Background: The decompensation accompanying acute heart failure (AHF) episodes generates a pro-inflammatory environment that may boost an adaptive immune response against myocardial antigens, thus contributing to progression of HF and poor prognosis.

Aims: In a post-hoc pilot study using prospectively sampled data, we assessed the prevalence of antimyocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF.

Methods and Results: Groups of equal size (n=6) were composed observing the following 1:1 strata: men vs women; de novo vs chronic HF; HF with reduced (<40%, HFrEF) vs preserved ejection fraction (≥50%, HFpEF), respectively (total n=48). Blood for AMyA was sampled during index hospitalization and at the 6-month follow-up visit (F6), and AMyA titers (limiting dilutions) were determined on primate heart tissue by indirect immunofluorescence. Patients were followed up to month 18 (F18). We monitored prevalence/generation of AMyA titers for 6 months following hospital admission, and evaluated their prognostic utility.

From the resulting 48 patients, AMyA titers could be analysed in all but one patient (poor blood quality): median age 71 (quartiles 60; 80) years.  At baseline, n=21 patients were AMyA positive. Out of 20 patients, in whom blood was sampled twice during hospitalization (day 3 and prior to discharge), n=12 were AMyA negative at day 3 and remained negative until discharge. Between baseline and F6, the prevalence of AMyA increased from n=21 to n=35 (p<0.001). At F6, the prevalence of AMyA was higher in patients with HFpEF (n=21) compared to HFrEF patients (n=14; p=0.036). In the 12 months following F6, i.e. at F18, patients with newly developed AMyA exhibited a significantly higher risk regarding the combined end-point death or hospitalization for HF, when compared to the other two patient groups (HR 4.79, 95% CI 1.13–20.21, p=0.033; figure).

Conclusions:

Our results strengthen the hypothesis that AHF may induce an adaptive immune response in both HFrEF and HFpEF. Further studies in larger collectives need a) to further clarify the role of the adaptive immune system in HF progression and b) to investigate the potential of presence of AMyA - as a biomarker of chronic inflammation - as selection criterion to initiate immunomodulatory therapies targeting adaptive immune responses.

Figure: Survival free of hospitalization for heart failure or death observing the period between 6 and 18 months after index hospitalization for AHF. Groups composed by presence of antimyocardial autoantibodies (AMyA) at baseline and 6 months after index hospitalization for AHF in n=47 patients. HR=hazard ratio, neg = negative, pos = positive