No increase in arrhythmia burden following aficamten treatment in obstructive hypertrophic cardiomyopathy: extended ambulatory electrocardiogram analysis from FOREST-HCM
E Rowin, A Masri, R Barriales-Villa, R M Cooper, P M Elliott, M E Nassif, A T Owens, S Saberi, S D Solomon, A Tower-Rader, J Godown, D Jacoby, J Wei, M S Maron, A OreziakAbstract
Background
Aficamten is a next-in-class cardiac myosin inhibitor that improves left ventricular outflow obstruction, exercise capacity, and symptoms in obstructive HCM (oHCM). The impact of aficamten on subclinical arrhythmia burden is unknown and of high importance given the frequency of atrial fibrillation (AF) and non-sustained ventricular tachycardia (NSVT) in oHCM.
Purpose
Assess the frequency of subclinical AF, NSVT and high-risk NSVT before and after aficamten treatment as detected by ambulatory electrocardiogram (ECG) monitoring.
Methods
Patients with oHCM enrolled in the open-label extension FOREST-HCM underwent 4–7 day ambulatory ECG at screening and at Weeks 48 and 96 of aficamten treatment. Occurrences of subclinical AF (asymptomatic AF lasting ≥30 seconds), NSVT, and high-risk NSVT (≥8 beats, >200 bpm, or ≥2 runs in 48 h) were compared from screening to 48 and 96 weeks. A subgroup analysis of patients who underwent withdrawal of beta-blocker therapy was performed.
Results
In all, 122 patients with ≥24 h of interpretable ambulatory ECG data at screening and Weeks 48 and 96 were included (mean age 60.2 ± 13 years; 19% with prior implantable cardioverter defibrillator placement). Total ambulatory ECG monitoring duration was 1895 days; mean duration 5.2 days per monitor per patient. Rates of AF were low (2.5%) and there was no increase in AF episodes at Weeks 48 (0.8%, P=0.15) or 96 (1.7%, P=0.57) after aficamten initiation, and with all episodes occurring in patients with prior clinical AF or history of AF. There were no newly identified subclinical AF episodes at any time point during monitoring. NSVT was present at screening in 41 (33.6%) patients, with a median of 0.4 runs/day (interquartile range 0.2–1.2), mean duration 5.2 beats, fastest run with median rate of 143 bpm, and 21 (17.2%) patients had high-risk NSVT. After aficamten initiation, there was no significant difference in the proportion of patients with NSVT detected at Weeks 48 (32%, P=0.72) or 96 (39%, P=0.28) vs screening. At Weeks 48 vs 96, number of runs/day (0.6 and 0.3), average duration (6.6 and 5.3 beats), median fastest speed (152 and 145 bpm), and proportion of patients with high-risk NSVT (19.7% each) was no different vs screening (Table 1, all P=NS). In all, 16 patients from the overall cohort underwent withdrawal of beta-blocker therapy during aficamten treatment. Pre-withdrawal, 7 (43.8%) had NSVT; this proportion was unchanged following withdrawal of beta-blockers (7 [43.8%], P=NS).
Conclusion
In FOREST-HCM, the incidence of arrhythmias on ambulatory ECG monitoring was stable over time in patients with oHCM after 96 weeks of aficamten treatment compared with baseline, and without an increase in frequency after beta-blocker withdrawal. These data are consistent with the previously reported low incidence of clinically detected arrhythmias for patients with oHCM treated with aficamten.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.