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Fibrosis and Cardiac Function in Obesity: A Randomised Controlled Trial of Aldosterone Blockade
Study Questions:
What are the effects of spironolactone on left ventricular (LV) function and serum fibrosis markers in patients with obesity and LV dysfunction?
Methods:
This was a prospective, randomized, double-blinded, placebo-controlled study at a single institution. A total of 113 patients were enrolled with body mass index ≥30 kg/m2 and impaired early diastolic mitral annular velocities with no other coexisting disease, and were randomized to spironolactone 25 mg daily or placebo for 6 months. The mean age was 58 ± 8 years, and all patients had ≤ New York Heart Association class II symptoms. The primary outcome assessed echocardiographic parameters of LV systolic function and diastolic function. The secondary outcome assessed collagen turnover as expressed by serum fibrosis markers (procollagen type III N-terminal propeptide [PIINP] and procollagen type I C-terminal propeptide [PICP]).
Results:
In the treatment group, there was improvement in systolic (based on an increase in strain, peal systolic strain rate, and Sm) and diastolic echocardiographic parameters (based on an increase in Em and a decrease in E/e’). There was also a decrease in serum fibrosis marker levels (PCIP, PIINP, and transforming growth factor [TGF]-β1). The independent predictors of improvement in LV systolic function on spironolactone were baseline strain (β = -0.43, p < 0.001), change in 1B (β = 0.26, p < 0.02), and baseline PICP (β = 0.24, p < 0.04). The independent predictors of LV diastolic function were an increase in Em-baseline Em (β = 0.44, p < 0.001), baseline PCIP (β = 0.35, p < 0.002), and a decrease in E/e’ (B = -0.35, p < 0.005) and change in PICP (β = 0.25, p < 0.04).
Conclusions:
Aldosterone antagonism can improve elements of LV systolic and diastolic function and decrease levels of serological fibrosis markers in patients who are obese with LV dysfunction.
Perspective:
Novel therapies that can improve heart failure in patients with obesity are becoming a more pertinent challenge for health care providers. The addition of aldosterone antagonism can improve myocardial fibrosis and myocardial function.
Keywords: Ventricular Function, Left, Mineralocorticoid Receptor Antagonists, Diuretics, Spironolactone, Procollagen, Heart Diseases, Collagen Type I, Body Mass Index, Transforming Growth Factors, Collagen Type III, Heart Failure, Obesity, Fibrosis, Ventricular Dysfunction, Left
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