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Charles Antzelevitch, PhD

Resident Faculty
Distinguished Professor Emeritus

Research interests include: cardiac electrophysiology and arrhythmia syndromes. Expertscape ranked Dr. Antzelevitch in the top 0.1% of scholars writing about electrocardiography.

APPOINTMENTS

2020–Present: Distinguished Professor Emeritus, Lankenau Institute for Medical Research (LIMR)
2015–Present: Executive Director of Cardiovascular Research Program, LIMR
2015–2020: Director of Research, Lankenau Heart Institute, Wynnewood, Pa.
2014–Present: Associate Editor, Heart Rhythm Journal
2017–Present: Professor of Medicine and Pharmacology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pa.
1995–2015: Professor of Pharmacology, SUNY Health Science Center at Syracuse, Syracuse, N.Y.

Dr. Antzelevitch recently discussed his team's focus on the diagnosis, prevention and treatment of arrhythmias, primarily those found in inherited cardiac diseases. Additionally, his team is researching methods to grow new hearts using stem cells, a process that may significantly advance heart transplantations.

Contact

antzelevitch@limr.org
484.476.8134

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EDUCATION, AWARDS & MEMBERSHIPS

Education

BA, Biology

Queens College, CUNY

PhD, Pharmacology

SUNY - Upstate Medical Center

Memberships & Activities

Fellow, American College of Cardiology (FACC)
Fellow, American Heart Association (AHA)
Fellow Cardiovascular Section, American Physiological Society
Fellow, Heart Rhythm Society (FHRS)
Fellow of New Westminster College, Vancouver, British Columbia, Canada
Secretary/Treasurer-Past President, Cardiac Electrophysiology Society
Member, Basic Science Council, AHA
Member, American Association for the Advancement of Science
Member, New York Academy of Sciences
Corresponding Member, Argentine Society of Cardiology
Honorary Lifetime Member, China Heart Rhythm Society
Member, American Society for Pharmacology and Experimental Therapeutics (ASPET)

Awards & Honors

HONORS, AWARDS, CITATIONS

Ranked by Expertscape in the top 0.1% of scholars writing about electrocardiography, and #13 among all scientists and physicians in the world in the field of electrocardiography and cardiac electrophysiology (out of about 72,000)
2020: Lifetime Achievement Award from the American College of Cardiology
1998–Present: Secretary/Treasurer, Cardiac Electrophysiology Society (CES)
2015: Distinguished Service Award, Cardiac Electrophysiology Society
2011: Distinguished Scientist Award, American College of Cardiology
2007: Carl J. Wiggers Award, American Physiological Society
2003: Excellence in Cardiovascular Science Award, NE Affiliate American Heart Association
2002: Distinguished Scientist Award, North American Society of Pacing and Electrophysiology (NASPE, currently Heart Rhythm Society)
1996–1998: President, International Cardiac Electrophysiology Society

RESEARCH

Research Description

Lay description

Cardiac arrhythmias or irregular heart rhythms claim more lives than any other mechanism of heart disease. Cardiac arrhythmias can be due to congenital defects in ion channels that generate the electrical impulse that sets the heart into motion or they may arise as a consequence of injury to the heart secondary to a heart attack or trauma. Electrical instability of the heart that develops under these conditions can lead to rapid and irregular rhythms of the heart, which can lead to sudden cardiac death. A principal focus of the Cardiovascular Research Program at the Lankenau Institute for Medical Research LIMR) is to understand how and why these arrhythmias develop, to identify those individuals who may be at risk for sudden cardiac death or sudden infant death syndrome (SIDS), and to develop treatments and cures.

Our work is focused in part on identifying defects in genes associated with these syndromes and by so doing, identifying the root cause of the disease. This will allow us to develop customized solutions for families afflicted with these syndromes. Genetic and genomic research is quickly transitioning us from a society in which treatment is empiric one-fits-all approach to one in which therapy is based on the specific cause of the disease and tailored to the individual patient. This knowledge is ushering in a new era that is changing the face of medicine as we know it today.

Atrial fibrillation (AF) is the most common arrhythmia encountered in the clinic. AF afflicts nearly one in 10 individuals 80 years of age and older and is increasing in prevalence as the longevity of Americans increases. Effective pharmacological treatment of AF is one of the greatest unmet medical needs facing our society today. Most available drugs have low efficacy and those with high efficacy, have high toxicity. Another critical focus of our team's effort will be to develop drugs that are both safe and effective. Working with Biotechnology companies we are developing drugs that target the upper chambers of the heart (atria), but not the ventricles, where most of the adverse effects arise.

Heart failure affects close to five million Americans. Each year close to 500,000 new cases are diagnosed. Heart failure is the leading cause of hospitalization in people over the age of 65 and it is often associated with atrial fibrillation, which worsens the prognosis and quality of life of patients with heart failure. Many of the medications employed to treat AF in individuals without heart failure are contra-indicated in individuals with heart failure. An important part of our efforts will therefore be directed to development of drugs capable of safely and effectively suppressing AF in the setting of heart failure.

Investigators in our cardiovascular research program are also pursuing studies designed to help us understand why there is such a dramatic increase in the prevalence of AF with age. Despite intensive research in this field, the mechanisms responsible are not known and animal models to study this phenomenon have not been readily available. We have recently identified and animal model that develops AF in old age and are using this unique model to investigate the mechanisms underlying the pathogenesis of AF with advancing age.

Over 3,000 American with heart failure die every year waiting for a donor heart. There is a dire need for alternative solutions. Our scientists have undertaken an exciting challenge to build new hearts using stem cells donated by the intended recipient of the transplanted heart. This approach involves the use of cadaver hearts from which all cells are removed using detergents. What is left is almost a pure white image of a heart made out of collagen. This is referred to as a "ghost heart". Using cells form the intended recipients skin or bone marrow, we will develop stem cells or progenitor cells that could be used to repopulate the heart with new heart cells. This high risk approach, if successful, will fill a sizable void and provide hearts to patients in end-stage heart failure that will hopefully not be rejected, thus avoiding anti-rejection medication.

Our cardiovascular research team is also pursuing a project designed to advance our understanding of mechanisms underlying Sudden Unexplained Death in Epilepsy (SUDEP). Epilepsy is one of the most common neurological diseases, affecting nearly one percent of the population. One of the more catastrophic yet enigmatic complication of epilepsy is a syndrome known as SUDEP. Individuals with epilepsy have up to a 24 times higher sudden death rate than the general population. We are pursuing the hypothesis that there is a genetic and pathophysiological link between electrical disturbances in the brain responsible for epilepsy and electrical disturbances in the heart responsible for cardiac arrhythmias, leading to sudden death. We are working with colleagues in Israel, Turkey and Taiwan to collect cases and genetically screen patients with epilepsy and inherited cardiac arrhythmia syndromes. Our goal is to find a common link between these two syndromes. Our pilot studies have identified several gene candidates and mutations in a variety of ion channels common to the brain and the heart.

Scientific description

Inherited syndromes that affect the electrical activity of the heart play a critical role in causing syndromes such as long QT, short QT and Brugada syndromes, taking the lives of infants, children and young adults, often with little or no warning. Using molecular genetic techniques, our scientists will conduct research aimed at unraveling the basis for a number of inherited diseases including the Long QT, Short QT, Brugada and early Repolarization syndromes. Using next generation and exome and genome wide screening techniques we seek to uncover new genes and mutations responsible for these syndromes. Using molecular biology and patch clamp technology will perform functional expression studies to help establish causality. These methodologies also permit us to look for drugs that can reverse the effect of the genetic defect and thus provide an effective treatment for the patient. These approaches will also be used to probe the genetic basis of why some patients develop life-threatening arrhythmias after a heart attack and others suffering with the same ischemic damage do not.

Our research team is also keen on understanding the basis for the very strong male predominance in the manifestation of the Brugada syndrome. This work is focused on demonstrating the effect of testosterone on the expression of the transient outward current, a cardiac potassium current at the heart of this syndrome.

On the atrial fibrillation front, we are pursuing studies aimed at development of drugs that exert atrial-selective inhibition of sodium channel current and thus of excitability in the atria. This field was pioneered by our team of investigators in 2007. We plan to expand on our recent discovery that rapidly dissociating sodium channel blockers when combined with agents that prolong action potential duration, via inhibition of IKr, IKur or IK-ACh, act synergistically to suppress and prevent the development of AF. We will also further explore our discovery that a combination of ranolazine and dronedarone act synergistically to provide safe and effective management of AF. Two heart failure models (ventricular tachypacing- and ischemia-induced injury) will be developed to study the effects of these drugs in the setting of heart failure. Our work focused on understanding the mechanisms underlying the marked increase in the prevalence of AF with advancing age is pointing us in the direction of intracellular calcium mishandling as an important contributing factor, which we are pursuing in earnest.

Our organ bioengineering program is a high-risk project with potentially great rewards. The first step in creating a cloned heart requires that they be decellularized using sodium dodecyl sulfate (SDS). Over the course of 48–72 hours, this detergent breaks down all cellular and genetic material from the donor heart leaving the collagen framework unharmed. The organ is termed a "ghost heart" because of its opaque white appearance. Progenitor cells generated from the patient's own fibroblasts, bone marrow or other sources will then be used in an attempt to repopulate the organ and thus form a fully functioning human heart. We envision that if successful it will be 15–20 years before this approach becomes a practical alternative to heart transplantation.

In more recent years, our team has focused on development of pluripotent stem cell-derived cardiomyocytes for 1) creation of human models of inherited cardiac arrhythmia diseases; 2) regenerative therapy to improve function of injured hearts; and 3) safety pharmacology. In this program, we develop human models of disease by reprogramming somatic cells from blood or skin into induced pluripotent stem cells from patients with a wide variety of inherited cardiac arrhythmia syndromes and then direct the differentiation of these cells into cardiomyocytes. This approach allows our team to delve further into the pathophysiology of disease and to develop patient-specific therapies.

We also are working to advance understanding of how genetic defects in ion channels that are common to both brain and heart may be responsible for development of epilepsy as well as life-threatening arrhythmias of the heart and thus contribute to sudden unexpected death in epilepsy and have identified ion channelopathies common to both syndromes.

These programs complement each other, enabling our team to evaluate and validate genetic, molecular and electrophysiologic findings and ultimately translate them into an understanding of human disease. These projects also provide us a platform to accelerate drug discovery and its implementation in the clinic.

Ranking: In 2019, Dr. Antzelevitch was ranked by Expertscape in the top 0.1% of scholars writing about electrocardiography. He ranked #2 in Pennsylvania, #2 in New York State, #10 in USA, and, #13 among all scientists and physicians in the world in the field of electrocardiography and cardiac electrophysiology (out of 72,000).

PUBLICATIONS

Publications

Books

Management of Cardiac Arrythmias. Yan G-X, Kowey PR, Antzelevitch C, eds. Springer; 2020.
J Wave Syndromes: Brugada and Early Repolarization Syndromes. Antzelevitch C, Yan G-X, eds. Springer; 2016.