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].