Faisal M Merchant1,2, Omid Sayadi2, Kwanghyun Sohn2, Eric H Weiss2,3, Dheeraj Puppala2, Rajiv Doddamani2, Jagmeet P Singh4, E Kevin Heist4, Chris Owen5, Kanchan Kulkarni2, Antonis A Armoundas2,3. 1. Cardiology Division, Emory University School of Medicine, Atlanta, GA (F.M.M.). 2. Cardiovascular Research Center (F.M.M., O.S., K.S., E.H.W., D.P., R.D., K.K., A.A.A.), Massachusetts General Hospital, Boston. 3. Institute for Medical Engineering and Science, Massachusetts Institute of Technology Cambridge (E.H.W., A.A.A.). 4. Cardiology Division, Cardiac Arrhythmia Service (J.P.S., E.K.H.), Massachusetts General Hospital, Boston. 5. Neurosurgery Division (C.O.), Massachusetts General Hospital, Boston.
Abstract
BACKGROUND: Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. METHODS: We have developed a real-time, closed-loop system to record and analyze RA from multiple intracardiac leads, and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. We have evaluated the ability of this system to control RA and reduce arrhythmia susceptibility, in vivo. RESULTS: R-wave triggered pacing can induce RA, the magnitude of which can be modulated by varying the amplitude, pulse width, and size of the pacing vector. Using a swine model (n=9), we demonstrate that to induce a 1 µV change in the alternans voltage on the body surface, coronary sinus and left ventricle leads, requires a delivered charge of 0.04±0.02, 0.05±0.025, and 0.06±0.033 µC, respectively, while to induce a one unit change of the Kscore, requires a delivered charge of 0.93±0.73, 0.32±0.29, and 0.33±0.37 µC, respectively. For all body surface and intracardiac leads, both Δ(alternans voltage) and ΔKscore between baseline and R-wave triggered paced beats increases consistently with an increase in the pacing pulse amplitude, pulse width, and vector spacing. Additionally, we show that the proposed method can be used to suppress spontaneously occurring alternans (n=7), in the presence of myocardial ischemia. Suppression of RA by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by a lower Srank score during programmed ventricular stimulation compared with baseline before ischemia. CONCLUSIONS: We have developed and evaluated a novel closed-loop method to dynamically modulate RA in a swine model. Our data suggest that suppression of RA directly reduces arrhythmia susceptibility and reinforces the concept that RA plays a critical role in the pathophysiology of arrhythmogenesis.
BACKGROUND: Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. METHODS: We have developed a real-time, closed-loop system to record and analyze RA from multiple intracardiac leads, and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. We have evaluated the ability of this system to control RA and reduce arrhythmia susceptibility, in vivo. RESULTS: R-wave triggered pacing can induce RA, the magnitude of which can be modulated by varying the amplitude, pulse width, and size of the pacing vector. Using a swine model (n=9), we demonstrate that to induce a 1 µV change in the alternans voltage on the body surface, coronary sinus and left ventricle leads, requires a delivered charge of 0.04±0.02, 0.05±0.025, and 0.06±0.033 µC, respectively, while to induce a one unit change of the Kscore, requires a delivered charge of 0.93±0.73, 0.32±0.29, and 0.33±0.37 µC, respectively. For all body surface and intracardiac leads, both Δ(alternans voltage) and ΔKscore between baseline and R-wave triggered paced beats increases consistently with an increase in the pacing pulse amplitude, pulse width, and vector spacing. Additionally, we show that the proposed method can be used to suppress spontaneously occurring alternans (n=7), in the presence of myocardial ischemia. Suppression of RA by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by a lower Srank score during programmed ventricular stimulation compared with baseline before ischemia. CONCLUSIONS: We have developed and evaluated a novel closed-loop method to dynamically modulate RA in a swine model. Our data suggest that suppression of RA directly reduces arrhythmia susceptibility and reinforces the concept that RA plays a critical role in the pathophysiology of arrhythmogenesis.
Authors: Juan Pablo Martínez; Rute Almeida; Salvador Olmos; Ana Paula Rocha; Pablo Laguna Journal: IEEE Trans Biomed Eng Date: 2004-04 Impact factor: 4.538
Authors: Omid Sayadi; Faisal M Merchant; Dheeraj Puppala; Theofanie Mela; Jagmeet P Singh; E Kevin Heist; Chris Owen; Antonis A Armoundas Journal: Circ Arrhythm Electrophysiol Date: 2013-07-24
Authors: Eric H Weiss; Faisal M Merchant; Andre d'Avila; Lori Foley; Vivek Y Reddy; Jagmeet P Singh; Theofanie Mela; Jeremy N Ruskin; Antonis A Armoundas Journal: Circ Arrhythm Electrophysiol Date: 2011-03-23