Background and aims: To evaluate differences in post-transplant outcomes by pre-transplant urgency status, focusing on early post-transplant infection and its contribution to mortality.
Methods: We retrospectively analysed 801 adult heart transplant recipients enrolled in the Korea Organ Transplant Registry (April 2014-December 2021). Recipients were classified as Status 0 (highest urgency; n = 287) and Status 1-3 (n = 514). Outcomes included all-cause mortality, post-transplant infection, acute allograft rejection, and cardiac allograft vasculopathy (CAV) up to 5 years. Mediation, landmark, and multivariable time-dependent Cox models assessed the impact and determinants of infection.
Results: During 5-year follow-up, 128 recipients (16.0%) died. Status 0 recipients had higher mortality than Status 1-3 recipients (28.0% vs. 13.5%; P < .001). Infection was the leading cause of death and was more frequent in Status 0 recipients at 1 and 6 months, whereas rejection and CAV rates were similar between groups. Infection at 1, 6, and 12 months was strongly associated with mortality and mediated the association between urgency status and mortality, accounting for 47.4%, 34.9%, and 34.2% of total effect, respectively. After adjustment for pre- and post-transplant organ support, urgency status was no longer independently associated with infection risk, whereas prolonged mechanical ventilation (>24 h) remained the strongest predictor.
Conclusion: Status 0 heart transplant recipients had higher mortality and early post-transplant infection risk than Status 1-3 recipients. Early infection, largely associated with greater clinical severity and prolonged mechanical ventilation, may explain the excess mortality in this high-urgency group.
Introduction: This study evaluated the feasibility, acceptability, and clinical effectiveness of a home-based body water monitoring and pre-emptive management system using bioelectrical impedance analysis (BIA) in patients with heart failure (HF).
Methods: In this multicentre, open-label, randomized controlled trial, 40 HF patients receiving loop diuretics were assigned to standard care or a home BIA group using a home-based BIA device with a linked application providing weekly feedback and guidance on diuretic management. Feasibility outcomes included study completion, adherence, usability and acceptability scores, and adverse events over 12 weeks. Effectiveness outcomes included changes in NT-proBNP, oedema index, New York Heart Association (NYHA) functional class, HF hospitalization, and all-cause mortality.
Results: Thirty-nine patients were included in the final analysis after exclusion of one patient lost to follow-up in the control group. Patients in the control group were older than those in the home BIA group (70.4 ± 8.3 vs 57.2 ± 13.5; P = .003), and baseline NT-proBNP levels were higher (2737.1 ± 3817.1 vs 1357.7 ± 2196.8 pg/ml; P = .013), while other baseline characteristics were comparable. In the home BIA group, the completion rate was 100.0% and adherence to BIA measurements was 82.5%. Acute kidney injury occurred in one patient (5.0%), with no discontinuations due to adverse events. Usability and acceptability were high (4.21 ± 0.59; 3.90 ± 0.53, respectively) on a 5-point Likert scale. There were no significant differences in changes in NT-proBNP or oedema index during follow-up between groups. Worsening NYHA class occurred less frequently in the home BIA group (10.0% vs 31.6%; P = .095). Changes in the oedema index correlated with changes in NT-proBNP (r = 0.544; P = .002), whereas changes in body weight did not (r = 0.237; P = .147). No HF hospitalizations or deaths occurred.
Conclusion: Home-based BIA monitoring with pre-emptive management is feasible, acceptable, and safe for patients with HF.
Introduction: AZD5462 is the first oral relaxin family peptide receptor 1 agonist in clinical development and is expected to reduce systemic vascular resistance and afterload and to increase natriuresis, decreasing circulating blood volume, benefitting patients with chronic heart failure (HF). LUMINARA is a Phase 2b study of the efficacy and safety of AZD5462 in participants with broad HF.
Study design: This randomized, placebo-controlled, double-blind, multi-centre, dose-ranging study will include ∼360 participants with HF: 220 with left ventricular ejection fraction (LVEF) ≤35% (Cohort A) and 140 with LVEF 41%-55% (Cohort B) will be randomized 1:1:1:1 to three once daily oral doses of AZD5462 or placebo for 24 weeks. Primary endpoints are changes in end-systolic volume index (Cohort A) and systemic vascular resistance index (Cohort B) after 24 weeks. Secondary endpoints include changes in echocardiographic parameters, health status, cardiorenal biomarkers and pharmacokinetics. The safety of AZD5462 will be monitored throughout the study.
Discussion: This study will evaluate AZD5462 as a novel oral therapy for patients with chronic HF, aiming to improve symptoms as well as haemodynamic and cardiorenal biomarkers. The findings may provide insights on the development of AZD5462 in a future Phase 3 trial.
Recent-onset cardiomyopathy represents a clinically dynamic and potentially reversible clinical framework of non-ischaemic cardiomyopathy, characterized by high variability in left ventricular (LV) function and arrhythmic risk. This clinical consensus statement provides a structured diagnostic and therapeutic approach based on two prognostic axes: the potential for LV reverse remodelling (LVRR) and the risk of sudden cardiac death (SCD). We operationalize four trajectories in the LV evolution, ranging from recovered LV ejection fraction (LVEF) to persistently reduced LVEF. Multimodal stratification including echocardiography, cardiac magnetic resonance, genetic profiling, biomarkers, and early treatment response allows tailored decision-making on pharmacological and device-based therapies. We propose a unified management algorithm emphasizing early initiation of guideline-directed medical therapy, structured reassessment at 3 and 6 months, and individualized consideration of defibrillators, resynchronization therapy, arrhythmia ablation, transcatheter valve leaflet edge-to-edge repair, and advanced heart failure assessment. This document aims to support clinicians in risk stratification and timely management or referrals.
Introduction: Early identification of patients with cardiogenic shock (CS) who will require temporary mechanical circulatory support (MCS) remains challenging. Right ventricular (RV) dysfunction is common in CS and affects haemodynamic stability. RV free wall longitudinal strain (RV FWLS) is a sensitive marker of myocardial dysfunction, but its role in predicting MCS escalation in CS remains unclear.
Methods: In this single-centre retrospective study, patients admitted with CS between January 2023 and December 2025 were screened. Inclusion required transthoracic echocardiography within 24 h of CS diagnosis and prior to MCS implantation. RV FWLS was measured using commercially available software. Primary outcome was temporary MCS implantation during hospitalization. Secondary outcomes included in-hospital mortality and intensive care and hospital length of stay.
Results: Ninety-two patients were included; 31 (34%) required temporary MCS. Severe RV FWLS impairment (<11%) was strongly associated with temporary MCS use (OR 10.49, 95% CI 3.72-29.59). Tricuspid annular plane systolic excursion and fractional area change were not significantly associated with temporary MCS. Severe RV FWLS was linked to longer intensive care stay (21 vs 8 days, P = .003) and hospital stay (25 vs 14 days, P = .003), but not mortality. RV FWLS demonstrated moderate discrimination (area under the curve, AUC 0.74), improving with left ventricular ejection fraction (LVEF) and Sequential Organ Failure Assessment (SOFA) score (AUC 0.82). A classification and regression tree -derived algorithm using RV FWLS, SOFA score, and LVEF stratified patients into distinct risk groups with 78% overall accuracy and 95% specificity.
Conclusion: Integration of RV FWLS with clinical parameters may improve early risk stratification in CS.
Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently recommended as one of the four pillars of treatment in heart failure (HF) with reduced ejection fraction (HFrEF). Following the approval of dapagliflozin in 2020, real-world data are relevant for the medical community and payers. This study aimed to characterize the patient population with dapagliflozin initiated for HFrEF in clinical practice in 9 countries from Central Eastern Europe and the Baltic Area (CEE-BA).
Methods: EVOLUTION-HF CEE-BA is a multicentre, multi-country, observational, longitudinal study conducted in 102 centres in Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovenia. All treatment decisions were at the discretion of the patient's healthcare providers, based on the locally approved product information and routine clinical practice. Patients with type 1 diabetes, prior treatment with dapagliflozin or other SGLT2i, and initiation of dapagliflozin outside the approved HFrEF indication were excluded. The baseline period covered 12 months prior to dapagliflozin initiation, with prospective follow-up continuing up to 12 months or until loss to follow-up, death, or study discontinuation, whichever occurred first. Descriptive statistics and Kaplan-Meier methods were used.
Results: A total of 1131 patients with HFrEF were included in the full analysis set. Ischaemic aetiology was present in 52% of patients. The mean left ventricular ejection fraction was 32%. The most frequent comorbidities were atrial fibrillation (46%), type 2 diabetes (37%), and chronic kidney disease (29%). At the time of dapagliflozin initiation, 93% of patients received any combination of a renin-angiotensin-aldosterone system inhibitor (RAASi), beta-blocker (BB), or mineralocorticoid receptor antagonists (MRA). Of all patients, 60% received concomitantly all three classes plus dapagliflozin for their HFrEF. Except for dapagliflozin, which was administered as 10 mg/day, optimal doses were recorded for 14% for any RAASi, 17% for BB, and 25% for MRA. At 6- and 12-month follow-up, maintenance of dapagliflozin treatment was recorded in 95% and 96% of patients, respectively. The real-world median time to discontinuation of dapagliflozin has not been reached. The percentage of patients receiving all four classes recommended in HFrEF remained stable over the study period. Adverse events were reported spontaneously, as in routine clinical practice in each centre.
Conclusion: This large non-interventional study provides a contemporary perspective of the treatments used in HFrEF over 1-year follow-up. Despite high dapagliflozin persistence rates, a low proportion of patients received complete guideline-directed medical therapy in optimal doses. Improvement of HF management decisions across the CEE-BA region is warranted.
Aims: To quantify central oxygen delivery (O2D), peripheral oxygen extraction, and muscle diffusive oxygen conductance (DmO2) during upper-extremity resistance and lower-extremity aerobic exercise in patients with arrhythmogenic cardiomyopathy (ACM).
Methods and results: Nineteen patients with ACM underwent invasive cardiopulmonary exercise testing with right heart and radial artery catheterization. Participants performed 1-min isometric handgrip (IM-HG) and bicep curl (BC) exercise at 70% maximal voluntary contraction, and 20- and 40-min supine cycling (CYC-20, CYC-40) at the first ventilatory threshold. Exercise pulmonary hypertension, defined by a cardiac output to mean pulmonary artery slope >3 mmHg/L/min, did not occur (mean 0.67 mmHg/L/min). Whole-body oxygen uptake (V̇O2) increased significantly across all modes (P < .001); however, central O2D did not increase significantly during IM-HG or BC and rose only modestly during cycling. In contrast, peripheral O2 extraction and DmO2 increased significantly across all modalities (P < .001). Dominance analysis revealed that DmO2 accounted for 77% of the variance in V̇O2 pooled across all conditions, whereas O2D accounted for only 23%.
Conclusions: Moderate-intensity isometric and dynamic resistance and aerobic exercise in ACM is mediated by a predominantly peripheral, rather than central, physiological stress in our small ACM sample. This may provide preliminary results for a physiological rationale for safe exercise in this population.
Background and aims: Optimizing guideline-directed medical therapy (GDMT) remains vital for heart failure (HF) management. However, non-labelled dosing of sacubitril-valsartan is increasingly reported.This global survey characterized real-world sacubitril-valsartan prescribing patterns and evaluated pharmacist involvement in HF teams.
Methods: The validated 26-item IKNOW-HF survey was disseminated globally to clinicians treating patients with HF. Participation was voluntary and anonymous.
Results: Out of 1829 responses from 76 countries, 1285 (70.3%) were complete, predominantly from cardiologists 1031 (80.2%). Non-labelled sacubitril-valsartan dosing was reported by 1107 (86.1%) respondents, heavily driven by general cardiologists 326 (90%) and clinicians in the low- and lower-middle-income countries 195 (96%). Predictors of non-labelled dosing included practicing in Asia [odds ratio (OR) 0.347; 95% confidence interval (CI) (0.214-0.563)] and having over 10 years of experience [OR 0.695; 95% CI (0.489-0.990)]. The presence of a cardiology pharmacist trended towards a fewer non-labelled prescriptions [OR 0.542; 95% CI (0.283-1.039), P-value = 0.065], whereas management by HF specialist trended towards increased non-labelled usage [OR 1.443; 95% CI (0.981-2.122), P-value = 0.063].
Conclusions: The IKNOW-HF survey reveals a substantial variation between guideline-recommended and real-world prescribing practices, with over 80% of responding clinicians utilizing non-labelled dosing. The higher prevalence among HF specialists likely reflects a pragmatic salvage strategy for advanced HF patients intolerant to standard target doses. These findings highlight the need for further education, pragmatic clinical trials evaluating real-world dosing outcomes, and broader integration of specialized pharmacists to optimize GDMT.
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