Right ventricular fibrosis and conduction delay in a patient with clinical signs of brugada syndrome : A combined electrophysiological, genetic, histopathologic, and computational study
The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown. A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2005-11, Vol.112 (18), p.2769-2777 |
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| creator | CORONEL, Ruben CASINI, Simona VAN DER WAL, Allard C TAN, Hanno L BRUGADA, Pedro WILDE, Arthur A. M DE BAKKER, Jacques M. T KOOPMANN, Tamara T WILMS-SCHOPMAN, Francien J. G VERKERK, Arie O DE GROOT, Joris R BHUIYAN, Zahurul BEZZINA, Connie R VELDKAMP, Marieke W LINNENBANK, André C |
| description | The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown.
A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.
In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.105.532614 |
| format | Article |
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A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.
In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.105.532614</identifier><identifier>PMID: 16267250</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Amino Acid Substitution ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular system ; Cell Line ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Electric Stimulation ; Humans ; Kidney ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Reference Values ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Sodium Channels - genetics ; Sodium Channels - physiology ; Syndrome ; Vasodilator agents. Cerebral vasodilators ; Ventricular Fibrillation - genetics ; Ventricular Fibrillation - pathology ; Ventricular Fibrillation - physiopathology</subject><ispartof>Circulation (New York, N.Y.), 2005-11, Vol.112 (18), p.2769-2777</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c363t-a2d77d09f6daebd80a2d87a64b45f2482d01e83867edff6de08496d7656c5013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3688,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17276773$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16267250$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CORONEL, Ruben</creatorcontrib><creatorcontrib>CASINI, Simona</creatorcontrib><creatorcontrib>VAN DER WAL, Allard C</creatorcontrib><creatorcontrib>TAN, Hanno L</creatorcontrib><creatorcontrib>BRUGADA, Pedro</creatorcontrib><creatorcontrib>WILDE, Arthur A. M</creatorcontrib><creatorcontrib>DE BAKKER, Jacques M. T</creatorcontrib><creatorcontrib>KOOPMANN, Tamara T</creatorcontrib><creatorcontrib>WILMS-SCHOPMAN, Francien J. G</creatorcontrib><creatorcontrib>VERKERK, Arie O</creatorcontrib><creatorcontrib>DE GROOT, Joris R</creatorcontrib><creatorcontrib>BHUIYAN, Zahurul</creatorcontrib><creatorcontrib>BEZZINA, Connie R</creatorcontrib><creatorcontrib>VELDKAMP, Marieke W</creatorcontrib><creatorcontrib>LINNENBANK, André C</creatorcontrib><title>Right ventricular fibrosis and conduction delay in a patient with clinical signs of brugada syndrome : A combined electrophysiological, genetic, histopathologic, and computational study</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown.
A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.
In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.</description><subject>Adult</subject><subject>Amino Acid Substitution</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Cell Line</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Electric Stimulation</subject><subject>Humans</subject><subject>Kidney</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Reference Values</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Sodium Channels - genetics</subject><subject>Sodium Channels - physiology</subject><subject>Syndrome</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><subject>Ventricular Fibrillation - genetics</subject><subject>Ventricular Fibrillation - pathology</subject><subject>Ventricular Fibrillation - physiopathology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O0zAUhSMEYjoDr4DMAlZN8U9sJ-yiCmYqVYw0KuvIsZ3EKLGL7YDyaLwdrhppxIqV5Xu_c8_VPVn2HsEdQgx92h-e9t-P9enw-K1-qHcI0h0lmKHiRbZBFBd5QUn1MttACKucE4xvstsQfqQvI5y-zm4Qw4xjCjfZnyfTDxH80jZ6I-dReNCZ1rtgAhBWAemsmmU0zgKlR7EAY4EAZxFNUoDfJg5AjsYaKUYQTG8DcB1o_dwLJUBYrPJu0uAzqNOkqTVWK6BHLaN352EJxo2uv2i3oNdWRyO3YDAhumQwXHvbdY3pPEdx2eNiFGe1vMledWIM-u363mWnr19O-4f8-Hh_2NfHXBJGYi6w4lzBqmNK6FaVMBVKLljRFrTDRYkVRLokJeNadQnSsCwqpjijTFKIyF328Tr27N3PWYfYTCZIPY7CajeHhpWcUl6W_wUxwqSoYJHA6grKdObgddecvZmEXxoEm0u-zb_5pjJtrvkm7bvVZG4nrZ6Va6AJ-LACIqS7dl5YacIzxzFnnBPyF7BotMA</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>CORONEL, Ruben</creator><creator>CASINI, Simona</creator><creator>VAN DER WAL, Allard C</creator><creator>TAN, Hanno L</creator><creator>BRUGADA, Pedro</creator><creator>WILDE, Arthur A. M</creator><creator>DE BAKKER, Jacques M. T</creator><creator>KOOPMANN, Tamara T</creator><creator>WILMS-SCHOPMAN, Francien J. G</creator><creator>VERKERK, Arie O</creator><creator>DE GROOT, Joris R</creator><creator>BHUIYAN, Zahurul</creator><creator>BEZZINA, Connie R</creator><creator>VELDKAMP, Marieke W</creator><creator>LINNENBANK, André C</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20051101</creationdate><title>Right ventricular fibrosis and conduction delay in a patient with clinical signs of brugada syndrome : A combined electrophysiological, genetic, histopathologic, and computational study</title><author>CORONEL, Ruben ; CASINI, Simona ; VAN DER WAL, Allard C ; TAN, Hanno L ; BRUGADA, Pedro ; WILDE, Arthur A. M ; DE BAKKER, Jacques M. T ; KOOPMANN, Tamara T ; WILMS-SCHOPMAN, Francien J. 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Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Sodium Channels - genetics</topic><topic>Sodium Channels - physiology</topic><topic>Syndrome</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><topic>Ventricular Fibrillation - genetics</topic><topic>Ventricular Fibrillation - pathology</topic><topic>Ventricular Fibrillation - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CORONEL, Ruben</creatorcontrib><creatorcontrib>CASINI, Simona</creatorcontrib><creatorcontrib>VAN DER WAL, Allard C</creatorcontrib><creatorcontrib>TAN, Hanno L</creatorcontrib><creatorcontrib>BRUGADA, Pedro</creatorcontrib><creatorcontrib>WILDE, Arthur A. M</creatorcontrib><creatorcontrib>DE BAKKER, Jacques M. T</creatorcontrib><creatorcontrib>KOOPMANN, Tamara T</creatorcontrib><creatorcontrib>WILMS-SCHOPMAN, Francien J. 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M</au><au>DE BAKKER, Jacques M. T</au><au>KOOPMANN, Tamara T</au><au>WILMS-SCHOPMAN, Francien J. G</au><au>VERKERK, Arie O</au><au>DE GROOT, Joris R</au><au>BHUIYAN, Zahurul</au><au>BEZZINA, Connie R</au><au>VELDKAMP, Marieke W</au><au>LINNENBANK, André C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Right ventricular fibrosis and conduction delay in a patient with clinical signs of brugada syndrome : A combined electrophysiological, genetic, histopathologic, and computational study</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>112</volume><issue>18</issue><spage>2769</spage><epage>2777</epage><pages>2769-2777</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown.
A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.
In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>16267250</pmid><doi>10.1161/CIRCULATIONAHA.105.532614</doi><tpages>9</tpages></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2005-11, Vol.112 (18), p.2769-2777 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Adult Amino Acid Substitution Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular system Cell Line Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Electric Stimulation Humans Kidney Male Medical sciences Pharmacology. Drug treatments Reference Values Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Sodium Channels - genetics Sodium Channels - physiology Syndrome Vasodilator agents. Cerebral vasodilators Ventricular Fibrillation - genetics Ventricular Fibrillation - pathology Ventricular Fibrillation - physiopathology |
| title | Right ventricular fibrosis and conduction delay in a patient with clinical signs of brugada syndrome : A combined electrophysiological, genetic, histopathologic, and computational study |
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