Researchers at Indiana University School of Medicine were pioneers in cardiac electrophysiology and contributed to the mechanics of fibrillation and defibrillation, the evolution of the electrocardiogram and the implantation of the transvenous cardioverter to prevent cardiac arrest. Today, investigators of the Electrophysiology Research Program at the Krannert Cardiovascular Research Center carry on that legacy. Currently, investigators are advancing electrophysiology at the molecular and cellular level, where they incorporate biomedical engineering to contribute new discoveries regarding arrhythmogenesis in adults. They focus primarily on molecular and cellular regulation of cardiac ion transport proteins; modeling cardiac arrhythmias with iPSC-derived cells and biomedical engineering approaches in electrophysiology.
IU Krannert Investigator Thomas H. Everett, PhD, associate professor of medicine at IU School of Medicine, is an expert in heart rate variability analysis and the sympathetic nerve system and was recently named an IU School of Medicine 2024 Showalter Scholar. His lab developed skin sympathetic nerve activity (SKNA) technology, a means to non-invasively measure sympathetic nerve activity using signals recorded from ECG electrodes placed on the skin. In 2024, Everett and collaborator Brad Duerstock, PhD, professor of engineering practice at the Weldon School of Biomedical Engineering at Purdue University, were funded a $1.5 million translational research award from the U.S. Department of Defense Congressionally Directed Medical Research Program (CDMRP) and will conduct a pilot clinical trial to evaluate whether a prototype wearable autonomic dysreflexia (AD) detection system that measures SKNA could accurately detect AD from participants with spinal cord injury, with reasonable satisfaction.
Along with the DoD study, Everett received an NIH R01 award to test the hypothesis that SKNA could be used as a biomarker for physiological events, including predicting neurological recovery during therapeutic hypothermia for cardiac arrest, and to risk stratify patients for recurrence of atrial fibrillation (AF) following catheter ablation.
The concept that sympathetic nerve activity (SNA) could be determined from recordings obtained from the skin that have shown sympathetic tone is important in cardiac arrhythmogenesis. In this proposal, Everett will apply SKNA recordings as a biomarker for neurological status in patients that are undergoing targeted temperature management (TTM) for cardiac arrest and risk stratify patients for AF recurrence after undergoing ablation therapy.
“With SKNA recordings, we can now visualize and analyze the nerve activity that can trigger AF, and risk stratify patients for AF recurrence post ablation,” Everett said. “We will test the hypothesis that SKNA is a useful biomarker and a potential surrogate end point for future clinical investigations in common cardiovascular diseases.”
Zhenhui Chen, PhD, associate professor of medicine, dedicates his research on biochemical and biophysical characterizations of ion transports, specifically pumps and ion channels, in cardiac myocytes. Chen has been studying phospholamban (PLB), a protein that regulates calcium levels in the heart, for more than 20 years. This protein facilitates cardiac contraction and relaxation.
IU Krannert's research in this area shows PLB is localized to the perinuclear/nuclear membranes of cardiomyocytes and that PLB modulates the lumenal Ca inside nuclear envelope of isolated cardiac nuclei and regulates nuclear Ca dynamics – leading to many hypotheses to be investigated in a current NIH R01 award. This discovery has been validated in published works by many labs that PLB may have expanded function in gene regulation of the heart.
