Abstract Introduction The Fibrosis-4 (FIB-4) Index has shown prognostic value in cardiovascular diseases, but its role in heart transplantation (HTx) and the impact of dynamic preoperative changes remain unclear. This study evaluated the prognostic value of preoperative FIB-4 for mortality after HTx and investigated whether dynamic changes in FIB-4 before transplantation are associated with post-transplant survival. Methods This single-centre retrospective cohort study included 791 adult patients who underwent orthotopic HTx between January 2015 and December 2024, with follow-up through June 2025. Patients were stratified by preoperative FIB-4 into low (<1.30), intermediate (1.30–2.67), and high (>2.67) risk groups. The primary outcome was all-cause mortality. Analyses employed Cox models, restricted cubic splines, and five machine learning survival models, including Random Survival Forest (RSF). Results During a median follow-up of 28.8 months, 218 patients (27.6%) died. Preoperative FIB-4 showed a non-linear association with mortality (inflection point: 2.03) and was an independent predictor of death [hazard ratio (HR) per unit increase, 1.04; 95% CI, 1.02–1.07; P < .001]. In the RSF model, FIB-4 was the most important prognostic variable (Variable Importance = 0.068), outperforming traditional donor and surgical factors. Sensitivity analyses confirmed that FIB-4’s prognostic value was independent of age (interaction P = .745) and superior to its individual components (aspartate aminotransferase, alanine aminotransferase, and platelet count). Correlation analyses showed no significant association between FIB-4 and invasive haemodynamic parameters, tricuspid regurgitation severity, or MELD/MELD-XI scores, supporting its distinction from haemodynamic congestion. Among high-risk patients (n = 153), preoperative improvement in FIB-4 category was associated with significantly lower mortality (adjusted HR, 0.49; 95% CI, 0.29–0.82; P = .007). Preoperative use of glutathione was independently associated with FIB-4 improvement [odds ratios (OR), 1.50; 95% CI, 1.01–2.22; P = .04]. Conclusion Preoperative FIB-4 is a robust and independent predictor of post-transplant mortality, with greater predictive importance than traditional surgical risk factors. Dynamic improvement in FIB-4 before transplantation is associated with better survival. Integrating FIB-4 into routine preoperative assessment may refine risk stratification and guide pre-transplant management.
Abstract Background and Aims The prognostic significance of moderate secondary mitral regurgitation (MR) after optimized guideline-directed medical therapy (GDMT) in heart failure (HF) remains uncertain. Methods We analysed 2468 ambulatory HF patients with paired transthoracic echocardiography at baseline and after 12 months of optimized GDMT. The primary composite was all-cause death or first heart failure hospitalization (HFH). Secondary endpoints included all-cause mortality and recurrent HFHs. Results The mean age of patients was 66.2 ± 12.5 years, 70.6% were male, and the mean baseline left ventricular ejection fraction was 36.1% ± 13.6%. At 12 months, 80.5% of patients had no/mild MR, 15.6% had moderate MR, and 3.9% had severe MR. During a median 6.9-year follow-up, 1240 patients experienced the primary endpoint. Compared with no/mild MR, both moderate and severe MR at 12 months were independently associated with a higher risk of the primary composite endpoint [moderate: hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.47–1.95; severe: HR 1.81, 95% CI 1.44–2.29; both P < .001). Moderate MR was also independently associated with increased all-cause mortality (HR 1.54, 95% CI 1.32–1.79; P < .001) and recurrent HFHs (incidence rate ratio 2.17, 95% CI 1.81–2.60). Heart failure hospitalization rates were 9.03, 20.0, and 26.1 per 100 person-years in patients with no/mild, moderate, and severe MR, respectively. Among patients with moderate MR at 12 months, outcomes did not differ according to baseline MR severity. Conclusions In this large-scale study, residual moderate secondary MR after 12 months of optimized GDMT was common and was independently associated with increased long-term mortality and HFHs.
Abstract Background Although beneficial effects of red wine and its polyphenols have been described, data on direct effects on pulmonary arteries and human myocardium are sparse, and claims remain controversial given well-known alcohol-related harms. Aims This study investigated acute and subacute effects of red wine, dealcoholized red wine and key polyphenols (trans/cis-resveratrol, caffeic acid, gallic acid) on human atrial and ventricular myocardium and pulmonary arteries. Methods and Results In human atrial trabeculae and failing left ventricular slices from heart transplant recipients (n = 6), polyphenols increased developed force significantly (+39% caffeic acid, +27% gallic acid, +17% trans-resveratrol, +10% cis-resveratrol; control −34%, p < 0.05) and red wine (10−4: +18%) compared with control (−23%, p < 0.0001), without affecting diastolic properties or inducing arrhythmias. In failing human left ventricular myocardium, twitch amplitude increased over 7 days with alcoholic and dealcoholized red wine (p = 0.0177) compared with control, while preserving the negative force–frequency relationship and post-rest potentiation. In preconstricted human pulmonary arteries, red wines induced a rapid, sustained 80% relaxation independent of ethanol content. L-NAME reduced human pulmonary artery relaxation from 59% to 28% (p < 0.05), confirming partial endothelial nitric-oxide mediation. Conclusion Red wine and its bioactive compounds exert robust dual inotropic and pulmonary vasodilatory actions independent of alcohol. Dealcoholized red wine as an adjunctive strategy may represent a promising avenue toward integrated cardiopulmonary therapy in heart failure and precapillary pulmonary hypertension. A clinical trial (DARE-WINE-PH, DRKS00035605) is underway to validate acute haemodynamic effects in patients with precapillary pulmonary hypertension.
Abstract The benefits of exercise in older patients with heart failure (HF) and frailty are twofold: (i) improvement in cardiopulmonary capacity, thus reducing HF-related sequelae; (ii) attenuation of decline in physical function, thus improving frailty status. Despite the clear benefits, exercise training (ET) remains underutilised as a treatment modality in this patient population. Guidelines on the specific type of exercise intervention best suited for this population are still lacking. In this review, we discuss (i) pathophysiology underlying exercise intolerance in patients with HF; (ii) impact of frailty on HF and exercise capacity; (iii) benefits and safety of ET; (iv) recommended ET programme for this population; (v) mode of delivery and (vi) potential barriers in the uptake of ET and strategies to overcome them. An effective ET intervention in this population warrants individualisation to patient’s physical capacity, while addressing possible barriers to uptake so as to ensure sustained participation in the programme.
