P1245In a prospective randomized study in familial hypertrophic cardiomyopathy, metoprolol maintains exercise-performance, with lower myocardial oxygen-cost, and prevents deterioration in exercise-ability
Authors: Ostman-Smith I , Bratt E.-L , Allahyari P , Petersson M 
Published: October 2019

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is an inherited disorder with a prevalence of 0.2% in young adults, with a significant risk of sudden death. Another feature of the disease is progressive fibrosis causing late heart failure. International guidelines suggest beta-blocker therapy for symptomatic patients, but that symptom-free patients need not be treated. Cohort studies on pediatric HCM-patients have suggested that beta-blocker therapy has a dose-related protective effect on the risk for sudden death, suggesting prophylactic beta-blocker therapy might benefit symptom-free patients.

Purpose
As prophylactic beta-blocker therapy is presumed to have a negative effect on exercise-ability, we assessed the effect of selective beta-blocker therapy on exercise hemodynamics and exercise performance in asymptomatic HCM patients.

Methods
Previously un-diagnosed cases of HCM were identified by family screening; those without symptoms and risk-factors were randomized to either life-style advice only (Obs-group; n=15), or to advice plus metoprolol therapy (Bbl-group; n=12). Patients performed bicycle ergometer testing before randomization, and yearly during follow-up. Performance in Watt was related to predicted normal for age, body size and sex; heart rate and blood pressure was recorded every minute during exercise terminated by patient tolerance.

Results
Median age was 18 [IQR 14–26]yrs, with a median follow-up of 6.0 [2.0–8.0]yrs. In the Obs-group the exercise-ability had deteriorated after two years (median 80% predicted vs. initial 88%, p=0.021), and remained lower at last follow-up, 78% (p=0.0017). Patients in the Bbl-group received a median final dose of 325mg metoprolol/day, corresponding to 3.8 [3.5–4.3]mg/kg, and had a reduction in maximal heart rate, 134 vs. 182 bpm (p=0.ehz748.02033], and systolic blood pressure 164 vs. 182 mmHg (p=0.0077), at maximal work load compared to Obs-group. In spite of reduction in maximal heart rate there was no reduction in maximal work capacity in Bbl-group (p=0.33 two year, p=0.50 last follow-up), with within patient change 2% of predicted [−3 to +5]% vs. −6% [−14 to −3]% in Obs-group (p=0.0039). Last visit work capacity was 180 [170–190]Watt in Obs-group and 205 [185–210]Watt in Bbl-group (p=0.015). Rate-pressure product (RPP) was 29% lower, and Watt/RPP was improved by 42% in Bbl-group compared to Obs-group (0.0084 vs. 0.0059; p=0.ehz748.02032).

Conclusions
Untreated patients with asymptomatic HCM show a slow deterioration in exercise-ability over follow-up, whereas patients treated with metoprolol do not decrease exercise performance compared with pre-treatment values, and do not deteriorate on medium-term follow-up. As myocardial oxygen consumption is linearly related to RPP, Bbl-group achieves a good exercise performance with substantially lower myocardial oxygen consumption than the Obs-group, which may have relevance for subendocardial ischaemia on exercise and future development of myocardial fibrosis.

Acknowledgement/Funding
Swedish Heart-Lung Fundation grant nr 20080510, Gothenburg University ALF grant nr ALFgbg-544981