Left Ventricular Strain and Progression of Hypertrophy in Danon Disease Cardiomyopathy: Insights from a Global Registry

Abstract

Danon Disease (DD) is a rare X-linked disorder due to mutations in the Lysosomal Associated Membrane Protein 2 (LAMP-2) gene. Patients present with cardiac manifestations of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The goal of this study is to characterize the longitudinal progression of hypertrophic phenotypes and descriptions of left ventricular strain in DD. We created an international registry including 44 adult and pediatric patients with DD. A retrospective review of pre-transplant echocardiographic data was performed. Medical records were supplied by the patients/families. Of 44 patients with DD, longitudinal echocardiographic data from 30 patients were available. Of these, 15 patients (50%) were male. Mean age of diagnosis of cardiomyopathy was younger in males compared to females (10.6 vs 28.3 yrs, p = 0.0004). Baseline echocardiograms demonstrated generally preserved ejection fraction on initial echocardiogram in both males and females (64.9% vs 60.8%, p=0.458). However, baseline measures of left ventricular wall thickness was abnormal; IVSDd thickness and LVPWd thickness were elevated in both males and females [12.73 vs 10.73 mm (p=0.364) and 11.14 vs 10.82 mm (p=0.871), respectively]. LV strain analysis was performed in 12 patients (50% male) during baseline evaluation. Abnormal strain patterns were present in 10 (83.3%) patients. Global LV strain was reduced (mean 11.8%). Severely reduced strain patterns predominantly affected basal ventricular segments (mean 8.5%) with relative apical sparing (mean 16.6%). Mean longitudinal follow up time with echocardiography was 5.4 yrs. On follow up, males demonstrated greater LV hypertrophy compared to females [IVSDd 19.34 vs 14.74 mm (p=0.27), LVPW thickness 18.3 vs 11.3 mm (p=0.047)]. Our data show DD affects males and females unequally. Males are more prone to develop severe HCM both earlier and more rapidly. Females exhibit variable presentation patterns with HCM or DCM, and disease course appears to be more protracted. Strain pattern in DD is similar to cardiac amyloid with overall reduction in global LV strain and relative apical sparing. Variability in presentation and lack of specific echocardiographic findings necessitates early clinical recognition and confirmatory genetic testing.