SCHOOL OF MEDICINE • DEPARTMENT OF MEDICINE

Cardiovascular Research

Overview of Research Programs

The research activities of the Cardiovascular Medicine Division are best viewed within the broader context of the Case Cardiovascular Center (CCC). The mission of the CCC is to develop premier clinical, research, and education programs in heart and vascular disease. The structure of the Center includes research (Case Cardiovascular Research Institute—CVRI) and clinical (University Hospitals Harrington-McLaughlin Heart & Vascular Institute—UH-HMHVI) arms.

One of the primary missions of the CCC is the development of premier research programs that span the full spectrum of activities from basic bench-side research to translational research (“first-in-man”) and clinical trials. The CVRI is focused on basic and translational studies. The Research & Innovation Center (RIC) of the UH-HMHVI is dedicated to innovative clinical trials and applied technology. Investigators in the CVRI and RIC are faculty members at UHCMC, CWRU, and the VAMC. In addition, research faculty and trainees in other Divisions (Pulmonary, Hematology-Oncology, Endocrinology, General Medicine), other SOM Departments (Physiology & Biophysics, Genetics, Biomedical Engineering, Pathology, Neuroscience, and Radiology) as well as Departments with the Lerner Research Institute (Cell Biology, Molecular Cardiology) collaborate with investigators in the CVRI and RIC.

The net result of these efforts has been (1) the establishment of premier research programs in basic/translational/and clinical research, (2) recruitment of outstanding clinician-scientists and research scientists (3) and acquisition of robust funding at both the R- and K-grant levels.

(1) Major Research Areas:

(a) Basic & Translational Research:

• Vascular Biology – Research efforts focus on the role of vascular cells in blood vessel development, angiogenesis, inflammation, injury & repair.
• Cardiac Myocyte Biology – Research efforts are focused on understanding fundamental mechanisms governing the development, progression, and complications of cardiac hypertrophy and failure.
• Gene Regulation – Research efforts are directed towards understanding basic molecular mechanisms governing gene regulation with a focus on DNA-binding proteins and chromatin-modifying factors.
• Inflammation & Immunity – The main focus is on the role of innate immunity – especially the development, differentiation and activation of myeloid lineage cells and their impact on the development of atherosclerosis, myocardial infarction, and insulin resistance syndromes.
• Stem Cell & Regenerative Medicine – These research efforts are investigating the potential of several types of adult stem cell (umbilical cord, bone marrow, and circulating EPCs) in the treatment of cardiovascular disease. These efforts include elucidating molecular mechanisms aimed at reprogramming, expanding and genetically modifying adult stem cells and evaluating their therapeutic potential.
• Arrhythmias – Using cardiac electrophysiological and pharmacological techniques, research efforts are focused on understanding mechanisms underlying the development of atrial flutter/fibrillation as well as novel pharmacologic and mechanical approaches to the treatment of this arrhythmia.

(b) Clinical Research (Center for Research & Innovation):

• Academic year 2008-2009 saw a major change in the organization of clinical research activities. Under the direction of Marco Costa MD PhD, clinical research changed from a traditional Division based activity to an Institute based efforts. All clinical research activities in Cardiovascular Medicine, Cardiac Surgery, and Vascular Surgery is within the umbrella of the Center for Research & Innovation. The Center is supported by a lead administrator (Stacey Mazzurco, RN), 8 nurse coordinators,1 research assistant, 2 regulatory and grants specialists and 1 grant accountant. At present, a total of 52 trials (>650 patients) with an estimated total budget of more than 3 million dollars.
  
  • Preventive Cardiovascular Medicine – Research efforts are focused on subclinical atherosclerosis testing using coronary calcium scoring. This program will also examine the correlation between coronary calcium scoring and novel biomarkers, non-invasive vascular function testing and dual energy radiographic imaging.
  • Advanced Heart Failure & Transplant - The primary research focus of this section is clinical investigation through participation in heart failure clinical trials, registries, and investigator initiated protocols. Major research areas include diastolic heart failure, mechanical circulatory support, sleep disordered breathing and heart failure, Vitamin D and heart failure, and novel genetic and biomarker correlations.
  • Electrophysiology - The primary research focus is clinical investigation through participation in clinical trials assessing new antiarrhythmic drugs, new oral anticoagulants, and advanced cardiac devices (including pacemakers, defibrillators, and special catheter electrodes).
  • Interventional Cardiovascular Medicine – Research activities include clinical trials testing novel coronary and vascular (renal, iliac, limb ischemia) devices, cardiac and vascular stem cell therapy, percutaneous repair of structural heart disease (PFO closure) and valve heart disease. Currently, faculty members of the CVIR serve as overall PIs of 3 multicenter, multinational trials testing novel drug-eluting stents to treat coronary artery disease. The experimental cathlab is also involved with development and pre clinical testing of novel devices and imaging systems, such as optical coherence tomography and novel drug-eluting stents, including biodegradable stents. The experimental lab also serves as a training site for both local and national/international physicians. There were 3
    training activities (devices: Impella, 3D-NOGA, OCT) in 2009.
  • Cardiovascular Imaging – Research efforts in this area have pioneered merged-image diagnostic modalities to achieve extreme precision and accuracy by combining conventional angiography with slice-CT imaging, 3-D intracardiac ultrasound and NOGA electromechanical mapping. The UH Cardiovascular Imaging Core Lab also provides indepth analysis and evaluation of diverse image modalities (e.g., angiography, intravascular ultrasound, optical coherence tomography, MRI, and CT), supporting both local physicians and national and international clinical trials. The core lab is the world leader in the development and application of OCT in clinical trials, with > 500 OCT images of human coronary arteries in its database.
  • Cardiovascular and Pulmonary Rehabilitation – Research efforts include participation in a variety of clinical trials focused on the exercise rehabilitation process, patient education, biobehavioral correlates of cardiovascular disease, and patient adherence to recommended therapy. Much of the research is multidisciplinary, and performed in conjunction with colleagues at the Francis Payne Bolton School of Nursing and Kent State University.
  • Vascular Medicine – The primary research focus in Vascular Medicine is clinical research in areas of atherthrombosis and venous thromboembolism. Vascular medicine plays a primary role in the critical limb ischemia stem cell therapy program. Trials focusing on new anticoagulants for prophylaxis in venous thromboemolism are ongoing. The endothelial function testing program utilizes carotid intima-media thickness (CIMT) measurement and brachial artery reactivity testing (BART) to support research in collaboration with Infectious Disease and Dermatology.

(2) Clinician-Scientist and Research Scientist Recruitments:

Bezerra, Hiram Grando Instructor HMS/MGH MD, PhD
Bilodeau, Matthew Instructor Vanderbilt MD, PhD
Mahabaleshwar, Ganapathi Instructor CCF/LRI PhD
Proweller, Aaron Assistant Professor U Penn MD
Ramirez-Bergeron, Diana Assistant Professor U Penn PhD
Stamler, Jonathan Professor Duke MD
Arruda, Maruicio Associate Professor CCF MD
Carman, Teresa Assistant Professor CCF MD
Jozic, Joe Assistant Professor UH MD
Orringer, Carl Associate Professor UHMP MD
Parikh, Sahil Assistant Professor HMS/MGH MD
Sipahi, Ilke Assistant Professor CCF MD

(3) Grants:

• Active Research Funding: see below
• New/pending Funding: see below

(4) Goals for AY09/10:

• Program Project – Efforts have been initiated to develop a PPG with colleagues in Hematology-Oncology as well as Pathology in the area of inflammation and thrombosis. Submission planned for AY09/10.
• Training Grant – In conjunction with Dr. Dubyak in Physiology & Biophysics, we plan to submit a new cardiovascular training grant in AY09/10.
• Junior faculty transition – The Division is fortunate to have a large number of K-grant awardees. Several of these trainees are at a stage where they need to transition towards independence and acquire first R01.
• Institute for Transformative Molecular Medicine – The recruitment of Dr. Stamler constitutes an important opportunity to develop novel lines of investigation in basic, translational, and clinical research. Establishing close collaborative interactions over the next year will allow for synergistic growth of both programs.

Active Research Funding by Faculty Member
Active Funding as of June 30, 2009