Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive
patients with diastolic failing heart remains unclarified.
Background: Nearly half of patients with clinical heart failure (HF) have normal left
ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction
(DD) and are referred as diastolic HF (DHF). The renin-angiotensin-aldosterone system is an
established major pathway that is operative in the pathogenesis of HF. The effects of
aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been
established in human and animal models. Furthermore, in these models, aldosterone antagonism
prevented the development of myocardial fibrosis independent of its effect on blood pressure
or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In
the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in
hypertensive patients with DHF.
Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF
defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as
impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and
LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25
mg per day or not for at least 6 months. At baseline before randomization and 6 months after
randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with
Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess
the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise,
we draw blood sampling at baseline and after randomization for quantifying and comparing
several biomarkers which are currently proved to be correlated with LV hypertrophy,
myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal
pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide,
procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected
results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving
the quality of life, echo-derived myocardial function, and reducing ventricular mechanical
stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.