https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Tübingen Innere Medizin III, Kardiologie und Kreislauferkrankungen Tübingen, Deutschland; 2Helmholtz Zentrum Munich Research Unit Analytical Pathology Neuherberg, Deutschland; 3Universitätsklinikum Tübingen Kardiopathologie Tübingen, Deutschland; 4Ostalb-Klinikum Aalen Innere Medizin II, Kardiologie und Angiologie Aalen, Deutschland
Aims: Tachycardiomyopathy (TCM) is commonly encountered in clinical practice. The pathophysiological mechanisms that lead to heart failure as well as diagnostic and prognostic parameters for clinical outcome are largely unknown. Thus, we prospectively investigated prognostic parameters for LVEF recovery in patients with suspected TCM. The analysis was focused on specific findings in endomyocardial biopsy specimen using cutting-edge technology for spatial analyses.
Methods and Results: In this prospective, observational study (EMPATHY study, ClinicalTrials.gov: NCT03418467) 51 patients with newly diagnosed HFrEF due to suspected TCM and planned rhythm control strategy and endomyocardial biopsy were enrolled after valvular or ischemic heart disease were ruled out. The main outcome was defined as recovery of left ventricular ejection fraction (LVEF). At baseline 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), indicating that acute phase reaction at the time of diagnosis is favorable for LVEF recovery. Classical risk factors, including troponin I, creatine kinase, and NTpro-BNP had no significant prognostic value. While bioptic specimen showed increased leukocyte recruitment and fibrosis, neither of them was predictive for LVEF recovery. Bioactive lipids, especially prostaglandins and ceramide derivatives, have been identified to play significant roles in inflammatory processes and immune responses. Using spatial high mass-resolution matrix assisted laser desorption ionisation-imaging (MALDI-FT-ICR-MS), we were able to identify distinct changes in the myocardial lipidome. We observed 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 demonstrate that acute phase reaction including elevated CRP and leukocyte counts are predictive for LVEF recovery in patients with suspected TCM. Elevated CRP is furthermore associated with distinct changes in myocardial ceramide and prostaglandin expression. As the underlying mechanisms that lead to heart failure in TCM are poorly understood further studies are needed to elucidate specific treatment strategies.