The benefits of adding a defibrillator to cardiac resynchronization therapy – systematic review and meta-analysis
Authors: Veres B , Gharehdaghi S , Engh M , Schwertner W , Kuthi L , Merkel E D , Masszi R , Fehervari P , Behon A , Osztheimer I , Hegyi P , Kovacs A , Zima E , Kosztin A , Merkely B 
Published: October 2022

Abstract

Background
There is an long-standing debate whether cardiac resynchronisation therapy-defibrillation (CRT-D) is preferred over CRT-pacemaker (CRT-P). No randomised controlled trials have been designed to compare these treatments. However, several observational studies have been performed so far providing 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. 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
Altogether 20 observational retrospective studies (69,124 patients) were included (CRT-P: 37,461, CRT-D: 31,663). CRT-D was superior to CRT-P regarding all-cause mortality in multivariate analysis (aHR: 0.79; 95% CI: 0.69–0.88; p&lt;0.01). Based on propensity matched studies (25,040 patients; 12,520 CRT-P, 12,520 CRT-D) CRT-D showed significantly better survival compared to CRT-P (HR: 0.83; 95% CI: 0.79–0.87; p&lt;0.001). 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). Three studies (4,623 patients. CRT-P: 2,518, CRT-D: 2,105) reported on heart failure death, where 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). 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 (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;0.001).

Conclusion
Our meta-analysis demonstrated that patients with CRT-D had a lower risk of all-cause mortality compared to CRT-P based on those studies that used multivariate analysis and propensity score matching. Univariate analysis showed a significantly lower rate of cardiovascular heart failure mortality, sudden cardiac death, and non-cardiac death in patients implanted with a CRT-D device compared to patients with a CRT-P. 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.

Funding Acknowledgement
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. - I agree that this information can be anonymised and then used for statistical purposes only