Primary aldosteronism (PA), the most frequent form of secondary arterial hypertension, is strictly associated to several cardiovascular complications and target organ damage, due to pro-inflammatory and oxidative effects, vascular and renal fibrosis and unfavorable metabolic effects of aldosterone.
Recently, we have shown that another adrenal hormone, cortisol, beyond systemic manifestations (hypertension, abnormalities in glucose and lipid metabolism), is associated with dilated cardiomyopathy, due to histological changes and molecular pathways, as well as cardiomyocyte hypertrophy, myofibrillolysis and myocardial fibrosis; changes reverted completely at 1-year follow-up from removal of cortisol excess (adrenalectomy).
In literature many studies have evaluated the potential pathophysiological links between myocardial remodeling and aldosterone behaviors, especially on animal models, nevertheless none pathophysiological process can be precisely identified in human model.
To this purpose, a prospective randomized study will be drawn up, involving homogeneous groups of patients in distinct groups: PA patients undergoing surgical (adrenalectomy) or conservative approach (pharmacological) matched patients with essential hypertension.
All patients will undergo to biochemical, hormonal and antropometric evaluation, echocardiographic and magnetic resonance evaluation of heart, endomyocardial biopsy in selected patients presenting with left ventricular dilation and dysfunction, distinct in accordance with the presence of PA and EH. Endomyocardial biopsy samples will be processed for histology, electronmicroscopy and immunohistochemistry and western blot.
The aims of the study are the more precise identification and type of myocardial alterations in patients affected by overt PA and cardiomyopathy compared with patients with equivalent severity of cardiomyopathy and EH, in order to understand the patho-physiological role of aldosterone in mediating cardiovascular damage.
The purposes of the following study are:
1) more precise identification and type of myocardial alterations (by imaging and histo-pathological methods, electronmicroscopy, immunohistochemistry and western blot assessment) in patients affected by overt PA and cardiomyopathy, independently by anatomical source (aldosterone-secreting adrenal adenoma or bilateral adrenal hyperplasia) compared with patients with equivalent severity of cardiomyopathy and EH.
2) evaluation of these myocardial changes after 6 months of effective treatment of aldosterone excess (surgical removal of aldosterone-secreting adrenal adenoma)
2) correlation of these changes comparing the histo-pathological findings in the patients with PA undergoing - surgical treatment, compared with group of PA patients pharmacologically treated with a conservative approach (antagonists of mineral-corticoid receptors - MR);
The innovation and main strength of the present study includes the understanding of patho-physiological role of aldosterone in mediating cardiovascular damage. In particular, cardiomyopathy associated to elevated aldosterone behaviors (in important human models as PA) will be analyzed to clarify the possible myocardial damage, as well as hypertrophy, fibrosis, myofibrillar disarrangement, vascular and endothelial changes, and if these abnormalities can be mediated by pathological tissue expression of myocardial aldosterone receptors and other transmembrane proteins and channels (for example aquaporines overexpression), associated with intracellular water overloading causing impaired cell relaxation and contraction.
The results of the study will help us to analyze the role of aldosterone in the heart failure in general and to which extent interference with anti-aldosterone drugs may improve patients outcome and should definitely be incorporated (see Ephesus trial) in the pharmacologic treatment of human heart failure.