The effect of mavacamten on electrical parameters in cardiac implantable electronic devices

Background

Mavacamten is a first-in-class cardiac myosin inhibitor that reduces left ventricular outflow obstruction and causes left ventricular re-modelling in hypertrophic cardiomyopathy (HCM) (1). Many HCM patients have implantable-cardioverter defibrillators (ICD) for prevention of sudden cardiac death or pacemakers for their haemodynamic benefits. It is plausible that left ventricular (LV) re-modelling related to mavacamten could affect cardiac implanted electronic device (CIED) parameters but these effects have not yet been characterized.

Purpose

To describe changes seen in CIED lead parameters after initiation and maintenance of mavacamten.

Methods

In this retrospective cohort study, patients on mavacamten with a CIED were identified at three hospitals using electronic records. Data was collected on baseline characteristics, mavacamten dosing and lead parameters before and after starting mavacamten. For the comparator arm, HCM patients with CIEDs not on mavacamten were analysed with lead parameters recorded over the same period, between January 2023 and November 2025.

Results

Ten patients across three sites had been initiated on mavacamten and had history of ICD implant. Patients on mavacamten with pre-existing transvenous ICDs (n=9) had mean age of 56 ± 13 (56% male) and median treatment duration 11 months (3 – 11). One subcutaneous ICD was excluded from analysis. Twenty-seven patients (25 ICD, 2 PPM) were included in the comparator arm with mean age 63 ± 11 (59% male). Full baseline characteristics are summarised in Fig. 1.

Following initiation of mavacamten, median absolute change in R wave sensing (mV) was -4.2 (IQR -5.60 to 0.00) vs. 0.0 (-0.25 to 0.10) in comparators (p=0.0096) (Fig. 2). A reduction ≥2 mV occurred more frequently with mavacamten (OR 25.0, 95% CI 3.4–184.5; p=0.0016. Median % change in R wave sensing was -17.4% (-36.8% to 0.0%) vs. 0.0% (-1.7 to 0.8%) in comparators (p=0.0319) with >10% reduction more common in patients on mavacamten (OR 11.5, 95% CI 2.0–65.9; p=0.0061).

There was a trend towards increasing RV threshold in the mavacamten group, with median % change of 20% (0.0% to 22.2%) compared to 0.0% (-11.3% to 18.2%) but the difference did not reach statistical significance (p=0.4949). There was no significant change in RV pacing impedance in either arm.

There were no clinical events, undersensing of intrinsic rhythm or arrhythmia in any patient during the study period.

Conclusion

Mavacamten use in HCM was associated with a significant reduction in R-wave sensing in transvenous CIEDs, without observed clinical undersensing during follow-up. This novel association is mechanistically plausible in the context of LV remodelling. Further prospective studies may help to identify potential safety implications for device monitoring and programming in patients treated with cardiac myosin inhibitors.Baseline CharacteristicsR wave sensing changes on mavacamten