Aims: Tachycardiomyopathy (TCM) is a commonly suspected diagnosis in patients presenting with impaired left ventricular ejection fraction (LVEF) and tachycardia. The pathophysiological mechanisms underlying this largely reversible entity of heart failure as well as diagnostic and prognostic parameters are scarce. Therefore, we prospectively investigated prognostic parameters for LVEF recovery in patients with suspected TCM, focusing on endomyocardial biopsy specimen using cutting-edge technology for spatial analyses.
Methods and Results: In this prospective, observational study (NCT03418467) 51 patients with newly diagnosed HFrEF due to suspected TCM were enrolled. In all patients a rhythm control strategy and endomyocardial biopsy (EMB) were planned and valvular or ischemic heart disease were ruled out. Clinical data as well as a EMB material was assessed. The primary outcome was defined as recovery of left ventricular ejection fraction (LVEF) at follow-up.
At baseline the mean LVEF was 32% (±9.5) and showed a recovery to 46% (±8.7) at follow-up. Increase in LVEF recovery correlated well with CRP levels and leukocyte count at study entry (p<0.05, respectively). Typical risk factors, including troponin I, creatine kinase, and NTpro-BNP had no significant prognostic impact on LVEF recovery. While bioptic specimen showed increased leukocyte recruitment and fibrosis, neither was associated with LVEF recovery. EMB specimen were furthermore analyzed using spatial high mass-resolution matrix assisted laser desorption ionisation-imaging (MALDI-FT-ICR-MS) to investigate changes in bioactive lipids. Especially prostaglandins and ceramide derivatives have been identified to play significant roles in inflammatory processes and immune responses. We observed distinct changes in the myocardial lipidome with a negative correlation between CRP and the ceramides N-(5-iso-prostaglandin F2VI)-17-sphingosine (Cer(d17:1/5-iso PGF2VI, p<0.05,) and N-(prostaglandin E2)-18-sphingosine (Cer(d18:1/PGE2, p<0.05).
Conclusion: In this prospective study we provide evidence that in patients with suspected TCM CRP and leukocyte count indicating acute phase reaction are predictive for LVEF recovery. Furthermore, CRP was associated with distinct changes in myocardial ceramide and prostaglandin abundance indicating intricate changes in the myocardial lipidome. Further studies are warranted to investigate the underlying mechanisms and potential therapeutic targets in these patients.
