Left atrial strain tracks abnormal ventricular mechanics in Fabry disease.

BACKGROUND

Fabry disease (FD) is an X linked lysosomal disorder with ventricular myocardial involvement that drives morbidity and mortality. Early diagnosis of cardiac involvement can be difficult. This study explored whether abnormal left atrial (LA) strain by cardiovascular magnetic resonance (CMR) may be an early sign of ventricular involvement in FD.

METHODS

A multicentre, multinational cohort of patients with FD was assembled with images centralised for core lab analysis. Adult patients with gene-positive FD and healthy volunteers (HV) underwent CMR. LA strain analyses included manually contouring the left atrium in end-diastole and end-systole to calculate LA volumes and ejection fraction, then semiautomatic analysis for LA reservoir strain.

RESULTS

There were n=214 patients with FD (mean age 45±15 years, 39% males) and n=76 HV (49±15 years, 53% males). CMR results in FD: left ventricular ejection fraction 73% (IQR=9), left ventricular mass index (LVMi) 89±39 g/m2, 99 (46%) had left ventricular hypertrophy (LVH), 36% had late gadolinium enhancement. In FD, LA strain correlated with LVMi (r=-0.52, p<0.01), left ventricular (LV) global longitudinal strain (GLS) (r=-0.61, p<0.01) and native myocardial T1 (r=0.34, p<0.01). FD had abnormal LA strain in overt disease (LVH positive) compared with HV (p<0.01). LVH-negative FD did not differ in LA strain compared with HV (p>0.5). FD with low T1+LVH negative did not differ in LA strain compared with normal T1/LVH-negative FD or HV (p>0.3).

CONCLUSIONS

LA strain is abnormal in FD with LVH (overt disease) and correlates with LVMi, native T1 and GLS. LA strain is normal in FD with early disease (LVH negative+low T1) and normal in FD with no myocardial disease (LVH negative+normal T1). These findings indicate that LA strain is a consequence of abnormal LV mechanics such as LVH and abnormal GLS, rather than isolated myocardial sphingolipid deposition.

TRIAL REGISTRATION NUMBER: NCT03199001.