Kinulpe Honorato-Sampaio et al. Carla de Oliveira Stanley de Almeida Araújo Frederico Soares Correa … Glauber Monteiro Dias Antônio Fernandino de Castro Bahia Neto Vinícius Lopes Cantuária Arash Yavari Maria da Consolação Vieira Moreira José Luiz Barros Pena Geraldo Brasileiro Filho Eduardo Back Sternick
Abstract
Background
The histopathological features of PRKAG2 cardiomyopathy have been reported in a fragmentary manner.
Objective
We aimed to systematically evaluate the cardiac pathological features of PRKAG2 cardiomyopathy in a large patient cohort and assess their diagnostic potential compared to genetic sequencing.
Methods
We conducted an observational, cross-sectional, case-control study including 18 patients with PRKAG2 cardiomyopathy and 11 heart transplant recipients as controls. All patients underwent percutaneous right ventricular endomyocardial biopsy. Tissue samples were analyzed using H&E staining, Periodic Acid-Schiff staining for glycogen, Masson’s trichrome for fibrosis, and ultrastructural assessment by transmission electron microscopy. Statistical significance was set at p < 0.05 for all analyses.
Results
PRKAG2 cardiomyopathy hearts exhibited significant cardiomyocyte enlargement, normal-appearing mitochondria, extensive vacuolization of most myofibers, minimal interstitial fibrosis (only two patients had mild fibrosis), and no inflammatory cell infiltration. Transmission electron microscopy revealed abundant cytosolic glycogen, primarily in the perinuclear region, with additional deposits in intermyofibrillar and subsarcolemmal areas. This pronounced glycogen accumulation, consistently observed in all PRKAG2 patients, was absent in controls.
Conclusion
Histological and ultrastructural examination of right ventricular endomyocardial biopsy samples reveals a distinct set of features that strongly suggest PRKAG2 cardiomyopathy.