Cardiopulmonary exercise testing in paediatric hypertrophic cardiomyopathy: functional profiles and prognostic value

Abstract Introduction Despite advances in imaging and genetic characterisation, functional assessment in paediatric hypertrophic cardiomyopathy (HCM) remains limited. While cardiopulmonary exercise testing (CPET) provides key insights into exercise tolerance and cardiovascular efficiency, paediatric data are scarce and mostly derived from small cohorts, and its prognostic relevance in children and adolescents is still not well established. Aims To describe CPET functional profiles in a large cohort of children and adolescents with HCM and explore their correlations with echocardiographic parameters, BNP levels, and clinical outcomes. Methods We conducted a single-centre retrospective study including 244 paediatric HCM patients evaluated at Great Ormond Street Hospital (2000–2024). A total of 587 cycle-ergometer CPETs with an echocardiogram performed within 12 months were analysed. Key indices included VO2 peak and VE/VCO2 slope, also expressed as Z-scores according to current paediatric reference values. In the 103 tests with available BNP measurements within 3 months, associations between the biomarker and functional performance were evaluated. Each CPET was considered as a separate entity and association with outcomes – death, heart failure (transplant or death for heart failure) and ventricular arrhythmias,(sudden cardiac death, cardiac arrest, appropriate ICD shock and ventricular tachycardia) within 5 years from the exam was assessed with cox regression analysis. Results Mean age at first CPET was 12.1 ± 2.8 years and 162 patients (66%) were male. Aerobic capacity was mildly reduced (VO2 peak 32.03 ± 9.96 ml/Kg/min; VO2 peak Z-score −1.72 ± 2.25), whereas ventilatory efficiency was preserved (VE/VCO2 slope 30.8 ± 5.1; Z-score 0.12 ± 1.18). VO2 Z-score negatively correlated with maximal wall thickness (r = −0.29, p 0.001) and LVOT gradient (r = −0.22, p ≤ 0.001), suggesting a direct relationship between hypertrophy and functional limitation. Higher BNP levels were associated with lower VO2 Z score (r= -0.29, p = 0.002) and higher VE/VCO2 slope (r = 0.27, p = 0.005), indicating a link between wall stress, functional capacity and ventilatory inefficiency. The outcomes (listed in table 2) occurred at a mean of 1.7 ± 1.3 years from the CPET during a mean follow up of 4.5±2.96 years. A one-unit reduction in VO2 peak Z-score was associated with an increase in 5-year risk of death (HR: 0.70, CI 95%: 0.64-0.97, p =0.02), heart failure (HR 0.68, CI 95%: 0.61-0.77, p 0.001), and ventricular arrhythmias (HR: 0.84, CI 95% 0.75-0.94, p=0.001). Conclusions This study demonstrates that functional capacity is often reduced in paediatric patients with HCM and that VO2 Z-score is an independent prognostic marker associated with adverse clinical outcomes, more severe phenotype and elevated BNP. The findings highlight the important role of CPET in the comprehensive functional evaluation and optimisation of clinical monitoring in children and adolescents with HCM.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.