Domenico Corradi1, Sergio Callegari2, Laura Manotti3, David Ferrara4, Matteo Goldoni5, Rossella Alinovi5, Silvana Pinelli5, Paola Mozzoni6, Roberta Andreoli6, Angeliki Asimaki7, Alberto Pozzoli4, Gabriella Becchi3, Antonio Mutti5, Stefano Benussi4, Jeffrey E Saffitz7, Ottavio Alfieri4. 1. Department of Biomedical, Biotechnological, and Translational Sciences (S.Bi.Bi.T.), Unit of Pathology, University of Parma, Parma, Italy. Electronic address: domenico.corradi@unipr.it. 2. Division of Cardiology, Vaio Hospital, Fidenza, Italy. 3. Department of Biomedical, Biotechnological, and Translational Sciences (S.Bi.Bi.T.), Unit of Pathology, University of Parma, Parma, Italy. 4. Cardiothoracic Surgery Unit, Department of Cardiology, San Raffaele University Hospital, Milan, Italy. 5. Department of Clinical and Experimental Medicine, Laboratory of Industrial Toxicology, University of Parma, Parma, Italy. 6. Department of Clinical and Experimental Medicine, Laboratory of Industrial Toxicology, University of Parma, Parma, Italy; Italian Workers' Compensation Authority (INAIL) Research Center at the University of Parma, Parma, Italy. 7. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: The extent to which atrial myocardium is remodeled in patients with persistent lone atrial fibrillation (LAF) is largely unknown. OBJECTIVE: The purpose of this study was to perform a clinicopathologic investigation in patients with persistent LAF. METHODS: We characterized structural and molecular remodeling in atrial biopsies from 19 patients (17 males, mean age 49 years) with persistent (>7 days; n = 8) or long-lasting persistent (>1 year; n = 11) LAF who underwent surgical ablation. Atrial tissue from 15 autopsy samples without clinicopathologic evidence of heart disease served as controls. RESULTS: Morphometric analysis showed cardiomyocyte hypertrophy and greater amounts of myolytic damage and interstitial fibrosis in persistent LAF patients compared to controls (P <.0001). Atrial tissue levels of heme oxygenase-1 and 3-nitrotyrosine were increased in persistent LAF patients (P <.001), consistent with oxidative stress. Levels of superoxide dismutase-2, interleukin-8, interleukin-10, tumor necrosis factor-α, and thiobarbituric acid reactive substance were greater in controls than in persistent LAF patients. Immunoreactive signal for connexin43 was reduced more frequently in persistent LAF patients than controls. There was no correlation between features of structural or molecular remodeling and clinical parameters, including persistent LAF duration. CONCLUSION: In persistent LAF patients, the atria are modified by structural remodeling and molecular changes of oxidative stress. Tissue changes in persistent LAF appear to occur early after its onset and are qualitatively no different than those observed in patients with atrial fibrillation related to conventional risk factors. These findings suggest that different types of atrial fibrillation are associated with the same spectrum of tissue lesions. Early intervention to restore sinus rhythm in persistent LAF patients may prevent irreversible tissue change, especially interstitial fibrosis.
BACKGROUND: The extent to which atrial myocardium is remodeled in patients with persistent lone atrial fibrillation (LAF) is largely unknown. OBJECTIVE: The purpose of this study was to perform a clinicopathologic investigation in patients with persistent LAF. METHODS: We characterized structural and molecular remodeling in atrial biopsies from 19 patients (17 males, mean age 49 years) with persistent (>7 days; n = 8) or long-lasting persistent (>1 year; n = 11) LAF who underwent surgical ablation. Atrial tissue from 15 autopsy samples without clinicopathologic evidence of heart disease served as controls. RESULTS: Morphometric analysis showed cardiomyocyte hypertrophy and greater amounts of myolytic damage and interstitial fibrosis in persistent LAFpatients compared to controls (P <.0001). Atrial tissue levels of heme oxygenase-1 and 3-nitrotyrosine were increased in persistent LAFpatients (P <.001), consistent with oxidative stress. Levels of superoxide dismutase-2, interleukin-8, interleukin-10, tumor necrosis factor-α, and thiobarbituric acid reactive substance were greater in controls than in persistent LAFpatients. Immunoreactive signal for connexin43 was reduced more frequently in persistent LAFpatients than controls. There was no correlation between features of structural or molecular remodeling and clinical parameters, including persistent LAF duration. CONCLUSION: In persistent LAFpatients, the atria are modified by structural remodeling and molecular changes of oxidative stress. Tissue changes in persistent LAF appear to occur early after its onset and are qualitatively no different than those observed in patients with atrial fibrillation related to conventional risk factors. These findings suggest that different types of atrial fibrillation are associated with the same spectrum of tissue lesions. Early intervention to restore sinus rhythm in persistent LAFpatients may prevent irreversible tissue change, especially interstitial fibrosis.
Authors: Andreas Goette; Jonathan M Kalman; Luis Aguinaga; Joseph Akar; Jose Angel Cabrera; Shih Ann Chen; Sumeet S Chugh; Domenico Corradi; Andre D'Avila; Dobromir Dobrev; Guilherme Fenelon; Mario Gonzalez; Stephane N Hatem; Robert Helm; Gerhard Hindricks; Siew Yen Ho; Brian Hoit; Jose Jalife; Young-Hoon Kim; Gregory Y H Lip; Chang-Sheng Ma; Gregory M Marcus; Katherine Murray; Akihiko Nogami; Prashanthan Sanders; William Uribe; David R Van Wagoner; Stanley Nattel Journal: Heart Rhythm Date: 2016-06-10 Impact factor: 6.343
Authors: Brian J Hansen; Jichao Zhao; Thomas A Csepe; Brandon T Moore; Ning Li; Laura A Jayne; Anuradha Kalyanasundaram; Praise Lim; Anna Bratasz; Kimerly A Powell; Orlando P Simonetti; Robert S D Higgins; Ahmet Kilic; Peter J Mohler; Paul M L Janssen; Raul Weiss; John D Hummel; Vadim V Fedorov Journal: Eur Heart J Date: 2015-06-08 Impact factor: 29.983
Authors: Kotaro Fukumoto; Mohammadali Habibi; Esra Gucuk Ipek; Irfan M Khurram; Stefan L Zimmerman; Vadim Zipunnikov; David D Spragg; Hiroshi Ashikaga; John Rickard; Joseph E Marine; Ronald D Berger; Hugh Calkins; Saman Nazarian Journal: Heart Rhythm Date: 2014-12-19 Impact factor: 6.343
Authors: Aaron Kunamalla; Jason Ng; Vamsi Parini; Shin Yoo; Kate A McGee; Todd T Tomson; David Gordon; Edward B Thorp; Jon Lomasney; Qiang Zhang; Sanjiv Shah; Suzanne Browne; Bradley P Knight; Rod Passman; Jeffrey J Goldberger; Gary Aistrup; Rishi Arora Journal: Circ Res Date: 2016-05-23 Impact factor: 17.367
Authors: Andreas Goette; Jonathan M Kalman; Luis Aguinaga; Joseph Akar; Jose Angel Cabrera; Shih Ann Chen; Sumeet S Chugh; Domenico Corradi; Andre D'Avila; Dobromir Dobrev; Guilherme Fenelon; Mario Gonzalez; Stephane N Hatem; Robert Helm; Gerhard Hindricks; Siew Yen Ho; Brian Hoit; Jose Jalife; Young-Hoon Kim; Gregory Y H Lip; Chang-Sheng Ma; Gregory M Marcus; Katherine Murray; Akihiko Nogami; Prashanthan Sanders; William Uribe; David R Van Wagoner; Stanley Nattel Journal: J Arrhythm Date: 2016-07-11