Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Background: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). Methods: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. Results: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01–3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27–0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day rehospitalization (wHR, 0.60; 95% CI, 0.37–0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48–0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59–0.99; P = 0.041). Conclusion Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Background: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). Methods: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. Results: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01–3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27–0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day rehospitalization (wHR, 0.60; 95% CI, 0.37–0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48–0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59–0.99; P = 0.041). Conclusion Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Background: β-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. Methods: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. Results: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34–0.82). Conclusion In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

Background: There are sparse data on the utilization rate of implantable cardioverterdefibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF). Methods: Among 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients. Results: Among 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16–0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01–0.63], P = 0.015).According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06– 0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069). Conclusion Follow-up data of this large, multicenter registry suggests a significant underutilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients.

BACKGROUND AND OBJECTIVES: Beta-blockers are indicated in patients with heart failure (HF) with reduced ejection fraction. However, their efficacy in patients with HF with preserved ejection fraction (HFpEF) is uncertain. We investigated the hypothesis that beta-blockers are associated with reduced adverse events in patients with HFpEF. METHODS: The Korea Acute Heart Failure (KorAHF) is a prospective observational multicentre cohort study. The 5,625 patients hospitalized for acute HF syndrome in 10 tertiary university hospitals across the country have been consecutively enrolled between March 2011 and February 2014. Of these patients, 2,152 patients with HFpEF (ejection fraction ≥40%) were investigated. The primary outcome was all-cause mortality according to beta-blocker use. RESULTS: During a median follow-up duration of 807 days, 702 patients died. In Cox proportional hazards model beta-blocker use was associated with a 14% reduced all-cause death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75–0.98), but not with reduce rehospitalization (HR, 1.03; 95% CI, 0.85–1.27). In the propensity-score matched population, beta-blockers were also associated with reduced all-cause death (HR, 0.80; 95% CI, 0.69–0.94) but not with reduced rehospitalization (HR, 1.08; 95% CI, 0.87–1.33). CONCLUSIONS: In Korean patients with HFpEF, use of beta-blockers is associated with reduced all-cause death but not with reduced rehospitalization.
Cohort Studies ; Diastole ; Follow-Up Studies ; Heart Failure ; Heart ; Hospitals, University ; Humans ; Korea ; Mortality ; Proportional Hazards Models ; Prospective Studies

BACKGROUND AND OBJECTIVES: Conflicting data exist regarding the prognostic implication of ventricular conduction disturbance pattern in patients with heart failure (HF). This study investigated the prognostic impact of ventricular conduction pattern in hospitalized patients with acute HF. METHODS: Data from the Korean Acute Heart Failure registry were used. Patients were categorized into four groups: narrow QRS (<120 ms), right bundle branch block (RBBB), left bundle branch block (LBBB), and nonspecific intraventricular conduction delay (NICD). The NICD was defined as prolonged QRS (≥120 ms) without typical features of LBBB or RBBB. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF aggravation within 1 year after discharge. RESULTS: This study included 5,157 patients. The primary endpoint occurred in 39.7% of study population. The LBBB group showed the highest incidence of primary endpoint followed by NICD, RBBB, and narrow QRS groups (52.5% vs. 49.7% vs. 44.4% vs. 37.5%, p<0.001). In a multivariable Cox-proportional hazards regression analysis, LBBB and NICD were associated with 39% and 28% increased risk for primary endpoint (LBBB hazard ratio [HR], 1.392; 95% confidence interval [CI], 1.152–1.681; NICD HR, 1.278; 95% CI, 1.074–1.520) compared with narrow QRS group. The HR of RBBB for the primary endpoint was 1.103 (95% CI, 0.915–1.329). CONCLUSIONS: LBBB and NICD were independently associated with an increased risk of 1-year adverse event in hospitalized patients with HF, whereas the prognostic impacts of RBBB were limited. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843
Bundle-Branch Block ; Heart Failure ; Heart ; Humans ; Incidence ; Mortality ; Prognosis

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), β-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34–0.95), mortality (HR, 0.41; 95% CI, 0.24–0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36–0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41–0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47–0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and β-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.
Angiotensins ; Cohort Studies ; Heart Failure ; Heart ; Humans ; Mortality ; Receptors, Mineralocorticoid

BACKGROUND AND OBJECTIVES: Conflicting data exist regarding the prognostic implication of ventricular conduction disturbance pattern in patients with heart failure (HF). This study investigated the prognostic impact of ventricular conduction pattern in hospitalized patients with acute HF. METHODS: Data from the Korean Acute Heart Failure registry were used. Patients were categorized into four groups: narrow QRS (<120 ms), right bundle branch block (RBBB), left bundle branch block (LBBB), and nonspecific intraventricular conduction delay (NICD). The NICD was defined as prolonged QRS (≥120 ms) without typical features of LBBB or RBBB. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF aggravation within 1 year after discharge. RESULTS: This study included 5,157 patients. The primary endpoint occurred in 39.7% of study population. The LBBB group showed the highest incidence of primary endpoint followed by NICD, RBBB, and narrow QRS groups (52.5% vs. 49.7% vs. 44.4% vs. 37.5%, p<0.001). In a multivariable Cox-proportional hazards regression analysis, LBBB and NICD were associated with 39% and 28% increased risk for primary endpoint (LBBB hazard ratio [HR], 1.392; 95% confidence interval [CI], 1.152–1.681; NICD HR, 1.278; 95% CI, 1.074–1.520) compared with narrow QRS group. The HR of RBBB for the primary endpoint was 1.103 (95% CI, 0.915–1.329). CONCLUSIONS LBBB and NICD were independently associated with an increased risk of 1-year adverse event in hospitalized patients with HF, whereas the prognostic impacts of RBBB were limited.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843

BACKGROUND AND OBJECTIVES: Beta-blockers are indicated in patients with heart failure (HF) with reduced ejection fraction. However, their efficacy in patients with HF with preserved ejection fraction (HFpEF) is uncertain. We investigated the hypothesis that beta-blockers are associated with reduced adverse events in patients with HFpEF. METHODS: The Korea Acute Heart Failure (KorAHF) is a prospective observational multicentre cohort study. The 5,625 patients hospitalized for acute HF syndrome in 10 tertiary university hospitals across the country have been consecutively enrolled between March 2011 and February 2014. Of these patients, 2,152 patients with HFpEF (ejection fraction ≥40%) were investigated. The primary outcome was all-cause mortality according to beta-blocker use. RESULTS: During a median follow-up duration of 807 days, 702 patients died. In Cox proportional hazards model beta-blocker use was associated with a 14% reduced all-cause death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75–0.98), but not with reduce rehospitalization (HR, 1.03; 95% CI, 0.85–1.27). In the propensity-score matched population, beta-blockers were also associated with reduced all-cause death (HR, 0.80; 95% CI, 0.69–0.94) but not with reduced rehospitalization (HR, 1.08; 95% CI, 0.87–1.33). CONCLUSIONS In Korean patients with HFpEF, use of beta-blockers is associated with reduced all-cause death but not with reduced rehospitalization.