Krannert Cardiovascular Research Center

Research focus pertains to cardiac rhythm disturbances and sudden cardiac arrest/death in special high-risk populations. Work on arrhythmia-related complications in patients with neuromuscular conditions including myotonic dystrophy less led to original research and care-related publications. Recently, research has focused on device-based therapy for the management of ventricular arrhythmias, in particular mechanisms and models of defibrillation failure and its impact on sudden death in ICD recipients.

Dr. Breall has an interest in and an extensive history of involvement with multi-center clinical trials involving new devices and drugs to potentially help patients in the cardiac catheterization suite. He has been the principle site investigator for over 30 studies. Many of the well-established devices and physiological concepts were used by Dr. Breall early on.

The main research focus of Dr. Chen's lab is on the electrophysiological (EP) and metabolic development and maturation of cardiomyocytes (CMs). His lab also successfully established several cardiac disease-specific induced pluripotent stem cell (iPSC) lines from human fibroblasts or blood cells of patients with arrhythmogenic diseases such as Arrhythmogenic Right Ventricular Dysplasia, Brugada Syndrome, Dilated/Hypertrophic Cardiomyopathy etc., to model human cardiac diseases in a dish. They have recently established the first metabolic maturation-based cardiac disease model in vitro using patient-specific iPSCs. Additionally, they established several co-culture systems of hESC-derived CMs with cells derived from neural or endothelial progenitor cells so as to elucidate factors from non-CMs that induce maturation of hESC-CMs. The main emphasis is placed on the neuro-cardiac interactions, which affect embryonic cardiac development and contribute to arrhythmogenesis in adults.

Dr. Chen’s research interests involve biochemical and biophysical characterizations of ion transports (pumps and ion channels) in the heart. Current research focuses on regulation of calcium signaling in normal and diseased cardiac myocytes.

Dr. Clary's clinical research is as the site Primary Investigator for multicenter trials and registries. Dr. Clary's focus is on lipidology, which is the study of cholesterol and fat disorders in the blood. Her current clinical trials and registries include Familial Hypercholesterolemia and elevated Lp(a) disorders, both of which are inherited cholesterol disorders as well as PCSK9-inhibitor therapies, which are drugs used to treat elevated LDL cholesterol.

In the past few years, there has been a dramatic growth in the field of Cardio-Oncology research, yet many clinical questions remain unanswered. Krannert Cardio-Oncology has partnered with collaborative networks with Medical Oncology, Radiation Oncology, and Precision Medicine departments to work towards answering these questions. The Cardio-Oncology Biobank was developed where prospective biobank and data was collected on all patients being evaluated at the Cardio-Oncology clinics. These data are shared with partners in Precision Medicine and Medical Oncology to better understand the genetics surrounding anthracycline-induced cardiomyopathies. Other research avenues include projects on improving stratification of cardiovascular risk associated with survivors of germ cell tumors exposed to platinum-based chemotherapy. Additional projects include joint research with colleagues in Radiation Oncology looking at radiation cardiotoxicity in socioeconomically disadvantaged populations.

The Dharmakumar Lab brings together a multifaceted, interdisciplinary approach focused on developing diagnostic and therapeutic strategies in the fight against ischemic heart disease. Using cutting-edge noninvasive technologies, the research program strives to release synergies in basic science research and build a rigorous scientific basis for rapid translation of pre-clinical findings for improved care for ischemic heart disease patients. Active research areas include, elucidation of mechanisms of post infarction heart failure and arrhythmogenesis, cardioprotection in acute myocardial infarction, MRI- and PET-based characterization of myocardium, multi-omic diagnostics for ischemic heart disease, and targeted development of interventional devices.

The Everett lab investigates the mechanisms of arrhythmias by performing cardiac mapping with optical mapping and contact mapping with high density epicardial plaques in animal models of cardiovascular disease. In addition, they have developed technology to simultaneously record the ECG and nerve activity from electrodes on the skin (SKNA). Currently, they are applying SKNA recordings as a biomarker for different physiological events including arrhythmias, sleep apnea, autonomic dysreflexia, and the effects of neuromodulation.

Dr. Field and his IU colleagues were the first to show that relatively simple genetic modifications can induce mammalian heart cells to regenerate. His current research is focused on identifying genes and molecules that promote heart muscle regeneration by coaxing healthy cells to proliferate. The success of this research would offer the potential for seriously ill patients whose tissue has been damaged by a heart attack to "re-grow" their own hearts.

Dr. Frick's research interests include perioperative cardiovascular care for patients receiving abdominal organ transplants, the effects of cirrhosis on the cardiovascular system, quality improvement, and smart health devices. Indiana University has a large liver transplant population, which makes this an ideal location to study patients with end-stage liver disease. Specific cardiovascular areas of interest in patients with cirrhosis include cardiac catheterization techniques and dual antiplatelet therapy in patients with coagulopathy due to cirrhosis, optimal approach for risk assessment, and coronary revascularization during pre-transplant evaluations, and cirrhotic cardiomyopathy, which is a highly prevalent cardiomyopathy unique to patients with cirrhosis, though under-recognized and poorly understood. In addition, Dr. Frick's team is actively enrolling patients in a trial that hopes to improve cardiac rehabilitation participation in patients with coronary artery disease by removing frequently cited barriers. He is also partnering with the Purdue Department of Electrical Engineering at IUPUI to develop novel wearable smart health devices.

Dr. Khemka's focus is primarily on cardiovascular outcomes. He is currently starting a retrospective cohort study looking at cardiovascular outcomes in patients with thymic cancers. Differences in patients with thymic cancers with paraneoplastic syndromes will also be evaluated against those without. Additionally, prognostic factors in patients that undergo surgical resection of their tumor is being researched. Drs. Clasen and Khemka are evaluating genetic mutations that predict cardiomyopathy in patients that receive anthracycline therapy. A database is being built of patients infected with the SARS Coronavirus 19 with the goal of using echocardiographic parameters to identify patients at the highest risk for mortality.

Dr. Kreutz' research includes clinical trials for patients with coronary artery disease and translational research related to thrombosis, antithrombotic therapies and ‘personalized medicine.’ He conducts pharmacogenetic analyses to study the effects of variations in the human genome on in-vivo drug responses. Dr. Kreutz studies variations in expression of non-coding miRNA and association with coronary and ex-vivo thrombosis phenotypes. In addition, he investigates the utility of thromboelastography and platelet function assays in risk stratification of patients with coronary artery disease.

Several investigative projects are in progress.  Included among these are devising new methods of accurately differentiating between supraventricular and ventricular causes of wide complex tachycardias on ECG. Several lines of investigation are focused on trying to understand some unusual phenomena observed during catheter ablation of atrial fibrillation and flutters. Other studies are evaluating different techniques of improving outcomes during complex catheter ablation procedures for treatment of atrial arrhythmias in different patient populations, including those with repaired congenital heart disease. Several studies are evaluating techniques for determining optimal catheter ablation approaches in patients with symptomatic premature ventricular complexes and ventricular tachycardia

Research in Dr. Rubart-von der Lohe's lab focuses on a) mechanisms underlying inherited cardiac arrhythmias associated with calmodulin gene mutations and b) the role of connexin gap junctions between myofibroblasts and cardiomyocytes in cardiac electrical remodeling. Major experimental approaches include the generation of genetically engineered mouse models, the patch-clamp technique, two-photon fluorescence microscopy, and optical voltage mapping.

Dr. Sawada’s research focuses on quantitative assessment of global and regional left and right heart function at rest and with exercise and pharmacologic stress in cardiac disease states including ischemic and non-ischemic cardiomyopathy, end stage liver disease, pulmonary hypertension, and valvular and pericardial disease. The goals of this research is development of quantitative techniques such as Doppler tissue imaging, and speckle tracking assessment of myocardial deformation (strain) for the purposes of improving the diagnostic and prognostic value of echocardiography in various cardiac disorders.   The application of these new techniques in the service of patients cared for at Krannert is in keeping with the 55-year tradition of clinical research in cardiac ultrasound established by the pioneer of echocardiography, Dr. Harvey Feigenbaum.

The Sharif Lab is focused on translational investigation of coronary microcirculation, specifically noninvasive MRI-based assessment of microvascular health and function, leveraging multi-disciplinary innovations in magnetic resonance physics, computational engineering, and machine learning. These investigations are driven by the need to address ongoing challenges in noninvasive cardiology; specifically, to enable reliable characterization of the relationship between myocardial imaging markers and progression of cardiovascular and cardio-metabolic diseases, with an emphasis on translational/mechanistic studies in the context of “small vessel” disease, coronary vasomotor/endothelial dysfunction, and heart failure with preserved ejection fraction. To this end, new functional imaging-based markers of coronary microcirculation as well as innovative artificial-intelligence-enabled MRI approaches are being developed, validated, and translated into clinical practice.

Dr. Tanawuttiwat's clinical research interests are in the treatment of atrial fibrillation in special populations (heart failure and TAVR populations) and physiologic pacing (His-purkinje system pacing). The current study used the data from the National Cardiovascular Data Registry (NCDR) to compare the outcomes of warfarin and non-vitamin K antagonists for stroke prevention in atrial fibrillation patients after transcatheter aortic valve replacement (TAVR). This study will provide the 1-year safety and effectiveness profile of these commonly used medications in TAVR patients with atrial fibrillation.