The overarching goal of improving the care of heart failure patients drives our research. Consequently, our research spans elucidating basic molecular mechanisms that govern how the heart contracts and relaxes to developing new clinical devices. We use a multifaced approach including molecular physics, molecular chemistry, novel optical systems, intact ex vivo measurements, invasive in vivo measurements, and non-invasive in vivo measurements. Our disease models include genetically modified mice, simulation, and human patients. Much of our work is done through multi-disciplinary partnerships. We aim to translate our discoveries to provide early detection of decompensating heart and develop new treatments for heart failure.
Basic Mechanism Example: Cardiac Myosin Binding Protein-C
Cardiac Myosin Binding Protein-C (cMyBP-C) is encoded by MyBPC3 gene. It is a 140 KD protein that resides on the thick filament of heart muscle. Mutations of MyBPC3 cause predominantly hypertrophic cardiomyopathy but dilated cardiomyopathy is also possible. In general, cMyBP-C modulates both force generation and relaxation of each heartbeat by its phosphorylation status. Phosphorylation levels of cMyBP-C are decreased in heart failure and hypertrophic cardiomyopathy. We aim to translate cMyBP-C modulation of contractility and lusitropy toward new treatments for all forms of heart failure.
Novel Method Example:
Increasing – decreasing intracellular calcium [Ca2+] transient is the molecular chemistry mechanism that triggers the entire heart to contract with each beat. However, this process occurs in an extremely non-linear manner. We developed an optical method to measure real time [Ca2+] transients within beating in vivo hearts of mice expressing endogenous intracellular fluorescent [Ca2+] sensor while directly measuring intracardiac pressure. These simultaneous [Ca2+] and intracardiac pressure measurements provided a method to determine how the [Ca2+] to cross-bridge coupling actually occur.
Clinical Device Example: Ambulatory Breath Analyzer for Monitoring Cardiac Output (ABAMCO)
All treatments of heart failure aim to improve cardiac output. However, the major 4 pillars of current guideline directed therapy can have significant side effects. It can be difficult to initiate and titrate medications to optimize cardiac output without compromising other organ systems such the kidneys. Importantly, patient’s heart failure can progress to needing advanced therapies. To solve this problem, we have developed a prototype ABAMCO to non-invasively measure cardiac output with eventual goal of patients using this monitoring method to guide treatment of heart failure at their homes.
Lab Members
Carl Tong, MD-PhD, FACC
For further information, contact Carl Tong, MD-PhD, FACC at EMAIL US