Objectives: Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). Absolute value and temporal behaviour of O₂-pulse (oxygen uptake/heart rate (VO₂/HR)), and the VO₂/work relationship during exercise reflect closely stroke volume (SV) and CO changes, respectively. We hypothesise that adding O₂-pulse absolute value and kinetics, and VO₂/work relationship to standard cardiopulmonary exercise testing (CPET) could help identify more exercise-limited patients with HCM. Methods: CPETs were performed in 3 HCM dedicated clinical units. We retrospectively enrolled non-end-stage consecutive patients with HCM, grouped according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuvre (72% of patients with LVOTO <30; 10% between 30 and 49 and 18% ≥50 mm Hg). We evaluated the CPET response in HCM focusing on parameters strongly associated with SV and CO, such as O₂-pulse and VO₂, respectively, considering their absolute values and temporal behaviour during exercise. Results: We included 312 patients (70% males, age 49±18 years). Peak VO₂ (percentage of predicted), O₂-pulse and ventilation to carbon dioxide production (VE/VCO₂) slope did not change across LVOTO groups. Ninety-six (31%) patients with HCM presented an abnormal O₂-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs 130±49 W), VO₂ (21.3±6.6 vs 24.1±7.7 mL/min/kg; 74%±17% vs 80%±20%) and O₂-pulse (12 (9–14) vs 14 (11–17) mL/beat), with higher VE/VCO₂ slope (28 (25–31) vs 27 (24–31)) (p<0.005 for all). Only 2 patients had an abnormal VO₂/work slope. Conclusion: None of the frequently used CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal temporal behaviour of O₂-pulse during exercise, which is strongly related to inadequate SV increase, correlates with reduced functional capacity (peak and anaerobic threshold VO₂ and workload) and increased VE/VCO₂ slope, identifying more advanced disease irrespectively of LVOTO.

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 <0.0001), global circumferential strain (−17.3±2.6 -versus -20.8±7.4; P <0.0001) and global longitudinal strain (−16.9±2.4 versus −20.5±2.6; 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.

Congenital long QT syndrome (LQTS) represents a disorder of myocardial repolarization characterized by a prolongation of QTc interval on ECG, which can degenerate into fast polymorphic ventricular arrhythmias. The typical symptoms of LQTS are syncope and palpitations, mainly triggered by adrenergic stimuli, but it can also manifest with cardiac arrest. At least 17 genotypes have been associated with LQTS, with a specific genotype–phenotype relationship described for the three most common subtypes (LQTS1, -2, and -3). β-Blockers are the first-line therapy for LQTS, even if the choice of the appropriate patients needing to be treated may be challenging. In specific cases, interventional measures, such as an implantable cardioverter-defibrillator (ICD) or left cardiac sympathetic denervation (LCSD), are useful. The aim of this review is to highlight the current state-of-the-art knowledge on LQTS, providing an updated picture of possible diagnostic algorithms and therapeutic management.

Mineralocorticoid receptor antagonism represents a therapeutic cornerstone in patients with HFrEF. However, the efficacy of MRAs in patients HFmrEF or HFpEF remains unclear. While the TOPCAT trial did not demonstrate a statistically significant reduction in cardiovascular mortality or hospitalizations for HF in this patient population, post hoc data suggested potential clinical benefits of MRAs in specific patient subgroups. More recently, the landscape has evolved with the FINEARTS-HF trial, which generated novel evidence regarding finerenone, a non-steroidal MRA, in the HFmrEF and HFpEF cohorts. This investigation established a statistically significant decrease in the primary composite endpoint, comprising cardiovascular death and worsening heart failure events. This positive outcome was principally attributable to a lower incidence of total WHF events. Key findings also highlighted the therapy’s rapid onset of action and favorable safety profile. Notably, finerenone’s benefit was consistent across the entire LVEF spectrum and was not influenced by baseline SGLT2i use, sex, or age. Finerenone’s established indication is for patients with type 2 diabetes mellitus and chronic kidney disease to reduce heart failure risk. However, based on the findings of the FINEARTS-HF trial, finerenone may represent a novel therapeutic pillar for patients with HFpEF and HFmrEF. In this review, we aim to describe the potential benefits of MRAs in the pathophysiology of HFpEF and HFmrEF and in different patient phenotypes, the results of the FINEARTS-HF trial, and the most important subanalyses of the study.