The adding value of non-invasive assessment of stroke volume during cardiopulmonary exercise testing in hypertrophic cardiomyopathy: beyond O2-pulse

Background Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder characterized by left ventricular (LV) hypertrophy (≥15 mm) without secondary causes. HCM patients frequently exhibit reduced exercise tolerance due to multifactorial mechanisms such as LV outflow tract obstruction (LVOTO), diastolic dysfunction, mitral regurgitation, myocardial ischemia, and arrhythmias. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity, with O2-pulse (VO2/heart rate) often used as a non-invasive surrogate for stroke volume (SV). However, O2-pulse indirectly reflects SV due to the influence of arterio-venous oxygen difference, limiting its accuracy. PhysioFlow® (PF), a non-invasive thoracic bioimpedance device, allows direct SV measurement during exercise, providing real-time hemodynamic monitoring without affecting exercise performance. While PF has been used in various cardiovascular contexts, its application in HCM remains underexplored. This study aimed to evaluate the added value of PF in detecting abnormal SV kinetcs in HCM patients during CPET and its correlation with exercise performance metrics. Methods We enrolled 102 HCM patients (53±16 years, 78% male, 74% non-obstructive phenotype) who underwent CPET integrated with PF. Resting and peak exercise SV values were recorded, and SV kinetics were analyzed. Abnormal SV trajectories (plateau or downsloping patterns) were compared with CPET-derived parameters, including VO2, ventilatory efficiency (VE/VCO2), and end-tidal CO2 (PetCO2). Results Abnormal O2-pulse kinetics were observed in 12 patients, all confirmed by abnormal SV trends with PF. Additionally, PF identified 28 more patients with altered SV kinetics. Abnormal SV trends were associated with higher peak VE/VO2 ratios (42.6 [37.4–47.5] vs. 38.0 [33.6–41.3]) and lower end-tidal CO2 values (31.8±4.9 mmHg vs. 34.3±5.6 mmHg, p<0.05). Patients with greater SV growth in the last 25% of exercise showed improved anaerobic threshold VO2 (49.8±12.3% vs. 43.9±15.2% predicted peak VO2), VO2/work slope (10.2±2.0 vs. 9.3±1.3 mL/min/Watt), and peak PetCO2 (34.5±5.6 mmHg vs. 32.3±5.2), alongside lower VE/VCO2 slope (28.7 [24.9–31.0] vs. 31.3 [27.3–34.2], p<0.05). Conclusions Integrating PF with CPET enhances the identification of hemodynamic abnormalities in HCM patients, detecting exercise-induced SV impairments not captured by O2-pulse alone. This approach offers valuable insights into the pathophysiology of exercise intolerance, potentially informing therapeutic strategies. Further studies are needed to explore its prognostic and therapeutic implications, particularly in the era of novel HCM treatments.