Changes of non-invasive myocardial work parameters under mavacamten therapy

Background:  Symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM) can meanwhile be treated with mavacamten, a direct myosin inhibitor which received a Class IIa recommendation in the European Society of Cardiology (ESC) guidelines. It reduces excessive contractility by modulating the interaction between actin and myosin filaments in the heart muscle. Hyperdynamic contraction and obstruction of the left ventricular outflow tract (LVOT) leads to high myocardial work in oHCM patients. Non-invasive myocardial work indices, which are derived from echocardiographic strain measurements combined with blood pressure, offer a way to monitor left ventricular performance. The aim of our study was to analyse the hemodynamic changes in patients who underwent the mavacamten initiating phase.

Methods: 36 mavacamten patients from our ongoing prospective single-centre hypertrophic cardiomyopathy registry were included in this study. Blood pressure and standard echocardiographic 2-, 3- and 4-chamber views were recorded at baseline and at 3-months follow up to perform strain analysis and assess myocardial work with the vendor-specific algorithm of GE HealthCare (Pewaukee, WI). 

Results: 36 oHCM patients initiated on mavacamten therapy were analysed. Median age was 59.3 (SD ± 13.47) years, 47.2 % (n = 17) were female. CYP2C19 metabolic status was normal in all patients and therefore starting dose was 5 mg per day. Left ventricular ejection fraction decreased mildly reaching statistic significance from 66 (SD ± 6.2) % to 63.6 (SD ± 6) % (p = 0.02), whereas global longitudinal strain (GLS) did not change significantly from -15.2 (SD ± 3.79) % to 15.3 (SD ± 2.72) % (p = 0.74). The LVOT gradient at rest decreased highly significant from 71.1 (SD ± 38,92) mmHg to 26.1 (SD ± 30,6) mmHg (p < 0.001) as well as the provoked LVOT gradient, from 104.9 (SD ± 35.78) mmHg to 54.6 (SD ± 40.26) mmHg (p < 0.001) and the work load index, median 2230.5 (IQR 1821.5 – 2504) mmHg% to 1558 (IQR 1363.75-1917.75) mmHg% (p = 0.001). Surprisingly, the global work efficiency stayed without significant alteration, median 89 (IQR 87-91,75) % to 90 (IQR 87,75-92,25) %. Additionally, myocardial contractility appears to become more synchronized throughout left ventricular systole, as indicated by a slight decrease in peak strain dispersion (PSD), from median 107 (IQR 75,25-146,5) msec to 91,5 (IQR 75,25-109,75) msec (p = 0,116).

Conclusion: Non-invasive myocardial work indices provide a quantitative approach to monitor mavacamten therapy. After three months therapy with mavacamten in oHCM patients these data show that besides LVOT gradient even the work load index decreases significantly. These indices can help optimize mavacamten dosage, providing a more personalized approach to managing hypertrophic cardiomyopathy. However, further investigation is needed to clarify the long-term effects of mavacamten on myocardial work an overall cardiac function.