Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy

Abstract

Background: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM.

Methods: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point.

Results: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls.

Conclusions: Septal convexity is an additional previously undescribed feature of subclinical HCM.

Fig. 1

Measurement of septal convexity (SCx) in apical 4 chamber view: performed as the maximal distance (A to B) between the LV endocardial border (B) and the intersection point (A), perpendicularly to a reference line joining at mid-wall the level of tricuspid valve insertion (C) and the apical right ventricular insertion point into the LV (D) in a 49-year old G + LVH- male (a), and in a matched healthy control (b)

Fig. 2

Measurement of septal convexity in short axis: views at papillary muscle level as the distance (A to B) between septal LV endocardial border (B) and the perpendicular intersection point (A) of a reference line connecting the epicardial RV insertion points into LV (anteriorly: C, and inferiorly: D)

Fig. 3

a Mean SCx in G + LVH- compared to healthy controls. b SCx for each G + LVH- and corresponding matched healthy control

Fig. 4

ROC curves for the SCx. SCx ≥ 3.55 mm had optimal sensitivity and specificity to differentiate the two groups

Fig. 5

Bland-Altman analysis: intra- and interobserver variability of SCx measurements