Regional myocardial function at preclinical disease stage of hypertrophic cardiomyopathy in female gene variant carriers

Rahana Y Parbhudayal,Tjeerd Germans,Albert C Van Rossum,Patrick Clarysse,Jolanda Van Der Velden,Celine Seegers,Pierre Croisille

doi:10.1007/s10554-020-02156-1

Abstract

We recently showed more severe diastolic dysfunction at the time of myectomy in female compared to male patients with obstructive hypertrophic cardiomyopathy. Early recognition of aberrant cardiac contracility using cardiovascular magnetic resonance (CMR) imaging may identify women at risk of cardiac dysfunction. To define myocardial function at an early disease stage, we studied regional cardiac function using CMR imaging with tissue tagging in asymptomatic female gene variant carriers. CMR imaging with tissue tagging was done in 13 MYBPC3, 11 MYH7 and 6 TNNT2 gene carriers and 16 age-matched controls. Regional peak circumferential strain was derived from tissue tagging images of the basal and midventricular segments of the septum and lateral wall. Left ventricular wall thickness and global function were comparable between MYBPC3, MYH7, TNNT2 carriers and controls. MYH7 gene variant carriers showed a different strain pattern as compared to the other groups, with higher septal peak circumferential strain at the basal segments compared to the lateral wall, whereas MYBPC3, TNNT2 carriers and controls showed higher strain at the lateral wall compared to the septum. Only subtle gene-specific changes in strain pattern occur in the myocardium preceding development of cardiac hypertrophy. Overall, our study shows that there are no major contractile deficits in asymptomatic females carrying a pathogenic gene variant, which would justify the use of CMR imaging for earlier diagnosis.

Highlights

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with an autosomal dominant pattern of inheritance [1]
End-diastolic wall thickness of basal and midventricular segments of the septum and lateral wall were comparable between MYBPC3, MYH7 and TNNT2 groups and controls (Table 2)
Septal-to-lateral wall thickness (S/L) ratio of basal and midventricular segments of the septum and lateral wall were comparable between gene variant carrier groups and controls (Table 2)

Summary

Introduction

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with an autosomal dominant pattern of inheritance [1]. A subsequent study in a cohort of genotype-positive subjects referred for family screening indicated that correcting maximal wall thickness for body size and applying specific cut-off values improved the predictive accuracy for HCM-related events [6]. These recent studies indicate that females may be underrepresented in HCM patient studies because of the current HCM diagnostic criterium of ≥ 15 mm LV wall thickness (≥ 13 mm in case of first-degree family members) [2], which does not take into account body size [7]. The percentage of female patients in HCM patient cohort studies is on average 30–40% [8,9,10], which may be explained by lower disease penetrance, but could imply that cardiac dysfunction remains undetected, in particular in the female HCM patient group, using cardiac remodeling, i.e. hypertrophy, rather than cardiac dysfunction as diagnostic criterium

Methods

Results

Conclusion