Early differences in regional myocardial deformation after mavacamten initiation for hypertrophic obstructive cardiomyopathy
F Loncaric, J F Fernandes, E K Lozo, A Reschner Planinc, D Milicic, I Planinc, M CikesAbstract
Background and introduction
Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by a hypercontractile ejection fraction but decreased global longitudinal deformation. Although mavacamten reduces left ventricular (LV) outflow tract obstruction within the first 4 weeks of treatment, improvement in global longitudinal strain (GLS) is noted only after 32 weeks (1). Notably, regional strain changes can be detected as early as 4 weeks after drug initiation - as previously demonstrated in a small cohort (2).
Purpose
The delayed impact of mavacamten on GLS may be due to averaging of regional changes in myocardial contractility that occur very early after drug initiation. We aim to expand our initial cohort and confirm findings of changes in regional strain 4 weeks after the start of mavacamten therapy.
Materials and methods
From 26 HOCM pts initiated on mavacamten at our centre, 4 were excluded due to image quality insufficient for strain analysis, 4 have not reached 4 weeks of follow-up (FUP) at time of analysis, and 1 was excluded due to a cardiac surgery procedure within 4 weeks after drug initiation. Echocardiographic assessment was performed at baseline and again at the 4-week FUP. Myocardial deformation was assessed using GE Echopac software. Apical (4-, 3-, and 2-chamber) views were used to obtain peak systolic deformation values for the apical, mid and basal regions. Deformation curves were exported as text files and used to generate average patient LV "bulls-eye" plots to aid in visualization of regional deformation changes (3).
Results
This analysis was performed on 17 patients (mean age 59 years, 47% female). All patients had increased myocardial thickness at the basal inferoseptum (22 ± 4 mm), with a resulting obstructive gradient at drug initiation (79±26 mmHg), reduced at 4-week FUP (43±23 mmHg). Figure 1 shows the average values of regional deformation at the initial visit and at 4-week FUP demonstrating differences in regional longitudinal strain (LS) with an improvement in the majority of LV segments, also seen in segments with most severe hypertrophy. Figure 2 visualises the interpatient differences in response to mavacamten, with an overall trend of improvement in regional strain, as seen in the mid anteroseptum (peak LS at initiation vs FUP – 10.3 vs -15.9%, p=0.041). Patient #9 showed no improvement in regional deformation, and in longer-term FUP is the only patient that has experienced a decrease of ejection fraction <50% resulting in heart failure (after 15 weeks of FUP).
Conclusions
The analysis of an expanded cohort reaffirms our previous results demonstrating a very early effect of mavacamten on regional deformation. While these changes likely predominantly reflect early changes in loading conditions and regional wall stress, they may also indicate myocardial response to an early drug effect. Further analysis is needed to determine patient characteristics related to regional improvement on mavacamten.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.