Predictors of death, heart transplantation and relapse in clinically suspected and biopsy-proven myocarditis in the pre-immunosuppression era. (25th November 2020) - Baritussio, A
Abstract: Background: Myocarditis is an infectious or autoimmune inflammatory disease of the myocardium; diagnosis relies on the exclusion of an acute coronary syndrome, and is confirmed by endomyocardial biopsy (EMB). Prognosis is highly variable, outcome predictors are not well defined. Purpose: To identify clinical, imaging and immunological predictors of death, heart transplantation (HTx) and relapse in patients with myocarditis in the pre-immunosuppression era. Methods: From 1993 to 2012 we consecutively enrolled 466 patients (68% male, mean age 37±17 years), 216 with clinically suspected and 250 with EMB-proven myocarditis. All patients underwent coronary angiogram and transthoracic echocardiogram, 44% of patients underwent cardiac magnetic resonance (CMR). Circulating auto-antibodies were measured in patients' sera by indirect immunofluorescence. All patients were prospectively followed-up at the local Cardio-immunology outpatient clinic. Results: After a median follow-up of 50 months (IQR 25–75), 366 patients (79%) were alive, while 42 (9%) were dead or underwent HTx; 58 were lost to follow-up. Ten-year survival free from death or HTx was overall 83%, but was lower in patients with EMB-proven myocarditis (76% vs 94% in patients with clinically suspected myocarditis, p<0.001). On univariate analysis, predictors of death and HTx were female gender (p=0.003), previous myocarditis (p=0.03), heart failure on presentation and advanced NYHA class (p<0.001, respectively), histological diagnosis of giant-cell myocarditis (p=0.002), positivity for anti-heart antibodies (AHA, p=0.04), anti-cardiac endothelial cell (AECA, p=0.002) and anti-nucleus antibodies (ANA, p=0.003). On multivariate analysis, female gender (HR 2.69, p=0.02), lower left ventricular ejection fraction on echocardiogram (p<0.001), positivity for high-titre organ-specific AHA (HR 4.1, p=0.02) and for ANA (HR 5.1, p<0.001) were independent predictors of death and HTx. Seventy-seven patients had relapsing myocarditis; on univariate analysis, young age (p<0.001), previous myocarditis (p<0.001), symptoms preceding diagnosis (p=0.004), positivity for anti-intercalated disk autoantibody (AIDA, p=0.02), and presence of diffuse late gadolinium enhancement (LGE) on CMR (p<0.001) were predictors of relapse. On multivariate analysis young age (p=0.02) and previous myocarditis (HR 8.4, p<0.001) were independent predictors of relapse. Predictors of death, HTx and relapse, respectively, did not differ when considering separately patients with EMB-proven myocarditis and those with clinically suspected myocarditis. Conclusions: In the pre-immunosuppressive era, young age and a previous episode of myocarditis were independent predictors of relapse, female gender, left ventricular dysfunction at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features in myocarditis predict worse prognosis. Funding Acknowledgement: Type of funding source: None