PRKAG2 Cardiomyopathy: A Case-Control Study on the Diagnostic Yield Of Histopathology and Ultrastructural Analysis from Endomyocardial Biopsy.

PRKAG2 cardiomyopathy hearts exhibited significant cardiomyocyte enlargement compared to controls.

• Study included 18 patients with PRKAG2 cardiomyopathy and 11 heart transplant recipients as controls
• All patients underwent percutaneous right ventricular endomyocardial biopsy
• Cardiomyocyte enlargement was identified as a distinguishing histopathological feature
• Mitochondria appeared normal in PRKAG2 cardiomyopathy hearts

Extensive vacuolization of most myofibers was observed in PRKAG2 cardiomyopathy hearts.

• Vacuolization was described as extensive and present in most myofibers
• Tissue samples were analyzed using H&E staining, Periodic Acid-Schiff staining for glycogen, and Masson's trichrome for fibrosis
• No inflammatory cell infiltration was detected in PRKAG2 cardiomyopathy hearts
• Only two patients had mild interstitial fibrosis, described as minimal overall

Transmission electron microscopy revealed abundant cytosolic glycogen accumulation in all PRKAG2 patients that was absent in controls.

• Glycogen was primarily located in the perinuclear region, with additional deposits in intermyofibrillar and subsarcolemmal areas
• This pronounced glycogen accumulation was consistently observed in all 18 PRKAG2 patients
• Glycogen accumulation was absent in all 11 control subjects
• Statistical significance was set at p < 0.05 for all analyses

The study systematically evaluated cardiac pathological features of PRKAG2 cardiomyopathy in a large patient cohort using multiple histological and ultrastructural methods.

• This was an observational, cross-sectional, case-control study design
• 18 PRKAG2 cardiomyopathy patients and 11 heart transplant recipients as controls were included
• Four analytical methods were employed: H&E staining, Periodic Acid-Schiff staining, Masson's trichrome, and transmission electron microscopy
• The study aimed to assess diagnostic potential of histopathology compared to genetic sequencing
• Prior histopathological features of PRKAG2 cardiomyopathy had been reported only in a fragmentary manner

The combination of histological and ultrastructural features from endomyocardial biopsy constitutes a distinct diagnostic profile for PRKAG2 cardiomyopathy.

• The distinct feature set includes cardiomyocyte enlargement, extensive vacuolization, minimal fibrosis, absence of inflammation, normal-appearing mitochondria, and abundant cytosolic glycogen
• These features were assessed for their diagnostic potential compared to genetic sequencing
• The consistent presence of glycogen accumulation in all PRKAG2 cases and its absence in all controls supports diagnostic utility
• Right ventricular endomyocardial biopsy was the tissue sampling method used