Abstract 4844: Serum Organ-Specific Anti-Heart Autoantibodies in Arrhythmogenic Right Ventricular Cardiomyopathy Patients and Relatives: Evidence for Autoimmune Involvement in a Genetically-Determined Myocarditis
Objective: Serum anti-heart autoantibodies (AHA) are organ and disease-specific autoimmune markers in myocarditis, dilated cardiomyopathy (DCM), and their relatives. Myocarditis is frequently reported in arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unknown whether it relates to immune-mediated damage.
Methods: We assessed serum AHA in 27 ARVC patients (pts), (15 male, aged 41±12 years, symptom duration prior to diagnosis 32±41 months, range 1–141), 22 affected relatives (AR) (16 male, aged 29±13 years) and 26 asymptomatic apparently healthy relatives (HR) (14 male, aged 33±16 years). ARVC pts and AR met the 1994 ESC/ISFC Task force diagnostic criteria: 2 major in 47%, 1 major and 2 minor in 51%, 4 minor in 2%; 22% of pts and AR were in NYHA class II, 6% in class III/IV, 22% had chest pain with angiographically normal coronary arteries, 59% palpitation, 51% syncope, 24% left ventricular involvement, 80% familial disease confirmed at necropsy/surgery, and 43% typical ARVC on endomyocardial biopsy. An ICD was implanted in 20%, 2 pts were transplanted. AHA were detected by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical diagnosis. AHA of the organ-specific type reacted with myocardium, but were unreactive with skeletal muscle. Control groups for AHA included sera from patients with non-inflammatory cardiac disease (NICD)(n=160, 80 male, aged 37±17), with ischemic heart failure (n=141, 131 male, age 51±12) and normal blood donors (n=270, 123 male, aged 35±11). Antibody frequencies in ARVC vs controls and clinical/diagnostic features in AHA positive vs negative pts were compared by ANOVA.
Results: The frequency of organ-specific AHA was higher (48%) in ARVC pts, AR (41%) and HR (35%) than in NICD (1%), ischemic heart failure (1%) or normal subjects (2.5%)(p=0.0001). Positive AHA status in pts was associated with palpitation (p=0.03), smaller left ventricular enddiastolic volume (p=0.02) and nonsignificantly with chest pain (p=0.07).
Conclusion: The finding of AHA supports the involvement of autoimmunity in about half of ARVC pts and one third of their HR, similar to DCM. AHA may be markers of genetically-determined immune-mediated myocarditis in ARVC.