Atrial Pathology Findings in a Patient With PRKAG2 Cardiomyopathy and Persistent Atrial Fibrillation

A white male patient aged 52 years with permanent atrial fibrillation and left ventricular hypertrophy because of glycogen storage cardiomyopathy, heterozygous for c.905G>A p.(Arg302Gln) PRKAG2 missense mutation on exon 7, was admitted because of partial pacemaker extrusion and pocket infection. His mother and 5 brothers carry the same mutation and were previously reported. A dual chamber pacemaker was implanted 20 years earlier because of third-degree atrioventricular block. Pacemaker leads and generator were explanted under extracorporeal circulation. A fragment from the base of the right atrial appendage was assessed for microscopic analysis. Percutaneous endomyocardial right ventricle (RV) biopsy was undertaken 1 year before. Morphological changes in ventricular myocardium in PRKAG2 cardiomyopathy have been reported, but there are no data on atrium pathology. Atrial section (Figure [A through C]) stained with periodic acid–Schiff (Figure [A]) and hematoxylin and eosin (Figure [B]) shows intense vacuolization of the myofibers with abundant gross granular inclusions— glycogen—(arrows) within vacuoles. There is no cardiomyocyte architecture disarray. Masson trichrome staining (Figure [C] and [F]) shows normal collagen fibers (blue) in the extracellular matrix, without fibrosis. Lower (Figure [D through F]) show histopathology findings in the RV, which were similar to those in the atrium, with vacuolization, absence of myocardial disarray, inflammatory cells, and fibrosis, findings consistent with RV histopathology previously reported. Transmission electron microscopy image from RV septum (D) shows mitochondria within abundant glycogen (small granules), between myofibrils. Patients with R302Q have a high incidence of atrial fibrillation. Ventricular preexcitation and hypertrophy, which are commonly present in these patients, may be contributors. It has also been suggested that in the absence of fibrosis, a reduction of pH because of increased glycogen content could influence ionic channels function, which may contribute to atrial fibrillation maintenance. Further studies are warranted in this model of persistent atrial fibrillation without fibrosis.