Repolarization Alternans: From the Patient to
the Bench and Back to the Patient

SPEAKER: Antonis Armoundas, PhD: HMS, MGH
MODERATOR: Richard J. Cohen, MD, PhD: MIT

(No Video Available)

9.25.2007 FORUM SUMMARY:

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.