BackgroundThere is conflicting evidence on the efficacy of primary prevention ICD implant in the elderly.ObjectiveTo determine the efficacy and safety of ICD implantation in patients 70 years and older.MethodsPatients (n=167) age 70 years or older, and eligible for ICD implantation were randomly assigned (1:1) to receive either optimal medical therapy (OMT, n=85) or OMT plus ICD (n=82).ResultsOf the 167 participants (mean age: 76.4 years; 165 men), 144 completed the study protocol according to their assigned treatment. Average participant follow-up was 31.5 months. Mortality was similar between the two groups: (27 deaths in OMT versus 26 in ICD) unadjusted HR = 0.92, 95% confidence interval: 0.53 – 1.57 but there was a trend favoring the ICD over the first 36 months of follow-up. Rates of sudden death (7 versus 5, P=0.81) and all-cause hospitalization (2.65 events per participant in OMT versus 3.09 in ICD, P=0.31) were not statistically significantly different. Eleven participants randomized to ICD receiving appropriate therapy; five participants received an inappropriate therapy that included at least one ICD shock.ConclusionThe study did not recruit to target sample size and accumulated data did not show benefit to ICD therapy in patients 70 years or older. Future similar in design studies might be feasible but will have to contend with patient treatment preference given the large number of patients who do not want an ICD implanted. Further research is needed to determine whether the ICD is effective in prolonging life among elderly device candidates.

BACKGROUND Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) <= 35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs countbased, respectively). OBJECTIVE The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF <= 35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS Of the 2521 patients with HF with LVEF <= 35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n 5 971) or MUGA (n 5 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.461.11), respectively (P 5.693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION We found no evidence that in patients with HF and LVEF <= 35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

OBJECTIVES This study sought to assess the rate and outcomes of premature ventricular contractions (PVC)-cardiomyopathy from the CHF-STAT (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) trial, a population with cardiomyopathy (left ventricular [LV] ejection fraction of <40%) and frequent PVCs (>10 PVCs per hour). BACKGROUND PVCs are associated with heart failure and PVC-cardiomyopathy. The prevalence of PVC-cardiomyopathy and outcome benefits of PVC suppression are not clear. METHODS A secondary analysis of the CHF-STAT study was performed to compare the rate of successful PVC suppression (>= 80% PVC reduction), LV recovery (defined as improvement in LV ejection fraction of >= 10% points), and PVC-cardiomyopathy between amiodarone and placebo groups at 6 months. PVC-cardiomyopathy was defined if both PVC reduction of >= 80% and LV ejection fraction improvement of >= 10% were present at 6 months. Cardiac events (death or resuscitated cardiac arrest) were compared between PVC-cardiomyopathy versus non-PVC-cardiomyopathy during a 5-year follow-up. Published by Elsevier on behalf of the American College of Cardiology Foundation. RESULTS The rates of successful PVC suppression and LV recovery were significantly higher in the amiodarone (72% and 39%, respectively) when compared to the placebo group (12% and 16%, respectively; p < 0.001), regardless of cardiomyopathy etiology. PVC-cardiomyopathy was present in 29% and 1.8% of patients in the amiodarone and placebo groups, respectively (p < 0.001). Similar PVC-cardiomyopathy rates were found in ischemic (24% amiodarone vs. 2% placebo; p < 0.001) and nonischemic populations (41% amiodarone vs. 1.5% placebo; p < 0.001). Death and resuscitated cardiac arrest were significantly lower in patients with PVC-cardiomyopathy and those treated with amiodarone. CONCLUSIONS The overall prevalence of PVC-cardiomyopathy in the CHF-STAT study was significant regardless of ischemic substrate (29%, overall population; 41%, nonischemic cardiomyopathy). Treatment of PVC-cardiomyopathy with amiodarone is likely to improve survival in this high-risk population.

Background: The use of opioids is associated with poor outcomes. Less is known about this association in patients with heart failure (HF) and whether it varies by the receipt of hospice care. Methods: Of the 7467 patients hospitalized for HF without previous opioid use, 124 received discharge opioids. We matched 123 of these patients with 123 not receiving opioids based on their propensity scores for opioid use, thus assembling a matched cohort of 246 patients balanced on 30 baseline characteristics (mean age, 76 years, 60% women, and 11% African American). We repeated the process in hospice (n = 155; 20 received opioids) and nonhospice (n = 7298; 104 received opioids) subgroups, thus assembling 2 matched cohorts of 22 and 208 patients, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) associated with opioid use were estimated from matched cohorts. Results: During 8.6 (median, 1.4) years of follow-up, all-cause mortality occurred in 80% and 68% of matched patients in the opioid and nonopioid groups, respectively (HR, 1.49; 95% CI, 1.11-1.99; P= 0.008). There was evidence of heterogeneity in this association between hospice and nonhospice patients (P for interaction, 0.027). Among matched hospice and nonhospice patients, HRs (95% CIs) for mortality were 6.37 (2.06-19.69; P = 0.001) and 1.42 (1.03-1.96; P = 0.035), respectively. HRs (95% CIs) for 30-day and 1-year mortality were 1.98 (1.06-3.70; P = 0.033) and 1.72 (1.18-2.49; P = 0.004), respectively. HRs (95% CIs) for all-cause, HF, and non-HF readmissions were 1.31 (0.97-1.76; P = 0.079), 1.03 (0.71-1.49; P = 0.866), and 1.75 (1.05-2.91; P = 0.031), respectively. Readmission associations were similar among matched nonhospice patients. There was no readmission among matched hospice patients receiving opioids. Conclusions: In older patients with HF, opioid use is associated with a higher risk of mortality, which is greater in the hospice subgroup, and a higher risk of non-HF readmission in the nonhospice subgroup.

Background: According to the ACC/AHA HF guideline, in patients (pts) with HFpEF and HTN, optimal systolic blood pressure (SBP) target is <130 mm Hg. Although SBP <130 has been shown to be associated with a higher risk of death in HFpEF (PMC5875342), the use of anti-HTN therapy in those with SBP ≥130 has not been well studied. We tested the hypothesis that anti-HTN therapy in pts with HFpEF, HTN and SBP ≥130 would be associated with improved outcomes. Methods: Of the 8873 hospitalized pts with HF w EF ≥50% in Medicare-linked OPTIMIZE-HF, 6781 (76%) had a history of HTN, of whom 3680 (54%) had a discharge SBP ≥130 mmHg. We assembled an inception cohort by excluding 1611 (44%) receiving anti-HTN drugs (HCTZ, hydralazine, or a CCB) before admission. Of the remaining 2069 pts, 430 (21%) received a new discharge prescription for anti-HTN drugs. Propensity scores for anti-HTN drug initiation, estimated for each of the 2069 pts, were used to assemble a cohort of 427 pairs of pts started and not started on anti-HTN therapy, balanced on 60 baseline characteristics including use of ACEI/ARBs and BBs. Results: The 854 matched pts had a mean age of 77 years, mean SBP of 149 mmHg, 67% were women, and 17% African American. 3-year all-cause mortality occurred in 45% and 53% of matched pts started vs. not started on anti-HTN therapy, resp. (HR 0.77; 95% CI, 0.64-0.94; p=0.009; Figure ). There was no association with readmissions. Conclusion: In pts with HFpEF, HTN and SBP ≥130 mm Hg, initiation of anti-HTN therapy is associated with a lower risk of death.

Poor outcomes associated with digoxin discontinuation have been shown to be significantly worse in the subgroup of patients with HFrEF not receiving (vs receiving) beta-blockers (p for interaction, 0.044; PMID: 31370952). We examined this association separately in patients with HFrEF receiving and

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study. METHODS: In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction >= 50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate >= 50 beats per minute, an estimated glomerular filtration rate >= 30 mL/min/1.73 m(2) or did not receive inpatient dialysis, and digoxin was initiated in 524 of these patients. Using propensity scores for digoxin initiation, calculated for each of the 5675 patients, we assembled a matched cohort of 513 pairs of patients initiated and not initiated on digoxin, balanced on 58 baseline characteristics (mean age, 80 years; 66% women; 8% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin initiation were estimated in the matched cohort. RESULTS: Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes. CONCLUSION: Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF. Published by Elsevier Inc.

Several studies examined the association between digoxin use and outcomes in patients with atrial fibrillation (AF). However, less is known about this association in patients with heart failure (HF) with AF, the examination of which was the objective of this study. In the OPTIMIZE-HF registry, of

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized controlled trial setting. Observational studies of digoxin use in patients with atrial fibrillation have suggested a higher risk for poor outcomes. Less is known about this association in patients with heart failure and atrial fibrillation, the examination of which was the objective of the current study. METHODS: We conducted an observational propensity score-matched study of predischarge digoxin initiation in 1768 hospitalized patients with heart failure and atrial fibrillation in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, balanced on 56 baseline characteristics (mean age, 79 years; 55% women; 7% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated for the 884 patients initiated on digoxin compared with 884 not initiated on digoxin. RESULTS: HRs (95% CIs) for 30-day, 2-year, and 4-year all-cause mortality were 0.80 (0.55-1.18; P = .261), 0.94 (0.87-1.16; P = .936), and 1.01 (0.90-1.14; P = .729), respectively. Respective HRs (95% CIs) for heart failure readmission were 0.67 (0.49-0.92; P = .014), 0.81 (0.69-0.94; P = .005), and 0.85 (0.74-0.97; P = .022), and those for all-cause readmission were 0.78 (0.64-0.96; P = .016), 0.90 (0.811.00; P = .057), and 0.91 (0.83-1.01; P = .603). These associations were homogeneous between patients with left ventricular ejection fraction <= 45% vs >45%. CONCLUSIONS: Among hospitalized older patients with heart failure (HFrEF and HFpEF) and atrial fibrillation, initiation of digoxin was associated with a lower risk of heart failure readmission but had no association with mortality. Published by Elsevier Inc.

Métodos Dos 11.900 pacientes hospitalizados com ICFEr (FE ≤45%) identificados ao se relacionar o registro OPTIMIZEHF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) com dados do Medicare, 3.499 receberam digoxina pré-internação, que foi interrompida em 721 pacientes. Utilizando escores de propensão para interrupção da digoxina, estimados para cada um dos 3.499 pacientes, foi composta uma coorte pareada de 698 duplas de pacientes, equilibradas em relação a 50 características basais (média de idade, 76 anos; FE média, 28%; 41% do sexo feminino; 13% afroamericanos; 65% em uso de betabloqueadores).

Racial differences in heart failure (HF) outcomes have been reported. However, less is known about outcomes of older African American patients with HFpEF. Of 8873 hospitalized patients with HFpEF (EF≥50%) in Medicare-linked OPTIMIZE-HF, 1040 were African American and 7158 were non-Hispanic white

BACKGROUND: Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking. METHODS: Of the 11,900 patients with HFrEF (ejection fraction <= 45%) in Medicare-linked OPTIMIZE-HF, 8401 were not on digoxin, of whom 1571 received discharge prescriptions for digoxin. We matched 1531 of these patients with 1531 not receiving digoxin by propensity scores for digoxin use. The matched cohort (n = 3062; mean age, 76 years; 44% women; 14% African American) was balanced on 52 baseline characteristics. We assembled a second matched cohort of 2850 patients after excluding those with estimated glomerular filtration rate < 15 mL/min/1.73 m(2) and heart rate < 60 beats/min. Hazard ratios (HRs) and 95% confidence intervals (CIs) for digoxin-associated outcomes were estimated in the matched cohorts. RESULTS: Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30 days (HR, 0.74; 95% CI, 0.59-0.93), 1 year (HR, 0.81; 95% CI, 0.72-0.92), and 6 years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6 years but not 30 days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission but not all-cause mortality. Published by Elsevier Inc.

BACKGROUND:A prior hospitalization resulting from heart failure is associated with poor outcomes in ambulatory patients with heart failure. Less is known about this association in hospitalized patients with heart failure and whether it varies by ejection fraction. METHODS:Of the 25,345 hospitalized patients in the Medicare-linked OPTIMIZE-HF registry, 22,491 had known heart failure, of whom 7648 and 9558 had heart failure with preserved (≥50%) and reduced (≤40%) ejection fraction (HFpEF and HFrEF), respectively. Overall, 927 and 1862 patients with HFpEF and HFrEF had hospitalizations for heart failure during the 6 months before the index hospitalization, respectively. Using propensity scores for prior heart failure hospitalization, we assembled two matched cohorts of 924 pairs and 1844 pairs of patients with HFpEF and HFrEF, respectively, each balanced for 58 baseline characteristics. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes during 6 years of follow-up. RESULTS:Among 1848 matched patients with HFpEF, HRs (95% CIs) for all-cause mortality, all-cause readmission, and heart failure readmission were 1.35 (1.21-1.50; P <0.001), 1.34 (1.21-1.47; P <0.001), and 1.90 (1.67-2.16; P <0.001), respectively. Respective HRs (95% CIs) in 3688 matched patients with HFrEF were 1.17 (1.09-1.26; P <0.001), 1.32 (1.23-1.41; P <0.001), and 1.48 (1.37-1.61; P <0.001). CONCLUSIONS:Among hospitalized patients with heart failure, a previous hospitalization for heart failure is associated with higher risks of mortality and readmission in both HFpEF and HFrEF. The relative risks of death and heart failure readmission appear to be higher in HFpEF than in HFrEF.

BACKGROUND:The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented. OBJECTIVES:The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists. METHODS:Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled. RESULTS:Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778). CONCLUSIONS:Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.

Atrial fibrillation (Afib) is common in heart failure (HF) and is associated with poor outcomes. Less is known about this association in HFpEF. In Medicare-linked OPTIMIZE-HF, of the 8,537 patients with HFpEF (EF≥50%), 2,759 had a history of Afib. Propensity scores for having Afib, estimated for

Fluid retention and weight gain often lead to decompensation of chronic heart failure (HF). Less is known whether diuresis and weight loss are associated with improved outcomes. Of the 7648 hospitalized patients with known HFpEF (>50%) in Medicare-linked OPTIMIZE-HF, 1240 lost 0-2 lbs of body

The new HTN guideline redefines HTN from systolic/diastolic blood pressure (SBP/DBP) >140/90 to >130/80 mmHg. We examined the association of ISH, defined per the new definition, with outcomes in older adults. In CHS, of 4431 community-dwelling adults age ≥65 yrs without baseline heart failure (HF

BACKGROUND: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. METHODS: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction <= 35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. RESULTS: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. CONCLUSION: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug. Published by Elsevier Inc.

BACKGROUND: The efficacy of mineralocorticoid receptor antagonists or aldosterone antagonists in heart failure with reduced ejection fraction (HFrEF) is well known. Less is known about their effectiveness in real-world older patients with HFrEF. METHODS: Of the 8206 patients with heart failure and ejection fraction <= 35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF registry, 6986 were eligible for spironolactone therapy based on serum creatinine criteria (men <= 2.5 mg/dL, women <= 2.0 mg/dL) and 865 received a discharge prescription for spironolactone. Using propensity scores for spironolactone use, we assembled a matched cohort of 1724 (862 pairs) patients receiving and not receiving spironolactone, balanced on 58 baseline characteristics (Creatinine Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the above process to assemble a secondary matched cohort of 1638 (819 pairs) patients with estimated glomerular filtration rate (eGFR) <= 30 mL/min/1.73 m(2) (eGFR Cohort: mean age, 75 years, 42% women, 17% African American). RESULTS: In the matched Creatinine Cohort, spironolactone-associated hazard ratios (95% confidence intervals) for all-cause mortality, heart failure readmission, and combined endpoint of heart failure readmission or all-cause mortality were 0.92 (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87 (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02). CONCLUSIONS: These findings provide evidence of consistent, albeit modest, clinical effectiveness of spironolactone in older patients with HFrEF regardless of renal eligibility criteria used. Additional strategies are needed to improve the effectiveness of aldosterone antagonists in clinical practice. Published by Elsevier Inc.

BACKGROUND: Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction (HErEF) but not for preserved ejection fraction (HEpEF). Treatment benefits are often more pronounced in high-risk subgroups, and patients with HEpEF with heart rate >= 70 beats per minute have emerged as such a high risk subgroup. We examined the associations of high-dose beta-blocker use with outcomes in these patients. METHODS: Of the 8462 hospitalized patients with heart failure with ejection fraction >= 50% in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, 5422 had a discharge heart rate >= 70 beats per minute. Of these, 4537 had no contraindications to beta-blocker use, of which 2797 (2592 with dose data) received prescriptions for beta-blockers. Of the 2592, 730 received high-dose beta-blockers, defined as atenolol >= 100 mg/day, carvedilol >= 50 mg/day, metoprolol tartrate or succinate >= 200 mg/day, or bisoprolol >= 10 mg/day, and 1740 received no beta-blockers. Using propensity scores for the receipt of high-dose beta-blockers, we assembled a matched cohort of 1280 patients, balanced on 58 characteristics. RESULTS: All-cause mortality occurred in 63% and 68% of matched patients receiving high-dose beta-blocker vs no beta-blocker, respectively, during 6 years (median, 2.8) of follow-up (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P = .027). The hazard ratios (95% confidence intervals) for all-cause readmission and the combined endpoint of all-cause readmission or all-cause mortality associated with high-dose beta-blocker use were 0.90 (0.81-1.02) and 0.89 (0.80-1.00), respectively. CONCLUSIONS: In patients with HFpEF and heart rate >= 70 beats per minute, high-dose beta-blocker use was associated with a significantly lower risk of death. Future randomized controlled trials are needed to examine this association. Published by Elsevier Inc.