Translational Pathway for Catheter Ablation
Unmet Clinical Needs
Gregory K. Feld, MD
Catheter ablation of common supraventricular tachyarrhythmias (SVTs) such as atrioventricular nodal reentry, atrioventricular reentry due to an accessory pathway, atrial tachycardia, and even atrial flutter, has become well established and commonplace since their first description nearly 3 decades ago (1-4). The acute and long-term success rates for treatment and cure of these arrhythmias has become relatively high, ranging from 90% to 100% in most published series (5,6). However, the prevalence of these more common arrhythmias in the general population has declined, primarily as a result of the advent of curative catheter ablation techniques, which have replaced medical management largely for these arrhythmias. Thus, despite the incidence of these arrhythmias not likely changing in the future, a regularly occurring but smaller proportion of these arrhythmias (i.e., the prevalence) has been noted in most electrophysiology laboratories in the recent decade. This is particularly true in tertiary referral centers, which typically deal with more complex arrhythmias and ablation procedures.
Therefore, more recently, catheter ablation for atrial fibrillation (AF) and ventricular tachycardia (VT) has become the primary focus of research and development by industry, basic scientists, engineers, and clinicians, especially as these arrhythmias become more common in our aging and sicker patient population. Unfortunately, the success rate of catheter ablation to cure or reduce the frequency of recurrence of these arrhythmias is lower than it is for the more common SVTs alluded to above. Therein lies the unmet clinical needs for catheter ablation for treatment of atrial fibrillation and ventricular tachycardia.
Unmet Needs in Catheter Ablation of AF and VT
Improved Long-term Outcome After AF Ablation
Currently AF still recurs in approximately 30% to 40% of patients with paroxysmal AF, and up to 40% to 50% of patients with persistent AF, after catheter ablation (7-8). Recurrence of AF has been shown to be to inadequate ablation with reconnection of pulmonary veins in many cases (i.e., pulmonary vein isolation is the main approach for preventing recurrence of AF after ablation) but may also be due to new trigger sources or abnormal underlying atrial substrate (that is, idiopathic myocardial scarring) not identified during initial ablation (9). These high recurrence rates have been the primary driver for continued research and development into new and improved methods and technologies for catheter ablation, with a commonly held goal of at least improving long-term outcomes (i.e., by statistically significant amounts) in current randomized clinical trials. And although possibly not achievable due to differences in underlying mechanisms and causes of AF compared to other SVTs, a goal of achieving long-term outcome of <10% recurrence rate would be desirable. To achieve such a lofty goal, research and development will likely need to be multifaceted including development and testing of alternative energy sources (10-14) for ablating cardiac tissue (e.g., cryoablation, laser, heat, microwave, and even a newer theoretical approach called electroporation); sophisticated three-dimensional cardiac mapping systems (e.g., Carto™, Ensite Precision™) that can generate accurate cardiac geometry to define critical tissue characteristics (such as voltage amplitude, impedance, conduction velocity, etc.), localize ablation and mapping catheters within this geometry, and identify previously unrecognized sources for recurrence and/or maintenance of AF (15,16); and finally systems that can display or confirm transmural lesion generation during ablation to ensure durability and improve long-term outcomes.
Improved Acute and Long-term Outcomes After VT Ablation
Although there are several mechanisms underlying ventricular tachycardia, reentrant VT due to ventricular scarring (structural heart disease) in patients with ischemic cardiomyopathy, nonischemic cardiomyopathy, or infiltrative diseases (e.g., sarcoidosis, arrhythmogenic right ventricular dysplasia, or Chagas disease) is the most difficult to ablate, with 1-year recurrence rates approaching 26% (17). And unlike AF, recurrence of VT may be fatal with mortality reaching 12% at 1 year (17), unless the patient has an implantable defibrillator as a backup. Idiopathic focal VT (i.e., also known as repetitive monomorphic VT) and idiopathic premature ventricular contractions (PVCs) arising from the left or right ventricular outflow tracts, in the absence of associated structural heart disease, may be readily ablated with a success rate >90% (18). If the origin of the VT or PVC focus is in the so-called ventricular summit, however, this location is not easily accessed from an endocardial or epicardial approach and may therefore be difficult to ablate, requiring a surgical, or other novel, approach for ablation (19). Reentrant VT in the ventricular myocardium may be difficult to ablate for other reasons as well, including the presence of large areas of myocardium that can support the reentry circuit and would require large areas of ablation (i.e., tissue homogenization), the presence of deep intramural reentry circuits that require a deep ablation lesion (e.g., reentry in the intra-ventricular septum), and the presence of epicardial circuits that require a complicated and somewhat risky approach to access for ablation (i.e., epicardial catheterization). Due to the high recurrence rates of VT after ablation, there is therefore a great need to develop new methodologies and technologies to improve outcomes after VT ablation, including initial and long-term success in prevention of arrhythmia recurrence. Such advances in methodologies and technologies may include development of more accurate mapping technologies to identify critical sites in the reentry circuit requiring ablation to prevent arrhythmia recurrence, development of more effective ablation catheters (e.g., needle ablation, cryoablation) and methods (e.g., bipolar radiofrequency ablation, radio-ablation, electroporation) to prevent arrhythmia recurrence.
Reduction of Risks of Complications During AF and VT Ablation
During AF ablation, there is a risk of complications, and although currently rare (<3% to 5% in worldwide surveys), they may be major including stroke, cardiac perforation and tamponade, and atrio-esophageal (AE) fistula (20). While the prevention of stroke has been minimized using uninterrupted anticoagulant therapy and cardiac perforation using contact force sensing catheters, the appropriate method for prevention of AE fistula is still controversial and under investigation (i.e., whether to use monitoring luminal esophageal temperature monitoring and adjust ablation power and catheter position accordingly versus esophageal manipulation). During VT ablation the risk of stroke is also high (1% to 2%) and methods for prevention of stroke need to be studied further (21-23). Such studies are underway, including the comparison of risks with a transseptal catheterization approach versus a retrograde aortic approach for catheter ablation of left ventricular VT.
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- Chan JY, Fung JW, Yu CM, Feld GK. Preliminary results with percutaneous transcatheter microwave ablation of typical atrial flutter. J Cardiovasc Electrophysiol. 2007;18:286-9.
- Wojtaszczyk A, Caluori G, Pešl M, et al. Irreversible electroporation ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2018;29:643-51.
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- Cappato R, Calkins H, Chen SA, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:32-8.
- Kuck KH, Schaumann A, Eckardt L, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicenter randomised controlled trial. 2010;375:31-40.
- Siontis KC, Killu AM. Silent and non-silent thromboembolic events after ventricular tachycardia ablation: Modifiable risk with postprocedure anticoagulation? J Cardiovasc Electrophysiol. 2019;3:1197-9.