Left ventricular apical aneurysm in Fabry disease: implications for clinical significance and risk stratification

Funding Acknowledgements Type of funding sources: None. Background More than 50% of patients with Fabry disease (FD) present with cardiac phenotype, and left ventricular hypertrophy (LVH) is the most frequent manifestation. Among FD patients with LVH, a rare and novel presentation of left ventricular apical aneurysm (LVAA) has been reported. Purpose This study aimed to investigate the clinical incidence of LVAA and its impacts on prognosis among FD patients. Methods We retrospectively analyzed 268 FD patients at a tertiary medical center between January 2003 to September 2020. Two patients with ischemic LVAA were excluded. LVH and LVAA were confirmed either by echocardiography (Figure 1A) or cardiovascular magnetic resonance imaging (Figure 1B). The primary endpoints were a composite of heart failure (HF) hospitalization, sustained ventricular tachycardia (VT), stroke, and death. Results Of 266 FD patients, there were 105 (39.5%) patients had LVH, and 11 (10.3%) of them had LVAAs (age 67.5 ± 9.5 years, 8 males [72.7%]). After a mean follow-up of 49.3 ± 34.8 months, 8 patients experienced primary endpoints, including 5 (45.5%) HF hospitalizations, 3 (27.3%) VT, 1 (9.1%) stroke, and 4 (36.4%) deaths. The risk for composite adverse events was significantly higher in patients with LVAA compared with those without (8 [72.7%] vs 17 [18.1%]), leading to significantly lower event-free survival in patients with LVAA (Log-Rank P < 0.001, Figure 2). The presence of LVAA was independently associated with an increased risk of composite adverse events (hazard ratio: 3.59; confidence interval: 1.30-9.91, P = 0.01) after adjusting for age, gender, advanced HF, renal function, dyslipidemia, atrial fibrillation, left ventricular ejection fraction of <40%, average E/e’, and LV mass index. Conclusions LVAA presents in around 10% of patients with Fabry cardiomyopathy and is strongly associated with an increased risk of adverse events. The identification of this phenotype would be useful to identify high-risk patients with Fabry cardiomyopathy, among whom more aggressive treatments may be considered. Abstract Figure. Apical aneurysm in Fabry cardiomyopathy Abstract Figure. KM curve of composite adverse events