Charles Antzelevitch

Charles Antzelevitch
Fields Cardiology, Electrophysiology, Pharmacology, Genetics
Institutions Lankenau Institute for Medical Research
Masonic Medical Research Laboratory
Alma mater Upstate Medical Center, SUNY at Syracuse (PhD)
Queens College, City University of New York (BA)
Notable awards North American Society of Pacing and Electrophysiology (currently Heart Rhythm Society) Distinguished Scientist Award (2002)
American Heart Association Northeast Affiliate (currently Founders Affiliate[55]) Excellence in Cardiovascular Science Award (2003)
American Physiological Society Carl J. Wiggers Award (2007)
American College of Cardiology Distinguished Scientist Award (2011)
Cardiac Electrophysiology Society Distinguished Service Award (2015)

Charles Antzelevitch, PhD, is an American cardiovascular research scientist internationally known for his work in cardiac electrophysiology and arrhythmia syndromes. Currently, he is professor and executive director of cardiovascular research at Lankenau Institute for Medical Research (LIMR), a biomedical research facility in Wynnewood, Pennsylvania, and director of research at Lankenau Heart Institute, both part of Main Line Health.[1]

Antzelevitch was president of the Cardiac Electrophysiology Society from 1996 to 1998[2] and has served as secretary/treasurer since 1998.[3] He is an associate editor of Heart Rhythm,[4] the official journal of the Heart Rhythm Society[5] and the Cardiac Electrophysiology Society,[6] and serves on the editorial board of several other peer-reviewed medical publications, including Journal of Electrocardiology[7] and Journal of the American College of Cardiology.[8]

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.[1] 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.[9][10] After his fellowship, he joined the staff at MMRL as a research scientist, where he continued his scientific work until 2015.[11] While at MMRL, Antzelevitch was named executive director and director of research (1984)[10] and became Gordon K. Moe Scholar, an endowed chair in experimental cardiology (1987).[9]

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.[9][10][12]

In 2015, Antzelevitch became professor and executive director of cardiovascular research at LIMR and director of research at Lankenau Heart Institute.[11]

Research

Antzelevitch wrote his doctoral thesis in 1977 on the cardiac actions of quinidine.[13] After joining MMRL, he began investigating and publishing scholarly articles on the mechanisms underlying ventricular arrhythmias, including parasystole and reentry.[14][15][16] Later, his interests expanded to include the genetic origins of inherited arrhythmia syndromes such as long QT,[17][18] short QT,[19] Brugada,[20][21] and early repolarization syndromes,[22][23] as well as the development of potential new treatments for atrial fibrillation (AF).[24][25][26] These investigations continue to be a focus of his current research at LIMR.[11]

In the 2010s, Antzelevitch began an ongoing investigation into genetic risk factors linked with the occurrence of life-threatening arrhythmias following myocardial infarction.[27] 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.[28][29] The first step in the organ bioengineering process is decellularization of cadaver hearts using detergents such as sodium dodecyl sulfate, leaving a collagen framework.[30] 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 achievements

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.[31][32][33] 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.[14][25][34]

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.[35][36] 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.[37][38]

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.[39][40] Validation of this hypothesis came 8 years later in clinical studies from leading centers around the world.[41][42][43][44]

With cardiac researcher Gan-Xin Yan, MD, PhD, Antzelevitch used coronary-perfused wedge preparation technology[45] to develop a research model that helped pinpoint the cellular, ionic and genetic mechanisms underlying inherited arrhythmia syndromes such as long QT,[17] short QT,[19] Brugada,[20][46] and early repolarization[22][23] 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.[47]

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.[38][48] In 2000, Antzelevitch participated in the first Brugada syndrome consensus conference, which culminated in the report of diagnostic criteria for the inherited syndrome.[49] 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.[50] "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,[51] Europace,[52] and Heart Rhythm.[53] 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.[54]

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.[55] 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.[26][56]

Publications

Antzelevitch has published 6 reference texts, more than 500 original peer-reviewed journal articles and book chapters, and over 370 abstracts.[11]

Selected peer-reviewed publications

Below are the top 20 most-cited journal articles authored or co-authored by Antzelevitch, according to Google Scholar:[57]

Reference texts

Honors

References

  1. 1 2 "Charles Antzelevitch, PhD, FACC, FAHA, FHR - LIMR - Researcher Profile". Limr.org. Retrieved 2016-04-14.
  2. ↑ "CES Past Presidents — Cardiac Electrophysiology Society". Cardiaceps.org. Retrieved 2016-04-14.
  3. ↑ "About CardiacEPS — Cardiac Electrophysiology Society". Cardiaceps.org. Retrieved 2016-04-14.
  4. ↑
  5. ↑ "Heart Rhythm Society". Hrsonline.org. Retrieved 2016-04-14.
  6. ↑ "Cardiac Electrophysiology Society". Cardiaceps.org. Retrieved 2016-04-14.
  7. ↑
  8. ↑ "JACC : Editorial Board and Staff". Content.onlinejacc.org. Retrieved 2016-04-14.
  9. 1 2 3 Amy Neff Roth (2010-10-16). "Charles Antzelevitch's profile - News - Uticaod - Utica, NY". Uticaod.com. Retrieved 2016-04-14.
  10. 1 2 3 "History". Mmrl.edu. Retrieved 2016-04-14.
  11. 1 2 3 4 "Prominent Cardiac Researcher, Charles Antzelevitch, PhD, Joins Lankenau Institute for Medical Research and Lankenau Heart Institute: Main Line Health, Philadelphia, Pennsylvania". Mainlinehealth.org. 2015-07-22. Retrieved 2016-04-14.
  12. ↑ "New Westminster College, British Columbia, Canada – Professor Dr. Charles Antzelevitch, B.A., Ph.D". Newwestminstercollege.ca. 2014-03-19. Retrieved 2016-04-14.
  13. ↑ Antzelevitch C (1977). Cardiac Actions of Quinidine (Thesis). Syracuse (NY): State University of New York Upstate Medical Center
  14. 1 2 "Characteristics of reflection as a mechanism of reentrant arrhythmias and its relationship to parasystole". Circ.ahajournals.org. 1980-01-01. Retrieved 2016-04-14.
  15. ↑ "The Case for Modulated Parasystole". Pacing and Clinical Electrophysiology. 5: 911–926. 2015-03-31. doi:10.1111/j.1540-8159.1982.tb00030.x. Retrieved 2016-04-14.
  16. ↑ "The Effects of Milrinone on Action Potential Characteristics... : Journal of Cardiovascular Pharmacology". Journals.lww.com. 2015-09-01. Retrieved 2016-04-14.
  17. 1 2 Gan-Xin Yan, MD; Charles Antzelevitch. "Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome". Circ.ahajournals.org. Retrieved 2016-04-14.
  18. ↑ Shimizu, W; Antzelevitch, C (2015-09-28). "Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome". J. Am. Coll. Cardiol. 35: 778–86. PMID 10716483.
  19. 1 2 Patel, C; Antzelevitch, C (2015-09-28). "Cellular basis for arrhythmogenesis in an experimental model of the SQT1 form of the short QT syndrome". Heart Rhythm. 5: 585–90. PMC 2361425 Freely accessible. PMID 18362027. doi:10.1016/j.hrthm.2008.01.022.
  20. 1 2 "The Brugada Syndrome". Journal of Cardiovascular Electrophysiology. 9: 513–516. doi:10.1111/j.1540-8167.1998.tb01844.x. Retrieved 2016-04-14.
  21. ↑
  22. 1 2
  23. 1 2
  24. ↑ Alexander Burashnikov, PhD; Charles Antzelevitch, PhD (2003-04-14). "Reinduction of Atrial Fibrillation Immediately After Termination of the Arrhythmia Is Mediated by Late Phase 3 Early Afterdepolarization–Induced Triggered Activity". Circ.ahajournals.org. Retrieved 2016-04-14.
  25. 1 2 "Late-Phase 3 EAD. A Unique Mechanism Contributing to Initiation of Atrial Fibrillation". Pacing and Clinical Electrophysiology. 29: 290–295. doi:10.1111/j.1540-8159.2006.00336.x. Retrieved 2016-04-14.
  26. 1 2 Burashnikov, A; Di Diego, JM; Zygmunt, AC; Belardinelli, L; Antzelevitch, C (2008-03-19). "Atrial-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation". Annals of the New York Academy of Sciences. 1123: 105–112. PMC 2366169 Freely accessible. PMID 18375582. doi:10.1196/annals.1420.012. Retrieved 2016-04-14.
  27. ↑
  28. ↑ "Maximum Diastolic Potential of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Depends Critically on IKr". PLoS ONE. 7: e40288. 2012-07-05. doi:10.1371/journal.pone.0040288. Retrieved 2016-04-14.
  29. ↑
  30. ↑ Ott, HC; Matthiesen, TS; Goh, SK; Black, LD; Kren, SM; Netoff, TI; Taylor, DA. "Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart". Nature Medicine. 14: 213–221. PMID 18193059. doi:10.1038/nm1684. Retrieved 2016-04-14.
  31. ↑ "Cardiovascular Research". Cardiovascres.oxfordjournals.org. Retrieved 2016-04-14.
  32. ↑ Antzelevitch C (2004). "Cellular basis for the repolarization waves of the ECG." In: Malik M, Camm AJ, editors. Dynamic Electrocardiography. Elmsford (NY): Blackwell Futura. p. 291–300. ISBN 1405119608
  33. ↑ Antzelevitch C (2002). "Cellular basis for J, T and U waves of the ECG". In: Ovsyshcher IE, editor. New Developments in Cardiac Pacing and Electrophysiology. Armonk (NY): Futura, p. 1–8. ISBN 0879937068
  34. ↑ "Cardiovascular Research". Cardiovascres.oxfordjournals.org. Retrieved 2016-04-14.
  35. ↑ Litovsky, SH; Antzelevitch, C (2015-09-28). "Transient outward current prominent in canine ventricular epicardium but not endocardium.". Circ. Res. 62: 116–26. PMID 2826039.
  36. ↑ "Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells". Circres.ahajournals.org. 1991-12-01. Retrieved 2016-04-14.
  37. ↑ S Sicouri; C Antzelevitch (2016-04-01). "A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell". Circres.ahajournals.org. Retrieved 2016-04-14.
  38. 1 2 Antzelevitch, C; Shimizu, W; Yan, GX; Sicouri, S; Weissenburger, J; Nesterenko, VV; Burashnikov, A; Di Diego, J; Saffitz, J; Thomas, GP (1999). "The M cell: its contribution to the ECG and to normal and abnormal electrical function of the heart". J. Cardiovasc. Electrophysiol. 10: 1124–52. PMID 10466495. doi:10.1111/j.1540-8167.1999.tb00287.x. Retrieved 2016-04-14.
  39. ↑ Gussak, I; Antzelevitch, C (2015-09-28). "Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms". J Electrocardiol. 33: 299–309. PMID 11099355.
  40. ↑ "Augmentation of J Waves and Electrical Storms in Patients with Early Repolarization". New England Journal of Medicine. 358: 2078–2079. doi:10.1056/NEJMc0708182. Retrieved 2016-04-14.
  41. ↑ Rosso, R; Kogan, E; Belhassen, B; Rozovski, U; Scheinman, MM; Zeltser, D; Halkin, A; Steinvil, A; Heller, K; Glikson, M; Katz, A; Viskin, S (2015-09-28). "J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. -". J. Am. Coll. Cardiol. 52: 1231–8. PMID 18926326. doi:10.1016/j.jacc.2008.07.010.
  42. ↑ "Sudden Cardiac Arrest Associated with Early Repolarization". New England Journal of Medicine. 358: 2016–2023. doi:10.1056/NEJMoa071968. Retrieved 2016-04-14.
  43. ↑ "Long-Term Outcome Associated with Early Repolarization on Electrocardiography". New England Journal of Medicine. 361: 2529–2537. doi:10.1056/NEJMoa0907589. Retrieved 2016-04-14.
  44. ↑ "The early repolarization pattern in the general population: clinical correlates and heritability". Pubfacts.com. Retrieved 2016-04-14.
  45. ↑ "Characteristics and Distribution of M Cells in Arterially Perfused Canine Left Ventricular Wedge Preparations". Circ.ahajournals.org. Retrieved 2016-04-14.
  46. ↑ Gan-Xin Yan, MD; Charles Antzelevitch, PhD. "Cellular Basis for the Brugada Syndrome and Other Mechanisms of Arrhythmogenesis Associated With ST-Segment Elevation". Circ.ahajournals.org. Retrieved 2016-04-14.
  47. ↑ "Molecular Link between the Sudden Infant Death Syndrome and the Long-QT Syndrome". Nejm.org. 343: 262–267. doi:10.1056/NEJM200007273430405. Retrieved 2016-04-14.
  48. ↑ Antzelevitch C, Brugada P, Brugada J, Brugada R, Nademanee K, Towbin JA. The Brugada Syndrome. Armonk (NY): Futura Publishing; 1999. (Camm AJ, editor. Clinical approaches to tachyarrhythmias; vol. 10). ISBN 0879934344.
  49. ↑ "Proposed Diagnostic Criteria for the Brugada Syndrome". Circ.ahajournals.org. 2000-09-01. Retrieved 2016-04-14.
  50. ↑ "Brugada Syndrome: Report of the Second Consensus Conference". Circ.ahajournals.org. 2005-01-17. Retrieved 2016-04-14.
  51. ↑ Antzelevitch, C; Yan, GX; Ackerman, MJ; Borggrefe, M; Corrado, D; Guo, J; Gussak, I; Hasdemir, C; Horie, M; Huikuri, H; Ma, C; Morita, H; Nam, GB; Sacher, F; Shimizu, W; Viskin, S; Wilde, AA (2016). "J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge". J Arrhythm. 32 (5): 315–339. PMC 5063270 Freely accessible. PMID 27761155. doi:10.1016/j.joa.2016.07.002.
  52. ↑ Antzelevitch, C; Yan, GX; Ackerman, MJ; Borggrefe, M; Corrado, D; Guo, J; Gussak, I; Hasdemir, C; Horie, M; Huikuri, H; Ma, C; Morita, H; Nam, GB; Sacher, F; Shimizu, W; Viskin, S; Wilde, AA (2016). "J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge: Endorsed by the Asia Pacific Heart Rhythm Society (APHRS), the European Heart Rhythm Association (EHRA), the Heart Rhythm Society (HRS), and the Latin American Society of Cardiac Pacing and Electrophysiology (Sociedad Latinoamericana de Estimulacifin Cardiaca y Electrofisiologia [SOLAECE])". Europace: euw235. PMID 27411360. doi:10.1093/europace/euw235.
  53. ↑ Antzelevitch, C; Yan, GX; Ackerman, MJ; Borggrefe, M; Corrado, D; Guo, J; Gussak, I; Hasdemir, C; Horie, M; Huikuri, H; Ma, C; Morita, H; Nam, GB; Sacher, F; Shimizu, W; Viskin, S; Wilde, AA (2016). "J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge". Heart Rhythm. 13 (10): e295–324. PMC 5035208 Freely accessible. PMID 27423412. doi:10.1016/j.hrthm.2016.05.024.
  54. ↑ Antzelevitch C, Yan GX, editors (2016). J Wave Syndromes: Brugada and Early Repolarization Syndromes. Cham (Switzerland): Springer. ISBN 3319315765.
  55. ↑ "Electrophysiological Effects of Ranolazine, a Novel Antianginal Agent With Antiarrhythmic Properties". Circ.ahajournals.org. 2004-08-09. Retrieved 2016-04-14.
  56. ↑ "Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation". Content.onlinejacc.org. Retrieved 2016-04-14.
  57. ↑ "Charles Antzelevitch - Google Scholar Citations". Scholar.google.com. Retrieved 2016-04-14.
  58. ↑ "Affiliate List by States". Professional.heart.org. Retrieved 2016-04-14.
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