Relationship between six-minute walk distance and cardiopulmonary exercise testing in non-obstructive hypertrophic cardiomyopathy

Abstract Background Recent studies have shown the promise of new approaches to the management of hypertrophic cardiomyopathy (HCM) symptoms. However, as HCM is a chronic disorder that evolves slowly over decades with low annual event rates, therapeutic trials in the disease rely on surrogate measures of disease severity and progression rather than hard endpoints such as mortality. Exercise capacity is one potential surrogate endpoint. Purpose To examine the relationship between peak oxygen uptake (VO2) and six-minute walk test distance (6MWD) in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) and describe the association with clinical parameters and quality of life. Methods We examined baseline data from patients with nHCM enrolled in a randomised placebo-controlled trial of trimetazidine therapy. The study was conducted in a single European centre. Cardiopulmonary exercise testing (CPET) was performed to assess peak oxygen consumption (pVO2), ventilatory anaerobic threshold (VAT) and ventilatory equivalent for carbon dioxide (minute ventilation to carbon dioxide production (VEVCO2). Health related quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). ECG and echocardiography were performed on the same day and biomarkers (NT-proBNP and cardiac Troponin T, cTnT) were measured prior to exercise testing. Results In 51 patients (age 50 ± 13 years; 71% male) with nHCM, pVO2 ranged from 10 to 24.3 ml/kg/min and 6MWD from 188 to 650 metres. 6MWD correlated with peak VO2 (Pearson r=0.41, 95% CI 0.15 to 0.67, p=0.003) and anaerobic threshold (r=0.32, 95%CI 0.04 to 0.55, p=0.024). After adjusting for age and sex, NT-proBNP concentration correlated with peak VO2 (radi=-0.35, 95% CI -0.69 to -0.01, p=0.042) but not 6MWD (radj=-0.05, 95% CI -0.42 to 0.32, p=0.779). Health related quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) correlated moderately with 6MWD (radi=-0.54, 95% CI -0.79 to -0.29, p<0.001) but weakly with peak VO2 (radi 0.28, 95% CI -0.55 to -0.01, p=0.042). I Conclusions There is a modest correlation between peak VO2 and 6MWD in nHCM. The pVO2 correlates more strongly with NT-proBNP whereas 6MWD better reflects quality of life. These data suggest pVO2 and 6MWD provide complementary information about health status in nHCM.Relationship between 6MWD and CPETCharacteristics of study cohort