Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in the U.S., affecting 2-5 million individuals in whom it may cause stroke, palpitations, heart failure, and even death. Unfortunately, therapy for AF is limited. Anti-arrhythmic or rate-controlling drugs are poorly tolerated, with frequent side effects and do not reduce stroke risk. Ablation is an emerging minimally invasive therapy that has attracted considerable attention because it may eliminate AF. Unfortunately, AF ablation is technically challenging, with a success of only 50-70 % (versus >90% for other arrhythmias), and serious risks. A major cause of these limitations is that the mechanisms for human AF are not known and thus ablation cannot be directed to them. As a result, AF ablation is empiric and results in extensive destruction of the atrium. In this Mid-Career Mentoring Award in Patient Oriented Research, the applicant proposes a mentored training program for clinician-scientists, applying bioengineering principles to address mechanistic hypotheses on the maintenance of human AF. From a training perspective, each mentee will receive continuous mentoring by the applicant and an interdisciplinary research committee comprising experts in heart rhythm medicine, bioengineering, computer modeling and biological physics. Through formalized collaborations, mentees will also be able to train in cellular electrophysiology. Structured didactic training is also outlined. Scientifically, our central hypothesis is that human AF is maintained by localized sources, as opposed to widely dispersed mechanisms (multi-wavelet reentry). We will create detailed maps of atrial activation and recovery (repolarization) in AF in patients at ablation, and then use computational analysis and pharmacologic interventions in near-real-time to study mechanisms that maintain AF. Personalized computer models will be unique in that predictions will be tested directly against observed AF in the same patient, with discrepancies used to directly design further clinical studies. Because the project is performed at ablation, results will be easily translated to practice. The candidate has a track-record of using bioengineering principles, signal processing and computer models to address mechanistic hypotheses in arrhythmia-focused patient oriented research. He also has a track record of training clinician-scientists who continue to pursue patient oriented research, many of whom have secured extramural funding. Proposed studies address three Aims: 1) To determine if localized sources maintain human AF;2) To determine if repolarization alternant, conduction slowing or anatomic factors explain disorganization to fibrillation;3) to determine the impact on AF of ablating at potential localized sources. Successful completion of our Aims will lead to a paradigm-change in the mechanistic understanding of human AF, and approaches to its ablation. Mentees will be trained in a rich interdisciplinary environment and, on completing this program, will be well prepared to embark upon careers in patient-oriented research in heart rhythm disorders.
fibrillation (AF) is an enormous public health problem that affects 2-5 million Americans, causing morbidity or death from stroke, rapid heartbeats and heart failure. Through this Mid-Career Mentoring Award in Patient Oriented Research, the applicant will perform research and train junior physician-researchers to better understand AF, and determine if abnormal activity in small regions or more widespread regions of the heart cause AF. By performing these studies in patients during clinical procedures, this project may lead to a paradigm-shift in understanding and treating AF. Narrative Atrial fibrillation (AF) is an enormous public health problem that affects 2-5 million Americans, causing morbidity or death from stroke, rapid heart beats and heart failure. Through this Mid-Career Mentoring Award in Patient Oriented Research, the applicant will perform research and train junior physician-researchers to better understand AF, and determine if abnormal activity in small regions or more widespread regions of the heart cause AF. By performing these studies in patients during clinical procedures, this project may lead to a paradigm-shift in understanding and treating AF.
|Gonzales, Matthew J; Vincent, Kevin P; Rappel, Wouter-Jan et al. (2014) Structural contributions to fibrillatory rotors in a patient-derived computational model of the atria. Europace 16 Suppl 4:iv3-iv10|
|McGarry, Thomas J; Narayan, Sanjiv M (2014) Defining arrhythmic risk and defibrillator therapy in ARVC: shocking rhythm? J Am Coll Cardiol 64:126-8|
|Rostamian, Armand; Narayan, Sanjiv M; Thomson, Louise et al. (2014) The incidence, diagnosis, and management of pulmonary vein stenosis as a complication of atrial fibrillation ablation. J Interv Card Electrophysiol 40:63-74|
|Narayan, Sanjiv M; Jalife, José (2014) CrossTalk proposal: Rotors have been demonstrated to drive human atrial fibrillation. J Physiol 592:3163-6|
|Schricker, Amir A; Lalani, Gautam G; Krummen, David E et al. (2014) Rotors as drivers of atrial fibrillation and targets for ablation. Curr Cardiol Rep 16:509|
|Krummen, David E; Hayase, Justin; Morris, David J et al. (2014) Rotor stability separates sustained ventricular fibrillation from self-terminating episodes in humans. J Am Coll Cardiol 63:2712-21|
|Baykaner, Tina; Lalani, Gautam G; Schricker, Amir et al. (2014) Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM). J Interv Card Electrophysiol 40:237-44|
|Narayan, Sanjiv M; Baykaner, Tina; Clopton, Paul et al. (2014) Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulat J Am Coll Cardiol 63:1761-8|
|Wyse, D George; Van Gelder, Isabelle C; Ellinor, Patrick T et al. (2014) Lone atrial fibrillation: does it exist? J Am Coll Cardiol 63:1715-23|
|Trulock, Kevin M; Narayan, Sanjiv M; Piccini, Jonathan P (2014) Rhythm control in heart failure patients with atrial fibrillation: contemporary challenges including the role of ablation. J Am Coll Cardiol 64:710-21|
Showing the most recent 10 out of 35 publications