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.
| Baykaner, Tina; Rogers, Albert J; Zaman, Junaid A B et al. (2018) Editorial commentary: What can lung transplantation teach us about the mechanisms of atrial arrhythmias? Trends Cardiovasc Med 28:62-63 |
| Navara, Rachita; Leef, George; Shenasa, Fatemah et al. (2018) Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation. J Cardiovasc Electrophysiol 29:687-695 |
| Rogers, Albert J; Tamboli, Mallika; Narayan, Sanjiv M (2018) Integrating mapping methods for atrial fibrillation. Pacing Clin Electrophysiol 41:1286-1288 |
| Zaman, Junaid A B; Sauer, William H; Alhusseini, Mahmood I et al. (2018) Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation. Circ Arrhythm Electrophysiol 11:e005258 |
| Sahli Costabal, Francisco; Zaman, Junaid A B; Kuhl, Ellen et al. (2018) Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/Physiological Study. Ann Biomed Eng 46:257-269 |
| Zaman, Junaid A B; Baykaner, Tina; Clopton, Paul et al. (2017) Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study. JACC Clin Electrophysiol 3:393-402 |
| Baykaner, Tina; Zografos, Theodoros A; Zaman, Junaid A B et al. (2017) Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi. Int J Cardiol 240:234-239 |
| Zaman, Junaid A B; Kowalewski, Christopher A B; Narayan, Sanjiv M (2017) Mapping Ripples or Waves in Atrial Fibrillation? J Cardiovasc Electrophysiol 28:383-385 |
| Baykaner, Tina; Zaman, Junaid A B; Rogers, Albert J et al. (2017) Spatial relationship of sites for atrial fibrillation drivers and atrial tachycardia in patients with both arrhythmias. Int J Cardiol 248:188-195 |
| Narayan, Sanjiv M; Vishwanathan, Mohan N; Kowalewski, Christopher A B et al. (2017) The continuous challenge of AF ablation: From foci to rotational activity. Rev Port Cardiol 36 Suppl 1:9-17 |
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