R01HL157740

Mr-Compatible Devices for the Diagnosis and Treatment of Cardiomyopathies

Cardiac Magnetic Resonance (CMR) is a non-invasive imaging technique with exquisite soft-tissue detail for the assessment of heart structure and function. It provides an excellent screening tool but cannot always obviate more invasive procedures, such as Endomyocardial Biopsy (EMB).

Interventional CMR (ICMR) is a minimally invasive technique without radiation, but it has been hampered by the lack of non-ferrous devices that can be easily visualized. This limitation hinders the navigation of tasks, such as EMB, safely.

Currently, one in nine deaths in the US is attributed to heart failure (HF), with healthcare costs exceeding $30 billion in 2013. Of the approximately 5.1 million Americans with HF, the definitive treatment is heart transplantation (HTX), where rejection is assessed with EMB. EMB is a procedure performed under X-ray guidance to obtain random samples of the right ventricular septum.

However, many patients, especially children with cardiomyopathy and after HTX, as well as HF caused by non-ischemic cardiomyopathies (NICM), do not have global changes to the myocardium. Instead, they have patchy disease, which is often restricted to limited portions of the left ventricle. As a result, EMB may yield a definitive diagnosis in less than 20% of the cases.

Complications of EMB include ventricular puncture, pericardial tamponade, stroke, and death, which limits its use due to the risk-benefit ratio. However, accurate diagnosis of cardiomyopathies or early recognition of heart rejection can lead to definitive treatment or measures to avoid heart rejection, respectively, with enormous individual patient impact.

Therefore, we propose to develop an MRI-compatible suite of interventional devices to allow direct targeting of diseased myocardium (based on CMR) for EMB and treatment of cardiomyopathies, for both right- and left-sided catheterization. To achieve this, we will develop an active pigtail catheter with a guidewire for ICMR cardiac catheterization, to be used in combination with an active MR-steerable sheath/bioptome device or transmyocardial injection catheter. These devices will enable direct targeting of the disease to increase diagnostic yield and decrease complications.

Currently, there are no commercially available active MR-visible EMB, pigtail, or injection catheters. Significant advances to our realization of a clinically relevant MR-EMB device include the creation of a sharp-jaw EMB mechanism that is safe from heating but provides a specific MR signature when the device is open versus closed. Additionally, injection devices that can determine myocardial apposition will ensure that therapeutics reach the intended target of the myocardium.

Furthermore, as pediatric HTX patients receive up to six EMBs in the first year, the ICMR suite of devices will significantly reduce ionizing radiation in a particularly vulnerable population.

Our research proposal will develop these devices in a canine model of spontaneous NICM that is similar in size to children's hearts, ensuring compatibility with pediatric interventions. We will leverage our extensive expertise in MRI interventional devices and CMR to achieve this objective. Thus, our goal is to develop these MR-guided devices to expand the reach of ICMR to children and adults.

The Johns Hopkins University

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]

Baltimore, Maryland 212051832 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 290% from $791,786 to $3,089,138.