The study investigates the characteristics and prognostic impact of different heart failure (HF) etiologies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data regarding the characterization of patients with HFmrEF and their outcomes is scarce. 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 ischemic cardiomyopathy (ICM) were compared to patients without ischemic cardiomyopathy (non-ICM). The primary endpoint was all-cause mortality at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. From a total of 1,832 patients hospitalized with HFmrEF, ICM was the most common HF etiology in 68.7 %, followed by hypertensive (9.7 %) and primary non-ischemic cardiomyopathies (NICM) (8.1 %). Within the entire study cohort, the presence of ICM was not associated with the risk of all-cause mortality (HR = 0.864; 95 % CI 0.723 - 1.031), however after multivariable adjustment (HR = 0.792; 95 % CI 0.646 - 0.972; p = 0.026) and propensity score matching (25.7% vs. 31.4 %; log rank p = 0.050), the presence of ICM was associated with lower risk of all-cause mortality at 30 months compared to patients without ICM. ICM is the most common etiology of HF in HFmrEF and may be associated with favorable outcomes. This may be related to better adherence to pharmacological treatment and improved revascularization strategies for HFmrEF patients with ICM.

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.

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.

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.

The aging population has led to a significant increase in heart failure (HF) patients. Related to demographic changes, the burden with comorbidities was shown to increase in patients with HF. Whereas chronic obstructive pulmonary disease (COPD) was yet demonstrated to be associated with adverse outcomes in patients with HF, the prognostic impact of COPD in HF with mildly reduced ejection fraction (HFmrEF) has not yet been clarified. The study investigates the prognostic impact of COPD in patients hospitalized with HFmrEF. Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with COPD were compared to patients without with regard to the primary endpoint all-cause mortality at 30 months (median follow-up). Secondary endpoints comprised in-hospital mortality, HF-related re-hospitalization, cardiac re-hospitalization and major adverse cardiac and cerebrovascular events (MACCE) at 30 months. A total of 2184 patients with HFmrEF were included with a prevalence of COPD of 12.0 %. Patients with COPD were older (median 77 vs. 75 years; p = 0.025), had increased burden of cardiovascular comorbidities and more advanced HF symptoms. At 30 months, patients with COPD had an increased risk of all-cause mortality compared to patients without (45 % vs. 30 %; HR = 1.667; 95 % CI 1.366-2.034; p = 0.001), alongside with a higher risk of re-hospitalization for worsening HF (20 % vs. 12 %; HR = 1.658; 95 % CI 1.218-2.257; p = 0.001). COPD is independently associated with adverse outcomes in patients hospitalized with HFmrEF.