Prognostic significance of right ventricular hypertrophy and systolic function in Anderson-Fabry disease

Abstract

Aims: Right ventricular hypertrophy (RVH) is a common finding in Anderson-Fabry disease (AFD), but the prognostic role of right ventricular (RV) involvement has never been assessed. The aim of our study was to evaluate the prognostic significance of RVH and RV systolic function in AFD.

Methods and results: Forty-five AFD patients (56% male patients) with extensive baseline evaluation, including assessment of RVH and RV systolic function, were followed-up for an average of 51.2 ± 11.4 months. RV systolic function was assessed by standard and tissue Doppler echocardiography. Cardiovascular events were defined as new-onset atrial fibrillation (AF), sustained ventricular arrhythmias, heart failure, or pacemaker/implantable cardioverter defibrillator implantation; renal events were defined as progression to dialysis and/or renal transplantation or significant worsening of glomerular filtration rate; and cerebrovascular events were defined as transient ischaemic attack or stroke. Fourteen patients (31.1%) presented RVH, while RV systolic function was normal in all cases. During the follow-up period, 13 patients (28.8%, 11 male) experienced 18 major events, including two deaths. Cardiovascular events occurred in eight patients (17.7%). The most common event was pacemaker/implantable cardioverter defibrillator implantation (six patients, 13.3%), followed by AF (three cases, 6.6%). Only one case of worsening New York Heart Association class (from II to III and IV) was observed. Ischaemic stroke occurred in three cases (6.6%). Renal events were recorded in three patients (6.6%). At univariate analysis, several variables were associated with the occurrence of events, including RVH (HR: 7.09, 95% CI: 2.17 to 23.14, P = 0.001) and indexes of RV systolic function (tricuspid annular plane systolic excursion HR: 0.77, 95% CI: 0.62 to 0.96, P = 0.02; and RV tissue Doppler systolic velocity HR: 0.76, 95% CI: 0.61 to 0.93, P = 0.01). At multivariate analysis, proteinuria (HR:8.3, 95% CI: 2.88 to 23.87, P < 0.001) and left ventricular mass index (HR: 1.02, 95% CI: 1.00 to 1.03, P = 0.03) emerged as the only independent predictors of outcome.

Conclusions: RVH and RV systolic function show significant association with clinical events in AFD, but only proteinuria and left ventricular mass index emerged as independent predictors of outcome. Our findings suggest that RV involvement does not influence prognosis in AFD and confirm that renal involvement and left ventricular hypertrophy are the main determinant of major cardiac and non-cardiac events.

Keywords: Anderson-Fabry disease; Prognosis; RV systolic function; RVH.

Figure 1

Example of a patient experiencing a major event (complete heart block requiring pacemaker implantation). (A) Parasternal long‐axis view; left ventricular hypertrophy is evident, with a maximun septal thickness of 26 mm (red line). (B) Four‐chamber view; biventricular hypertrophy is clear, with a right ventricular free wall thickness of 10 mm (purple line). (V) Tissue Doppler interrogation of the right ventricle, with normal S values (9.5 cm/s). (D) Twelve‐lead electrocardiogram (ECG), performed the same day of the echocardiogram. The ECG shows sinus rythm with heart rate 65 bpm, normal PR interval (187 ms), delayed intraventricular conduction, and LVH with repolarization abnormalities. (E) Twelve‐lead ECG recorded when the patient presented to the emergency room for dizziness, 30 months after the initial evaluation, showing complete heart block with heart rate of 24 bpm.

Figure 2

(A) Kaplan–Meier event‐free survival curves for occurrence of major adverse clinical events in patients with (red) and without (blue) left ventricular hypertrophy. (B) Kaplan–Meier event‐free survival curves for occurrence of major adverse clinical events in patients with (red) and without (blue) high proteinuria levels.