Associate Professor in the Department of Environmental Health
Associate Professor of Medicine
Beth Israel Deaconess Medical Center
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.
Verrier RL, d'Avila A.
Trends Cardiovasc Med. 2021 May 07. PMID: 33965552
Rabêlo Evangelista AB, Monteiro FR, Nearing BD, Belardinelli L, Verrier RL.
Heart Rhythm. 2021 Apr 10. PMID: 33848647
Positive Psychotherapy Improves Cardiac Electrical Stability and Mood in ICD Patients: PAM-ICD Trial Results.
Serber ER, Christon LM, Fava JL, Verrier RL, Nearing BD, Buxton AE, Gold MR, Rodrigue JR, Frisch MB.
Psychosom Med. 2021 Apr 01. 83(3):300-301. PMID: 33534391
Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF.
Nearing BD, Libbus I, Carlson GM, Amurthur B, KenKnight BH, Verrier RL.
Clin Auton Res. 2021 Jun. 31(3):453-462. PMID: 33590355
T-wave heterogeneity in standard resting 12-lead ECGs is associated with 90-day cardiac mortality in women following emergency department admission: A nested case-control study.
Monteiro FR, Rabelo Evangelista AB, Nearing BD, Medeiros SA, Tessarolo Silva F, Pedreira GC, Ullman E, Gervino EV, Verrier RL.
Ann Noninvasive Electrocardiol. 2021 05. 26(3):e12826. PMID: 33543816
Indian Pacing Electrophysiol J. 2021 Mar-Apr. 21(2):139. PMID: 33503470
Vagus Nerve Stimulation Provides Multiyear Improvements in Autonomic Function and Cardiac Electrical Stability in the ANTHEM-HF Study.
Nearing BD, Anand IS, Libbus I, Dicarlo LA, Kenknight BH, Verrier RL.
J Card Fail. 2021 Feb. 27(2):208-216. PMID: 33049374
Regadenoson-induced T-wave heterogeneity complements coronary stenosis detection by myocardial perfusion imaging in men and women.
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. 2020 Jul 04. PMID: 32620962
Preimplantation interlead ECG heterogeneity is superior to QRS complex duration in predicting mechanical super-response in patients with non-left bundle branch block receiving cardiac resynchronization therapy.
Bortolotto AL, Verrier RL, Nearing BD, Marum AA, Araujo Silva B, Pedreira GC, Tessarolo Silva F, Medeiros SA, Sroubek J, Zimetbaum PJ, Chang JD.
Heart Rhythm. 2020 11. 17(11):1887-1896. PMID: 32497764