Author + information
- Received April 18, 2019
- Revision received August 15, 2019
- Accepted September 9, 2019
- Published online November 18, 2019.
- Niraj Varma, MD, PhDa,∗ (, )@ClevelandClinic,
- John Boehmer, MDb,
- Kartikeya Bhargava, MDc,
- Dale Yoo, MDd,
- Fabio Leonelli, MDe,
- Mariarosa Costanzo, MDf,
- Anil Saxena, MDg,
- Lixian Sun, MSh,
- Michael R. Gold, MD, PhDi,
- Jagmeet Singh, MDj,
- John Gill, PhDh and
- Angelo Auricchio, MD, PhDk
- aCleveland Clinic, Cleveland, Ohio
- bPenn State Hershey Heart and Vascular Institute, Hershey, Pennsylvania
- cMedanta-The Medicity Hospital, Gurgaon, India
- dNorth Texas Heart Center, McKinney, Texas
- eU.S. Department of Veterans Affairs, Tampa, Florida
- fAdvocate Heart Institute, Naperville, Illinois
- gEscorts Heart Institute and Research Center, New Delhi, India
- hAbbott, Sylmar, California
- iMedical University of South Carolina, Charleston, South Carolina
- jMassachusetts General Hospital, Boston, Massachusetts
- kCardiocentro Ticino, Lugano, Switzerland
- ↵∗Address for correspondence:
Dr. Niraj Varma, Cardiac Pacing & Electrophysiology, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue J2-2, Cleveland, Ohio 44195.
Background “Nonresponse” to cardiac resynchronization therapy (CRT) is recognized, but definition(s) applied in practice, treatment(s), and their consequences are little known.
Objectives The authors sought to assess nonresponse in the prospective, international, ADVANCE CRT registry (Advance Cardiac Resynchronization Therapy Registry).
Methods Each subject’s response was assessed at 6 months post-implantation using site-specific definitions and compared with the independently derived clinical composite score (CCS). Treatment(s) and hospitalization(s) were tracked during the following 6 months.
Results Of 1,524 subjects enrolled in 69 centers (68 ± 12 years of age, 32% female, ischemic disease 39%), 74.3% received CRT-defibrillator devices, using mainly quadripolar LV leads (75%) deployed laterally (78%). Indications for CRT were wider than past trials. Among 1,327 evaluable subjects, site-defined nonresponse was 20.0% (greater age, comorbidities, ischemic cardiomyopathy, non-left bundle branch block, and lower %CRT pacing vs. responders). Site definitions used mainly clinical criteria (echocardiography infrequently), and underestimated nonresponders by 35% compared with CCS (58% sensitivity vs. CCS). Overall, more site-defined nonresponders received treatment (55.9% vs. 38.3% of responders; p < 0.001) using medication changes and heart failure education, but device programming less frequently. Intensification of in-clinic/remote evaluations and involvement of heart failure specialists remained minimal. Remarkably, 44% of site-defined nonresponders received no additional treatment. Frequency and duration of hospitalizations, and death, among site-defined nonresponders was significantly higher than responders.
Conclusions A high incidence of CRT nonresponders persists despite good patient selection and LV lead position, but site identification methods have modest sensitivity. Following diagnosis, nonresponders are often passively managed, without specialty care, with poor outcome. ADVANCE CRT exposes a vulnerable group of heart failure patients. (Advance Cardiac Resynchronization Therapy Registry [ADVANCE CRT]; NCT01805154)
This registry was funded by Abbott. Dr. Varma has received consulting fees/honoraria from St. Jude Medical, Boston Scientific, Biotronik, and Medtronic. Dr. Boehmer has received consulting fees/honoraria from Boston Scientific, Abbott, and Medtronic; and has received research grants from Abbott. Dr. Costanzo has been a consultant for Abbott, Medtronic, and Boston Scientific; and has received institutional research funds from Abbott. Ms. Sun is an employee of Abbott/St. Jude Medical. Dr. Gold has been a consultant for and/or received funding from St. Jude Medical, EBR, Medtronic, and BSC. Dr. Singh has been a consultant for Biotronik, Boston Scientific, Medtronic, Abbott, Microport, EBR, Respicardia, Impulse Dynamics, BackBeat Inc., and Toray Inc. Dr. Gill is an employee of Abbott/St. Jude Medical. Dr. Auricchio has received speaker fees from and/or holds intellectual property with Abbott, Biosense Webster, Boston Scientific, Medtronic, Microport-CRM, Philips, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 18, 2019.
- Revision received August 15, 2019.
- Accepted September 9, 2019.
- 2019 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.