THE INFLUENCE OF GENOTYPE ON THE CARDIOPULMONARY TEST RESPONSE IN PATIENTS AFFECTED BY HYPERTROPHIC CARDIOMYOPATHY

In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. However, there is limited data on how these genetic variants affect cardiopulmonary exercise test (CPET) performance in HCM patients. In our study, we analysed asymptomatic and slightly symptomatic HCM patients (NYHA I-II) who had both genetic analysis and CPET results available. At baseline, all participants had normal left ventricular function and severe left ventricular outflow trait obstruction was excluded. Out of 120 HCM patients, we excluded 13 who carried variants of uncertain significance; Among the remaining 107 patients, 54 were genotype negative [gene (−)], and 53 had a P/LP variant in sarcomeric genes [gene (+)]. The two groups had similar NYHA class, cardiovascular risk factors and echocardiographic characteristics. However, gene (+) patients demostrated a lower peak VO2% and O2 pulse % (p < 0.05). Additionally, among the gene (+), those with P/LP variants in the so called “thin-filament” genes (TNNT2, TPM1 and MYL3) exhibited the poorest CPET performance. Thus, in asymptomatic or slightly symptomatic HCM patients with similar echocardiographic features, exercise tolerance is influenced by their genetic background. Specifically, gene (+) patients have reduced exercise capacity compared to gene (−) patients, and those with P/LP variants in “thin-filament” genes experience the worst performance during exercise testing.