Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. Mavacamten, the first-in-class drug approved by the FDA for the treatment of HCM, has shown efficacy in improving clinical symptoms. However, the impact of mavacamten on arrhythmic events remains inadequately explored. We previously reported an increase in atrial fibrillation risk in the weeks following mavacamten initiation and now seek to assess other arrhythmic events.
This retrospective study included patients with HCM treated with mavacamten at a multi-site tertiary referral center. To assess the impact of mavacamten on the frequency of arrhythmic events, data from Holter monitoring was assessed at three time points: baseline (at treatment initiation), an intermediate follow-up, and the most recent follow-up available. The frequencies of premature ventricular contractions (PVCs), supraventricular premature contractions (SVPCs), supraventricular tachycardia (SVT), and non-sustained ventricular tachycardia (NSVT) were recorded and corrected for the total duration of Holter monitoring. The rates of arrhythmic events at different time points were analyzed using the Wilcoxon signed-rank test. Statistical significance was set at p<0.05.
Eighteen patients were enrolled, 50% female, with median age 66.3 years (IQR 61.7-73 years). Median duration to intermediate follow-up was 3.7 months (IQR 0-7 months), while median duration to the most recent follow-up was 11.3 months (IQR 3-24 months). The number of SVT runs was higher during the intermediate and most recent follow-up periods compared to baseline (3 [0.12 – 6.3] and 1 [0 – 2.6] vs. 0.25 [0 – 3], respectively), however, these differences were not statistically significant (p = 0.753 and p = 0.645, respectively). Duration of SVT was significantly higher at the intermediate follow-up compared to baseline (10 [IQR 7-24] beats vs 1.5 [IQR 0-9] beats, p= 0.028). However, there was no significant difference in SVT duration between the most recent follow-up and baseline (4.5 [IQR 0-9.5] beats vs 1.5 [IQR 0-5.75] beats, p= 0.14). Rates of PVCs, SVPCs, and NSVT trended higher at intermediate follow-up but did not reach statistical significance. Conversely, at the most recent follow-up, the rates of all arrhythmic outcomes trended lower compared to baseline, but again lacked statistical significance.
The data indicates an initial rise in arrhythmic events upon starting mavacamten treatment, followed by a subsequent decline. Despite the small sample size, these findings provide important insights into potential patterns of response to the medication. Larger studies are necessary to confirm these observations and deepen our understanding of mavacamten's impact on arrhythmic events.