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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalInternational Journal of Cardiology
DOIs
Publication statusPublished - Jun 20 2019

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Hyperaldosteronism
Aquaporin 1
Mineralocorticoid Receptors
Aldosterone
Cardiomyopathies
Cardiac Myocytes
Biopsy
Organelles
Cytosol
Fibrosis
Aquaporin 4
Water
Myofibrils
Adrenalectomy
Vacuoles
Coronary Angiography
Adenoma
Hypertrophy
Smooth Muscle Myocytes
Coronary Vessels

Keywords

  • Cardiomyopathy
  • Myocardial aldosterone
  • Water overloading

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization",
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",
author = "Andrea Frustaci and Claudio Letizia and Romina Verardo and Claudia Grande and Marco Francone and Luigi Sansone and Russo, {Matteo Antonio} and Cristina Chimenti",
year = "2019",
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TY - JOUR

T1 - Primary aldosteronism-associated cardiomyopathy

T2 - Clinical-pathologic impact of aldosterone normalization

AU - Frustaci, Andrea

AU - Letizia, Claudio

AU - Verardo, Romina

AU - Grande, Claudia

AU - Francone, Marco

AU - Sansone, Luigi

AU - Russo, Matteo Antonio

AU - Chimenti, Cristina

PY - 2019/6/20

Y1 - 2019/6/20

N2 - 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.

AB - 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.

KW - Cardiomyopathy

KW - Myocardial aldosterone

KW - Water overloading

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U2 - 10.1016/j.ijcard.2019.06.055

DO - 10.1016/j.ijcard.2019.06.055

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JF - International Journal of Cardiology

SN - 0167-5273

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