First step toward predicting Sudden Cardiac Death

About the School of Medicine Paper of the Month

The School of Medicine newsletter spotlights a recently published faculty research paper in each issue. The goals are to highlight the great research happening at OHSU and to share this information across departments, institutes and disciplines. The monthly paper summary is selected by Senior Associate Dean for Research Mary Stenzel-Poore, Ph.D., Associate Dean for Clinical Science Eric Orwoll, M.D., and Assistant Dean for Basic Research Mary Heinricher, Ph.D.

December 22, 2014

December's featured paper is called "Electrocardiographic Deep Terminal Negativity of the P Wave in V1and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities (ARIC) Study," published in the Journal of the American Heart Association. The paper is published by a team from the Tereshchenko Lab.

Sudden Cardiac Arrest (SCA) is a condition where the heart unexpectedly stops beating, causing loss of blood flow to the brain and other vital organs. SCA, if not treated immediately, leads to death within minutes. 

SCA incidence in the general population is high and can occur in people who appear healthy and have no known heart disease or other risk factors for cardiovascular disease. In fact, in more than half the cases of SCA, death is the first manifestation of cardiovascular disease. Victims of SCA are usually unaware of any danger; therefore, screening of asymptomatic individuals is necessary in order to identify individuals at risk. 

"Sudden cardiac death, or SCD, is a common and dramatic event that remains poorly understood," said Eric Orwoll, M.D., associate dean for clinical science.  "I chose this paper because these authors evaluated and identified a novel electrocardiogram finding that might predict sudden cardiac death."

ECG predictors

tarenshchenko lab

Electrocardiograms (ECGs) are used to measure the heart's electrical conduction system. ECG readout consists of waveform components which track complex electrical events during a heartbeat. These waveforms are labeled P, Q, R, S, T and U, and are read off of a variety of electrodes placed around the body. The V1 electrode is placed between ribs 4 and 5 just to the right of the breastbone. A normal P wave is typically positive.

An ECG with abnormal P-terminal waveform as measured by the V1 electrode was originally considered a sign of "left atrial enlargement" and was not associated with the risk of sudden cardiac death. Subsequent studies have shown the deep terminal negativity of P-prime waveforms can represent an inter-atrial conduction defect. 

Work by Larisa Tereshchenko, M.D., Ph.D., assistant professor of medicine, OHSU School of Medicine, recently demonstrated that fibrosis in the left atrium and left ventricle is the mechanism of deep terminal negativity of P-prime in V1 (DTNPV1); however, it was unknown if this ECG marker could predict sudden cardiac death.

Her lab's paper follows over 15,000 patients from the Atherosclerosis Risk in Communities (ARIC) study. 

"In this study, we investigated a large cohort and for the first time we have found that an ECG sign of deep terminal negativity of P-prime in V1 was independently associated with SCD," said Dr. Tereshchenko, a member of the OHSU Knight Cardiovascular Institute.  "Importantly, this association occurs in individual with or without prevalent cardiovascular disease, even after adjustment for other coronary heart disease risk factors and events." 

Easily recognizable

The association of DTNPV1 with SCD exceeded the risk of non-fatal coronary heart disease, heart failure and stroke.  This suggests that DTNPV1 is an intermediate marker on the pathway linking cardiac fibrosis with atrial and ventricular arrhythmias and SCD.  "Our finding of an independent association between DTNPV1 and SCD supports the unifying hypothesis of the key role of fibrosis in arrhythmogenesis," said Dr. Tereshchenko. 

"One reason why this work is important is that DTNPV1 is an easily recognizable ECG sign," continued Dr. Tereshchenko, "which means that without any special equipment the risk of sudden cardiac death could be determined in any small village far from a large hospital by a simple and inexpensive test. This is the first step towards development of ECG risk score of sudden cardiac death in the general population – in the future, it will help to save the lives of thousands of people."

Dr. Tereshchenko's laboratory is continuing their research in two major directions. First, they continue to study the ARIC cohort in order to identify other ECG predictors of sudden cardiac death. At the same time, they are starting a new study at OHSU.

"We reviewed the OHSU database and selected those individuals who have this ECG sign," said Dr. Tereshchenko. "It appears that only half of them are diagnosed with cardiac disease and are under the care of cardiologist. Another half had ECG recorded as a part of evaluation before surgery, or at ED, and these patients are not on any medications. We are planning to start randomized controlled trial and to invite these individuals to participate."   

Since deep terminal negativity can predict risk of any arrhythmia, Dr. Tereshchenko's lab will start a randomized controlled trial of primary prevention of atrial fibrillation.  "We are organizing an arrhythmia patient council to get patients involved as co-investigators of this trial, to make sure that their voice is heard," continued Dr. Tereshchenko. "We are hoping that our studies will change clinical practice and will help to save lives."   



Electrocardiographic Deep Terminal Negativity of the P Wave in V1 and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities (ARIC) Study
Larisa G. Tereshchenko, MD, PhD; Charles A. Henrikson, MD, MPH; Nona Sotoodehnia, MD, MPH; Dan E. Arking, PhD; Sunil K. Agarwal, MD, MPH, PhD; David S. Siscovick, MD, MPH; Wendy S. Post, MD, MS; Scott D. Solomon, MD; Josef Coresh, MD, PhD; Mark E. Josephson, MD; Elsayed Z. Soliman, MD, MSc, MS
J Am Heart Assoc. 2014 Nov 21;3(6). pii: e001387. doi: 10.1161/JAHA.114.001387



Pictured above from left to right: Muammar Kabir, Ph.D., postdoctoral fellow; Elyar Ghafoori, M.S., research assistant; Dr.Tereshchenko; Lauren Hawkins, B.S., clinical research assistant; Charles Henrikson, M.D., MPH, associate professor of medicine, OHSU School of Meciine, director of clinical electrophysiology.