Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction

Aims Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling. Methods and results Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8 +/- 0.6 mm in MI vs. 3.6 +/- 0.3 mm in sham; P < 0.0001), as was atrial fibrosis (26.7 +/- 3.8% in MI vs. 10.5 +/- 2.2% in sham; P < 0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration. Conclusion Atrial fibrosis caused by chronic CHF is reduced by spironolactone.