Chicken or egg in tachycardia-induced cardiomyopathy
It is intriguing to speculate in clinical settings whether atrial fibrillation itself, the resulting tachycardia (of any reason), or the combination of both leads to severely reduced left ventricular ejection fraction. A study demonstrated impaired myocardial energetics resulting in subtle left ventricular dysfunction despite successful catheter ablation in patients with ”lone” atrial fibrillation [22]. Moreover, although the majority of TCM patients usually have a substantial improvement in mean ejection fraction, not all of them have a normalized LVEF at FU. Also, in our study, there was a group of TCM patients with excellent recovery (mean absolute LVEF improvement 34 ± 6.1 %) and almost normalization of LVEF to a mean of 52 %, but 56 % of our TCM patients had significantly less improvement of LVEF (8.1 ± 11 %) with a mean LVEF of 41 % after six months. This raises the possibility that underlying cardiomyopathy may have been exacerbated by uncontrolled tachycardia. Even if the LVEF improves, it is unclear whether this means cure [18] as the recovery of LVEF may not imply normalization of LV structure and function [18]. Notably, we found a relevant amount of fibrosis in TCM and also elevated markers of cardiomyocyte apoptosis (cleaved caspase 3) comparable to ICM patients in our series. This was also demonstrated in a study with 19 TCM patients [8] and might contribute to incomplete LVEF recovery after a ”point of no return” has been passed.
To further address the chicken and egg issue, we compared the endomyocardial biopsy results of patients with atrial fibrillation (AF) on admission and those in sinus rhythm irrespective of admission heart rate. We were not able to demonstrate any significant differences between the AF or sinus rhythm group, which is supported by similar results reported by Mueller et al. [8].
The potential role of human activated pluripotent stem cell cardiomyocytes (iPSC-KM), which mainly mediate the contractile dysfunction in persistent tachycardia, is currently investigated. The underlying functional electrophysiologic mechanisms will be assessed by measuring the action potential and ion-currents as well as by analyzing the cellular ion homeostasis [23]. Next-generation sequencing and gene-expression profiles will help to analyze the underlying targets of persistent tachycardia in the myocardium and the type of regulation [23]. This is especially important as defined subgroups, e.g., patients with homozygous deletion polymorphism in the angiotensin-converting enzyme gene, have a higher probability of developing TCM when faced with persistent tachycardia, suggesting a potential genetic link [18,24].