Clinical outcomes of cardiac synchronization with or without an implantable cardioverter defibrillator based on pooled data from 5 clinical trials: a patient-level meta-analysis
Abstract Body (Do not enter title and authors here): Background: Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with heart failure with reduced ejection fraction (HFrEF) and wide QRS. Whether CRT-defibrillators (CRT-D) reduce mortality more than CRT-pacemakers (CRT-P) remains controversial. Aims: To compare the clinical outcomes of CRT-D vs CRT-P using data from 5 landmark CRT trials, both overall and stratified by etiology of cardiomyopathy (ischemic vs non-ischemic), sex (male vs female), age (≥ 70 y/o vs < 70 y/o), and QRS morphology (IVCD, LBBB, RBBB). Methods: We performed a meta-analysis of patient level data from 5 prospective CRT trials (MIRACLE, REVERSE, RAFT, COMPANION and MADIT-CRT). Inclusion criteria were CRT-P vs CRT-D status (randomized comparison only in COMPANION), age ≥ 18 y/o and LVEF ≤ 35%. Exclusion criteria included secondary prevention ICD, QRS < 120ms, pacemaker upgrade, ventricular pacing indication, or missing data. Primary outcome was composite of time to heart failure hospitalization (HFH) or all-cause death. Secondary outcomes were time to HFH and death. Outcomes were analyzed using a frequentist Cox Proportional Hazards mixed effects model adjusted for 17 variables. Results: A total of 3407 patients met inclusion criteria. Relative to patients with CRT-P (n=843), those with CRT-D (n=2564) were of similar age (66 y/o, p=0.5), less often female (24% vs 34%, p<0.001), and more often had ischemic cardiomyopathy (59.4% vs 52.4%, p<0.001), Fig 1A. Primary outcome was similar across groups (HR 0.902 [0.752, 1.081], p=0.26), but all-cause mortality was lower with CRT-D vs CRT-P (HR 0.77 [0.603, 0.983], p=0.036), Fig 1B. Interaction analyses suggested lower all-cause mortality with CRT-D vs CRT-P in patients with non-ischemic cardiomyopathy (HR 0.502 [0.346, 0.726], p=0.0003) and patients age ≥70 y/o (HR 0.679 [0.502, 0.919], p=0.012), with significance preserved after Bonferroni correction (Fig 1B). Conclusion: In patients receiving CRT for HFrEF, those with CRT-D had lower all-cause mortality than patients with CRT-P, driven mainly by a lower mortality with CRT-D in older patients and those with non-ischemic cardiomyopathy. No significant interactions were noted between ICD & sex or ICD & QRS morphology.
Shadrin, Ilya
( DUKE UNIVERSITY MEDICAL CENTER
, Durham
, North Carolina
, United States
)
Kutyifa, Valentina
( UNIVERSITY OF ROCHESTER
, Rochester
, New York
, United States
)
Linde, Cecilia
( Karolinska Institutet
, Stockholm
, Sweden
)
Young, James
( CLEVELAND CLINIC
, Chagrin Falls
, Ohio
, United States
)
Tang, Anthony
( Western University
, London
, Ontario
, Canada
)
Al-khatib, Sana
( DUKE UNIVERSITY MEDICAL CENTER
, Durham
, North Carolina
, United States
)
Inoue, Lurdes
( University of Washington
, Seattle
, Washington
, United States
)
Schmidler, Gillian
( Duke Clinical Research Institute
, Durham
, North Carolina
, United States
)
Mackenzie, Michael
( Duke Clinical Research Institute
, Durham
, North Carolina
, United States
)
Friedman, Daniel
( DUKE UNIVERSITY MEDICAL CENTER
, Durham
, North Carolina
, United States
)
Abraham, William
( Ohio State University
, Powell
, Ohio
, United States
)
Cleland, John
( University of Glasgow
, Glasgow
, United Kingdom
)
Curtis, Anne
( University at Buffalo
, Buffalo
, New York
, United States
)
Gold, Michael
( MEDICAL UNIVERSITY SOUTH CAROLINA
, Charleston
, South Carolina
, United States
)
Author Disclosures:
Ilya Shadrin:DO NOT have relevant financial relationships
| Valentina Kutyifa:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Boston Scientific:Past (completed)
; Speaker:Biotronik:Past (completed)
; Speaker:Abbott:Past (completed)
; Speaker:Medtronic:Past (completed)
; Research Funding (PI or named investigator):Zoll:Past (completed)
; Consultant:Biotronik:Active (exists now)
; Consultant:Zoll:Active (exists now)
; Research Funding (PI or named investigator):NIH:Active (exists now)
; Research Funding (PI or named investigator):Spire Inc:Active (exists now)
; Research Funding (PI or named investigator):Biotronik:Active (exists now)
| Cecilia Linde:DO have relevant financial relationships
;
Consultant:astra zeneca:Active (exists now)
; Research Funding (PI or named investigator):swedish academy of science:Active (exists now)
; Research Funding (PI or named investigator):swedish heart lungfoundation:Active (exists now)
; Advisor:medtronic:Active (exists now)
; Speaker:Impulse dynamics:Active (exists now)
; Speaker:boehringer ingelheim:Past (completed)
; Speaker:vifor:Past (completed)
; Speaker:medtronic:Active (exists now)
| James Young:DO NOT have relevant financial relationships
| Anthony TANG:DO NOT have relevant financial relationships
| Sana Al-Khatib:DO have relevant financial relationships
;
Other (please indicate in the box next to the company name):AHA:Active (exists now)
| Lurdes Inoue:DO NOT have relevant financial relationships
| Gillian Schmidler:No Answer
| Michael MacKenzie:DO NOT have relevant financial relationships
| Daniel Friedman:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Boston Scientific:Active (exists now)
; Research Funding (PI or named investigator):Phillips:Active (exists now)
; Consultant:MicroPort CRM:Past (completed)
; Consultant:Alleviant:Active (exists now)
; Consultant:Boston Scientific:Active (exists now)
; Consultant:Medtronic :Active (exists now)
; Consultant:Abbott:Active (exists now)
; Research Funding (PI or named investigator):Merit Medical:Past (completed)
; Research Funding (PI or named investigator):Medtronic:Active (exists now)
| William Abraham:No Answer
| John Cleland:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Pharmacosmos:Active (exists now)
; Individual Stocks/Stock Options:Viscardia:Active (exists now)
; Individual Stocks/Stock Options:Heartfelt:Active (exists now)
; Research Funding (PI or named investigator):CSL Vifor:Past (completed)
| Anne Curtis:DO have relevant financial relationships
;
Consultant:Medtronic:Active (exists now)
; Speaker:Sanofi Aventis:Active (exists now)
; Consultant:Janssen Pharmaceuticals:Active (exists now)
; Consultant:Abbott:Active (exists now)
; Speaker:Medtronic:Active (exists now)
| Michael Gold:DO have relevant financial relationships
;
Consultant:Boston Scientific:Active (exists now)
; Speaker:Abbott:Past (completed)
; Consultant:Medtronic:Past (completed)
Bueno Claudia, Souza Barbara, Santos Aline, Da Silva Ferreira Laíse Jorrana, Varao Thawanny, Cunha Carneiro Maria Angelica, Gomes Laysa, Teixeira Costa Ana Carolina, Miranda Luana, Martin Joelma, Rocha Nathalia, Dias Adria