Heart failure has a significant impact on every aspect of life for an estimated 6.2 million Americans living with with this condition: decreased quality of life, physical capacity, and independence; increased stress on patients, their families, and caregivers due to substantial financial costs; frequent hospitalizations; and premature death. Conduction system disease is present in approximately one-third of patients with heart failure. Cardiac-resynchronization therapy (CRT), the only HF therapy that simultaneously improves cardiac function and functional capacity, reduces hospitalization, and prolongs survival, is the standard therapy in patients with heart failure with reduced ejection fraction (HFrEF) and a wide QRS complex. CRT can be accomplished by two strategies: biventricular pacing (BiVP) or conduction system pacing performed at either the level of His or left bundle (His/LBBP). BiVP is the standard of care and results in improvement in heart failure in 60 percent to 70 percent of patients by pacing simultaneously from two discreet muscle sites: the right ventricular apex and the left lateral wall.
Conduction system pacing relies on pacing directly rapidly conducting cells, either the His or left bundle to reestablish activation of the entire arborized conduction system and cardiac muscle in a highly choreographed and efficient manner that closely reproduces nature. Both pacing strategies are used but it is not currently known which achieves a better improvement in heart failure and in a larger number of patients and which is safer.
This project seeks to answer questions that have the potential to affect more than 100,000 patients implanted with CRT devices annually in the United States.
1. To test the comparative effectiveness of His/LBBP to BiVP in relation to patient-centered outcomes (quality of life and patient activity, HF hospitalization, mortality) in patients with HFrEF meeting traditional CRT criteria
2. To determine the factors that predict response/nonresponse to either His/LBBP and BIVP treatments
3. To test the comparative His/LBBP and BiVP safety for device-related adverse events (e.g., lead dislodgement, infection)
The research team will randomly assign 1,068 patients over the age of 18 with HFrEF and an indication for CRT to either one of the two pacing treatments and follow them for up to five years. If patients have a left ventricular ejection fraction (LVEF) equal to or less than 35 percent, they will be randomly assigned to receive either a biventricular or His/LB defibrillator due to higher risk of sudden cardiac death. If patients have a LVEF of 36 percent to 50 percent, they will be randomly assigned to receive either a biventricular or His/LB pacemaker.
The knowledge resulting from this study will allow patients and their physicians to make an informed decision on what is the most suitable pacing treatment for an individual patient.
The project’s primary outcome is a composite of death of any cause or heart failure hospitalization. The first secondary main outcome the Kansas City Cardiomyopathy Questionnaire-12 questionnaire measured before device implant and annually after device implant. The second main secondary outcome is the primary outcome plus a more than 15 percent increase in the left ventricular end-systolic volume index, which is measured by echocardiogram before device implant and annually after device implant.
The research team engaged patients with HF and/or implanted devices, caregivers, patient advocacy groups, scientific and clinical societies, the device industry, and payers. The project’s patient partners and other stakeholders contributed to the design of all study aspects.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.