Cardiac resynchronization therapy (CRT) is a demonstrably effective device intervention for patients with broad QRS and ventricular dysfunction and is a class I indication for patients in sinus rhythm, LBBB and EF ? 30-35%. However, many patients with heart failure (HF) are unable to maintain sinus rhythm and approximately 30-36% of CRT patients are in atrial fibrillation (AF). Unfortunately, there is lack of evidence for the benefits of CRT in the absence of sinus rhythm. The recent RAFT study in patients with less advanced HF found no benefit at all for CRT for permanent AF patients although most patients did not achieve sufficient biventricular pacing. Approximately 100,000 CRT implants were performed in the US in 2011 at a cost of approximately $1.8 billion. The absence of CRT benefit in the high-risk subset of AF patients who undergo CRT would generate substantial utilization of health care resources in the form of hospitalization and rehospitalization, urgent care for HF decompensation, and intensified frequent outpatient management. There is retrospective and observational data that suggest that only CRT patients with AF who undergo atrioventricular junctional (AVJ) ablation can respond as well as patients in sinus rhythm. AVJ ablation regularizes rhythm, eliminates tachycardia, and forces 100% biventricular pacing without fusion or pseudofusion. In the absence of a randomized clinical trial, however, there are concerns regarding making a significant proportion of CRT patients pacemaker dependent. It is believed that AVJ ablation is performed in only small numbers of patients at the present time. We propose a randomized controlled clinical trial in 80 patients with permanent AF who are eligible for CRT to test the benefit of AVJ on clinical outcome. The primary aim of the study is to determine if patients with permanent AF who meet conventional criteria for CRT and undergo AVJ ablation have reduced ventricular remodeling (i.e. echocardardiographic improvement of LV end systolic volume), a potent marker of subsequent clinical deterioration, compared to patients who do not undergo AVJ ablation. This study is designed to test feasibility of enrollment and short-term improvement in surrogate endpoints, with anticipation of a full-scale large randomized clinical trial using hard outcome events if this phase is promising. The secondary aims are to examine: a) change in LVEF from baseline to 6 months; b) LV end systolic and diastolic volumes and change from baseline to 6 months; c) HF hospitalization including repeated HF hospitalizations; d) all-cause death; e) VT/VF arrhythmic events requiring ICD therapy; f) inappropriate ICD therapy; g) percentage biventricular pacing; h) quality of life scores; and i) complications related to AVJ ablation procedure.

Public Health Relevance

The twin epidemics of cardiovascular health have been identified as irregular heart beating (atrial fibrillation) and a weakened heart (heart failure). When both are present, in association with disordered electrical activation, the prognosis is poor and management decisions uncertain. This trial will test whether permanently blocking impulses as they pass from the top to the bottom of the heart (ablation) can improve heart function in patients who receive heart failure devices.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Planning Grant (R34)
Project #
5R34HL133526-02
Application #
9337500
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Sopko, George
Project Start
2016-09-01
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627