Fibrosis and cardiac function in obesity: a randomised controlled trial of aldosterone blockade

Kosmala, Wojciech, Przewlocka-Kosmala, Monika, Szczepanik-Osadnik, Hanna, Mysiak, Andrzej and Marwick, Thomas H. (2013) Fibrosis and cardiac function in obesity: a randomised controlled trial of aldosterone blockade. Heart, 99 5: 320-326. doi:10.1136/heartjnl-2012-303329


Author Kosmala, Wojciech
Przewlocka-Kosmala, Monika
Szczepanik-Osadnik, Hanna
Mysiak, Andrzej
Marwick, Thomas H.
Title Fibrosis and cardiac function in obesity: a randomised controlled trial of aldosterone blockade
Journal name Heart   Check publisher's open access policy
ISSN 1355-6037
1468-201X
Publication date 2013-03
Sub-type Article (original research)
DOI 10.1136/heartjnl-2012-303329
Volume 99
Issue 5
Start page 320
End page 326
Total pages 7
Place of publication United Kingdom
Publisher B M J Group
Collection year 2014
Language eng
Formatted abstract
Objectives As myocardial fibrosis might be an important contributor to the association of obesity with left ventricular (LV) dysfunction and heart failure, we investigated the effects of spironolactone on LV function and serological fibrosis markers (procollagen type III N-terminal propeptide (PIIINP) and procollagen type I C-terminal propeptide (PICP)) in patients with obesity and abnormal LV performance.

Design A prospective, randomised, double-blind, placebo-controlled study.

Setting A university hospital.

Patients and intervention 113 patients (mean±SD age 58±8 years) with body mass index≥30, without any comorbidities, with impaired early diastolic mitral annular velocity, randomised to spironolactone 25 mg/day or placebo for 6 months.

Main outcome measures Echocardiographically derived indices of LV systolic (strain and strain rate) and diastolic (E velocity, tissue e′ and E/e′ ratio) function, myocardial reflectivity (calibrated integrated backscatter (IB)), and serum PICP and PIIINP.

Results In the spironolactone group, significant improvements in myocardial deformation, peak early diastolic velocity (Em), E/e′ and IB were noted with a simultaneous decrease in PICP and PIIINP. No corresponding alterations were found with placebo. Improvement in LV systolic function (increase in strain) was independently associated with baseline strain (β=−0.43, p<0.001), change in IB (β=0.26, p<0.02) and baseline PICP (β=0.24, p<0.04). Among the independent determinants of LV diastolic improvement were for increase in Em – baseline Em (β=−0.44, p<0.001) and baseline PICP (β=0.35, p<0.002), and for decrease in E/e′ – baseline E/e′ (β=−0.35, p<0.005) and change in PICP (β=0.25, p<0.04).

Conclusions In patients with obesity without other comorbidities, aldosterone antagonism improves LV function and myocardial acoustic properties, and reduces circulating procollagen levels. Beneficial changes in cardiac performance are independently predicted by baseline LV dysfunction and baseline disturbances, as well as treatment-induced improvements in fibrosis markers.

Clinical Trial Registration http://www.anzctr.org.au ACTRN12609000655246.
Keyword Acute myocardial-infarction
Left-ventricular function
Insulin-resistance
Heart-failure
Hypertensive patients
Collagen turnover
Dysfunction
Antagonism
Risk
Cardiomyopathy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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