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Aim: We sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM)., Methods: Well-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO 2 ); 2) VO 2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO 2 ) production slope; 5) VE/VCO 2 at AT (VE/VCO 2 _AT); 6) VE/VCO 2 nadir; 7) VE/VCO 2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (P ET CO 2 ) change during CPET., Results: Of 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO 2 intercept and P ET CO 2 change, whereas the differences between medical regimens were detected by differences in VE/VCO 2 nadir and VE/VCO 2 _AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO 2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14-0.79, 0.15-1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO 2 nadir., Conclusion: Ventilatory efficiency parameters outperform peak VO 2 in gauging therapy effects in patients with HCM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This review emphasizes the importance of cardiopulmonary exercise testing (CPET) in patients diagnosed with hypertrophic cardiomyopathy (HCM). In contrast to standard exercise testing and stress echoes, which are limited due to the ECG changes and wall motion abnormalities that characterize this condition, CPET allows for the assessment of the complex pathophysiology and severity of the disease, its mechanisms of functional limitation, and its risk stratification. It is useful tool to evaluate the risk for sudden cardiac death and select patients for cardiac resynchronization therapy (CRT), cardiac transplantation, or mechanical circulatory support, especially when symptomatology and functional status are uncertain. It may help in differentiating HCM from other forms of cardiac hypertrophy, such as athletes' heart. Finally, it is used to guide and monitor therapy as well as for exercise prescription. It may be considered every 2 years in clinically stable patients or every year in patients with worsening symptoms. Although performed only in specialized centers, CPET combined with echocardiography (i.e., CPET imaging) and invasive CPET are more informative and provide a better assessment of cardiac functional status, left ventricular outflow tract obstruction, and diastolic dysfunction during exercise in patients with HCM., Competing Interests: The authors declare no conflict of interest.