Arrhythmias, Cardiac; Atrial Fibrillation; Cardiology; Catheter Ablation; Defibrillators
I have dedicated my clinical and academic work over the past two decades to the study and treatment of atrial fibrillation (AF). I take a systems biology approach to the study of AF, from the cellular to the population science level. My PhD thesis during fellowship focused on the study of the subcellular distribution of elements during the development of electrical and structural remodeling in AF. I continue to examine the atrial structural remodeling process using non-invasive imaging of matrix metalloproteases in large animal models. I have collaborated closely with biomedical engineers using signal analysis techniques to quantify spatiotemporal organization in AF, and continue to utilize in silico computer modeling and non-linear dynamics methodology to study the basic mechanisms of AF. Clinically, I have expertise in intracardiac echocardiographic (ICE) atrial imaging and using it to eliminate ionizing radiation use during AF ablation. I hold special interest in AF outcomes research and have compiled the only device database capable of relating AF burden to clinical outcomes. I am the PI of the YALE-CORE data analytic site for the national ACC/NCDR Atrial Fibrillation Ablation Registry, and I sit on the steering Committee of the ACC/NCDR Left Atrial Appendage Occlusion Registry. My expertise in atrial remodeling and AF ablation is reflected in nominations for the writing group of the 2016 EHRA/HRS Expert Consensus Statement on Atrial Cardiomyopathies and the 2017 Heart Rhythm Society Expert Consensus Statement on AF Ablation. The current application is the natural extension of my expertise and work on atrial remodeling and AF pathogenesis.
Specialized Terms: Mechanisms of atrial fibrillation; Ablation of atrial fibrillation; Molecular imaging of structural remodeling; Pericardial fat and arrhythmogenesis; Effect of remote device monitoring on patient outcomes; Atrial fibrillation burden; Clinical outcomes
Extensive Research Description
I take a systems biology approach to the study of AF, from the cellular to the population science level.
1. Electrical and Structural Remodeling in Atrial Fibrillation. A major focus of pre-clinical and clinical research interest is the study of processes that lead to the development of AF. This has been a major theme of my academic work over the past two decades. During my fellowship training at the University of Virginia I pursued a PhD in Molecular Physiology and Biological Physics, focusing on the just recently described phenomena of electrical and structural remodeling in AF. I used animal models of AF to examine changes in the mitochondrial and subcellular distribution of different elements (Na, K, Cl, Mg) during the development of electrical remodeling. I also determined the relative contribution of atrial electrical and structural remodeling to the spatiotemporal organization of AF. Given the importance of identification of individuals at high risk of AF before the onset of irreversible fibrosis, we have developed methods to non-invasively image the molecular processes leading to the development of fibrosis using targeted imaging of matrix metalloproteinases in the atrium. I am currently the co-PI of an extramural NIH R01 grant performing molecular imaging of activated matrix metalloproteinases as a substrate for the development of atrial structural remodeling and the precursor of fibrosis. The grant aims at developing novel techniques for early non-invasive assessment of AF vulnerability. This holds the potential for early detection and treatment of the disease before the onset of fibrosis. I have been collaborating with Dr. Lawrence Young and Dr. Fadi Akar to study the mouse model of AF induced by LKB1 deletion. My expertise in atrial remodeling has provided the opportunity to be a writing group member of the 2016 EHRA/HRS Consensus Statement on Atrial Cardiomyopathy.
A.Akar JG, Everett TH, Kok LC, Moorman JR, Haines DE. Effect of electrical and structural remodeling on spatiotemporal organization in acute and persistent atrial fibrillation. J Cardiovasc Electrophysiol 2002; 13:1027-1034.
B.Akar JG, Everett TH, Ho RH, Craft J, Haines DE, Somlyo AP, Somlyo AV. Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation. Circulation 2003; 107:1810-1815.
C.Mukherjee R, Akar JG, Wharton JM, Adams DK, McClure CD, Stroud RE, Rice AD, Desantis SM, Spinale FG, Gold MR. Plasma profiles of matrix metalloproteinases and tissue inhibitors of the metalloproteinases predict recurrence of atrial fibrillation following cardioversion. J Cardiovasc Transl Res. 2013; 6:528-35.
D.Kim GE, Ross JL, Xie C, Su KN, Zaha VG, Wu X, Palmeri M, Ashraf M, Akar JG, Russell KS, Akar FG, Young LH. LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovasc Res 2015; 108:197-208.
2. Spatiotemporal AF organization. I have a long-standing interest in using signal analysis techniques to quantify pathophysiological mechanisms of AF. Given the clinical importance of objectively measuring the level of AF electrogram fractionation, I worked closely with biomedical engineers to use signal analysis techniques (Fourier transforms, entropy, cross correlations and wavelet analysis) to quantify AF organization in time and space. More recently, I have turned my attention to using the non-linear dynamics methodology of Recurrence Quantitative Analysis (RQA) to examine basic pathophysiological mechanisms of AF. Using computer modeling I am applying RQA in silico to differentiate differentiate different AF mechanisms (i.e spiral wave reentry “rotors” versus multiple wavelet reentry), and subsequently applying the RQA analysis on human AF signals obtained at the time of ablation.
A.Everett TH, Moorman JR, Kok LC, Akar JG, Haines DE. Assessment of global atrial fibrillation organization to optimize the timing of atrial defibrillation. Circulation 2001; 103:2857-2861.
B.Everett TH, Akar JG, Kok LC, Moorman JR, Haines DE. Use of global atrial fibrillation organization to optimize the success of burst pace termination. J Am Coll Cardiol 2002; 40:1831-1840.
C.Porter M, Spear W, Akar JG, Helms R, Brysiewicz N, Santucci P, Wilber DJ. Prospective Study of Atrial Fibrillation Termination During Ablation Guided by Automated Detection of Fractionated Electrograms. J Cardiovasc Electrophysiol 2008 May 5.
D.Webber Jr. CL, Hu Z, Akar JG. Unstable Cardiac Singularities May Lead to Atrial Fibrillation. Int J Bifurc Chaos. 2011; 21: 1141–1151.
3. Intracardiac Echocardiography and AF Ablation. I have significant expertise in the clinical use of intracardiac echocardiography (ICE) in order to eliminate ionizing radiation during AF ablation. I performed the first-in-man evaluation of the novel 3D ICE catheters and under my direction, the Yale-New Haven Hospital EP laboratory frequently hosts physicians interested in learning ICE skills and fluoroscopy reduction techniques. I am a writing group member of the 2014 Heart Rhythm Society Consensus Statement on EP Laboratory Standards, and the 2017 Heart Rhythm Society Consensus Statement on AF Ablation.
A.Ruisi CP, Brysiewicz N, Asnes JD, Sugeng L, Marieb M, Clancy J, Akar JG. Use of Intracardiac Echocardiography during Atrial Fibrillation Ablation. Pacing Clin Electrophysiol. 2013; 36:781-8.
B.Brysiewicz N, Mitiku T, Haleem K, Bhatt P, Al-Shaaraoui M, Clancy JF, Marieb MA, Sugeng L, Akar JG. Three-Dimensional Real-Time Intracardiac Echocardiographic Visualization of Atrial Structures Relevant to Atrial Fibrillation Ablation. JACC Imaging. 2014;7:97-100.
C.Haines DE, Beheiry S, Akar JG, Baker JL, Beinborn D, Beshai JF, Brysiewicz N, Chiu-Man C, Collins KK, Dare M, Fetterly K, Fisher JD, Hongo R, Irefin S, Lopez J, Miller JM, Perry JC, Slotwiner DJ, Tomassoni GF, Weiss E. Heart Rhythm Society Expert Consensus Statement on Electrophysiology Laboratory Standards: Process, Protocols, Equipment, Personnel, and Safety. Heart Rhythm. 2014 May 7, S1547-5271.
4. Registry Studies and Cardiovascular Outcomes Research. I have strong interest and expertise in registry studies examining cardiovascular outcomes. I headed the development a unique database of patients with cardiac devices by linking multiple different data sources. We used the ACC NCDR ICD Registry to derive baseline characteristics, the Boston Scientific Altitude registry to obtain a wealth of device and physiological data obtained via remote monitoring, Medicare claims to examine hospitalizations, and the social security death index to ascertain vital status. This one-of-a-kind database of ~30,000 patients allows the examination of cardiovascular outcomes associated with detailed device-, disease- and physiological device information. Our initial projects were to examine the determinants of remote monitoring and its effect on outcomes. We are now examining the relationship between device parameters (e.g. AF burden, RV pacing, etc…) on outcomes. Not only was this work presented as a Late Breaking Trial at the Heart Rhythm Society Scientific Sessions 2014, but also the registry expertise has provided me the opportunity be a writing group member of the 2015 Consensus Statement on Remote Monitoring, lead the Yale-CORE Data Analytical Site for the national ACC NCDR AF Ablation Registry, as well being a steering committee member of the ACC NCDR Left Atrial Appendage Occlusion registry.
A.Akar, JG, Bao H, Jones P, Wang Y, Chaudhry SI, Varosy P, Masoudi FA, Stein K, Saxon LA, Curtis JP. Use of Remote Monitoring of Newly Implanted Cardioverter-Defibrillators: insights from the Patient RElated Determinants of ICD Remote Monitoring (PREDICt RM) study. Circulation. 2013;128:2372-2378.
B.Slotwiner D, Varma N, Akar JG, Annas G, Beardsall M, Fogel RI, Galizio NO, Glotzer TV, Leahy RA, Love CJ, McLean RC, Mittal S, Morichelli L, Patton KK, Raitt MH, Pietro Ricci R, Rickard J, Schoenfeld MH, Serwer GA, Shea J, Varosy P, Verma A, Yu CM. Heart Rhythm Society Expert Consensus Statement on remote interrogation and monitoring for cardiovascular implantable electronic devices. Heart Rhythm 2015;12:e69-e100.
C.Akar JG, Bao H, Jones P, Wang Y, Varosy P, Masoudi FA, Stein K, Saxon LA, Normand ST, Curtis JP. Use of Remote Monitoring Is Associated with Lower Risk of Adverse Outcomes Among Patients with Implanted Cardiac Defibrillators. Circ Arrhythm Electrophysiol 2015; 8:1173-80.
D.Ranasinghe I, Parzynski, Freeman JV, Dreyer RP, Ross JS, Akar JG, Krumholz HM, Curtis JP. Long-Term Risk for Device-Related Complications and Reoperations After Implantable Cardioverter-Defibrillator Implantation. An Observational Cohort Study. Ann Intern Med 2016;165:20-29.
- Pericardial Fat is Independently Associated with Human Atrial Fibrillation Al-Chekakie MO, Welles CC, Metoyer R, Ibrahim A, Shapira AR, Cytron J, Santucci P, Wilber DJ, Akar JG. Pericardial Fat is Independently Associated with Human Atrial Fibrillation. J Am Coll Cardiol 2010; 56:784-788. Focus Issue on Heart Rhythm Disorders.
- Acute onset human atrial fibrillation is associated with local cardiac platelet activation and endothelial dysfunction Akar JG, Jeske W, Wilber DW. Acute onset human atrial fibrillation is associated with local cardiac platelet activation and endothelial dysfunction. J Am Coll Cardiol 2008; 51:1790-1793.
- Endothelial Dysfunction in Heart Failure Identifies Responders to Cardiac Resynchronization Therapy. Akar JG, Al-Chekakie MO, Fugate T, Moran L, Froloshki B, Varma N, Santucci P, Wilber DJ, Matsumura ME. Endothelial Dysfunction in Heart Failure Identifies Responders to Cardiac Resynchronization Therapy. Heart Rhythm 2008; 5:1229-1235 (Featured Article).
- Surface Electrocardiographic Patterns and Electrophysiological Characteristics of Atrial Flutter Following Modified Radiofrequency MAZE Procedures. Akar JG, Al-Chekakie MO, Hai A, Brysiewicz N, Porter M, Varma N, Santucci P, Wilber D. Surface Electrocardiographic Patterns and Electrophysiological Characteristics of Atrial Flutter Following Modified Radiofrequency MAZE Procedures. J Cardiovasc Electrophysiol 2007; 18:349-355.
- Idiopathic epicardial left ventricular tachycardia originating remote from the sinus of Valsalva: electrophysiological characteristics, catheter ablation, and identification from the 12-lead electrocardiogram. Daniels DV, Lu YY, Morton JB, Santucci PA, Akar JG, Green A, Wilber DJ. Idiopathic epicardial left ventricular tachycardia originating remote from the sinus of Valsalva: electrophysiological characteristics, catheter ablation, and identification from the 12-lead electrocardiogram. Circulation 2006; 113:1659-1666.
- Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation. Akar JG, Everett TH, Ho RH, Craft J, Haines DE, Somlyo AP, Somlyo AV. Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation. Circulation 2003; 107:1810-1815.