Noah Abel

Background: Patients with malignancies were commonly excluded from prior heart failure (HF) trials resulting in limited data regarding the outcomes of patients with HF accompanied by concomitant malignancies. The study sought to assess the prevalence and prognostic impact of malignancies in patients with HF and HF with mildly reduced ejection fraction. Methods: Consecutive patients hospitalized with HF with mildly reduced ejection fraction were retrospectively included at 1 institution from 2016 to 2022. The prognosis of patients with malignancies was investigated regarding the primary end point all‐cause mortality at 30 months (median follow‐up). The key secondary end point was rehospitalization for worsening HF. Results: Among 2184 patients with HF with mildly reduced ejection fraction, 15.3% (n=335) suffered from concomitant malignancies. In patients with active malignancies (n=257), most patients had solid (n=175) followed by hematological malignancies (n=73) (both: n=9), whereas cancer‐therapy HF was observed in 3.9%. Patients with malignancies had lower rates of ischemic cardiomyopathy and were less commonly treated with beta blockers, renin‐angiotensin aldosterone antagonists, and statins. The presence of malignancies was associated with a higher risk of long‐term all‐cause mortality (59.4% versus 26.2%; P =0.001; adjusted hazard ratio, 2.568 [95% CI, 2.101–3.138]; P =0.001), which was already observed during index hospitalization (8.4% versus 2.5%; P =0.001) and mainly attributed to noncardiac mortality. In contrast, the risk of HF‐related rehospitalization did not significantly differ in both groups. Conclusions: Malignancies were present in 15% of patients with HF with mildly reduced ejection fraction and independently associated with long‐term all‐cause mortality, mainly attributed to an increased risk of in‐hospital noncardiac mortality. The risk of HF‐related rehospitalization was not affected by the presence of concomitant malignancies.

Background: Evidence regarding potential agent-specific differences among β-blockers in heart failure with mildly reduced ejection fraction (HFmrEF) remains limited. Objective: The present study sought to investigate the association of metoprolol versus carvedilol prescribed at hospital discharge with 30-month all-cause mortality and HF-related rehospitalization, and to explore potential effect modification by atrial fibrillation (AF). Methods: Consecutive patients hospitalized with HFmrEF between 2016 and 2022 were included. Exposure was β-blocker therapy at discharge (metoprolol succinate or carvedilol). Outcomes were analyzed using Kaplan–Meier estimates, multivariable Cox regression and propensity score matching. Results: Among 2109 patients discharged alive, 1625 (77.5%) received β-blockers (metoprolol n = 1033; carvedilol n = 283). Carvedilol recipients were younger (median 72 vs. 76 years) and more frequently had prior heart failure (44.2% vs. 33.2%). Thirty-month mortality occurred in 25.5% of metoprolol-treated and 31.8% of carvedilol-treated patients (unadjusted hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61–0.98; p = 0.031). This association was observed in patients without AF, but not in those with AF. After multivariable adjustments, the association remained directionally similar (adjusted HR 0.76, 95% CI 0.58–1.00). In the matched cohort (n = 246 per group), metoprolol was still associated with lower mortality (HR 0.65, 95% CI 0.46–0.93; p = 0.017). By contrast, HF-related rehospitalization did not differ significantly between the two groups. Conclusions: In this observational HFmrEF cohort, treatment with metoprolol at index hospital discharge was associated with lower 30-month mortality compared with carvedilol. Given the observational study design in line with the higher burden of comorbidities in patients discharged on carvedilol, further prospective studies are needed to clarify the impact of different β-blocker types in heart failure patients.

Background: This study investigates the prevalence and prognostic impact of coronary chronic total occlusions (CTO) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Although coronary artery disease (CAD) represents the leading HF etiology in HFmrEF, data about CTO in this population are rare. Methods: All consecutive patients with HFmrEF (ie, left ventricular ejection fraction 41%–49% with signs and/or symptoms of heart failure) undergoing invasive coronary angiography from 2016 to 2022 were included retrospectively. Patients with at least one CTO were compared to patients without CTO, further risk stratification was performed according to the extend of CAD. The primary end point was long‐term all‐cause mortality at 30 months (ie, median follow‐up). Secondary end points comprised of major adverse cardiac and cerebrovascular events (MACCE), HF‐related and cardiac rehospitalization at 30 months. Furthermore, the association of percutaneous coronary intervention (PCI) with long‐term outcomes was investigated. Results: 71% of patients with HFmrEF (1545/2184, primary cohort) underwent invasive coronary angiography. In patients undergoing invasive coronary angiography related to the index hospitalization, CAD was present in 81% (836/1037, final cohort), with a corresponding rate of CTO at 17% (n=141). Coronary CTO was associated with the highest rate of the primary end point (33%) compared with non‐CTO (19%), single‐vessel (12%) and multivessel CAD (21%) in HFmrEF ( P =0.001). Accordingly, HFmrEF patients with CTO had the highest rates of various secondary endpoints, including long‐term MACCE compared to non‐CTO patients (60% versus 32%, P =0.001). Successful CTO‐PCI was associated with improved long‐term survival (21% versus 38%; hazard ratio, 0.49 [95% CI, 0.24–0.99]; P =0.046). Conclusions: Coronary CTO are common in HFmrEF with a significant impact on long‐term prognosis. Registration: URL: https://www.clinicaltrials.gov ; unique identifier: NCT0560339.

Background: The study investigates the prognostic impact of sex and sex‐related differences in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). More data regarding the characterization of patients and their outcomes in the presence of HFmrEF are needed. Methods and Results: Consecutive patients hospitalized with HFmrEF (ie, left ventricular ejection fraction 41%–49% and signs or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Female patients were compared with male patients with regard to the primary end point of all‐cause mortality at 30 months (median follow‐up). Statistical analyses comprised Kaplan–Meier, multivariable Cox proportional regression analyses and propensity score matching. From a total of 2184 patients hospitalized with HFmrEF, 64.6% were male. Female patients with HFmrEF were older than male patients (median age 78 versus 73 years; P =0.001) and had lower rates of ischemic cardiomyopathy (46.6% versus 63.6%; P =0.001). Within the entire study cohort, sex was not associated with the risk of all‐cause mortality (hazard ratio [HR], 0.931 [95% CI, 0.797–1.088]; P =0.372). However, male sex was associated with a lower risk of HF‐related rehospitalization at 30 months (HR, 0.761 [95% CI, 0.600–0.966]; P =0.026), which was confirmed after multivariable adjustment (HR, 0.759 [95% CI, 0.592–0.973]; P =0.029) and propensity score matching (HR, 0.722 [95% CI, 0.539–0.967]; P =0.029). Conclusion: Although almost two thirds of patients hospitalized with HFmrEF were male, sex was no predictor for the risk of all‐cause mortality at 30 months. However, female sex was associated with a higher risk of HF‐related rehospitalization. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT05603390.

Objective: This study investigates age-related differences and outcomes in patients hospitalized with heart failure with a mildly reduced ejection fraction (HFmrEF). Background: The characterization of patients with HFmrEF and the prognostic value of age has rarely been investigated. Methods: Patients with HFmrEF were retrospectively included at one institution between 2016 and 2022. The distribution of HF aetiology and prognostic outcomes were investigated comparing patients with ≤40, >40 to ≤60, >60 to ≤80, and >80 years of age. The primary endpoint was long-term all-cause mortality. Kaplan–Meier and multivariable Cox proportional regression analyses were applied for statistics. Results: For the present study, 2184 patients with HFmrEF with a median age of 76 years were included. Non-ischemic cardiomyopathy was the most common HF aetiology in patients 80 years of age (58.2%) had the higher rates of ischemic cardiomyopathies. The risk of long-term all-cause mortality at 30 months was highest in patients with >80 years of age (HR = 2.167; 95% CI 1.928–2.436; p = 0.001), even after multivariable adjustment. Furthermore, patients with >80 years of age had the highest risk of HF-related rehospitalization (HR = 1.529; 95% CI 1.293–1.807; p = 0.001). Conclusions: Ischemic cardiomyopathy represents the most common cause of HF in elderly patients with HFmrEF, whereas younger patients were more likely to suffer from non-ischemic HF aetiologies. Increasing age was an independent predictor of long-term all-cause mortality in patients hospitalized with HFmrEF.

Background: Data regarding the characterization and outcomes of diabetics with heart failure with a mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the prevalence and prognostic impact of type 2 diabetes in patients with HFmrEF. Methods: Consecutive patients with HFmrEF (i.e., left ventricular ejection fraction 41–49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Patients with type 2 diabetes (dia-betics) were compared to patients without (i.e., non-diabetics). The primary endpoint was all-cause mortality at 30 months. Statistical analyses included Kaplan–Meier, multivariable Cox regression analyses and propensity score matching. Results: A total of 2169 patients with HFmrEF were included. The overall prevalence of type 2 diabetes was 36%. Diabetics had an increased risk of 30-months all-cause mortality (35.8% vs. 28.6%; HR = 1.273; 95% CI 1.092–1.483; p = 0.002), which was confirmed after multivariable adjustment (HR = 1.234; 95% CI 1.030–1.479; p = 0.022) and propensity score matching (HR = 1.265; 95% CI 1.018–1.572; p = 0.034). Diabetics had a higher risk of HF-related rehospitalization (17.8% vs. 10.7%; HR = 1.714; 95% CI 1.355–2.169; p = 0.001). Finally, the risk of all-cause mortality was increased in diabetics treated with insulin (40.7% vs. 33.1%; log-rank p = 0.029), whereas other anti-diabetic pharmacotherapies had no prognostic impact in HFmrEF. Conclusions: Type 2 diabetes is common and independently associated with adverse long-term prognosis in patients with HFmrEF.

Cardiac remodeling is frequently observed in patients with heart failure (HF) and serves as an indicator of disease progression and severity. Septal hypertrophy represents an aspect of remodeling that can be easily assessed via an echocardiographic measurement of the interventricular septal end diastole (IVSd), but it has not been evaluated for its prognostic value, particularly in patients with heart failure with mildly reduced ejection fraction (HFmrEF). We retrospectively included 1881 consecutive patients hospitalized with HFmrEF (i.e., a left ventricular ejection fraction of 41–49% and signs and/or symptoms of HF) at one institution during a study period from 2016 to 2022. Septal hypertrophy, defined as an IVSd > 12 mm, was prevalent in 34% of the HFmrEF patients. Although septal hypertrophy was not associated with all-cause mortality at 30 months (median follow-up) (HR = 1.067; 95% CI: 0.898–1.267; p = 0.460), it was associated with an increased risk of hospitalization due to worsening HF at 30 months (HR = 1.303; 95% CI: 1.008–1.685; p = 0.044), which was confirmed even after multivariable adjustment (HR = 1.340; 95% CI: 1.002–1.792; p = 0.049) and propensity score matching (HR = 1.399; 95% CI: 1.002–1.951; p = 0.048). Although septal hypertrophy was not associated with the risk of all-cause mortality in patients with HFmrEF, it was identified as an independent predictor of long-term HF-related rehospitalization.