Research

My current research looks at predictors of false positive and false negative stress echo and stress echo predictors of outcomes. I also have work in progress on prevalence and significance of myocardial fat on CT chest. I am looking to start work on troponin elevation in patients presenting to the ER.

My research focus pertains to cardiac rhythm disturbances and sudden cardiac arrest/death in special high-risk population.  My work on arrhythmia-related complications in patients with neuromuscular conditions including myotonic dystrophy less led to original research and care-related publications.  Recently, my 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.

Our lab research is focused on studying pathogenesis of Arrhythmogenic Cardiomyopathy (ACM) and developing new and effective drug therapies to slow down the progression of ACM. Currently, there are no proven disease-modifying treatments in ACM despite advances in clinical management. Our research combines in vitro disease models using cardiac mesenchymal stromal cells generated from induced pluripotent stem cells (iPSC-MSCs) to define disease mechanisms, identify drug targets and develop drug leads. As iPSCs-MSCs are derived from patient biopsies, these cells allow us to study the effect of individual patient genetics on disease, and develop novel and effective drugs. Our lab also employs a plethora of techniques including stem cell biology, molecular biology and cardiovascular biology.

The main research focus of my laboratory (lab) is on the electrophysiological (EP) & metabolic development and maturation of cardiomyocytes (CMs). My 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. We have recently established the first metabolic maturation-based cardiac disease model in vitro using patient-specific iPSCs. In addition, we 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. Main emphasis is placed on the neuro-cardiac interactions, which affect embryonic cardiac development and contribute to arrhythmogenesis in adults.

Dr. Z Chen’s research interests involve biochemical and biophysical characterizations of ion transports (pumps and ion channels) in 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. We at IU Krannert Cardio-Oncology have partnered with collaborative networks with Medical Oncology, Radiation Oncology, as well as Precision Medicine departments to work towards answering these questions. We have developed the IU Cardio-Oncology Biobank, where we prospectively biobank and data collected all patients getting evaluated at the IU Cardio-Oncology clinics. These data are shared with our partners in Precision Medicine and Medical Oncology to better understand the genetics surrounding anthracycline-induced cardiomyopathies. Other exciting research avenues include projects on improving stratification of cardiovascular risk associated with the survivors of germ cell tumors exposed to platinum-based chemotherapy. We are also working on joint research projects with our colleagues in Radiation Oncology looking at radiation cardiotoxicity in socioeconomically disadvantaged populations.

Our lab is dedicated to understanding the molecular mechanisms of the development of pulmonary hypertension (PH) as well as sickle cell cardiomyopathy. Our lab group utilizes genome-wide strategies to prioritize functional and animal studies of candidate genes and pathways involved in PH and SCD, with a particular focus on endothelial cell biology. Some of the current projects include:

1. Role of IL-18 signaling in sickle cell cardiomyopathy and ventricular tachycardia
2. Role of SOX17 in PAH
3. Determining contribution of NAD+ biology in PAH
4. Dissecting mechanisms of mitophagy in PAH
5. Role of SNX29 in vaso-responsive PAH
6. Role of ubiquitin pathways in PAH

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, we have developed technology to simultaneously record the ECG and nerve activity from electrodes on the skin (SKNA). We are now 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 identify 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 heart attack to "re-grow" their own hearts.

I have been working  on using Thromboelastrography (TEG) to manage the  doses of  AA inhibitors  (aspirin)  and in select cases the doses ADP inhibitors (clopidogrel, ticagrelor ) to reduce the incidence of bleeding events in Left Ventricular Assist  Device patients.  Events such as GI bleeding, strokes( both embolic and hemorrhagic) , nose bleeds, excessive bruising. In a few cases of chronic thrombosis of the LVAD, TEG is used to enhance anticoagulation. The LVAD service has been doing TEGs on all LVAD patients for the last 4-5 years at least every month. We have an abundance of data which should be evaluated.

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

Dr. Raman’s investigative efforts focus earlier detection of myocardial disease in at-risk populations with mechanistically-based imaging biomarkers that guide the development of novel, effective therapies. Her work, supported by the U.S. National Institutes of Health since 2005, seeks to improve the cardiovascular health of individuals with neuromuscular disorders, cardiometabolic risk, and systemic inflammation. Her collaborative approach to science pulls together teams to accelerate the translation of basic discoveries through preclinical research and multicenter clinical trials. 

Research in my laboratory focuses on a) mechanisms underlying inherited cardiac arrhythmias associated with calmodulin gene mutations and b) 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 IU is in keeping with the 55 year tradition of clinical research in cardiac ultrasound established by the pioneer of echocardiography, Dr. Harvey Feigenbaum.

My research interests include: Genetic contribution to cardiovascular disease, Implementation and impact of genetic counseling services in cardiology, Utilization of genetic testing in cardiovascular disease, Effective education and communication of cardiovascular genetics information.

My clinical research interest is on the treatment of atrial fibrillation in special populations. In the current study, we use the data from 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.