The benefits of adding a defibrillator to cardiac resynchronization therapy - Systematic review and meta-analysis
Authors: Veres B , Schwertner WR , Engh M , Masszi R , Kuthi L , Behon A , Merkel ED , Osztheimer I , Fehervari P , Ghare S , Pinter A , Zima E , Hegyi P , Kosztin A , Merkely B 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): The research presented here, carried out by Semmelweis University was supported by Semmelweis 250+ Excellence Scholarship (EFOP-3.6.3-VEKOP-16-2017-00009)as well as the Centre for Translational Medicine, Semmelweis University. This work was financed by the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programmes of the Semmelweis University.

Background
There is an enduring controversy whether cardiac resynchronisation therapy-defibrillation (CRT-D) is preferred over CRT-pacemaker (CRT-P). No head-to-head randomised controlled trials have been designed to compare the treatments. However, several observational studies were performed during previous years, but they got controversial results.

Methods
PubMed, CENTRAL and Embase until October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on all-cause mortality, cardiovascular mortality, sudden cardiac death, and non-cardiac death. Both interventional and observational studies comparing CRT-D and CRT-P patients were included. Studies only available as conference abstracts were excluded. Odds ratio with 95% confidence interval (CI) was calculated, data from the selected studies were pooled using a random effect model (Mantel-Haenszel method, where more than 5 studies with Hartung-Knapp adjustment). τ2 was estimated by Paule-Mandel method with CI calculated by Q profile method. Statistical heterogeneity was assessed by Cochrane Q test and I2 test. Results were summarized by Forest and drapery plots.
Results: 16 observational studies(57,337 patients) were included(CRT-P: 32 591, CRT-D: 24 746). CRT-D was superior to CRT-P regarding all-cause mortality in univariate analysis(HR:0.73; 95% CI:0.64-0.83; p &lt;0.01). The between-study heterogeneity (I2) value was not significant. The random-effects τ2 value was 0.02 (95% CI:0-0.06). Three studies(47,846 patients, CRT-P: 27,344, CRT-D: 20,502) compared cardiovascular mortality between CRT-D and CRT-P. Univariate analysis showed a significantly lower rate of cardiovascular mortality in patients implanted with a CRT-D device compared to patients with a CRT-P device.(HR:0.61; 95% CI:0.50-0.73; p=0.002) Five studies (6,434 patients. CRT-P:3,475, CRT-D:2,959) were analyzed for sudden cardiac death, CRT-D was superior in univariate analysis(HR:0.33; 95% CI:0.28-0.89; p=0.03). Three studies (4,623 patients. CRT-P:2,518, CRT-D:2,105) reported on heart failure death, CRT-D was associated with decreased heart failure mortality compared to CRT-P(HR:0.68; 95% CI: 0.41-0.95; p=0.008). Three studies(48,770 patients ,CRT-P:28,398, CRT-D: 20,372) reported on non-cardiac death, CRT-D showed significantly better survival than CRT-P(HR:0.58; 95% CI:0.55-0.60; p&lt;0.0001).
Conclusion: Our work demonstrates an association between CRT-D and lower all-cause mortality, cardiovascular and heart failure mortality, sudden cardiac death, and non-cardiac death. However, due to the heterogeneity of the articles coming from the selection bias of patients for CRT-D/CRT-P implantation, this question requires further analysis.