R01HL153390

Factors Associated with Response to Cardiac Resynchronization Therapy in Heart Failure Patients with Non-LBBB ECG Pattern

PI: Valentina Kutyifa, MD, PhD
University of Rochester Medical Center, Rochester, NY

Morbidity, mortality, and healthcare costs associated with the treatment of systolic heart failure (HF) are rapidly increasing. Cardiac resynchronization therapy with a defibrillator (CRT-D) has been shown to effectively reduce HF events and death in HF patients with a wide QRS and low ejection fraction, making it a cost-effective treatment option. However, not all patients respond unequivocally to CRT-D, and those without the presence of an ECG abnormality, specifically left bundle branch block (non-LBBB), pose a significant treatment challenge.

Due to conflicting and limited data on response to CRT-D in this cohort, it is possible that a large proportion of HF patients with non-LBBB are currently being treated with limited or no benefit from the device. Therefore, there is a need for better selection of patients for this expensive therapy. One of our recent studies suggested a clinical benefit in patients with non-LBBB and marked echocardiography response, and identified predictors. However, there is a need to prospectively validate these predictors of echocardiography response to CRT-D in non-LBBB in this hard-to-treat patient population, and identify potential novel ECG and echocardiography predictors, utilizing novel statistical methods of machine learning.

We propose a prospective, observational, single-arm study in a currently guideline-indicated cohort to validate and identify predictors of echocardiography response to CRT-D, including novel ECG and echocardiography markers, and to assess subsequent clinical outcomes in 270 HF patients with an implanted CRT-D and non-LBBB ECG pattern. The primary aim of the study is to prospectively validate our previously identified clinical predictors of echocardiography response to CRT-D in HF patients with non-LBBB that could enable better patient selection. Our secondary aim is to identify the incremental value of novel ECG and echocardiography variables to predict echocardiography response to CRT-D in non-LBBB patients, including ECG variables of sum absolute QRST integral and ventricular electrical activation delay, and echocardiography-derived variables of left ventricular dyssynchrony and contractility.

Then, we will apply the developed predictive model to prospectively identify non-LBBB patients with CRT-D at risk of heart failure, ventricular arrhythmias, or death. The tertiary aim is to identify novel ECG and echocardiography predictors of response in non-LBBB using machine learning analysis. The study population will include 270 HF patients with non-LBBB (135 with mild HF and 135 with advanced HF) and an implanted CRT-D with 6 months echocardiography follow-up analyzed by an echocardiography core lab, and assessing clinical outcomes of heart failure, ventricular arrhythmias, or death.

University Of Rochester

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Rochester, New York 146113847 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 365% from $734,112 to $3,413,377.