Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization

Andrea Frustaci; Claudio Letizia; Romina Verardo; Claudia Grande; Marco Francone; Luigi Sansone; Matteo Antonio Russo; Cristina Chimenti

doi:10.1016/j.ijcard.2019.06.055

Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization

Int J Cardiol. 2019 Oct 1:292:141-147. doi: 10.1016/j.ijcard.2019.06.055. Epub 2019 Jun 20.

Authors

Andrea Frustaci¹, Claudio Letizia², Romina Verardo³, Claudia Grande³, Marco Francone⁴, Luigi Sansone⁵, Matteo Antonio Russo⁶, Cristina Chimenti⁷

Affiliations

¹ Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, La Sapienza University, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy. Electronic address: biocard@inmi.it.
² Department of Translational and Precision Medicine, Center for Secondary Hypertension, La Sapienza University, Italy.
³ Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
⁴ Department of Radiological, Oncological and Pathological Sciences, La Sapienza University, Rome, Italy.
⁵ Cellular and Molecular Pathology Lab, IRCCS S. Raffaele Pisana, Rome, Italy.
⁶ Cellular and Molecular Pathology Lab, IRCCS S. Raffaele Pisana, Rome, Italy; MEBIC Consortium, San Raffaele Open University, Rome, Italy.
⁷ Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, La Sapienza University, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.

PMID: 31256994
DOI: 10.1016/j.ijcard.2019.06.055

Abstract

Background: Primary aldosteronism (PA) causes a cardiomyopathy (CM) which substrate and evolution after aldosterone normalization are unreported.

Methods: Four male patients with aldosterone-secreting adrenal adenoma and cardiomyopathy (PACM, group A) were evaluated with 2D-echo, Magnetic Resonance (CMR), coronary angiography and left ventricular endomyocardial biopsy. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin 1 and 4. Results were compared with endomyocardial samples from 5 patients with hypertensive cardiomyopathy of equivalent severity and normal plasma aldosterone (group B) and surgical samples from 5 controls (group C). One PACM patient was re-examined with CMR and endomyocardial biopsy 12 months after adrenalectomy with aldosterone and cardiac normalization.

Results: Coronary arteries were normal in all. Group A showed prominent myocardial hypertrophy and fibrosis, with water accumulation in the cytosol and organelles of cardiomyocytes and microvascular smooth muscle cells, associated to reduced myofibril concentration and 2.8-fold increase in myocardial aldosterone receptors and aquaporin 1. At CMR, LGE areas were diffusely present. After aldosterone normalization, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, recovery of electron-density of cytosol and cell organelles, and myofibrillar content, persisting fibrosis and down-regulation of aldosterone receptors and aquaporin 1 channels. At CMR, myocardial mass reduced with recovery of cardiac contractility. LGE signal remained unchanged.

Conclusion: PACM is a reversible entity characterized by over-expression of aldosterone receptors and aquaporin 1. It induces a reversible intracellular water overloading causing impaired cardiomyocyte relaxation, contraction and ultrastructural integrity.

Keywords: Cardiomyopathy; Myocardial aldosterone; Water overloading.

MeSH terms

Adrenalectomy / trends*
Adult
Aged
Aldosterone / blood*
Cardiomyopathies / blood*
Cardiomyopathies / diagnostic imaging*
Cardiomyopathies / surgery
Humans
Hyperaldosteronism / blood*
Hyperaldosteronism / diagnostic imaging*
Hyperaldosteronism / surgery
Male
Middle Aged
Receptors, Mineralocorticoid / blood

Substances

Receptors, Mineralocorticoid
Aldosterone