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Aims: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients., Methods and Results: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54)., Conclusions: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Although sustained ventricular arrhythmias (VAs) are a common complication after durable left ventricular assist device (LVAD) implantation, the incidence, risk factors, and prognostic implications of postoperative early VAs (EVAs) in contemporary patients with LVAD are poorly understood., Methods and Results: A single-center retrospective analysis was performed of patients who underwent LVAD implantation from October 1, 2006, to October 1, 2022. EVA was defined as an episode of sustained VA identified ≤30 days after LVAD implantation. A total of 789 patients underwent LVAD implantation (mean age 62.9 ± 0. years 5, HeartMate 3 41.4%, destination therapy 43.3%). EVAs occurred in 100 patients (12.7%). A history of end-stage renal disease (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.45-21.70), preoperative electrical storm (OR 2.82, 95% CI 1.11-7.16), and appropriate implantable cardiac defibrillator therapy before implantation (OR 2.8, 95% CI 1.26-6.19) are independently associated with EVAs. EVA was associated with decreased 30-day survival (hazard ratio 3.02, 95% CI 1.1-8.3, P = .032). There was no difference in transplant-free survival time between patients with and without EVAs (hazard ratio 0.82, 95% CI 0.5-1.4, P = .454)., Conclusions: EVAs are common after durable LVAD implantation and are associated with an increased risk of 30-day mortality., Competing Interests: CONFLICT OF INTEREST Farooq H. Sheikh reports institutional research support and honorarium for speaking at educational conferences from Abbott. No company or agency had any role in this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest Dr. Gupta: CVRx: honorarium for educational presentations. Dr. Sheikh: Abbott: institutional research support and honorarium for educational presentations. Alnylam: consultant, institutional research support. Akcea: institutional research support. Dr. Weissman: institutional research grants through MedStar Health Research Institute Corelab from Abbott, Boston Scientific, Medtronic. The remaining authors have no conflicts of interest to declare.

Aims: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes., Methods and Results: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m 2 , present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m 2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m 2 . Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations., Conclusion: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria., (© 2024 European Society of Cardiology This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Sudden cardiac arrest (SCA) is the leading cause of cardiovascular mortality in heart failure with preserved ejection fraction (HFpEF), contributing to around 25% of deaths observed in pivotal HFpEF trials. However, predictors and outcomes of in-hospital SCA in HFpEF have not been well characterized. We queried the Nationwide Inpatient Sample (2016 to 2017) to identify adult hospitalizations with a diagnosis of HFpEF. Patients with acute or chronic conditions associated with SCA (e.g., acute myocardial infarction, acute pulmonary embolism, sarcoidosis) were excluded. We ascertained whether SCA occurred during these hospitalizations, identified predictors of SCA using multivariate logistic regression, and determined outcomes of SCA in HFpEF. Of 2,909,134 hospitalizations, SCA occurred in 1.48% (43,105). The mean age of the SCA group was 72.3 ± 12.4 years, 55.8% were women, and 66.4% were White. Presence of third-degree atrioventricular block (odds ratio [OR] 5.95, 95% confidence interval [CI] 5.31 to 6.67), left bundle branch block (OR 1.96, 95% CI 1.72 to 2.25), and liver disease (OR 1.87, 95% CI 1.73 to 2.02) were the leading predictors of SCA in HFpEF. After excluding patients with do-not-resuscitate status, the SCA group versus those without SCA had higher mortality (25.9% vs 1.6%), major bleeding complications (4.1% vs 1.7%), increased use of percutaneous coronary intervention (2.5% vs 0.7%), and mechanical circulatory assist device (1.2% vs 0.1%). These observational inpatient data suggest identifiable risk factors for SCA in HFpEF including cardiac arrhythmias. Further research is warranted to identify the best tools to risk-stratify patients with HFpEF to implement targeted SCA prevention strategies., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease., Methods: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m 2 ). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs., Results: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85)., Conclusions: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients., (Published by Elsevier Inc.)

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 count-based, 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 = 971) or MUGA (n = 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 (0.46-1.11), respectively (P = .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., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) and consists of the four main drug classes: renin-angiotensin system inhibitors, evidence-based β-blockers, mineralocorticoid inhibitors and sodium glucose cotransporter 2 inhibitors. The recommendation for use of GDMT is based on the results of multiple major randomized controlled trials demonstrating improved clinical outcomes in patients with HFrEF who are maintained on this therapy. The effect is most beneficial when medications from the four main drug classes are used in conjunction. Despite this, there is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications. In this review article, we describe the different drug classes included in GDMT and offer an approach to initiation and effective titration in both the inpatient as well as outpatient setting., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF., Competing Interests: Disclosures Dr. Fonarow reports consulting with Abbott, Amgen, Astra Zeneca, Bayer, cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis. The other authors have no conflicts of interest to declare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients., Methods: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing)., Results: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02)., Conclusion: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF., Methods: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated., Results: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up., Conclusions: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: National heart failure (HF) guidelines recommend that in patients with HF with preserved ejection fraction (EF;HFpEF) and hypertension, systolic blood pressure (SBP) should be maintained below 130 mmHg. The objective of the study is to examine the association between initiation of anti-hypertensive drugs and outcomes in patients with HFpEF with persistent hypertension., Methods: Of the 8873 hospitalized patients with HFpEF (EF ≥50%) with a history of hypertension without renal failure in Medicare-linked OPTIMIZE-HF, 3315 had a discharge SBP ≥130 mmHg, of whom 1971 were not receiving anti-hypertensive drugs, thiazides and calcium channel blockers, before hospitalization. Of these, 366 received discharge prescriptions for those drugs. We assembled a propensity score-matched cohort of 365 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 37 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort., Results: Matched patients (n = 730) had a mean age of 78 years; 67% were women and 17% African Americans. During 6 (median 2.5) years of follow-up, 66% of the patients died and 45% had HF readmission. HRs (95% CIs) for all-cause mortality at 30 days, 12 months and 6 years associated with anti-hypertensive drug initiation were 0.64 (0.30-1.36), 0.70 (0.51-0.97), and 0.95 (0.79-1.13), respectively. Respective HRs (95% CIs) for HF readmission were 1.65 (0.97-2.80), 1.18 (0.90-1.56) and 1.09 (0.88-1.35)., Conclusions: Among hospitalized older patients with HFpEF with uncontrolled hypertension, the initiation of therapy with anti-hypertensive drugs was not associated with all-cause mortality or hospital readmission., (Published by Elsevier Inc.)

Background: In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association between anti-hypertensive drug initiation and outcomes in patients with HFrEF., Methods: In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort., Results: Matched patients (n = 1374) had a mean age of 74 years, 41% were female, 17% were African-American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83-1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80-1.07). Similar associations were observed during 30 days and 12 months of follow-up., Conclusions: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Beta-blockers improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their role in older nursing home residents with HFrEF., Methods: From the combined OPTIMIZE-HF and Alabama Heart Failure Project data sets, we assembled a propensity score-matched balanced cohort of 6494 hospitalized patients ≥65 years with HFrEF (ejection fraction ≤40%). In our primary approach, hazard ratios (HRs) and 95% confidence intervals (CI)s for outcomes associated with discharge prescriptions for beta- blockers were estimated, examining for heterogeneity by admission from nursing homes. In our sensitivity approach, we examined these associations in a separately assembled propensity score-matched cohort of 122 patients admitted from nursing homes., Results: In the matched primary cohort of 6494 patients, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.80 (0.74-0.87) and 0.94 (0.86-1.02), respectively. Respective HRs (95% CIs) in the nursing home and non-nursing home subgroups were 0.77 (0.51-1.16) and 0.81 (0.74-0.87) for all-cause mortality (interaction P: 0.653) and 1.06 (0.53-2.12) and 0.89 (0.82-0.96) for heart failure readmission (interaction P: 0.753). In the matched sensitivity cohort of 122 patients admitted from nursing homes, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.86 (0.55-1.35) and 1.07 (0.52-2.22), respectively. Similar associations were observed for 30-day outcomes., Conclusions: Beta-blocker use was associated with a lower risk of all-cause mortality but not of heart failure readmission in older patients with HFrEF, which were similar for patients admitted and not admitted from nursing homes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To examine the association between income and cardiovascular disease (CVD) in community-dwelling older adults., Methods: Of the 5795 Medicare-eligible community-dwelling older Americans aged 65-100 years in the Cardiovascular Health Study (CHS), 4518 (78%) were free of baseline CVD, defined as heart failure, acute myocardial infarction, stroke, or peripheral arterial disease. Of them, 1846 (41%) had lower income, defined as a total annual household income <$16,000. Using propensity scores for lower income, estimated for each of the 4518 participants, we assembled a matched cohort of 1078 pairs balanced on 42 baseline characteristics. Outcomes included centrally adjudicated incident CVD and mortality., Results: Matched participants (n = 2156) had a mean age of 73 years, 63% were women, and 13% African American. During an overall follow-up of 23 years, incident CVD, all-cause mortality and the combined endpoint of incident CVD or mortality occurred in 1094 (51%), 1726 (80%) and 1867 (87%) individuals, respectively. Compared with the higher income group, hazard ratio (HR) for time to the first occurrence of incident CVD in the lower income group was 1.16 with a 95% confidence interval (CI) of 1.03 to 1.31. A lower income was also associated with a significantly higher risk of all-cause mortality (HR, 1.19; 95% CI, 1.08-1.30), and consequently a higher risk of the combined endpoint of incident CVD or death (HR, 1.20; 95% CI, 1.09-1.31)., Conclusion: Among community-dwelling older Americans free of baseline CVD, an annual household income <$16,000 is independently associated with significantly higher risks of new-onset CVD and death., (Copyright © 2021. Published by Elsevier Inc.)

Background: A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown., Methods and Results: Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251)., Conclusions: The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy., Competing Interests: Declaration of Competing Interest The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. Dr Fonarow reports consulting with Abbott, Amgen, Astra Zeneca, Bayer, CHF Solutions, Janssen, Medtronic, Merck, and Novartis, and was the Principal Investigator of OPTIMIZE-HF. Dr Filippatos participated in committees of trials and registries sponsored by Medtronic, Vifor, BI, and Servier, and has received research grants from the European Union. None of the other authors report any conflicts of interest related to this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The effect of loop diuretics on clinical outcomes in heart failure has not been evaluated in randomized controlled trials. In hospitalized patients with heart failure, a discharge loop diuretic prescription has been shown to be associated with improved 30-day outcomes, which appears to be more pronounced in subgroups with congestion. In the current study, we examined these associations and association modifications during longer follow-up., Methods: We assembled a propensity score-matched cohort of 2191 pairs of hospitalized heart failure patients discharged with, vs without, a prescription for loop diuretics, balanced on 74 baseline characteristics (mean age 78 years; 54% women; 11% African American)., Results: Hazard ratio (HR) and 95% confidence interval (CI) for 6-year combined endpoint of heart failure readmission or all-cause mortality was 1.02 (0.96-1.09). HRs and 95% CIs for this combined endpoint in patients with no, mild-to-moderate, and severe pulmonary rales were 1.19 (1.07-1.33), 0.95 (0.86-1.04), and 0.77 (0.63-0.94), respectively (P for interaction, < .001). Respective HRs (95% CIs) for no, mild-to-moderate, and severe lower extremity edema were 1.16 (1.06-1.28), 0.94 (0.85-1.04), and 0.71 (0.56-0.89; interaction P < .001)., Conclusions: The association between a discharge loop diuretic prescription and long-term clinical outcomes in hospitalized patients with heart failure is modified by admission congestion with worse, neutral, and better outcomes in patients with no, mild-to-moderate, and severe congestion, respectively. If these findings can be replicated, congestion may be used to risk-stratify patients with heart failure for potential optimization of loop diuretic prescription and outcomes., (Published by Elsevier Inc.)

Background: New hypertension and heart failure guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with preserved ejection fraction (HFpEF) and hypertension be lowered to <130 mm Hg., Methods: Of the 6778 hospitalized patients with HFpEF and a history of hypertension in the Medicare-linked OPTIMIZE-HF registry, 3111 had a discharge SBP <130 mm Hg. Using propensity scores for SBP <130 mm Hg, we assembled a matched cohort of 1979 pairs with SBP <130 versus ≥130 mm Hg, balanced on 66 baseline characteristics (mean age, 79 years; 69% women; 12% African American). We then assembled a second matched cohort of 1326 pairs with SBP <120 versus ≥130 mm Hg. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with SBP <130 and <120 mm Hg were separately estimated in the matched cohorts using SBP ≥130 mm Hg as the reference., Results: HRs (95% CIs) for 30-day, 12-month, and 6-year all-cause mortality associated with SBP <130 mm Hg were 1.20 (0.91-1.59; P = 0.200), 1.11 (0.99-1.26; P = 0.080), and 1.05 (0.98-1.14; P = 0.186), respectively. Respective HRs (95% CIs) associated with SBP <120 mm Hg were 1.68 (1.21-2.34; P = 0.002), 1.28 (1.11-1.48; P = 0.001), and 1.11 (1.02-1.22; P = 0.022). There was no association with readmission., Conclusions: Among older patients with HFpEF and hypertension, compared with SBP ≥130 mm Hg, the new target SBP <130 mm Hg had no association with outcomes but SBP <120 mm Hg was associated with a higher risk of death but not of readmission. Future prospective studies need to evaluate optimal SBP treatment goals in these patients., (Published by Elsevier Inc.)

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 (0.81-1.00; 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.)

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.)

Background: Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes., Objectives: The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF., Methods: Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort., Results: Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up., Conclusions: Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF., (Published by Elsevier Inc.)

Aims: Hypokalaemia is a risk factor for ventricular arrhythmias and sudden death in ambulatory patients with chronic heart failure (HF). The objective of this study was to examine the association between hypokalaemia and outcomes in hospitalized patients with decompensated HF in whom sudden death is less common., Methods and Results: Of the 5881 hospitalized patients with HF, 1052 had consistent hypokalaemia (both admission and discharge serum potassium <4.0 mmol/L), and 2538 had consistent normokalaemia (both admission and discharge serum potassium 4.0-5.0 mmol/L). Propensity scores for consistent hypokalaemia, estimated for each of 3590 (1052 + 2538) patients, were used to assemble a matched cohort of 971 pairs of patients with consistent hypokalaemia vs. consistent normokalaemia, balanced on 54 baseline characteristics (mean age, 75 years; 60% women; 28% African American). We repeated the above process to assemble 2327 pairs of patients with discharge potassium <4.0 vs. 4.0-5.0 mmol/L and 449 pairs of patients with discharge serum potassium <3.5 vs. 4.0-5.0 mmol/L. Hazard ratios (HR) and 95% confidence intervals (CIs) associated with hypokalaemia were estimated in matched cohorts. 30 day all-cause mortality occurred in 5% and 4% of patients with consistent normokalaemia vs. consistent hypokalaemia, respectively (HR, 0.78; 95% CI, 0.52-1.18; P = 0.241). HRs (95% CI) for 30 day mortality associated with discharge serum potassium <4.0 and <3.5 mmol/L were 0.90 (0.70-1.16; P = 0.419) and 1.69 (0.94-3.04; P = 0.078), respectively. Hypokalaemia (<4.0 or <3.5 mmol/L) had no association with long-term mortality or other outcomes., Conclusions: In hospitalized older patients with HF, compared with normokalaemia (serum potassium 4.0-5.0 mmol/L), hypokalaemia (<4.0 or <3.5 mmol/L) had no significant associations with outcomes., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Early generation left ventricular assist devices (LVAD) for treatment of refractory heart failure attempted to mimic the pulsatility of a native heart and were bulky and less durable due to valves within the inflow and outflow pathways. The next disruption came with the introduction of continuous flow pumps characterized by a low-pulse pressure circulation. Since the mechanism of action did not involve displacement of blood, these pumps were much smaller and less noisy in part due to fewer moving parts. Such devices include the HeartMate II axial-flow pathway pump which is implanted thoraco-abdominally and the HVAD, a centrifugal-flow pathway pump which is smaller and is implanted entirely within the thoracic cavity and uses a combination of hydrodynamic and magnetic levitation of the internal rotor. These pumps improved survival compared with the early generation LVADs and in a trial, the HVAD demonstrated non-inferiority compared with the HeartMate II but with an increase in ischemic and hemorrhagic strokes. The HeartMate 3 LVAD is an intrapericardial centrifugal-flow pathway pump with a full magnetically levitated, frictionless rotor with a fixed intrinsic pulse. In a randomized trial, the HeartMate 3 "hybrid" pump was associated with near-elimination of pump thrombosis, a reduction in strokes of any type or severity and lower mucosal bleeding rates. Despite improvements in hemocompatibility, right heart failure and infections contribute to significant morbidity, and devices designed to be internally contained with a wireless power source and physiological flow characteristics are still required despite great strides in the field., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents., Methods: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients., Results: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026)., Conclusions: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.

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: 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: National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg., Objectives: This study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF., Methods: Of the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg., Results: Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively., Conclusions: Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF., (Published by Elsevier Inc.)

Heart failure (HF) is the leading cause for 30-day all-cause readmission in older Medicare beneficiaries and 30-day all-cause readmission is associated with a higher risk of mortality. In the current analysis, we examined if that association varied by timing of 30-day all-cause readmission. Of the 8,049 Medicare beneficiaries hospitalized for HF, 1,688 had 30-day all-cause readmissions, of whom 1,519 were alive at 30 days. Of these, 626 (41%) had early (first 10 days) 30-day readmission. Propensity scores for early 30-day readmission, estimated for all 1,519 patients, were used to assemble a matched cohort of 596 pairs of patients with early versus late (11 to 30 days) all-cause readmission balanced on 34 baseline characteristics. Two-year all-cause mortality occurred in 51% and 57% of matched patients with early versus late 30-day all-cause readmissions, respectively (hazard ratio [HR] associated with late 30-day readmission, 1.22; 95% confidence interval [CI], 1.04 to 1.42; p = 0.014). This association was not observed in the subset of 436 patients whose 30-day all-cause readmission was due to HF (HR, 1.01; 95% CI, 0.79 to 1.28; p = 0.963), but was observed in the subset of 756 patients whose 30-day all-cause readmission was not due to HF (HR, 1.37; 95% CI, 1.12 to 1.67; p = 0.002; p for interaction, 0.057). In conclusion, in a high-risk subset of older hospitalized HF patients readmitted within 30 days, readmission during 11 to 30 (vs 1 to 10) days was associated with a higher risk of death and this association appeared to be more pronounced in those readmitted for non-HF-related reasons., (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., (Copyright © 2019. Published by Elsevier Inc.)

Background: Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction (HFrEF) but not for preserved ejection fraction (HFpEF). Treatment benefits are often more pronounced in high-risk subgroups, and patients with HFpEF 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.)

Importance: Lower systolic blood pressure (SBP) levels are associated with poor outcomes in patients with heart failure. Less is known about this association in heart failure with preserved ejection fraction (HFpEF)., Objective: To determine the associations of SBP levels with mortality and other outcomes in HFpEF., Design, Setting, and Participants: A propensity score-matched observational study of the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 25 354 patients who were discharged alive; 8873 (35.0%) had an ejection fraction of at least 50%, and of these, 3915 (44.1%) had stable SBP levels (≤20 mm Hg admission to discharge variation). Data were collected from 259 hospitals in 48 states between March 1, 2003, and December 31, 2004. Data were analyzed from March 1, 2003, to December 31, 2008., Exposure: Discharge SBP levels less than 120 mm Hg. A total of 1076 of 3915 (27.5%) had SBP levels less than 120 mm Hg, of whom 901 (83.7%) were matched by propensity scores with 901 patients with SBP levels of 120 mm Hg or greater who were balanced on 58 baseline characteristics., Main Outcomes and Measures: Thirty-day, 1-year, and overall all-cause mortality and heart failure readmission through December 31, 2008., Results: The 1802 matched patients had a mean (SD) age of 79 (10) years; 1147 (63.7%) were women, and 134 (7.4%) were African American. Thirty-day all-cause mortality occurred in 91 (10%) and 45 (5%) of matched patients with discharge SBP of less than 120 mm Hg vs 120 mm Hg or greater, respectively (hazard ratio [HR], 2.07; 95% CI, 1.45-2.95; P < .001). Systolic blood pressure level less than 120 mm Hg was also associated with a higher risk of mortality at 1 year (39% vs 31%; HR, 1.36; 95% CI, 1.16-1.59; P < .001) and during a median follow-up of 2.1 (overall 6) years (HR, 1.17; 95% CI, 1.05-1.30; P = .005). Systolic blood pressure level less than 120 mm Hg was associated with a higher risk of heart failure readmission at 30 days (HR, 1.47; 95% CI, 1.08-2.01; P = .02) but not at 1 or 6 years. Hazard ratios for the combined end point of heart failure readmission or all-cause mortality associated with SBP level less than 120 mm at 30 days, 1 year, and overall were 1.71 (95% CI, 1.34-2.18; P < .001), 1.21 (95% CI, 1.07-1.38; P = .004), and 1.12 (95% CI, 1.01-1.24; P = .03), respectively., Conclusions and Relevance: Among hospitalized patients with HFpEF, an SBP level less than 120 mm Hg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in patients with HFpEF.

Background: Digoxin use has been associated with a lower risk of 30-day all-cause admission and readmission in patients with heart failure and reduced ejection fraction (HFrEF)., Hypothesis: Digoxin use will be associated with improved outcomes in patients with HFrEF receiving β-blockers., Methods: Of the 3076 hospitalized Medicare beneficiaries with HFrEF (EF <45%), 1046 received a discharge prescription for β-blockers, of which 634 were not on digoxin. Of the 634, 204 received a new discharge prescription for digoxin. Propensity scores for digoxin use, estimated for each of the 634 patients, were used to assemble a matched cohort of 167 pairs of patients receiving and not receiving digoxin, balanced on 30 baseline characteristics. Matched patients (n = 334) had a mean age of 74 years and were 46% female and 30% African American., Results: 30-day all-cause readmission occurred in 15% and 27% of those receiving and not receiving digoxin, respectively (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.31-0.83, P = 0.007). This beneficial association persisted during 4 years of follow-up (HR: 0.72, 95% CI: 0.57-0.92, P = 0.008). Digoxin use was also associated with a lower risk of the combined endpoint of all-cause readmission or all-cause mortality at 30 days (HR: 0.54, 95% CI: 0.34-0.86, P = 0.009) and at 4 years (HR: 0.76, 95% CI: 0.61-0.96, P = 0.020)., Conclusions: In hospitalized patients with HFrEF receiving β-blockers, digoxin use was associated with a lower risk of 30-day all-cause readmission but not mortality, which persisted during longer follow-up., (© 2018 Wiley Periodicals, Inc.)

Aims: To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial., Methods and Results: Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695)., Conclusion: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF)., Objectives: The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF., Methods: Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics., Results: The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers., Conclusions: Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission., (Published by Elsevier Inc.)

Positive inotropic drugs have long been studied for their potential benefits in patients with heart failure and reduced ejection fraction (HFrEF). Although there has been an extensive amount of research about the clinical effects of these drugs in general, few studies examined their effect in older patients. Therefore, there is little or no evidence to guide the use of positive inotropes in older patients with HFrEF. However, recommendations from national heart failure guidelines may be generalized to older HFrEF patients on an individual basis, taking into consideration the basic geriatric principles of pharmacotherapy: start low and go slow., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Heart failure is a disease of poor prognosis marked by frequent hospitalizations, premature death, and impaired quality of life. Despite advances in medical therapy for patients with heart failure and reduced ejection fraction, mortality and hospitalizations with advanced disease are still increased and the quality of life continues to be poor in this population. The advent of cardiac resynchronization therapy has led to a significant improvement in both survival and symptom management in patients with heart failure and reduced ejection fraction. Its beneficial effects in the elderly population, however, are not well-defined., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults., Methods: In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP<60mmHg (n=821), DBP≥90 and SBP<140mmHg (n=28), normal BP, taking anti-hypertensive drugs (n=1138), normal BP, not taking anti-hypertensive drugs, history of hypertension (n=193), and baseline HF (n=101). Of the remaining 3495, 1838 had ISH (SBP≥140 and DBP<90mmHg) and 240 had SDH (SBP≥140 and DBP≥90mmHg). The main outcome was centrally-adjudicated incident HF over 13years of follow-up., Results: Participants had a mean (±SD) age of 73 (±6)years, 57% were women, and 16% African American. Incident HF occurred in 25%, 22% and 11% of participants with ISH, SDH and no hypertension, respectively. Compared to no hypertension, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident HF associated with ISH and SDH were 1.86 (1.51-2.30) and 1.73 (1.23-2.42), respectively. Cardiovascular mortality occurred in 22%, 24% and 9% of those with ISH, SDH and no hypertension, respectively with respective multivariable-adjusted HRs (95% CIs) of 1.88 (1.49-2.37) and 2.30 (1.64-3.24)., Conclusion: Among older adults with hypertension, both SDH and ISH have similar associations with incident HF and cardiovascular mortality., (Published by Elsevier B.V.)

Background: Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF)., Methods: We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤2.5 for men and ≤2mg/dl for women, and serum potassium <5mEq/L). After excluding 186 patients already receiving spironolactone on admission, the inception cohort consisted of 1874 patients eligible for a new discharge prescription for spironolactone, of which 329 received one. Using propensity scores for initiation of spironolactone therapy, we assembled a matched cohort of 324 pairs of patients receiving and not receiving spironolactone balanced on 34 baseline characteristics (mean age 72years, 42% women, 33% African American)., Results: Thirty-day all-cause readmission occurred in 17% and 19% of matched patients receiving and not receiving spironolactone, respectively (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.64-1.32; p=0.650). Spironolactone had no association with 30-day all-cause mortality (HR, 0.84; 95% CI, 0.38-1.88; p=0.678) or HF readmission (HR, 0.74; 95% CI, 0.41 1.31; p=0.301). These associations remained unchanged during 12months of post-discharge follow-up., Conclusion: A discharge prescription for spironolactone had no association with 30-day all-cause readmission among older, hospitalized Medicare beneficiaries with HFrEF eligible for spironolactone therapy., Competing Interests: Disclosures: None, (Published by Elsevier Ireland Ltd.)

Background: Heart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure., Methods: Of the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American)., Results: During 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P <.001). This harmful association of 30-day all-cause readmission with mortality persisted during an average follow-up of 3.1 (maximum, 8.7) years (hazard ratio 1.33; 95% confidence interval 1.22-1.45; P <.001). Patients with a 30-day all-cause readmission had higher cumulative all-cause readmission (mean, 6.9 vs 5.1; P <.001), a longer cumulative length of stay (mean, 51 vs 43 days; P <.001), and a higher cumulative cost (mean, $38,972 vs $34,025; P = .001) during 8.7 years of follow-up., Conclusions: Among Medicare beneficiaries hospitalized for heart failure, 30-day all-cause readmission was associated with a higher risk of subsequent all-cause mortality, higher number of cumulative all-cause readmission, longer cumulative length of stay, and higher cumulative cost., (Published by Elsevier Inc.)

IntroductionHospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF).Material and methodsEight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1-5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1-5 vs. 6-10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts.ResultsIn the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04-1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06-1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days.ConclusionsIn propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.

BackgroundIsolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults.MethodsIn the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP

BackgroundTherapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF).MethodsWe examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤2.5 for men and ≤2mg/dl for women, and serum potassium