What is the clinical evidence from this study?

Study design: Other. Population: Congestive heart failure. Intervention: Spironolactone vs. Lisinopril, atenolol, or sham. Primary outcome: Atrial fibrosis (MI vs. sham) (p=<0.0001).

September 1, 2005

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

Q: What are the key findings of this study?

In rats with chronic congestive heart failure post-myocardial infarction, 1 month of spironolactone therapy attenuated atrial fibrosis and reduced P-wave duration.

Key Result

In rats with chronic congestive heart failure post-myocardial infarction, 1 month of spironolactone therapy attenuated atrial fibrosis and reduced P-wave duration.

Structured PICO

Does spironolactone, lisinopril, or atenolol reduce atrial fibrosis in rats with post-MI heart failure?

Population

Rats with congestive heart failure 3 months post-myocardial infarction, treated for 1 month.

Intervention

Spironolactone, lisinopril, or atenolol alone or in combination for 1 month

Comparator

Sham-operated rats and comparison between active treatments

Outcome

Atrial fibrosis quantified with Picrosirius Red stainingsurrogate

Spironolactone uniquely reduces atrial fibrosis and P-wave duration in a rat model of chronic heart failure, suggesting a specific anti-remodeling effect not seen with ACE inhibitors or beta-blockers.

Main Result

Absolute Event Rate: 26.7% vs 10.5%

p-value: p=<0.0001

Abstract

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.

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