Thanks to major advances in medicine and biomedical innovations there had been a steady decline in cardiovascular deaths over the last century. However, over the last decade, heart disease has regained its status as the leading cause of death in the US, which has coincided with the growing epidemic of obesity, a complex and multifactorial disease interconnected with metabolic syndrome (high blood pressure, insulin resistance, and high cholesterol).
Obesity poses a significant health care burden with rising morbidity and mortality associated with increased risk of heart failure and/or sudden cardiac death linked to cardiac arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF). While obesity is an established cardiovascular risk factor, there exists a seemingly counterintuitive phenomenon called the “obesity paradox” associated with survival advantage in the obese patients as compared with normal weight individuals in multiple settings of heart failure, acute coronary syndrome, among others.
The pathological mechanisms by which cardiac obesity could result in the development of cardiac arrhythmias, while also under certain conditions potentially provide cardioprotection is not well understood.
My work focuses on investigating the role of both intrinsic (e.g., autonomic dysfunction) and extrinsic factors (e.g., cardiac adiposity) in promoting cardiac arrhythmias. My research takes a unique approach to investigating acute and chronic effects of cardiac obesity on arrhythmogenesis by combining small and large animal model studies with donor human hearts, which provides an optimal balance between basic research and direct clinical impact.
Using spatiotemporal multi pronged (integrated omics, functional and structural imaging) and multi scale (molecule to whole heart) approach, I will seek to characterize the role of obesity and metabolic syndrome in promoting arrhythmias as well as develop and validate novel diagnostic tools and strategies for effective therapy of obesity mediated cardiac conduction and rhythm disorders.
THE INNOVATIONS AND DISCOVERIES
What determines arrhythmia susceptibility in the human RVOT?
Human RVOT electrophysiology is characterized by shorter APD relative to the RV apical region and drives the transmural dispersion of repolarization and transmural APD dispersion, which may be a contributing factor in making the RVOT region intrinsically susceptible to arrhythmogenesis (idiopathic arrhythmias). Incidentally, the arrhythmogenic effects of adrenergic stimulation (shortened APD and increased PVC frequency) can be attenuated by cholinergic stimulation, making the region less susceptible to adrenergically induced arrhythmias.
What determines arrhythmia sustainability in the human left ventricle?
Cardiac 3D wavelength volume, defined as the product of cardiac wavelengths in longitudinal, transverse, and transmural directions, can determine arrhythmia sustainability. Moreover, ventricular arrhythmia is sustained only when cardiac tissue volume is greater than critical cardiac wavelength volume.
What will the next generation of implantable electronics devices for arrhythmia treatment will look like?
Current state of the art arrhythmia treatment includes ablation therapy (radio frequency ablation or cryoablation of cardiac tissue) or electrotherapy (implantable cardioverter defibrillator devices). The next generation bioelectronics will include tissue conforming, bioresorbable, and wireless implantable electronic devices (IEDs) that are capable of high-density spatiotemporal mapping of temperature, pressure and electrical signals and also allow for integrated arrhythmia therapeutic solutions including programmable electrical stimulation, radiofrequency ablation and irreversible electroporation.