Increased mechanical dispersion during exercise echocardiography is associated with incomplete response to mavacamten in obstructive hypertrophic cardiomyopathy

Background

Mavacamten effectively reduces left ventricular outflow tract (LVOT) obstruction in patients (pts) with obstructive hypertrophic cardiomyopathy (HOCM). However, determinants of hemodynamic response remain incompletely understood, and data integrating exercise echocardiography and myocardial mechanics are limited.

Purpose

To assess serial echocardiographic changes at rest and during exercise in pts with HOCM treated with mavacamten.

Methods

We prospectively evaluated 18 consecutive pts with HOCM treated with mavacamten in a single tertiary referral centre. Comprehensive transthoracic echocardiography was performed at baseline and after 6 months, both at rest and during exercise. LVOT gradients, LVEF, LV GLS and mechanical dispersion, LA strain (reservoir, conduit, contraction), LA volumes (LAV max, LAV min, LAV preP), LA emptying fraction (total, passive, active), LA coupling index (LAVi max/septal a`), LA stiffness index (Septal E/e`/reservoir strain) were assessed.

All pts were treated with mavacamten at a maximum daily dose of 5 mg. Incomplete responders were defined as pts with persistent LVOT gradient above 50 mmHg at 6 months, assessed at rest, during Valsalva manoeuvre, at peak exercise or post-exercise.

Results

The pts included in our study had a mean age of 62.5 ± 12.6 years, equal sex distribution, and HF symptoms (72% were NYHA II and 28% NYHA III at baseline). Beta-blocker monotherapy was used in 89% of pts, and 33% had a history of atrial fibrillation.

At 6 months, mavacamten therapy resulted in a marked reduction in LVOT gradient both at rest (median [IQR]: 100 [82–130] to 15 [10–72] mmHg, p = 0.002) and during exercise (105 [75–150] to 45 [10–75] mmHg, p = 0.006).

At rest, significant improvements were observed in LV mechanical dispersion (95 [84–132] to 69 [53–88] ms, p < 0.001), LACI (p = 0.003), maximal LAVi (p = 0.012), minimal LAVi (p = 0.044), mean E/e′ (p = 0.005) and tricuspid regurgitation pressure gradient (p = 0.026).

During exercise, further favourable changes were noted in minimal LAVi (p = 0.046) and LASI (p = 0.021).

No significant changes were observed between baseline and 6 months in LVEF, LV GLS, LA strain (reservoir, conduit and contraction), or total, passive and active LA emptying fractions, both at rest and during exercise.

Overall, 6 of 18 pts were classified as incomplete responders. Baseline LV mechanical dispersion during exercise was significantly higher in incomplete responders compared with complete responders (75 (74-79) vs 62 (52-71), p = 0.01), whereas dispersion at rest showed only a non-significant trend (p = 0.07).

Conclusion

Mavacamten induces significant haemodynamic and structural improvement at rest and during exercise in HOCM. Exercise-induced LV mechanical heterogeneity is associated with incomplete LVOT gradient reduction and may help identify pts less likely to achieve optimal response. Stress echocardiography provides incremental insight beyond resting evaluation.For image description, please refer to the figure legend and surrounding text.