Abstract
Background: Carriers of pathogenic DNA variants (G+) causing hypertrophic cardiomyopathy (HCM) can be identified by genetic testing. Several abnormalities have been brought forth as pre-clinical expressions of HCM, some of which can be identified by cardiovascular magnetic resonance (CMR). In this study, we assessed morphological differences between G+/left ventricular hypertrophy-negative (LVH-) subjects and healthy controls and examined whether CMR-derived variables are useful for the prediction of sarcomere gene variants.Methods: We studied 57 G+ subjects with a maximal wall thickness (MWT) < 13 mm, and compared them to 40 healthy controls matched for age and sex on a group level. Subjects underwent CMR including morphological, volumetric and function assessment. Logistic regression analysis was performed for the determination of predictive CMR characteristics, by which a scoring system for G+ status was constructed.Results: G+/LVH- subjects were subject to alterations in the myocardial architecture, resulting in a thinner posterior wall thickness (PWT), higher interventricular septal wall/PWT ratio and MWT/PWT ratio. Prominent hook-shaped configurations of the anterobasal segment were only observed in this group. A model consisting of the anterobasal hook, multiple myocardial crypts, right ventricular/left ventricular ratio, MWT/PWT ratio, and MWT/left ventricular mass ratio predicted G+ status with an area under the curve of 0.92 [0.87–0.97]. A score of ≥3 was present only in G+ subjects, identifying 56% of the G+/LVH- population.Conclusion: A score system incorporating CMR-derived variables correctly identified 56% of G+ subjects. Our results provide further insights into the wide phenotypic spectrum of G+/LVH- subjects and demonstrate the utility of several novel morphological features. If genetic testing for some reason cannot be performed, CMR and our purposed score system can be used to detect possible G+ carriers and to aid planning of the control intervals.
Highlights
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, which is caused by sarcomere gene variants in up to 60% of the cases [1]
CMR imaging was Abbreviations: anterior mitral valve leaflet (AMVL), Anterior mitral valve leaflet length; CMR, Cardiovascular Magnetic Resonance; extracellular volume (ECV), Extracellular volume; G+, Genotype positive; HCM, Hypertrophic cardiomyopathy; interventricular septum (IVS), Interventricular septum; left ventricular (LV), Left ventricle; left ventricular hypertrophy (LVH), Left ventricular hypertrophy; LV mass (LVM), Left ventricular mass; LVMi,n, Left ventricular mass indexed by body surface area and normalized by sex; maximal wall thickness (MWT), Maximal wall thickness; PWT, Posterior wall thickness; ROC, Receiver operator characteristic; right ventricular (RV), Right ventricle; SA, Short-axis
AMVL, Anterior mitral valve leaflet; CMR, cardiovascular magnetic resonance; ECV, Extracellular volume; G+, Genotype-positive; LV, Left ventricle; LVH, Left ventricular hypertrophy negative; LVMi,n, Left ventricular mass indexed by body surface area and normalized by sex; RV, Right ventricle. *Data available in 44/57 G+/LVH- subjects and in 40/40 healthy controls, respectively. †Data available in 21/57 G+/LVH- subjects and in 26/40 healthy controls, respectively. ‡Data available in 54/57 G+/LVH- subjects
Summary
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, which is caused by sarcomere gene variants in up to 60% of the cases [1]. Relatives of HCM patients are offered genetic testing, which enables identification of carriers of pathogenic DNA variants, even before manifestation of left ventricular hypertrophy (LVH). These genotype-positive (G+)/LVH- subjects are subject to routine cardiac evaluation to monitor phenotypic progression [1,2,3,4]. When genetic testing is refused by relatives of HCM patients or is impractical/impossible, genotype risk prediction from preclinical expressions of HCM may be useful In this present study, we assessed morphological and functional differences between a cohort of genotype-positive (G+)/LVH- subjects and healthy controls and examined whether CMR-derived variables are useful for the prediction of pathogenic DNA variants. We assessed morphological differences between G+/left ventricular hypertrophy-negative (LVH-) subjects and healthy controls and examined whether CMR-derived variables are useful for the prediction of sarcomere gene variants
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