Cardiopulmonary Exercise Testing in Hypertrophic Cardiomyopathy: Refining a Proven Tool for Better Risk Prognostication

ypertrophic cardiomyopathy (HCM) is a common heritable cardiac condition, characterized by variable clinical expression/trajectory with a manifold constellation of clinical symptoms.The clinical profile of HCM ranges from an asymptomatic phenotype to debilitating functional intolerance, overt heart failure, stroke, intractable arrythmias, and in the worst clinical scenario, sudden cardiac death.Although many patients with HCM are asymptomatic and attain relatively normal life expectancy, 30% to 40% of patients exhibit symptoms. 1,2The pathophysiological mechanisms undergirding the wide spectrum of HCM symptoms is complex 3 (Figure ), posing challenges in risk stratification and prognostic ascertainment.In this sense, cardiopulmonary exercise testing (CPET), a valuable noninvasive diagnostic modality, provides an integrated assessment of cardiac, pulmonary, hemodynamic, musculoskeletal, and cellular oxidative pathways.CPET has traditionally been used to enhance risk stratification and prognostication in patients with HF but is increasingly being used and has an expanding role in HCM with endorsements by both the American and European consensus guidelines for the management of HCM. 4,5The most commonly used CPET metrics include peak O 2 uptake (pVO 2 ), minute ventilation (V E ) to CO 2 production (VCO 2 ) (V E /VCO 2 ) slope, and abnormal blood pressure response to exercise. See Article by Landsteiner et al.Landsteiner and colleagues must therefore be congratulated for their well-done systematic review and metaanalysis in this issue of the Journal of the American Heart Association (JAHA).They explore the usefulness of CPET variables in the risk assessment and prognostic ascertainment of adverse outcomes in HCM. 6he meta-analysis included a systematic search of eligible studies of CPET and HCM in databases through 2023 comprising 60 full-length articles and 12 914 patients (predominantly men; mean age, 48-50 years).The authors then assessed the primary end point of mortality, defined as all-cause mortality or sudden cardiac death, and the secondary end point that was a composite of cardiovascular-related adverse events.These composite outcomes included combinations of sudden cardiac death, heart failure hospitalization, appropriate implantable cardioverter-defibrillator therapy, stroke, and septal reduction therapy.Univariable Cox proportional hazards models were then used to assess the prognostic value of CPET-derived parameters