Nikita Baracchini

Background: The RoMa classification, based on peak heart rate and oxygen pulse derived from cardiopulmonary exercise testing, was recently proposed to stratify patients with hypertrophic cardiomyopathy by physiological reserve during exercise. We aimed to externally validate RoMa in an independent multicenter cohort with hypertrophic cardiomyopathy and assess its association with long‐term clinical outcomes. Methods: In this retrospective multicenter cohort study patients with hypertrophic cardiomyopathy, undergoing cardiopulmonary exercise testing, were consecutively enrolled. Patients were enrolled regardless of left ventricular outflow tract obstruction and were naïve to disease‐specific therapy (eg, mavacamten). Patients were categorized into RoMa I to IV based on percentage of predicted heart rate and oxygen pulse. The primary end point was a composite of all‐cause and cardiovascular death, sudden cardiac death, or aborted sudden cardiac death, heart failure–related hospitalization, stroke, systemic embolism, surgical myectomy, and heart transplantation. Results: The study included 292 patients (age 51 [36–63] years, 70% male sex, 30% with obstructive left ventricular outflow tract). Functional capacity declined hierarchically across RoMa groups (peak oxygen uptake 29.2 to 17.9 mL/kg/min; P ‐trend P =0.019). In multivariable analysis, RoMa II to IV compared with RoMa I were independently associated with higher hazard ratios (HRs) for the composite outcome (HRs, 3.89–5.37; all P <0.05), whereas genotype, LVEF <50%, male sex, and left ventricular outflow tract obstruction were not predictive. Conclusions: The RoMa classification independently predicts long‐term, clinically relevant outcomes in hypertrophic cardiomyopathy regardless of left ventricular outflow tract obstruction and may provide a novel approach to risk stratification.

Introduction: In heart failure (HF) patients, guidelines recommend scores for assessing outcomes and heart transplant (HTX) eligibility. However, scores use remains limited and cut-off values for HTX listing not well established. Among the available tools, MECKI score is easy to calculate and likely offers the best prognostic accuracy. Compare MECKI score-based survival with that of HTX recipients and identify a MECKI threshold above which survival is inferior to that of HTX recipients at 5-year. Methods: Consecutive ambulatory HF patients enrolled in MECKI score programme between January 2010 and January 2022 were evaluated. Primary endpoint was a composite of cardiovascular death, HTX, or left ventricular assist device implantation. Heart transplant survival data were obtained from the International Society of Heart and Lung Transplantation registry updated through 2023. To identify the MECKI score threshold beyond which prognosis is worse than that of HTX recipients, patients were stratified by deciles of MECKI score. Results: We analysed 3865 HF patients (mean age 62.4 ± 12.6 years). Peak VO₂ was 58.2 ± 18.3% predicted; VE/VCO₂ slope 33.2 ± 8.2, haemoglobin 13.5 ± 1.7 g/dL, Na⁺ 139 ± 3 mmol/L, LVEF 33.7 ± 10.4%, and eGFR 73 ± 26 mL/min/1.73 m². Periodic breathing occurred in 15.8% of patients. At 5 years, mean survival was 83.7%. The average 5-year survival of HTX recipients (71.2%) lies between the eighth and ninth MECKI score deciles suggesting a MECKI score value ≥0.1368 as the proper cut-off for HTX listing. Conclusion: MECKI score ≥0.1368 may warrant HTX listing, while lower scores support clinical deferral.

Functional impairment is a hallmark of heart failure (HF) and a strong prognostic factor. Cardiopulmonary exercise testing (CPET) provides a robust and objective assessment of exercise capacity; however, the impact of new pharmacotherapies on CPET parameters remains largely uncharacterized systematically. This review examines the influence of contemporary HF therapies on functional capacity, with particular focus on CPET-derived metrics, such as peak oxygen uptake (VO2 peak), ventilatory efficiency (VE/VCO2 slope), and oxygen uptake efficiency slope (OUES). A critical synthesis of randomized trials, observational studies, and meta-analyses was performed to assess the effects of both conventional (angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs)) and novel agents (angiotensin receptor neprilysin inhibitor (ARNIs), sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP)-1 receptor agonists, vericiguat, finerenone) on CPET outcomes. Conventional therapies provide modest improvements in CPET indices, whereas sacubitril/valsartan and SGLT2 inhibitors show more consistent and clinically meaningful benefits across different HF phenotypes. Vericiguat provided preliminary promise in improving VO2 peak and ventilatory parameters. Meanwhile, evidence for GLP-1 receptor agonists and finerenone remains limited or inconclusive. Heterogeneity across studies, in terms of the timing of CPET follow-up and baseline functional status, emerged as important modulators of the observed outcomes. Novel HF therapies can potentially improve exercise capacity beyond symptomatic relief, supporting a shift toward CPET-based endpoints in HF clinical trials. Personalized CPET monitoring may optimize therapeutic strategies and better reflect meaningful functional gains in HF populations.

BACKGROUND: Assessing myocardial strain by cardiac magnetic resonance feature tracking (FT) has been found to be useful in patients with overt hypertrophic cardiomyopathy (HCM). Little is known, however, of its role in sarcomere gene mutation carriers without overt left ventricular hypertrophy (subclinical HCM). METHODS: Thirty-eight subclinical HCM subjects and 42 healthy volunteers were enrolled in this multicenter case-control study. They underwent a comprehensive cardiac magnetic resonance study. Two-dimensional global radial, circumferential, and longitudinal strain of the left ventricle (LV) were evaluated by FT analysis. RESULTS: The subclinical HCM sample was 41 (22–51) years old and 32% were men. FT analysis revealed a reduction in global radial strain (29±7.2 versus 47.9±7.4; P P P <0.0001) in subclinical HCM compared with control subjects. The significant differences persisted when considering the 23 individuals free of all the structural and functional ECG and cardiac magnetic resonance abnormalities previously described. Receiver operating characteristic curve analyses showed that the differential diagnostic performances of FT in discriminating subclinical HCM from normal subjects were good to excellent (global radial strain with optimal cut-off value of 40.43%: AUC, 0.946 [95% CI, 0.93–1.00]; sensitivity 90.48%, specificity 94.44%; global circumferential strain with cut-off, −18.54%: AUC, 0.849 [95% CI, 0.76–0.94]; sensitivity, 88.10%; specificity, 72.22%; global longitudinal strain with cut-off, −19.06%: AUC, 0.843 [95% CI, 0.76–0.93]; sensitivity, 78.57%; specificity, 78.95%). Similar values were found for discriminating those subclinical HCM subjects without other phenotypic abnormalities from healthy volunteers (global radial strain with optimal cut-off 40.43%: AUC, 0.966 [95% CI, 0.92–1.00]; sensitivity, 90.48%; specificity, 95.45%; global circumferential strain with cut-off, −18.44%: AUC, 0.866 [95% CI, 0.76–0.96]; sensitivity, 92.86%; specificity, 77.27%; global longitudinal strain with cut-off, −17.32%: AUC, 0.838 [95% CI, 0.73–0.94]; sensitivity, 90.48%; specificity, 65.22%). CONCLUSIONS: Cardiac magnetic resonance FT-derived parameters are consistently lower in subclinical patients with HCM, and they could emerge as a good tool for discovering the disease during a preclinical phase.