CIMIT FORUM AGENDA

Beth Israel Deaconess Medical Center
Simulation and Skills Center

September 25, 2007

4:00 – 6:00 PM

4:00PM  Repolarization Alternans: From the Patient to the Bench and Back to the Patient

Speaker: Antonis Armoundas , PhD, Instructor in Medicine, Harvard Medical School, Massachusetts General Hospital, Massachusetts Institute of Technology, aarmoundas@partners.org
Moderator: Richard J. Cohen, MD, PhD, Whitaker Professor in Biomedical Engineering, Massachusetts Institute of Technology, rjcohen@mit.edu

Electrical alternans is a cardiac pattern in which every other heartbeat produces a variant waveform on an electrocardiogram (ECG). When the alternating waveforms differ in terms of ventricular repolarization, the pattern is referred to as repolarization alternans (RA). For the last hundred years, physicians have anecdotally observed that RA often precedes ventricular fibrillation (VF), ventricular tachyarrhythmia (VT), and sudden cardiac death (SCD). The cellular mechanisms behind RA are only beginning to be understood, and the knowledge that is being gained may someday be used to reduce the average patient’s risk of VF/VT and SCD.

A team of researchers led by Antonis Armoundas, PhD, of Harvard Medical School is experimentally investigating cellular changes that accompany RA. They induced action potentials in left ventricular myocytes, and they measured calcium movement from the sarcoplasmic reticulum (SR) into the cytoplasm. Stimulating the myocytes at ever-increasing rates, they were able to elicit RA. Their experiments showed that on every other beat, calcium channels in the SR opened to emit a secondary release of calcium into the cytoplasm. They created models based on the timing and amplitude of these secondary releases, and these models were fairly successful at predicting RA patterns. Their results suggest that RA is caused at a cellular level by a calcium overload in the SR that leads to a spontaneous release of calcium into the cytoplasm, which then triggers a secondary wave of calcium extrusion. According to their hypothesis, if many cells in a certain area of the heart experience these secondary pulses of calcium, local regions of the myocardium will exhibit delayed repolarization visible on an ECG.

Understanding RA patterns may soon lead to improved clinical treatments. The results obtained by the Armoundas group raise the possibility that new drugs designed to prevent excess calcium from building up in the SR could be developed to prevent arrhythmias. RA patterns could also be used to help clinicians accurately detect the onset of arrhythmias. Implantable cardiac defibrillators (ICD’s) are capable of measuring electrical patterns in the heart and of delivering electrical defibrillation if the heart develops an abnormal rhythm. Programming ICD’s look for RA could potentially improve the effectiveness of the devices at preventing SCD.

Video of this presentation to be made available at a later date.

5:00PM  Dynamic Tracking of ECG Heterogeneity to Estimate Risk of Life-threatening Arrhythmias

Speaker: Richard L. Verrier, PhD, FACC, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard-Thorndike Electrophysiology Institute, Harvard Institutes of Medicine, rverrier@bidmc.harvard.edu
Moderator: Steven Schachter, MD, Professor of Neurology, Harvard Medical School; Director of Research, Department of Neurology, Beth Israel Deaconess Medical Center; Associate Director, Clinical Research, Harvard Medical School Osher Institute; Member, Board of the Epilepsy Therapy Development Project; Founder & Editor-in–Chief, Epilepsy & Behavior; Editor-in-Chief of Epilepsy.com; CIMIT Program Leader, Neurotechnology; CIMIT Site Miner, BIDMC, sschacht@bidmc.harvard.edu

There are over 350,000 cases of sudden cardiac death (SCD) in the United States each year, and over twenty percent of these cases involve people with no outward signs of serious heart disease. For decades, researchers have been attempting to come up with methods of identifying electrocardiogram (ECG) patterns that reliably precede dangerous arrhythmias. As these methods are found, devices are being created that monitor the heart in order to detect the onset of dangerous rhythms and to correct them before they cause death.

Recent research suggests that ECG heterogeneity, or waveforms that vary from one heartbeat to the next, often precedes arrhythmias. This heterogeneity can be measured by placing multiple ECG electrodes on the chest and by then computing the variance in waveform morphology across the signals from these electrodes. A crescendo in T-wave heterogeneity often signals the start of ventricular fibrillation, and R-wave heterogeneity has also been shown to precede ischemia-induced ventricular fibrillation. In patients with coronary artery disease, exercise increases T-wave heterogeneity, but this effect is not seen in normal patients. These results, when combined with other pieces of emerging evidence, suggest that R-wave and T-wave heterogeneity both have predictive value.
In the future, researchers led by Richard L. Verrier, PhD, of Harvard Medical School hope to automate the process of heterogeneity detection and to augment the clinical evidence supporting the validity of ECG heterogeneity as a predictor of arrhythmia. Someday soon, implantable devices may be programmed to measure and track heterogeneity. These devices could help ward off arrhythmias by stimulating nerves such as the vagus nerve, by delivering drugs such as beta-blockers, and if necessary, by defibrillating the heart.

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