TY - JOUR
T1 - Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy
AU - Verdonschot, Job A. J.
AU - Merken, Jort J.
AU - van Stipdonk, Antonius M. W.
AU - Pliger, Philipp
AU - Derks, Kasper W. J.
AU - Wang, Ping
AU - Henkens, Michiel T. H. M.
AU - van Paassen, Pieter
AU - Hamid, Myrurgia A. Abdul
AU - van Empel, Vanessa P. M.
AU - Knackstedt, Christian
AU - Luermans, Justin G. L. M.
AU - Crijns, Harry J. G. M.
AU - Brunner-La Rocca, Hans-Peter
AU - Brunner, Han G.
AU - Poelzl, Gerhard
AU - Vernooy, Kevin
AU - Heymans, Stephane R. B.
AU - Hazebroek, Mark R.
N1 - Funding Information:
The research leading to these results has received funding from the European Union Commission’s Seventh Framework program under grant agreement no. 305507 (HOMAGE [Heart Omics in Ageing]) and IMI2-CARDIATEAM (Cardiomyopathy in Type 2 Diabetes Mellitus; No. 821508).
Funding Information:
This article has been possible thanks to the support of the ERA-Net-CVD project MacroERA, 01KL1706. We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF (Heart Failure With Preserved Ejection Fraction), 2015-10, CVON She-PREDICTS, grant 2017-21, CVON Arena-PRIME, 2017-18. Furthermore, we acknowledge the support of FWO G091018N and FWO G0B5930N; Kootstra Talent Fellowship of the Maastricht UMC+ to Dr Hazebroek.
Publisher Copyright:
© 2020 American Heart Association, Inc.
PY - 2020/11
Y1 - 2020/11
N2 - 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/mm(2). 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 PConclusions: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.
AB - 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/mm(2). 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 PConclusions: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.
KW - cardiac resynchronization therapy
KW - cardiomyopathies
KW - fibrosis
KW - inflammation
KW - transcriptome
KW - DEFIBRILLATOR IMPLANTATION TRIAL
KW - BUNDLE-BRANCH BLOCK
KW - EUROPEAN-SOCIETY
KW - ESC GUIDELINES
KW - PREDICTORS
KW - DIAGNOSIS
KW - IMPROVEMENT
KW - STATEMENT
U2 - 10.1161/circep.120.008727
DO - 10.1161/circep.120.008727
M3 - Article
C2 - 32997547
SN - 1941-3149
VL - 13
SP - 1311
EP - 1320
JO - Circulation-Arrhythmia and Electrophysiology
JF - Circulation-Arrhythmia and Electrophysiology
IS - 11
M1 - 008727
ER -