Antonis A. Armoundas
Assistant Professor, Harvard Medical School, USA
Title: Real-time detection and suppression of repolarization alternans as antiarrhythmic therapy
Biography
Biography: Antonis A. Armoundas
Abstract
Background: This study investigates the spatio-temporal variability of intracardiac repolarization alternans (RA) and its relationship to arrhythmia susceptibility in a swine acute myocardial ischemia (MI) model.
Methods & Results: We developed a real-time multi-channel repolarization signal acquisition, display and analysis system to record electrocardiographic signals from catheters in the right ventricle, coronary sinus and left ventricle prior to and following circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes following the onset ischemia, and is most prominently seen during the first half of the repolarization interval. We developed a novel, clinically-applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular (RV) and coronary sinus (CS) catheters which provided the highest sensitivity for intracardiac RA detection when compared to any other far-field bipolar sensing configurations (p < 0.0001). The magnitude of RA was used to adjust pacing stimuli delivered during the absolute refractory period (ARP) aimed to reduce RA. We found that the pacing pulse polarity and the phase polarity are sufficient parameters to suppress RA. To calibrate the pacing stimuli, we estimated the required charge to induce one μV [one unit] change in the alternans voltage [and Kscore] on CS and LV leads as 0.05 ± 0.025 [0.32 ± 0.29] and 0.06 ± 0.033 [0.33 ± 0.37] μC, respectively. Using this approach, we demonstrated the ability to suppress spontaneous RA following acute MI. Overall, pacing during the ARP resulted in a significant decrease in alternans
voltage and Kscore and reduced arrhythmia susceptibility (p<0.01).
Conclusion: RA can be reliably detected through a novel triangular RV-CS lead configuration. Electrical stimulation during the ARP can be used to suppress RA, in vivo. Our findings may have important implications in developing methods to prevent the onset of ventricular arrhythmias.
Recent Publications
1. Merchant FM and Armoundas A A. Role of substrate and triggers in the genesis of cardiac alternans, from the myocyte to the whole heart: Implications for therapy. Circulation. 2012;125:539-549.
2. Sayadi O, Puppala D, Ishaque N, Doddamani R, Merchant F M, Barrett C, Singh J P, Heist E K, Mela T, Martinez J P, Laguna P and Armoundas A A. A novel method to capture the onset of dynamic electrocardiographic ischemic changes and its implications to arrhythmia susceptibility. J Am Heart Assoc. 2014;3.
3. Sayadi O, Merchant F M, Puppala D, Mela T, Singh J P, Heist E K, Owen C and Armoundas A A. A novel method for determining the phase of t-wave alternans: Diagnostic and therapeutic implications. Circ Arrhythm Electrophysiol. 2013;6:818-826.
4. Merchant F M, Sayadi O, Moazzami K, Puppala D and Armoundas A A. T-wave alternans as an arrhythmic risk stratifier: State of the art. Curr Cardiol Rep. 2013;15:398.
5. Merchant F M, Sayadi O, Puppala D, Moazzami K, Heller V and Armoundas A A. A translational approach to probe the proarrhythmic potential of cardiac alternans: A reversible overture to arrhythmogenesis? Am J Physiol Heart Circ Physiol. 2014;306:H465-474.