Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart
Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart
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.
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). Hypertensive heart disease occurs in the majority of patients with DHF,
 and several key aspects of heart failure secondary to hypertensive heart disease are the
 relatively highly prevalent LV hypertrophy, cardiac fibrosis, and endothelial
 dysfunction-mediated myocardial injury caused by changes in the local and systemic
 neurohormonal environment, and all of which are associated with LV diastolic dysfunction and
 tissue-Doppler derived systolic myocardial function. 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.
Inclusion Criteria:

 -  well-controlled hypertensive patients with diastolic HF defined as the presence of
 diastolic dysfunction, normal LVEF (> 50 %), and exertional dyspnea (≧ New York Heart
 Association functional class II) or other HF signs/symptoms fulfilled with the
 Framingham criteria despite optimal pharmacological therapy

 Exclusion Criteria:

 -  secondary hypertension

 -  restrictive, constrictive or hypertrophic cardiomyopathy

 -  more than moderate (mitral or tricuspid regurgitant jet area/atrial area more than
 20%; aortic regurgitant jet to the tip of the mitral valve leaflets) valvular heart
 diseases

 -  chronic atrial fibrillation

 -  usage of aldosterone antagonist within 3 months

 -  chronic pulmonary disease

 -  myocardial infarction within 3 months or active ischemia needing revascularization

 -  LVEF less than 50% by echocardiography

 -  renal failure (serum creatinine concentration more than 2.0 mg/dL).