Acylation-stimulating protein and heart failure progression in arrhythmogenic right ventricular cardiomyopathy.

Abstract

Our previous studies suggested that the complement system was critical in the prognosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). The acylation-stimulating protein (ASP), generated through the alternate complement pathway, was reported to regulate lipogenesis and triglyceride storage. This study aimed to investigate the role of ASP in predicting adverse cardiac events in an ARVC cohort. We enrolled 111 ARVC patients and 106 healthy volunteers, and measured their plasma ASP levels using enzyme-linked immunosorbent assays. Plasma ASP levels were significantly higher in the ARVC patients than in the healthy controls (2325.22±20.08 vs. 2189.75±15.55, P<0.001), with a similar trend observed in the myocardial explant assay. Spearman correlation analysis indicated plasma ASP level associated with cardiac structural (right ventricular internal dimension, P=0.006) and functional remodelling (left ventricular ejection fraction, P=0.002) in ARVC patients. The ARVC patients were followed up for an average of 17.79±1.09months. Heart failure-associated events (HFAEs) were defined as heart transplantation, on a cardiac transplant list, or death due to end-stage heart failure. Plasma ASP levels in patients with HFAEs were significantly higher than in those without clinical events (2486.03±26.70 vs. 2268.83±23.51, P<0.001) or those with malignant arrhythmic events (2486.03±26.70 vs. 2297.80±60.46, P=0.008). LASSO (least absolute shrinkage and selection operator) and multivariable Cox regression analyses showed the ASP level (HR=1.004, 95% CI [1.002,1.006], P=0.002) was an independent predictor for adverse HFAEs in ARVC patients. The spline-fitting procedure was applied to illustrate the HFAE-free probabilities at different time points. Our results suggest that plasma ASP may be a useful biomarker in prediction of adverse HF-associated events in ARVC patients.