Cardiopulmonary exercise testing in hypertrophic cardiomyopathy: the role of reduced O2 pulse and chronotropic incompetence in myocardial adaptation

Aims: Hypertrophic cardiomyopathy (HCM) is associated with functional limitations during exercise. We aimed to evaluate oxygen pulse (O2p) as a stroke volume (SV) surrogate and to propose a new HCM classification (RoMa) based on haemodynamic profiles during exercise: predicted peak O2p (O2pp) and peak heart rate (HRpp). Methods and results: This multicentre, prospective study included 90 clinically stable HCM patients who underwent cardiopulmonary exercise testing with simultaneous impedance cardiography (PhysioFlow®). We assessed the relationship between SV and O2p. Patients were stratified into four groups based on HRpp (≥80% predicted) and O2pp (≥100% predicted): RoMa I (high HRpp-high O2pp), RoMa II (high HRpp-low O2pp), RoMa III (low HRpp-high O2pp), and RoMa IV (low HRpp-low O2pp). Oxygen uptake (VO2), minute ventilation-to-carbon dioxide production (VE/VCO2) slope, SV, and mitral regurgitation (MR) were analysed. Patients (80% male, 53 [42-64] years) had preserved left ventricular ejection fraction (62 [58-68]%) and peakVO2 (23.1 ± 7.8 mL/min/kg = 81 ± 21% predicted). SV correlated with O2p (r = 0.48, P < 0.001; β = 3.59, P < 0.001). Resting moderate to severe MR was more prevalent in RoMa class IV (41%) vs. RoMa I (18%, P = 0.038). PeakVO2 declined across groups, from 29.7 ± 8.3 (RoMa I) to 16.2 ± 5.1 mL/min/kg (RoMa IV, P < 0.001). VE/VCO2 slope increased from 26.4 ± 4.5 (RoMa I) to 38.6 ± 6.0 (RoMa IV, P = 0.002). Peak SV decreased from 128.7 ± 24.8 (RoMa I) to 104.7 ± 28.0 mL (RoMa IV, P = 0.019), while rest to peak SV difference dropped from 38.6 (30.4-52.8) to 15.8 (8.2-27.9) mL (P = 0.002). Conclusion: SV and O2p are significantly related, and the RoMa classification effectively distinguished HCM patients. Key findings: O2p is a reliable indicator of SV, helping to better understand exercise limitations in HCM patients.The newly introduced RoMa classification effectively distinguishes different levels of exercise impairment in HCM, linking poorer heart function to lower oxygen uptake and higher breathing inefficiency.