{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:20:35Z","timestamp":1792268435767,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,12,13]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We studied 18 consecutive patients (15 males, 3 females; mean age 42.0\u00b112.4 years) with clinical phenotype of Brugada syndrome and normal cardiac structure and function on noninvasive examinations. Clinical presentation was ventricular fibrillation in 7 patients, sustained polymorphic ventricular tachycardia in 7, and syncope in 4. All patients underwent cardiac catheterization, coronary and ventricular angiography, biventricular endomyocardial biopsy, and DNA screening of the\n            <jats:italic>SCN5A<\/jats:italic>\n            gene. Biopsy samples were processed for histology, electron microscopy, and molecular screening for viral genomes. Microaneurysms were detected in the right ventricle in 7 patients and also in the left ventricle in 4 of them. Histology showed a prevalent or localized right ventricular myocarditis in 14 patients, with detectable viral genomes in 4; right ventricular cardiomyopathy in 1 patient; and cardiomyopathic changes in 3. Genetic studies identified 4 carriers of\n            <jats:italic>SCN5A<\/jats:italic>\n            gene mutations that cause in vitro abnormal function of mutant proteins. In these patients, myocyte cytoplasm degeneration was present at histology, whereas terminal dUTP nick end-labeling assay showed a significant increase of apoptotic myocytes in right and left ventricle versus normal controls (\n            <jats:italic>P<\/jats:italic>\n            =0.014 and\n            <jats:italic>P<\/jats:italic>\n            =0.013, respectively).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Despite an apparently normal heart at noninvasive evaluation, endomyocardial biopsy detected structural alterations in all 18 patients with Brugada syndrome. Mutations in the\n            <jats:italic>SCN5A<\/jats:italic>\n            gene, identified in 4 of the 18 patients, may have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.520999","type":"journal-article","created":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T22:02:56Z","timestamp":1134424976000},"page":"3680-3687","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":315,"title":["Cardiac Histological Substrate in Patients With Clinical Phenotype of Brugada Syndrome"],"prefix":"10.1161","volume":"112","author":[{"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia G.","family":"Priori","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Pieroni","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Napolitano","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Rivolta","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Sanna","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Bellocci","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Antonio","family":"Russo","sequence":"additional","affiliation":[{"name":"From the Heart and Great Vessels Department, Attilio Reale, La Sapienza University (A.F., M.P., C.C.), Rome, Italy; Molecular Cardiology Laboratory (S.G.P., C.N., I.R.), Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy; Cardiology Department, Catholic University (T.S., F.B.), Rome, Italy; and Pathology and Experimental Medicine Department, La Sapienza University and San Raffaele Pisana Institute (M.A.R.), Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(89)90011-2"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90253-J"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/32675"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.105.11.1342"},{"key":"e_1_3_3_5_2","first-page":"53","volume":"5","year":"2004","unstructured":"Martini B, Nava A. 1988\u20132003: Fifteen years after the first Italian description by Nava-Martini-Thiene and colleagues of a new syndrome (different from the Brugada syndrome?) in the Giornale Italiano di Cardiologia: do we really know everything on this entity? 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