Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 5;25(10):euad289.
doi: 10.1093/europace/euad289.

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis

Boglárka Veres  1   2 , Péter Fehérvári  2   3 , Marie Anne Engh  2 , Péter Hegyi  2   4 , Sara Gharehdaghi  2   5 , Endre Zima  1   2 , Gábor Duray  2   6 , Béla Merkely  1 , Annamária Kosztin  1   2
Affiliations

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis

Boglárka Veres et al. Europace. .

Abstract

Aims: This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades.

Methods and results: PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time.

Conclusion: The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Keywords: CRT-P vs. CRT-D; Cardiac resynchronization therapy; Heart failure; Meta-analysis; Sudden cardiac death.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Béla Merkely reports grants from Boston Scientific, NRDIF Hungary, National Heart Program; personal fees from Biotronik, Abbott, Astra Zeneca, Novartis, and Boehringer-Ingelheim; and grants from Medtronic outside the submitted work. Annamária Kosztin reports grants from Bolyai Research Scholarship, consulting fees from Medtronic, personal fees from Biotronic, Boehringer-Ingelheim, Boston Scientific, AstraZeneca, Bayer, and Novartis outside the submitted work, and travel fees from AstraZeneca and Novartis outside the submitted work and reports participation on a Data Safety Monitoring Board or Advisory Board with Boehringer Ingelheim and Boston Scientific outside the submitted work. She is a committee member of the Hungarian Society of Cardiology and the secretary of the Working Group on Cardiac Arrhythmias and Pacing, Hungarian Society of Cardiology outside the submitted work. All other authors declare no competing interests.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
PRISMA flow chart of searching for publications. HR, hazard ratio.
Figure 2
Figure 2
(A) Risk of all-cause mortality based on hazard ratio in CRT-D vs. CRT-P patients. Forest plot of studies with data on all-cause mortality using hazard ratios. The analysis included 18 studies comparing 36 421 CRT-D patients with 26 473 CRT-P patients. The HR was 0.74 (95% CI: 0.66–0.82). (B) Risk of all-cause mortality based on adjusted hazard ratio in CRT-D vs. CRT-P patients. Forest plot of studies with data on all-cause mortality using adjusted hazard ratios. The analysis included 22 studies comparing 40 434 CRT-D patients with 33 054 CRT-P patients. The aHR was 0.85 (95% CI: 0.76–0.94). (C) Risk of all-cause mortality based on PSM in CRT-D vs. CRT-P patients. Forest plot of studies with data on all-cause mortality using PSM. The analysis included eight studies comparing 13 220 CRT-D patients with 13 220 CRT-P patients. The HR was 0.83 (95% CI: 0.80–0.87). aHR, adjusted hazard ratio; CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; CRT-P, cardiac resynchronization therapy with pacemaker.
Figure 3
Figure 3
(A) Risk of mortality from progressions of heart failure. Forest plot of studies with data on heart failure mortality using hazard ratios. The analysis included three studies comparing 2618 CRT-D patients with 2105 CRT-P patients. The HR was 0.59 (95% CI: 0.41–0.85). (B) Risk of mortality from sudden cardiac death. Forest plot of studies with data on sudden cardiac death using hazard ratios. The analysis included five studies comparing 3475 CRT-D patients with 2959 CRT-P patients. The HR was 0.45 (95% CI: 0.32–0.62). (C) Risk of mortality from cardiovascular mortality. Forest plot of studies with data on cardiovascular mortality using hazard ratios. The analysis included four studies comparing 28 452 CRT-D patients with 21 382 CRT-P patients. The HR was 0.68 (95% CI: 0.49–0.94). CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; CRT-P, cardiac resynchronization therapy with pacemaker; HR, hazard ratio.
Figure 4
Figure 4
(A) Risk of mortality by aetiology in CRT-D vs. CRT-P patients, Forest plot of studies with data on all-cause mortality by ischaemic and non-ischaemic aetiology using hazard ratios. The ischaemic analysis included five studies comparing 3171 CRT-D patients with 1643 CRT-P patients. The HR was 0.80 (95% CI:0.67–0.94). The non-ischaemic analysis included seven studies comparing 7021 CRT-D patients with 3248 CRT-P patients. The HR was 0.95 (95% CI: 0.79–1.15), but there was no mortality difference between CRT-D and CRT-P patients. (B) Risk of mortality over 75 years in CRT-D vs. CRT-P patients. Forest plot of studies with data on all-cause mortality by age. Only patients above 75 years were included. The analysis included six studies comparing 3623 CRT-D patients with 1788 CRT-P patients. The HR was 1.08 (95% CI: 0.96–1.21) There was no mortality difference between CRT-D and CRT-P patients. CI, confidence interval; CRT-D, cardiac resynchronization therapy with defibrillator; CRT-P, cardiac resynchronization therapy with pacemaker; HR, hazard ratio.
Figure 5
Figure 5
(A) Time-trend variation of all-cause mortality by device type. To assess the temporal effect on all-cause mortality HRs, we first took each study’s reported timespan (in years) and calculated the midpoint for each time period. These central values were used in a meta-regression. Hazard ratios were slightly decreased, and CRT-D showed a better treatment effect of CRT-D on mortality could be observed over the years. (B) Time-trend variation of ischaemic aetiology. The percentage of ischaemic patients was shown over time. A trend could be observed for a higher prevalence of ischaemic patients among CRT-P candidates. (C) Time-trend variation of reported mean age. A time trend in age was shown, and the mean age of CRT-P patients increased, which was not such pronounced in the CRT-D cohorts. CRT-D, cardiac resynchronization therapy with defibrillator; CRT-P, cardiac resynchronization therapy with pacemaker; HR, hazard ratio.
See this image and copyright information in PMC

Comment in

  • CRT-D or CRT-P?: the endless debate!
    Daubert JC. Daubert JC. Europace. 2023 Oct 5;25(10):euad285. doi: 10.1093/europace/euad285. Europace. 2023. PMID: 37713248 Free PMC article. No abstract available.

References

    1. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JPet al. . Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:1329–38. - PubMed
    1. Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IMet al. . 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the European Heart Rhythm Association (EHRA). Eur Heart J 2021;42:3427–520. - PubMed
    1. Cleland JGF, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger Let al. . The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539–49. - PubMed
    1. Rohde LE, Chatterjee NA, Vaduganathan M, Claggett B, Packer M, Desai ASet al. . Sacubitril/valsartan and sudden cardiac death according to implantable cardioverter-defibrillator use and heart failure cause: A PARADIGM-HF analysis. JACC Heart Fail 2020;8:844–55. - PubMed
    1. Fernandes GC, Fernandes A, Cardoso R, Penalver J, Knijnik L, Mitrani RDet al. . Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: A meta-analysis of 34 randomized controlled trials. Heart Rhythm 2021;18:1098–105. - PubMed