https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; 2Universitätsklinikum Heidelberg Klinik für Herzchirurgie Heidelberg, Deutschland
Background: The electrical activity of atrial cardiomyocytes (CMs) is essential for the rhythmic contraction of the left (LA) and right atria (RA). Changes in the electrical function of atrial CMs have been linked to the development of arrhythmias, such as atrial fibrillation (AF). Atrial arrhythmias may originate in the LA or RA, and many specific arrhythmias can acutely be triggered in different parts of the atria. Some arrhythmias have also been demonstrated to occur more frequently in men vs. women. Understanding the electrical differences between CMs of the LA and RA is important to optimise targeted treatment strategies for specific atrial arrhythmias, such as AF.
Purpose: Our aim was to compare the action potentials (APs) of isolated cardiomyocytes (CMs) from the LA and RA of men and women with end-stage heart failure (HF) of different aetiologies.
Methods: We performed whole-cell patch clamp recordings on isolated human atrial CMs obtained from RA and LA tissue samples of explanted hearts during heart transplantation (HTx) at Heidelberg University Hospital from a total of 16 patients with end-stage HF. The study included 8 male and 8 female patients, of whom 6 had dilatative cardiomyopathy (DCM), 4 had non-obstructive hypertrophic cardiomyopathy (HNOCM), 2 had cardiac sarcoidosis, 2 had ischaemic cardiomyopathy (ICM) and 2 had other causes of HF. 3 patients had paroxysmal AF, 2 had atrial flutter (AFL), none had permanent AF.
Results: 13 patients had at least 1 recorded AP from the LA and the RA, whilst 2 only had APs from the RA and 1 only from the LA. Overall, we noted a significantly longer AP duration (APD) in LA CMs vs. RA CMs (+41.8 ms, p=0.0017). This was regardless of gender, underlying HF aetiology or whether AF/AFL was present. In LA CMs of the female patients in this study, significant prolongation of the APD at 30% (+5.8 ms, p=0.004), at 50% (+10.8 ms, p= 0.008) and at 90% repolarisation (+47.7 ms, p=0.001) was observed compared to RA CMs. There was a similar trend towards prolongation of the APD in LA vs. RA CMs of the 8 male patients in this study (p=0.12 for the APD90). No statistically significant differences in APD between the 8 male and 8 female patients was observed. There was no significant difference in AP amplitude between the LA CMs and RA CMs, whilst the maximum upstroke velocity was decreased in LA CMs of the females (-26.38 mV/ms, p=0.026).
Conclusions: This study demonstrates that the APs of single human CMs from the RA are significantly shorter than from the LA in patients with end-stage heart failure. Moreover, this difference was appreciable in both female and male patients and persisted regardless of the underlying heart failure aetiology or the presence of AF. A short APD in atrial CMs has been associated with proarrhythmogeneity due to decreases in atrial refractoriness, suggesting an, as yet, underappreciated role of the RA in the development of atrial arrhythmias, including AF.