adverse events included localized non-device-related infection (4/6), arrhythmias (3/6) and percutaneous lead infection (1/6). There were no re-thoracotomies for bleeding and no strokes or pump replacements. All patients were alive at 6 months and all were transplanted after 1.96-3.58 years of LVAD support. The results in Japan of the HMII LVAD for BTT are consistent with results from the US pivotal clinical trial. The expanded use of this technology to Japanese heart failure patients is appropriate.

Clinical characteristics and long-term clinical outcomes of Japanese heart failure patients with preserved versus reduced left ventricular ejection fraction: A prospective cohort of Shinken Database 2004–2011

BackgroundClinical data on the mortality and morbidity of unselected Japanese patients with heart failure (HF) are limited. In this study, we aimed to determine the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with preserved or reduced left ventricular ejection fraction (LVEF). Methods and resultsWe used a single hospital-based cohort from the Shinken Database 2004–2011 that comprised all new patients (n=17,517) visiting the Cardiovascular Institute Hospital. A total of 1,525 patients diagnosed with symptomatic HF at the initial visit were included in the analysis. Of these, 1121 patients (74%) exhibited a preserved LVEF (>50%) and 404 patients (26%) had a reduced LVEF (≤50%). HF patients with preserved LVEF (HFpEF) were older and more often female than patients with reduced LVEF (HFrEF). Kaplan–Meier curves and log-rank test results showed that HFpEF patients had a better prognosis than HFrEF patients. However, there were no significant differences in clinical outcomes between HFpEF and HFrEF patients when the analysis was limited to inpatients. Cox regression analysis showed that HFpEF patients had a significantly lower risk of all-cause death (p=0.027; hazard ratio, 0.547, 95% confidence interval, 0.321–0.933). Multivariate analyses performed separately showed that the independent predictors of all-cause death in HFrEF were advanced age, lower body mass index, diabetes mellitus, and the absence of statin treatment, whereas those for HFpEF were advanced age, absence of dyslipidemia, anemia, and left ventricular hypertrophy. ConclusionsThis prospective cohort study identified the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with reduced and preserved ejection fractions in a real-world clinical setting.

Clinical Status and Outcome of Japanese Heart Failure Patients With Reduced or Preserved Ejection Fraction Treated With Carvedilol

The effect of beta-blockers in treating Japanese heart failure (HF) patients with preserved left ventricular (LV) ejection fraction (EF) is unclear. This prospective observational study enrolled 1,682 Japanese HF patients who received carvedilol for the first time. Patients were followed for a mean of 1.6 years. The 1,492 patients with baseline LVEF measurements were allocated to the following groups: reduced EF (LVEF < 40%; n = 724), borderline EF (LVEF 4050%; n = 355), and preserved EF (LVEF ≥ 50%; n = 413). Baseline characteristics, New York Heart Association (NYHA) class, change in B-type natriuretic peptide (BNP) level, and long-term outcome were compared among the groups. Patients with preserved EF were more likely to be older, female, and have ischemic etiology and hypertension than patients with reduced EF. Carvedilol maintenance dosage was lower in patients with preserved EF (7.9 mg/day versus 6.6 mg/ day). NYHA class and BNP level were lower in patients with preserved EF at baseline but improved to the same level in all groups at 6 months. After adjusting for baseline characteristics, the hazard ratio for death or hospitalization due to cardiovascular disease in patients with preserved EF versus those with reduced EF was 1.031 (P = 0.847). This study elucidated the characteristics of HF patients given carvedilol in "real world" clinical settings. A comparative controlled study is necessary to elucidate whether the improvements in NYHA and BNP as well as the outcome profile observed in patients with preserved EF were caused by the favorable effects of carvedilol.

Current Status of the Use of ASV in Japanese Heart Failure Patients - Results form SAVOIR-R Study

Current Status of the Use of ASV in Japanese Heart Failure Patients - Results form SAVOIR-R Study

Impact of renal insufficiency on long-term clinical outcome in patients with heart failure treated by cardiac resynchronization therapy

BackgroundRenal insufficiency is recognized as a predictor of mortality and adverse outcome in heart failure (HF) patients. However, the long-term clinical outcome of cardiac resynchronization therapy (CRT) in Japanese HF patients with renal insufficiency remains uncertain. MethodsWe evaluated 67 consecutive patients who underwent CRT at our hospital. The patients were divided into two groups according to a baseline estimated glomerular filtration rate (e-GFR) cut-off value of 50ml/min, which is defined as the time at which patients should be referred to a nephrologist, by the Japanese Society of Nephrology. Follow-up echocardiographic findings and renal function were examined at 3–6 months after CRT. Then, we compared long-term clinical outcomes between the two groups, and analyzed the effect of CRT on renal function, echocardiographic parameters and cardiac survival. ResultsDuring a mean follow-up period of 30.3 months, patients with advanced renal insufficiency (e-GFR<50ml/min) had significant higher all-cause mortality (log-rank p=0.033) and higher cardiac mortality combined with HF hospitalization (log-rank p=0.017) than patients with e-GFR≥50ml/min. Multivariate analysis revealed that advanced renal insufficiency was an independent predictor of cardiac mortality combined with HF hospitalization (odds ratio=3.01, p=0.008). Subgroup analysis in the baseline advanced renal insufficiency group revealed that patients with preserved renal function by CRT (<10% reduction in e-GFR) had a higher rate of decrease of left ventricular end-systolic diameter (−14.0% vs. −0.8%, p=0.023) and lower cardiac mortality combined with HF hospitalization (log-rank p=0.029) compared with patients with deterioration of renal function (≥10% reduction in e-GFR). ConclusionsThe present study suggests that advanced renal insufficiency is quite useful for the prediction of worsening clinical outcomes in HF patients treated by CRT. Preservation of renal function by CRT brings about better cardiac survival through prevention of adverse cardiac events, even in HF patients with advanced renal insufficiency.

Development of self‐care educational material for patients with heart failure in Japan: a pilot study

This study assessed the need for information regarding heart failure and self-care, developed self-care educational material, and investigated the feasibility of the material. A total of 22 hospitalized heart failure patients (mean age: 63 years) completed a self-administered questionnaire. We found that more than 90% of patients desired information, particularly about heart failure symptoms, time to notify healthcare providers, prognosis, and exercise/physical activity. After examining the eight existing brochures for Japanese heart failure patients, we developed self-care educational material. This was based on heart failure guidelines and on the results of our inquiry regarding information needs. Finally, a pilot study was conducted in nine hospitalized heart failure patients (mean age: 57 years). None of the patients had difficulty reading or understanding the educational material. The self-administrated questionnaire survey revealed that comprehension of the following improved after the educational sessions with the material: heart failure symptoms, medication, weighing, sodium intake, and fluid intake (P < 0.05). In conclusion, heart failure patients have a great need for information about heart failure. Our pilot study suggests that the material was readable and had a beneficial effect on heart failure comprehension.

Efficacy and Safety of Tolvaptan in Heart Failure Patients with Sustained Volume Overload despite the Use of Conventional Diuretics: A Phase III Open-Label Study

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Effects of Tolvaptan on Volume Overload in Japanese Patients with Heart Failure: Results of a Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study

Tolvaptan may reduce the signs of volume overload in heart failure (HF) patients who experience volume overload despite using conventional diuretics. In this study, we evaluated the dose-response effects of tolvaptan on weight loss, urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload. In the study, 117 HF patients with volume overload on stable doses of furosemide (≥ 40 mg/day) were treated with tolvaptan (15, 30 or 45 mg) or placebo once-daily for 7 days. The decrease in body weight from baseline to the day after the final dose with 15, 30 or 45 mg tolvaptan (-1.62 ± 1.55, -1.35 ± 1.54 and -1.85 ± 1.10 kg, respectively), was significantly greater compared with that in the placebo group (-0.53 ± 0.96 kg) (p < 0.05). However, the decrease in body weight with tolvaptan was not significantly dose-dependent. Signs of volume overload improved at all doses of tolvaptan. Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality, but did not affect urinary sodium or potassium excretion. Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan. Once-daily tolvaptan (15, 30 or 45 mg) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload.

Phase III Clinical Pharmacology Study of Tolvaptan

This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist. This was a multicenter, randomized, double-blind, parallel group study. Tolvaptan was administered at 7.5 or 15 mg, in combination with furosemide, for 7 days in Japanese heart failure (HF) patients with volume overload that had not resolved despite receiving furosemide. The blood concentration of tolvaptan was maintained at a higher concentration for a longer time in patients who received 15 mg/day when compared with patients who received 7.5 mg/day. Tolvaptan increased urine volume and increased weight loss dose-dependently when used in combination with furosemide. Importantly, tolvaptan enhanced water diuresis without affecting blood electrolyte levels. Tolvaptan exerts diuretic effects and causes body weight loss at the low dose of 7.5 mg; however, these effects were less than those elicited by 15 mg tolvaptan.

The Clinical Efficacy of CRT-D in Japanese Heart Failure Patients. Comparison of MOMIJI (MIRACLE-ICD Outcome Measured in Japanese Indication) Study and MIRACLE ICD

The Clinical Efficacy of CRT-D in Japanese Heart Failure Patients. Comparison of MOMIJI (MIRACLE-ICD Outcome Measured in Japanese Indication) Study and MIRACLE ICD

Atrial Fibrillation Was Associated with Sleep-Disordered Breathing in Heart Failure Patients

Background: Sleep-disordered breathing (SDB) is frequently observed in heart failure patients. Central sleep apnea and Cheyne-Stokes respiration (CSR) have been reported predictors of mortality in systolic heart failure patients. However, little is known about association between atrial fibrillation and SDB in heart failure patients among Japanese population. Methods: Consecutive patients (n=45) with congestive heart failure admitted to our hospital between June 2009 and August 2010 were enrolled. SDB examination was performed using portable monitoring and polysomnography immediately before discharge after stabilizing heart failure by optimal pharmacological therapy. Those patients were classified into two groups according to apnea hypopnea index (AHI): L group (AHI 15). Clinical characteristics were compared between the groups. Results: Twenty-three (51%) patients were classified into L group (AHI=6.9±4.6) and 22 (49%) patients into H group (AHI=33.0±12.6). There was no significant difference in age, body mass index, medication (β-blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, spironolactone), cardiac function and eGFR between the groups. Prevalence of atrial fibrillation (33% vs. 16%, p=0.025) and CSR (47% vs. 2%, p<0.001) and plasma BNP level (480±443 pg/ml vs. 246±262 pg/ml, p=0.035) were significantly higher in H than in L group. Conclusions: Japanese heart failure patients with SDB had higher prevalence of atrial fibrillation and CSR and higher plasma BNP level compared with the patients without SDB.

What is the Determinant for Beta-Blocker use in Japanese Heart Failure Patients?

What is the Determinant for Beta-Blocker use in Japanese Heart Failure Patients?