2025-02-252022-03-30https://repositorio.cmmg.edu.br/handle/123456789/73Background: PRKAG2gene mutation, which encodes the ɣ2 subunitof protein kinase activated by adenosine monophosphate (AMPK), is an autossomic dominant inherited disease with early adulthoodclinical onset, characterized by pre-excitation, atrial tachyarrhythmias, atrioventricular conduction abnormalities and cardiac hypertrophy. Half of the patients will need pacemaker implantation. One tenth will have sudden death, before the fourth decade.Early detection of the condition is advisable to ensure adequate care. Genetic sequencingis considered the gold standard diagnostic test, but it is not available in the Brazilian “Sistema Único de Saúde”. The diagnostic efficacy of biopsy in identifying PRKAG2 cardiomyopathy remains to be assessed.Objectives: To evaluate the magnetic resonance imaging with T1 mapping, extracellular volume, and late gadolinium enhancement of PRKAG2 cardiomyopathy and assess thehistologic, histochemical, and ultrastructural findings of myocardium fragments of patients with PRKAG2 gene mutations harvested by percutaneous endomyocardium biopsy. To compare the diagnostic efficiencyof endomyocardial biopsy with genetic sequencing as a gold standard. Methodology: The first study was an observational cross-sectional analysis of 30 patients with PRKAG2 cardiomyopathy. The second study was a cross-sectional with case-control study. We included18patientswith PRKAG2mutations(Arg302Gln and His401Gln). Acontrol group comprised of biopsies of 11 recipients of a heart transplant (within 10 days), and another control group with3 patients with hypertrophic sarcomeric cardiomyopathy.A single patient had a pathogenic variant -MYL3 Ala57Asp. Next Generation Sequencing was carried out in the probands with PRKAG2 cardiomyopathy and hypertrophic cardiomyopathy, while family members underwent cascade Sanger sequencing. Results: LV hypertrophy was found in 16 individuals (53.3%). Myocardial thickness increased in 25 individuals (83.3%), severe in 9 (30%) and extreme in 3. Hypertrophy patterns as septal, apical, and diffuse, without outflow tract obstruction. T1 mapping and ECV were normal in all. LGE was found in 16.6% (5/30), all with severe hypertrophy(5/9) of those, as compared with 0/21 patients with mild or no hypertrophy (p=0.009).The myocardium fragments inPRKAG2cardiomyopathy showed a significant increase in cardiomyocyte diameter, pronounced vacuolation, absence of fibrosis, except in two patients, who had focal low intensity interstitial fibrosis, absence of architectural disarray, and absence of inflammatory infiltrates as compared with normal controls (post heart transplant).Transmission electron microscopy showed large amounts of glycogen granules in the cytosol, particularly in perinuclear region. Polls of glycogen were also seen in interfibrillar space and in subsarcolemmal regions. The large amount of glycogen observed in patients with PRKAG2cardiomyopathy was not seen in any of the controls. A composite of pathology features like pronounced vacuolation, absence of inflammation, fibrosis, and architectural disarray, together with large amounts of glycogen granules in the cytosol as seen in transmission electron microscopy, was able to identify all cases of genotyped PRKAG2cardiomyopathy, even those patients without clinical hypertrophy in echocardiogram. Conclusion: CMR with T1 mapping techniques may help identify xi PRKAG2patients among individuals with unexplained hypertrophy. Endomyocardial biopsy was as efficient as genetic sequencing in identifying PRKAG2 cardiomyopathy.Acesso abertoPRKAG2, Cardiomiopatia por depósito de glicogênio, Hipertrofia ventricular esquerda, Estudo eletrofisiológico, Pré-excitação ventricular; PRKAG2, Glycogen Storage Cardiomyopathy, left ventricular hypertrophy, electrophysiologic study, ventricular pre-excitationDissertação4.01.00.00-6 - Medicina