https://doi.org/10.1007/s00392-025-02737-x
1LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland
Introduction:
Hypertrophic obstructive cardiomyopathy (oHCM) is characterized by dynamic left ventricular (LV) outflow tract (LVOT) obstruction, diastolic dysfunction, and progressive atrial remodeling. While left atrial reservoir strain (LASr) has emerged as a marker of diastolic impairment, right atrial strain parameters in particular RA reservoir strain (RASr) remain poorly understood in oHCM. Mavacamten, a recently introduced cardiac myosin inhibitor, improves LVOT gradients and clinical parameters. Cardiac reverse remodeling was previously described in subset analysis. However, the impact of mavacamten on ventricular and bilateral atrial interdependence is so far underexplored.
Material and Methods:
43 patients (mean age 61.0±17.4 years, 51.2% male) under mavacamten were analyzed using a semiautomated echocardiography post-processing software (TOMTEC Arena TTA2, Germany). Longitudinal assessment included LASr, RASr, conduit (LAScd, RAScd), and contraction strain (LASct, RASct), body-surface area indexed LV-mass (BSI-LVmass), resting and peak LVOT gradients, and left ventricular global longitudinal strain (LV-GLS) at baseline (BL), 4-weeks and 8-weeks, and last follow-up (FU) together with clinical parameters such as Kansas-City-Cardiomyopathy-12 questionnaires (KCCQ-12). Since LASct and RASct evaluates atrial contraction, 7 patients were excluded from analysis due to permanent atrial fibrillation. 2 and 3 patients discontinued mavacamten during FU and were excluded from 8-week and last-FU analyses, respectively.
Results:
Median FU was 39 weeks (IQR: 9 weeks). Strain analysis indicated a mean LASr of 19.8±5.0%, LAScd of -10.5±5.6% and LASct of -10.0±5.4% at BL. LASr showed a significant increase at 4-weeks, 8-weeks and last-FU with a mean difference of 1.7±4.6% (95% CI:0.2–3.2, p=0.0249), 1.95±4.91% (95% CI:0.4-3.6, p=0.0176) and 3.4±3.7% (95%CI:2.2–4.6, p<0.0001), respectively. LAScd significantly improved comparing BL and last-FU with a mean change of -3.4±5.4% (95% CI:-4.0 to -0.5, p=0.015); changes in LASct did not reach statistical significance. Mean RASr, RAScd and RASct at BL were 22.8±7.1%, -13.0±5.6%, and -10.0±6.2%, respectively. RASr and RAScd showed a non-linear progression and improved significantly, with a mean change of 2.2±4.1% (95% CI:0.8-3.5, p=0.0027) and -2.3± 6.4% (95% CI:-4.5 to -0.4, p=0.0242) at 4-weeks, while not reaching significance at 8-weeks. At last-FU, RASr showed a significant change of 4.4±4.6%, 95%CI:2.8 to 5.9, p<0.0001) while RAScd and RASct remained non-significant. Alongside with changes in atrial strain parameters significant changes in BSI-LVmass were observed. Mean values declined from 129.9±42.5g/m2 at BL to 116.9±27.3g/m2 at 4-weeks, 110.2±31.5g/m2 at 8-weeks, and 99.9 ± 24.7 g/m2 during last-FU, indicating a mean change of -31.5±39.0g/m (95% CI:-46.3-16.7, p=0.0002) from BL to last-FU. Notably, BSI-LVmass demonstrated an inverse correlation with LASr both at BL (R2=-0.38, p=0.023) and last-FU (R2=-0.39, p=0.025). Interestingly, RASr values ≥21.9% at BL predicted relevant clinical response (improvement of KCCQ-12 score >10 points (AUC=0.63)). Resting and peak LVOT gradients significantly and consistently decreased. Mean LVEF and LV-GLS remained unchanged during FU.
Conclusion:
Mavacamten significantly improves bilateral atrial strain and reduces LV-mass. Potential impact of atrial strain on the clinical outcome needs further investigation in larger cohorts.