Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy.

Autor: Verdonschot, Job A.J., Merken, Jort J., van Stipdonk, Antonius M.W., Pliger, Philipp, Derks, Kasper W.J., Wang, Ping, Henkens, Michiel T.H.M., van Paassen, Pieter, Abdul Hamid, Myrurgia A., van Empel, Vanessa P.M., Knackstedt, Christian, Luermans, Justin G.L.M., Crijns, Harry J.G.M., Brunner-La Rocca, Hans-Peter, Brunner, Han G., Poelzl, Gerhard, Vernooy, Kevin, Heymans, Stephane R.B., Hazebroek, Mark R.
Zdroj: Circulation: Arrhythmia & Electrophysiology; Nov2020, Vol. 13 Issue 11, pe008727-e008727, 1p
Abstrakt: Background: 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. Methods: 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 >14 infiltrating cells/mm2. Echocardiographic left ventricular end-systolic volume reduction >=15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders. Results: 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 [0.12-0.76]; P =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 P <0.001).> COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGF[beta]1, PDGFRA, TNC, BGN , and TSP2 were significantly higher expressed in the hearts of nonresponders. Conclusions: 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. * One-third of the dilated cardiomyopathy patients shows less than expected reverse remodeling as response to cardiac resynchronization therapy despite having an indication. * A native left bundle branch block pattern, female sex, sinus rhythm, and a wider QRS duration are associated with a positive response to cardiac resynchronization therapy. * Cardiac inflammation is a negative predictor for response to cardiac resynchronization therapy in dilated cardiomyopathy patients, odds ratio 0.3 (95% CI, 0.12-0.76), and significantly improved prediction of cardiac resynchronization therapy response when added to the clinical parameters, area under the curve 0.714+/-0.1 versus 0.628+/-0.11, likelihood ratio test P <0.001.> * Proinflammatory genes are upregulated in the hearts of dilated cardiomyopathy patients who do not respond to cardiac resynchronization therapy. * Determining cardiac inflammation before device implantation can help to predict which patient will benefit most from cardiac resynchronization therapy. This study may help shape the development of future studies, which aim to treat the inflammation before device implantation, to see whether it is possible to turn a nonresponder into a responder. [ABSTRACT FROM AUTHOR]
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