Charles Antzelevitch

Education and career

Antzelevitch graduated from Queens College, City University of New York with a BA in biology. He earned a PhD in pharmacology from State University of New York (SUNY) Upstate Medical University in 1978. From 1977 to 1980, he held a postdoctoral fellowship in the department of experimental cardiology at the Masonic Medical Research Laboratory (MMRL) in Utica, New York. After his fellowship, he joined the staff at MMRL as a research scientist, where he continued his scientific work until 2015. While at MMRL, Antzelevitch was named executive director and director of research (1984) and became Gordon K. Moe Scholar, an endowed chair in experimental cardiology (1987).

He was a member of the faculty at SUNY Health Science Center in Syracuse, New York, from 1980 until 2015. In 1980, he received an appointment as assistant professor in the department of pharmacology. He was later promoted to associate professor (1983), research professor (1986), and professor (1995) of pharmacology.

In 2015, Antzelevitch became professor and executive director of cardiovascular research at LIMR and director of research at Lankenau Heart Institute.

Research

Antzelevitch wrote his doctoral thesis in 1977 on the cardiac actions of quinidine. After joining MMRL, he began investigating and publishing scholarly articles on the mechanisms underlying ventricular arrhythmias, including parasystole and reentry. Later, his interests expanded to include the genetic origins of inherited arrhythmia syndromes such as long QT, short QT, Brugada, and early repolarization syndromes, as well as the development of potential new treatments for atrial fibrillation (AF). These investigations continue to be a focus of his current research at LIMR.

In the 2010s, Antzelevitch began an ongoing investigation into genetic risk factors linked with the occurrence of life-threatening arrhythmias following myocardial infarction. Additionally, with cardiac researcher Jose Di Diego, MD, Antzelevitch is exploring the heart-related therapeutic applications of human induced pluripotent stem cells and progenitor cells, including a possible role in the engineering of bioartificial hearts suitable for heart transplantation. The first step in the organ bioengineering process is decellularization of cadaver hearts using detergents such as sodium dodecyl sulfate, leaving a collagen framework. This bioartificial organ platform is termed a "ghost heart" because of its opaque white appearance. Induced pluripotent stem cells or progenitor cells generated from a patient's skin, blood, bone marrow or other sources will then be used in an attempt to repopulate the organ and to form a fully functioning human heart.

Scientific discoveries

Antzelevitch's body of research has expanded scientific understanding of the heart's electrical system in a number of ways. His work has been instrumental in identifying the cellular and ionic basis for the various waves that make up the electrocardiogram (ECG), including the J wave, T wave and U wave. He and his research team helped to identify reflected reentry, late phase 3 early afterdepolarizations, and phase 2 reentry (electrical dysfunctions that promote extra heart beats) as potential trigger mechanisms for dangerous tachycardia and fibrillation.

His research team pioneered work demonstrating electrical heterogeneity within ventricular myocardium, showing that cells in the epicardium and endocardium differ with respect to electrical properties and response to pharmacologic agents. In 1990, his team at MMRL, including Serge Sicouri, MD, discovered the M cell, a unique type of heart cell in the deep layers of the ventricular myocardium. The researchers observed that the M cell has different electrical properties from other heart cells, responds differently to drugs that affect the heart, and may be associated with potentially dangerous wave formations on ECGs.

In 2000, Antzelevitch and colleagues reported experimental findings challenging the belief that early repolarization (an ECG variant often seen in athletes) is always a benign condition by demonstrating that early repolarization is linked to the development of arrhythmias leading to sudden cardiac death in experimental modules. Validation of this hypothesis came 8 years later in clinical studies from leading centers around the world.

With cardiac researcher Gan-Xin Yan, MD, PhD, Antzelevitch used coronary-perfused wedge preparation technology to develop a research model that helped pinpoint the cellular, ionic and genetic mechanisms underlying inherited arrhythmia syndromes such as long QT, short QT, Brugada, and early repolarization syndromes. With his research team, Antzelevitch has discovered 10 of the 18 genes found to be associated with Brugada syndrome and 5 of the 7 genes associated with early repolarization syndrome. In 2000, his research team, along with international colleagues, described a possible genetic link between long QT syndrome and sudden infant death syndrome.

Contributions to clinical practice

Antzelevitch's research has helped to establish diagnostic criteria and treatment approaches for both inherited and acquired arrhythmia syndromes. With his colleagues, he demonstrated that quinidine could be used to treat ventricular tachycardia in experimental models of Brugada syndrome. In 2000, Antzelevitch participated in the first Brugada syndrome consensus conference, which culminated in the report of diagnostic criteria for the inherited syndrome. In 2005, he organized and was the lead co-author of the second Brugada syndrome consensus conference report, which elaborated on diagnostic criteria and addressed risk stratification and treatment approaches. "In April 2015, Antzelevitch and LIMR colleague Yan convened a consensus conference to update the scientific and clinical communities on the mechanisms, diagnosis, prognosis, risk stratification, and treatment of Brugada syndrome and early repolarization syndrome, collectively known as J wave syndromes. In 2016, the report of the J-Wave Expert Consensus Conference was published simultaneously in Journal of Arrythmia, Europace, and Heart Rhythm. Additionally, Antzelevitch and Yan edited J Wave Syndromes: Brugada and Early Repolarization Syndromes, a medical textbook containing further material to help clinicians identify and manage patients with these conditions.

In the realm of acquired arrhythmias, Antzelevitch's research team was the first to recognize that the antianginal drug ranolazine blocks the electrical pathway in the heart known as the late sodium channel, an atrial-selective action that has potential benefit in the treatment of AF. With cardiac electrophysiologist Alexander Burashnikov, PhD, Antzelevitch subsequently hypothesized and then demonstrated that combining ranolazine with dronedarone, a drug with a similar action but different mechanism, can significantly suppress the occurrence of AF.

Publications

Antzelevitch has published 6 reference texts, more than 500 original peer-reviewed journal articles and book chapters, and over 370 abstracts.

Selected peer-reviewed publications

Below are the top 20 most-cited journal articles authored or co-authored by Antzelevitch, according to Google Scholar:

Honors