Inflammation in endomyocardial biopsies correlates with improved cardiac recovery and correlates inversely with mortality in patients with non-ischemic heart failure with reduced ejection fraction

Abstract

Abstract Background Heart failure (HF) is a major cause of morbidity, mortality and healthcare costs worldwide. Although the overall mortality is high, individual outcomes show a large variability, reflecting our incomplete comprehension of the complex pathophysiology. Effective treatment requires rapid therapy initiation addressing the specific etiology. Purpose As reliable predictors of the outcome of HF remain ambiguous, we retrospectively analyzed patients with non-ischemic HF with reduced ejection fraction (HFrEF) to identify prognostic factors of myocardial recovery and mortality. Methods We included N = 305 consecutive patients from our MyBiopsy-HF study (DRKS #00022178)) who presented with non-ischemic, non-valvular HFrEF (Left ventricular ejection fraction LVEF ≤40%) as quantified by echocardiography and received a comprehensive medical workup including endomyocardial biopsy (EMB) at the time of initial diagnosis and follow-up echocardiography at 6 months. We defined HF with improved LVEF (HFimpEF) as LVEF>40% and ≥10% increase from initial LVEF. Myocardial inflammation was classified according to the current recommendations by the Dallas criteria or immunohistologic criteria (≥14 leucocytes/mm² with the presence of CD3 positive T-lymphocytes ≥7 cells/mm²). Viral persistence was quantified by qPCR from the EMB tissue. We obtained patients’ mortality data from the Rhineland-Palatinate mortality register. Results The presence of myocardial inflammation in the EMB at the time of initial diagnosis was a significant predictor of increased transition to HFimpEF (83 of 143 patients, 58,0% with inflammation vs 63 of 151 patients, 41,7% without inflammation, odds ratio (OR) 1,93, confidence interval (CI) = 1,20-3,09, p-value 0,006). Viral persistence did not differ significantly between groups. Also, female patients (55 of 91 patients, 60,4%) were more likely to transition to HFimpEF compared to male patients (94 of 214 patients, 43,9%, OR 2,27, 95% CI = 1,35-3,85, p-value 0,002). Transition to HFimpEF was associated with better survival: After five years, 71 of the 78 patients with HFimpEF were alive (91,0%) as compared to 68 of the 88 patients (77,3%) with persistent HFrEF (OR 2,58, CI = 1,08-6,20, p-value 0,03). Transition of HFimpEF was the lone age-adjusted significant predictor of five-year survival. All other factors (presentation with dyspnea, angina pectoris, palpitations, history of hypertension, diabetes, or hyperlipidemia, initial LVEF, heart failure medication and immunosupressive treatment) were not found to be of significance. Conclusion Presence of myocardial inflammation and female sex are predictors of increased recovery of cardiac systolic function as measured by LVEF in patients with HFrEF. Recovery of cardiac systolic function in turn predicts five-year survival. These findings may help to stratify HF therapy and indicate that further studies are needed to foster our understanding of the phenomenon of myocardial inflammation.