T-wave heterogeneity crescendo in the surface EKG is superior to heart rate acceleration for seizure prediction.
Pang TD, Nearing BD, Verrier RL, Schachter SC.
Epilepsy Behav. 2022 May. 130:108670. PMID: 35367725
Associate Professor in the Department of Environmental Health
Environmental Health
Associate Professor of Medicine
;Medicine-Beth Israel Deaconess
Harvard Medical School
My research concentrates on the major public health problem of sudden cardiac death, which claims approximately 325,000 lives per year in the United States alone and occurs without prodromes in at least 30% of cases. The main challenges have been to elucidate the complex pathophysiologic factors involved and to develop novel approaches for identifying individuals at risk for this mode of demise.
In an extensive series of studies, my colleagues and I explored the mechanisms responsible for sudden arrhythmic death. Our investigations demonstrated the pivotal role played by sympathetic nerve activity in triggering life-threatening arrhythmias and defined contributions of beta-adrenergic receptors acting primarily on intracellular calcium handling. We also determined that vagus nerve activity opposes the deleterious influence of adrenergic activity by opposition to presynaptic release of norepinephrine and direct antagonism of second messenger effects. I developed an experimental model in canines that emulated the angerlike state and allowed us to demonstrate that intense behavioral arousal profoundly alters cardiac electrical instability and coronary reactivity, which in turn predispose to malignant arrhythmias. My group and I also systematically studied the impact of sleep states on coronary hemodynamic and cardiac electrophysiologic function. The knowledge base generated was published in Science, Circulation, New England Journal of Medicine, and other leading journals. My basic science studies on neural control of heart rhythm received NIH funding for more than 35 years.
My most significant contributions to clinical innovation emerged during my appointment at Harvard Medical School in Beth Israel Deaconess Medical Center’s Division of Cardiovascular Medicine. In collaboration with my junior colleague, Dr. Bruce D. Nearing, a biomedical engineer, I discovered and published in Science in 1991 evidence that a fundamental electrophysiologic phenomenon, “T-wave alternans,” a beat-to-beat fluctuation in the magnitude of this waveform, is capable of stratifying risk for life-threatening arrhythmia. An extensive series of experiments revealed that T-wave alternans is tracks effects of neural factors, myocardial ischemia, and other proarrhythmic influences. Conversely, antiarrhythmic physiologic and pharmacologic interventions reduce the magnitude of alternans. These findings provided essential scientific underpinnings for utilizing alternans as a clinical marker of arrhythmic risk and target for therapeutic interventions. We developed, patented, and implemented methodologies for quantifying alternans that are compatible with routine ambulatory ECG monitoring and exercise stress testing and employed them to demonstrate that this phenomenon is capable of assessing risk for arrhythmic events in >1,600 post-myocardial infarction and heart failure patients based on ambulatory ECGs recordings. Prediction was also demonstrated in >3,500 consecutive patients with preserved left ventricular function who were referred for routine exercise testing. In 2011, I was lead author of a clinical consensus guideline on T-wave alternans by international experts that was published in Journal of the American College of Cardiology.
In summary, my research program focuses on sudden cardiac death, with dual emphasis on elucidation of pathophysiologic mechanisms and translation from bench to bedside. Our patented, FDA-approved diagnostic risk assessment technology is now in use in clinics and hospitals worldwide.
Pang TD, Nearing BD, Verrier RL, Schachter SC.
Epilepsy Behav. 2022 May. 130:108670. PMID: 35367725
Verrier RL, Libbus I, Nearing BD, KenKnight BH.
Front Physiol. 2022. 13:855756. PMID: 35431984
Mehra R, Tjurmina OA, Ajijola OA, Arora R, Bolser DC, Chapleau MW, Chen PS, Clancy CE, Delisle BP, Gold MR, Goldberger JJ, Goldstein DS, Habecker BA, Handoko ML, Harvey R, Hummel JP, Hund T, Meyer C, Redline S, Ripplinger CM, Simon MA, Somers VK, Stavrakis S, Taylor-Clark T, Undem BJ, Verrier RL, Zucker IH, Sopko G, Shivkumar K.
JACC Basic Transl Sci. 2022 Mar. 7(3):265-293. PMID: 35411324
Verrier RL, D'Avila A.
Heart Rhythm. 2022 Jan 15. PMID: 35041925
Verrier RL, Pang TD, Nearing BD, Schachter SC.
Heart Rhythm. 2022 Apr. 19(4):585-587. PMID: 35033664
Verrier RL, Kumar K.
J Cardiovasc Electrophysiol. 2022 02. 33(2):296-298. PMID: 34908210
Araujo Silva B, Hauser TH, Nearing BD, Bortolotto AL, Marum AA, Tessarolo Silva F, Medeiros SA, Pedreira GC, Gervino EV, Verrier RL.
Eur Heart J Cardiovasc Imaging. 2021 10 19. 22(11):1341-1349. PMID: 32620962
Burke GM, Araujo Silva B, Marum AA, Bortolotto AL, Nearing BD, Chen MJ, Fostello S, Popma JJ, Verrier RL, Chang JD.
Open Heart. 2021 10. 8(2). PMID: 34611017
Verrier RL, Nearing BD, D'Avila A.
Ann Noninvasive Electrocardiol. 2021 11. 26(6):e12894. PMID: 34592018
Verrier RL, Pang TD, Nearing BD, Schachter SC.
Epilepsia. 2021 08. 62(8):1780-1789. PMID: 34236079