Ommen, Steven R.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Background: The assessment of pulmonary pressure is elementary in the management of patients with pulmonary hypertension. Presently, pulmonary artery systolic pressure (PASP) can be reliably estimated using non-invasive means, but mean pulmonary pressure (MPAP) cannot be derived. The aim of this study was to derive a formula to non-invasively predict MPAP from PASP. Methods: Invasive hemodynamic pressures at steady state were examined in 198 consecutive patients who underwent right heart catheterization in the Mayo Clinic (Rochester, MN). Simple regression techniques were used to determine the relationship between MPAP and PASP separately for derivation and validation samples. Bland-Altman analysis was performed to examine predicted vs. observed MPAP values. Results: Over a wide range of MPAP (10 to 80 mmHg), MPAP and SPAP were strongly related (r2=0.89, n=198). The relation of MPAP to PASP in the derivation sample (n=100; MPAP=0.6133*SPAP + 1.1; r2=0.90) was validated in the test sample with an r2 value of 0.91 for predicted versus observed MPAP (p=x). The relation of predicted vs. observed MPAP values was significant across different degrees of pressure elevation, as well as different etiologies of pulmonary hypertension. Conclusion: MPAP can be accurately predicted from SPAP over a wide pressure range and among different etiologies for pulmonary hypertension. This relation may help to define MPAP non-invasively and assist in the clinical management of patients with pulmonary hypertension.