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Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial


Varma, Niraj; Sogaard, Peter; Bax, Jeroen J; Abraham, William T; Borer, Jeffrey S; Dickstein, Kenneth; Singh, Jagmeet P; Gras, Daniel; Holzmeister, Johannes; Brugada, Josep; Ruschitzka, Frank (2018). Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial. Journal of the American Heart Association, 7(11):e009592.

Abstract

BACKGROUND Longer QRS duration (QRSd) improves, but increased left ventricular (LV) end-diastolic volume (LVEDV) reduces, efficacy of cardiac resynchronization therapy (CRT). QRSd/LVEDV ratios differ between sexes. We hypothesized that in the EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial enrolling patients with heart failure with QRSd <130 ms, those with larger LVEDV would deteriorate but those with the highest QRSd/LVEDV would with CRT. METHODS AND RESULTS Primary outcome in patients (n=787, 72% men, 93% New York Heart Association class III, QRSd <130 ms, LV ejection fraction ≤35%, LV dilation and dyssynchrony) randomized to CRT-ON or CRT-OFF and followed up for 19 months was compared according to LVEDV (height indexed) or QRSd/LVEDV ratio, in multivariable analysis. Structural remodeling was assessed echocardiographically 6 months after implantation. Patients with baseline LVEDV higher than or equal to median worsened with CRT (death/heart failure hospitalization: CRT-ON versus CRT-OFF, 35.2% versus 24.5% [hazard ratio, 1.64; 95% confidence interval, 1.11-2.42; =0.012]), but those with LVEDV lower than median remained unaffected. Patients with the highest QRSd/LVEDV ratio improved with CRT (death/heart failure hospitalization in top quartile: 20.9% in CRT-ON [n=91] versus 28.3% in CRT-OFF [n=106] [hazard ratio, 0.64; 95% confidence interval, 0.34-1.24; =0.188], versus the remaining quartiles: 31.7% in CRT-ON [n=300] versus 24.8% in CRT-OFF [n=290] [hazard ratio, 1.47; 95% confidence interval, 1.07-2.02; =0.016], test for interaction =0.046). QRSd and dyssynchrony were similar between groups. The 3-way test for interaction indicated no sex-specific effects. However, numerically, men with LVEDV higher than or equal to median accounted for worse outcomes of CRT-ON. Women, with the highest QRSd/LVEDV ratio exhibited significant reverse remodeling. CONCLUSION CRT has opposite effects among patients with heart failure with QRSd <130 ms according to LV size: worsening outcomes in patients with larger LV, but inducing beneficial effects in those with smaller LV. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00683696.

Abstract

BACKGROUND Longer QRS duration (QRSd) improves, but increased left ventricular (LV) end-diastolic volume (LVEDV) reduces, efficacy of cardiac resynchronization therapy (CRT). QRSd/LVEDV ratios differ between sexes. We hypothesized that in the EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial enrolling patients with heart failure with QRSd <130 ms, those with larger LVEDV would deteriorate but those with the highest QRSd/LVEDV would with CRT. METHODS AND RESULTS Primary outcome in patients (n=787, 72% men, 93% New York Heart Association class III, QRSd <130 ms, LV ejection fraction ≤35%, LV dilation and dyssynchrony) randomized to CRT-ON or CRT-OFF and followed up for 19 months was compared according to LVEDV (height indexed) or QRSd/LVEDV ratio, in multivariable analysis. Structural remodeling was assessed echocardiographically 6 months after implantation. Patients with baseline LVEDV higher than or equal to median worsened with CRT (death/heart failure hospitalization: CRT-ON versus CRT-OFF, 35.2% versus 24.5% [hazard ratio, 1.64; 95% confidence interval, 1.11-2.42; =0.012]), but those with LVEDV lower than median remained unaffected. Patients with the highest QRSd/LVEDV ratio improved with CRT (death/heart failure hospitalization in top quartile: 20.9% in CRT-ON [n=91] versus 28.3% in CRT-OFF [n=106] [hazard ratio, 0.64; 95% confidence interval, 0.34-1.24; =0.188], versus the remaining quartiles: 31.7% in CRT-ON [n=300] versus 24.8% in CRT-OFF [n=290] [hazard ratio, 1.47; 95% confidence interval, 1.07-2.02; =0.016], test for interaction =0.046). QRSd and dyssynchrony were similar between groups. The 3-way test for interaction indicated no sex-specific effects. However, numerically, men with LVEDV higher than or equal to median accounted for worse outcomes of CRT-ON. Women, with the highest QRSd/LVEDV ratio exhibited significant reverse remodeling. CONCLUSION CRT has opposite effects among patients with heart failure with QRSd <130 ms according to LV size: worsening outcomes in patients with larger LV, but inducing beneficial effects in those with smaller LV. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00683696.

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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:27 May 2018
Deposited On:15 Feb 2019 09:56
Last Modified:15 Feb 2019 10:08
Publisher:Wiley Open Access
ISSN:2047-9980
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/JAHA.118.009592
PubMed ID:29807890

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