{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:44:21Z","timestamp":1789753461570,"version":"4.0.1"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as &gt;14 infiltrating cells\/mm\n              <jats:sup>2<\/jats:sup>\n              . Echocardiographic left ventricular end-systolic volume reduction \u226515% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12\u20130.76];\n              <jats:italic>P<\/jats:italic>\n              =0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular,\n              <jats:italic>COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGF\u03b21, PDGFRA, TNC, BGN<\/jats:italic>\n              , and\n              <jats:italic>TSP2<\/jats:italic>\n              were significantly higher expressed in the hearts of nonresponders.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.120.008727","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T16:39:24Z","timestamp":1601483964000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-1298","authenticated-orcid":true,"given":"Job A.J.","family":"Verdonschot","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."},{"name":"Clinical Genetics (J.A.J.V., K.W.J.D., P.W., H.G.B.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jort J.","family":"Merken","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius M.W.","family":"van Stipdonk","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Pliger","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology and Angiology, Innsbruck Medical University, Austria (P.P., G.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5609-5008","authenticated-orcid":true,"given":"Kasper W.J.","family":"Derks","sequence":"additional","affiliation":[{"name":"Clinical Genetics (J.A.J.V., K.W.J.D., P.W., H.G.B.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8876-4210","authenticated-orcid":true,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Genetics (J.A.J.V., K.W.J.D., P.W., H.G.B.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-071X","authenticated-orcid":true,"given":"Michiel T.H.M.","family":"Henkens","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-7995","authenticated-orcid":true,"given":"Pieter","family":"van Paassen","sequence":"additional","affiliation":[{"name":"Immunology (P.v.P.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrurgia A.","family":"Abdul Hamid","sequence":"additional","affiliation":[{"name":"Pathology (M.A.A.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0296","authenticated-orcid":true,"given":"Vanessa P.M.","family":"van Empel","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-3010","authenticated-orcid":true,"given":"Christian","family":"Knackstedt","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin G.L.M.","family":"Luermans","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1073-5337","authenticated-orcid":true,"given":"Harry J.G.M.","family":"Crijns","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Brunner-La Rocca","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (CARIM), Departments of Cardiology (J.A.J.V., J.J.M., A.M.W.v.S., M.T.H.M.H., V.P.M.v.E., C.K., J.G.L.M.L., H.J.G.M.C., H.-P.B.-L.R., K.V., S.R.B.H., M.R.H.), Maastricht University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-8865","authenticated-orcid":true,"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Clinical Genetics (J.A.J.V., K.W.J.D., P.W., H.G.B.), Maastricht University Medical Center, the Netherlands."},{"name":"GROW Institute for Developmental Biology and Cancer (H.G.B.), Maastricht University Medical Center, the Netherlands."},{"name":"Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour (H.G.B.), Radboud University Medical Center, Nijmegen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Poelzl","sequence":"additional","affiliation":[{"name":"Clinical Division of Cardiology and Angiology, Innsbruck Medical University, Austria (P.P., 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