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AimsCardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort.Methods and resultsThis multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death.ConclusionThe primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Aims: The aim of the study was to assess the incidence and predictive factors of the development of heart failure with improved ejection fraction (HFimpEF) category during a 1 year follow‐up period in a heart failure with reduced ejection fraction (HFrEF) patient population managed in a heart failure outpatient clinic. Methods and results: The study evaluated data from patients enrolled in the Hungarian Heart Failure Registry (HHFR). The incidence and predictive factors of the development of the HFimpEF category after 1 year follow‐up were assessed in the group of patients who had HFrEF at baseline. We evaluated the incidence and predictors of the development of HFimpEF after a 1 year follow‐up in relation to time since diagnosis of HFrEF in patients diagnosed within 3 months, between 3 months and 1 year, and beyond 1 year. The predictive factors of the development of HFimpEF were analysed using univariate and multivariate logistic regression analysis. Of the 833 HFrEF patients enrolled in the HHFR, the development of HFimpEF was observed in 162 patients (19.5%) during 1 year follow‐up. In the whole patient population, independent predictors of the development of HFimpEF were female gender [odds ratio (OR): 1.73; 95% confidence interval (CI): 1.01–2.96; P < 0.05], non‐ischaemic aetiology (OR: 1.95; 95% CI: 1.15–3.30; P < 0.05), and left ventricular end‐diastolic diameter (LVEDD) <60 mm (OR: 2.04; 95% CI: 1.18–3.51; P < 0.05). The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The incidence of HFimpEF was 27.1% in patients diagnosed within 3 months, 18.4% in patients diagnosed between 3 months and 1 year, and 12.2% in patients diagnosed beyond 1 year. Non‐ischaemic aetiology (OR: 4.76; 95% CI: 1.83–12.4; P < 0.01) and QRS width (OR: 0.81; 95% CI: 0.71–0.94; P < 0.01) for patients diagnosed within 3 months, LVEDD (OR: 0.54; 95% CI: 0.32–0.90; P < 0.05) and left atrial diameter ≤45 mm (OR: 5.44; 95% CI: 1.45–20.4; P < 0.05) for patients diagnosed between 3 months and 1 year, and LVEDD < 67 mm (OR: 2.71; 95% CI: 1.07–6.88; P < 0.05) for patients diagnosed beyond 1 year were found to be independent predictive factors. Conclusions: In our study, in this HFrEF patient population managed in a heart failure outpatient clinic, the 1 year incidence of HFimpEF was found to be ~20%. The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The most important predictors of the development of HFimpEF were female sex, non‐ischaemic aetiology, narrower QRS width, and smaller diameter of the left ventricle and left atrium. [ABSTRACT FROM AUTHOR]

Background: Kidney dysfunction (KD) is a main limiting factor of applying guideline‐directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). Hypothesis: We aimed to assess the success of optimization, long‐term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + βB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. Methods: The data of 247 real‐world, consecutive patients were analyzed who were hospitalized in 2019−2021 for HFrEF and then were followed‐up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60−89, 45−59, 30−44, <30 mL/min/1.73 m2). Moreover, 1‐year all‐cause mortality and rehospitalization rates in KD subgroups were investigated. Results: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p <.05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p <.05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One‐year all‐cause mortality (14%, 15%, 16%, 33%, 48%, p <.001), the ratio of all‐cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p =.028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p =.001) were significantly higher in more severe KD categories. Conclusions: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up‐titration of GDMT. [ABSTRACT FROM AUTHOR]