Background:
Mavacamten, a selective cardiac myosin inhibitor, plays an increasingly important role in the treatment of hypertrophic obstructive cardiomyopathy (HOCM). We analyzed electrocardiographic (ECG) changes before and after initiation of mavacamten therapy and up to a 12-month follow-up to explore the potential of the ECG as a tool to monitor therapy response and potential proarrhythmic effects in the context of treatment with mavacamten.
Methods:
This single-center retrospective study included consecutive HOCM patients treated with mavacamten due to symptomatic left ventricular outflow tract obstruction. A total of 45 patients were screened, 5 patients were excluded after premature discontinuation of the drug. Of the remaining 40 patients (32% female, 68% male; mean age 59 ± 12 years), the mean time from first diagnosis to treatment initiation was 3.3 years. 95% were initially treated with 5 mg Mavacamten, and 5% received 2.5 mg as the starting dose. During mavacamten treatment, 75% had concomitant beta-blocker therapy and 25% received calcium channel blockers. At 3, 6, and 12 months, clinical, serological, echocardiographic, and ECG parameters were analyzed.
Results:
A significant improvement in New York Heart Association (NYHA) functional class was observed under mavacamten, decreasing from a mean of 1.88 ± 0.49 at baseline to 1.37 ± 0.51, 1.20 ± 0.41, and 1.08 ± 0.28 at 3, 6, and 12 months, respectively (p < 0.0001 for all follow-ups). N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels declined significantly from baseline (810 ± 740 pg/mL) to month 3 (502 ± 665 pg/mL; p = 0.0241) and month 6 (236 ± 276 pg/mL; p = 0.0003). Echocardiography demonstrated a significant reduction of the resting LVOT gradient compared to baseline (44 ± 30 mmHg) at month 3 (20 ± 32 mmHg; p = 0.0073), with further reduction at 6 months (11 ± 8 mmHg; p < 0.0001) and 12 months (10 ± 8 mmHg; p = 0.0002). The LVOT gradient under the Valsalva maneuver also showed a significant reduction from baseline (baseline (108 ± 49 mmHg) to 3, 6, and 12 months (53 ± 40, 24 ± 20, and 15 ± 16 mmHg, p < 0.0001 in comparison to baseline for all). On ECG, the Sokolow–Lyon Index decreased and reached significance at 6 months (2.47 ± 0.76 mV; p = 0.002) and 12 months (2.00 ± 0.98 mV; p = 0.004) compared to baseline (3.22 ± 1.1 mV). The reduction in Sokolow–Lyon Index showed good predictive accuracy for NT-proBNP normalization to <50 ng/mL (area under the curve [AUC] = 0.686). Also in univariate regression analysis, the reduction of the Sokolow–Lyon Index after 6 months was a significant predictor of NT-proBNP improvement (p = 0.035). Furthermore, a negative Sokolow–Lyon Index (<3.5 mV) at 6 months correlated with LVOT gradient reduction under Valsalva (AUC = 0.65). Under mavacamten therapy, PQ, QT, and QTc intervals remained stable and comparable to baseline throughout all follow-up visits.
Conclusion:
In patients with HOCM, significant decreases in NT-proBNP and LVOT gradients after initiation of mavacamten correlate with a significant reduction of the Sokolow-Lyon Index in the 12-lead resting ECG. Mavacamten was not associated with proarrythmic ECG changes such as PQ, QT, and QTc intervals.
