A collaborative, multi-institutional team spearheaded by researchers at Baylor College of Medicine has been awarded a $31 million grant by the Patient-Centered Outcomes Research Institute (PCORI) to determine the safety and effectiveness of commonly used pacing treatments for cardiac resynchronization therapy in people with heart failure.
The research team is led by Dr. Mihail G. Chelu, Associate Professor of Medicine–Cardiology at Baylor College of Medicine, who is the study’s Principal Investigator; Dr. Kenneth A. Ellenbogen, Professor of Cardiology at Virginia Commonwealth University; and Dr. Richard Holubkov, a biostatistician with the University of Utah. The study will focus on the use of conduction system pacing for cardiac resynchronization therapy in patients with heart failure and conduction system disease.
Heart failure affects every aspect of life for an estimated 6.2 million Americans. This debilitating disease not only decreases quality of life but puts stress on patients and their families by imposing a substantial financial burden. Patients with heart failure are also often faced with frequent hospitalizations and an increased risk of premature death.
What is cardiac resynchronization therapy?
More than one-third of all patients with heart failure have conduction system disease—a disorder of the heart’s electrical system, which controls the heart’s rhythm and rate of the heartbeat. Cardiac resynchronization therapy treats this conduction system disease by improving cardiac heart function while also increasing the patient’s functional capacity, thereby reducing hospitalizations and prolonging survival. Cardiac resynchronization therapy is the standard treatment in patients with heart failure with reduced ejection fraction and a wide QRS complex. (QRS represents the electrical impulses in the heart as they spread through the ventricles.)
Cardiac resynchronization therapy can be accomplished by one of two strategies: biventricular pacing or conduction system pacing.
Biventricular pacing is the standard of care, improving heart failure in 60% to 70% of patients by pacing simultaneously from two discrete muscle sites: the right ventricular apex and the left lateral wall. On the other hand, conduction system pacing relies on the direct, rapid pacing of conducting cells, either at the His bundle—the part of the heart that carries signals to the atria and ventricles—or the left bundle branch—the branch that distributes the electrical impulses to the left ventricle. This re-establishes activation of the entire arborized conduction system and cardiac muscle in a highly choreographed and efficient manner that closely reproduces the heart’s natural function.
In their study, Drs. Chelu and Ellenbogen will evaluate the safety and effectiveness of these two pacing treatments in a cohort of 2,136 patients enrolled at 65 sites in the U.S. and Canada.
In the initial stages of the study, these investigators have worked with patients, leaders in health care, and research collaborators to identify the outcomes most relevant to patients: quality of life, patient activity, hospitalization for heart failure, and death. They have also collaborated with the Heart Rhythm Society, American Heart Association, American College of Cardiology, the National Hispanic Latino Cardiovascular Collaborative, the Pacemaker Patient Advocacy Group, WomenHeart, and Mended Hearts.
“In 30 to 40 percent of patients with heart failure and conduction system disease, treatment with biventricular pacing does not improve the heart’s function,” said Dr. Chelu, Principal Investigator of the study. “This might be explained by the slower activation of the heart muscle from only two points. Conduction system pacing, however, has the potential to advance the treatment of heart failure. Pacing in the His bundle or left bundle branch leverages the rapid propagation of electrical impulses through the network of the conduction system, leading to more efficient contraction of the left heart. Furthermore, conduction system pacing involves less expensive generators and leads and sometimes fewer leads, as well as a simpler implant procedure than biventricular pacing. We anticipate that conduction system pacing will lower the great burden of health care costs for patients with heart failure.”
Drs. Chelu and Ellenbogen’s study was selected through a highly competitive review process in which patients, caregivers, and other stakeholders joined scientists to evaluate the proposals. The funding is awarded through a PCORI initiative to support large-scale, high-impact comparative effectiveness research trials that are conducted in multiple phases, allowing the testing and refinement of the study approach. Therefore, this study will involve an initial feasibility phase to maximize the likelihood of full trial success. The study was launched on January 1, 2023 and is anticipated to enroll participants in October 2023.
“This study has the potential to fill an important gap in the evidence that is relevant to a range of health care decision makers, helping them better assess their care options,” said PCORI Executive Director Dr. Nakela L. Cook. “We look forward to following the study’s progress and working with Baylor College of Medicine in Houston and Virginia Commonwealth University in Richmond to share its results.”
PCORI is an independent, nonprofit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers, and clinicians with the evidence-based information needed to make better-informed health care decisions. For more information about PCORI’s funding, visit www.pcori.org.