Catheter Ablation in the Treatment of Atrial Fibrillation

Abstract

Catheter ablation (CA) of the pulmonary veins for atrial fibrillation (AF) is growing exponentially and is the most commonly performed electrophysiologic procedure. Initial descriptions focused on CA for paroxysmal AF, and now more recently expanded in application to persistent AF and those with comorbid heart failure. Efforts to improve success have and continue to address issues such as pulmonary vein “reconnection” following ablation through different ablative energy modalities, and the use of a “hybrid” surgical/endocardial combined approach in persistent forms of AF. Technologic advances as well are concurrently seeking to improve safety, particularly regarding the incidence of atrio-esophageal fistula in this seemingly ever-growing ablation population.

Catheter ablation (CA) for atrial fibrillation (AF) has increased dramatically in the last two decades, and to date it is the most commonly performed ablative electrophysiologic (EP) procedure. Factors attributing to expanding utilization include superiority of CA to antiarrhythmic drugs for maintaining normal sinus rhythm, ¹ the resultant improvement in quality of life, left ventricular ejection fraction (EF), exercise capacity, and lower mortality in heart failure patients when compared with medical therapy. ² This review will summarize previously conducted studies of CA leading to the present time, discuss the contemporary issues relating to AF ablation targets, and briefly provide some insight as to what the future may hold for CA in AF.

Ablation Targets

The foundation of CA begins with targeting the pulmonary veins (PVs) as the primary source for AF initiation. This was shown through the seminal work of Haïssaguerre et al describing CA of ectopic pulmonary vein (PV) triggers for AF over 20 years ago. ³ The PVs have since been shown to possess both anatomic and EP properties that increase arrhythmogenicity for AF. ^{4 5} Enhanced automaticity, susceptibility to calcium-loading causing triggered activity, shorter action potential duration, and myocyte fiber orientation creating a micro-reentry substrate within PV sleeves have all been demonstrated. Additionally, four major autonomic ganglionated plexi consisting primarily of parasympathetic neurons exist in close proximity to the PVs and can initiate AF from rapid PV firing when stimulated. ^{6 7} As such, CA has evolved to include PV encirclement that extends to the antrum ( Fig. 1 ), which accounts for both PV intrinsic and proximal autonomic factors for AF initiation.

Fig. 1.

Posterior left atrium in paroxysmal atrial fibrillation. The three-dimensional postprocedure rendering with pulmonary vein encircling ablation lesions (anterior lesions not seen) appears on the left. The preprocedure computed tomography scan is on the right. The arrows delineate the antral connection to the atrium posteriorly, and the red dots anterior to the pulmonary veins. ARGP, anterior right ganglionated plexus; ILGP, inferior left ganglionated plexus; IRGP, inferior right ganglionated plexus; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.

Between 10 and 33% of patients may present with AF owing to other non-PV triggers. ^{8 9 10 11 12} These include the superior vena cava, left atrial appendage, coronary sinus/vein of Marshall, posterior left atrial wall, and crista terminalis. Programmed atrial stimulation and use of high dose isoproterenol infusions during EP study are typically used to help elucidate these sources so that they may be targeted for ablation.

Catheter Ablation Results

While the role that the PVs play in paroxysmal AF is undeniable, in persistent forms of AF, CA has not had comparable successful results. ^{2 13 14 15 16 17 18 19} Success of pulmonary vein isolation (PVI) ablation alone is typically around 80% for paroxysmal atrial fibrillation (PAF) ablation and 60% for persistent AF at 1 year. Maladaptive electrical remodeling and fibrosis of the atria proper from a complex combination of inflammatory effects, and cellular/molecular alterations occur in persistent AF. These mechanisms behind maintenance of AF are only more recently being appreciated. ^{5 20 21 22 23 24 25} CA targets beyond the PVs have been the subject of numerous studies; most notably including, posterior wall isolation, ^{26 27 28} complex fractionated atrial electrogram (CFAE) elimination, ^{19 29} left atrial appendage elimination, ^{30 31} ablation of focal and rotational electrical activity detected during AF, ^{32 33 34 35} and renal artery ablation denervation. ^{36 37}

The STAR AF II trial (Approaches to Catheter Ablation for Persistent Atrial Fibrillation) compared multiple ablative strategies: PVI alone versus PVI plus CFAE versus PVI plus linear lesions in persistent AF. ¹⁹ Additional ablation beyond PVI did not improve freedom from AF/AT, and in fact seemed to worsen the ultimate outcomes. Focal impulse and rotor modulation (FIRM) ablation in addition to PVI guided by a specialized basket catheter (Topera Basket Catheter, Abbott Electrophysiology, CA) deployed in the atria during persistent AF has yielded superior results to PVI alone in multiple single-center studies. ^{32 33 34} The multicenter REAFFIRM (Randomized Evaluation of Atrial Fibrillation Treatment with Focal Impulse and Rotor Modulation) trial compared PVI alone to FIRM ablation plus PVI. The PVI plus FIRM did slightly better than PVI alone, 69.3 versus 67.5% freedom from AF/atrial tachycardia (AT) at 3 to 12 months ( p  = NS). ³⁸ The basket catheter used for FIRM mapping in this study drew significant criticism. Suboptimal spatial resolution and coverage of the atrial anatomy may have negatively affected the results. The multicenter nonrandomized RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) trial utilized proprietary software and catheter design for a FIRM type ablation. ³⁹ Freedom from AF was 83% at 1 year. The methodology and catheter design for FIRM mapping, presumably, overcomes limitations of the basket catheter in the REAFFIRM trial. A randomized trial using this technology will likely provide definitive guidance on whether FIRM ablation is beneficial in the persistent AF population. Isolation of the posterior wall in addition to PVI reported in a 2018 multicenter study showed improved freedom from arrhythmia compared with PVI alone, ²⁸ and is commonly employed as a result ( Fig. 2 ).

Fig. 2.

Posterior left atrium in persistent atrial fibrillation. The three-dimensional postprocedure rendering is on the left, and preprocedure computed tomography scan is on the right. The arrows delineate roof and inferior ablation lines that connect to the encircling pulmonary vein lesions, and allow isolation of the posterior wall. The blue dots represent the ablation lesions anterior to the pulmonary veins. LAA, left atrial appendage; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein, RMPV, right middle pulmonary vein; RSPV, right superior pulmonary vein.

The aMAZE trial (Left Atrial Appendage Ligation Adjunctive to PVI for Persistent or Longstanding Persistent Atrial Fibrillation) is presently enrolling patients with persistent AF comparing PVI alone versus PVI plus left atrial appendage occlusion using the Food and Drug Administration approved Lariat device (SentreHeart, Redwood City, CA). ⁴⁰ The occluded appendage ultimately atrophies, thus taking away the autonomic inputs that reside within the vein/ligament of Marshall and that may be involved in persistence of AF. The ERADICATE-AF trial (Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation) randomized 294 patients with PAF and hypertension to PVI alone versus PVI plus renal artery catheter ablation denervation (RDN). Freedom from AF at 12 months was 71.4% (PVI + RDN) versus 57.8% (PVI alone; p  = 0.011). ³⁷ This suggests a potential neuro-hormonal role for AF maintenance. This ablation adjunct awaits further study before becoming more commonplace.

Durable Pulmonary Vein Isolation

Inability to attain durable PVI after CA is a problem that has been implicated in arrhythmia recurrence regardless of AF type. Neuzil et al looked at patients 3 months after radiofrequency ablation and found 65% had at least one PV electrically reconnected. ⁴¹ Correlating with the areas of electrical reconnection was a decreased force time integral. This has sparked generous interest in the factors affecting the quality of radiofrequency lesion formation. Catheter tip force, stability, power, and duration of application are all implicated as playing important roles in durable lesion formation.

Alternatively, PVI can occur with other energy sources. Cryo-ablation with the Arctic Front catheter (Medtronic, Minneapolis, MN) system has proven equivalent to radiofrequency ablation for treating AF in head-to-head study. ⁴² Utilization of a laser balloon that allows focused directionality of the signal while less common is also commercially available. The results of “pulsed field ablation” for AF delivered through a circular catheter deployed outside each of the PVs in 81 patients were recently reported. ⁴³ This modality can apply a circular lesion set around a PV in the matter of seconds. The direct current energy required for ablation of cardiac tissue is significantly lower than that causing irreversible damage to smooth muscle and nerve tissues. This ability to selectively affect cardiac tissue, as demonstrated in this study, and not phrenic and vagal nerve or esophageal tissues could dramatically lower if not eliminate, the incidence of atrio-esophageal fistula, gastric dysmotility, and diaphragmatic paralysis that are rarely documented with other energy sources. ^{44 45 46 47 48 49 50} As well, the success of durable PV isolation in repeat EP study at follow-up was 100% for those with refined bipolar ablation in this study.

Ablation in Heart Failure

Application of CA to patients with congestive heart failure (CHF) has also received considerable attention. The CASTLE-AF trial (Catheter Ablation for Atrial Fibrillation with Heart Failure) reported significant improvement from a PVI ablation alone in the combined endpoint of death and CHF hospitalization as compared with medical rate or rhythm control, 28.5 versus 44.6% of patients at 37.8 months ( p  = 0.007), in patients with either paroxysmal or persistent AF and EF >35%. ⁵¹ Likewise, the CAMERA-MRI trial (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction) demonstrated superiority of radiofrequency ablative restoration of normal sinus rhythm with PVI and posterior wall isolation, as opposed to rate control in patients with either paroxysmal or persistent AF and EF ≤45%. EF increased 18 versus 4% at 6 months ( p  < 0.0001). ⁵² Those patients, particularly without late gadolinium enhancement, seemed to have an even significantly greater improvement in EF with sinus rhythm restoration with ablation. This finding suggests an unappreciated mechanism besides tachycardia in AF that may contribute to depression of EF. While these studies have certainly provided significant data supporting the benefits of CA, the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation) results; however, they were not quite clear. ⁵³ CABANA was the largest trial studying ablation versus medical rhythm or rate management in an AF population (paroxysmal or persistent), including those with CHF. The primary intention to treat composite endpoints of death, disabling stroke, serious bleeding, and cardiac arrest (hazard ratio: 0.86; p  = 0.303) or all-cause mortality alone (hazard ratio: 0.85, p  = 0.377) did not reach statistical significance. The primary endpoints in the on-treatment analysis demonstrated statistically significant improvement with ablation; however, it should be noted generous crossover occurred.

Patients with class IV systolic CHF are not well represented in clinical trials. Successful CA of persistent AF, even in those on continuous inotropic infusions such as milrinone, has been achieved. ⁵⁴ Ultimately, pooled data from multiple centers will describe how successfully such patients may be addressed with CA.

Hybrid Ablation

Ablation, particularly of long-standing persistent AF, has also been accomplished in a “hybrid” procedure. ⁵⁵ This combines an initial minimally invasive epicardial surgical technique, followed by an endocardial study from an electrophysiologist. The electrophysiologist is able to take advantage of the endovascular approach and address inducible arrhythmia and/or structures not reached by the surgeon, as well as provide “touch-up” of the epicardial lesion sets. Multiple single-center results have accrued; ⁵⁶ however, results of three multicenter trials, DEEP (Epicardial and Endocardial Procedure), ⁵⁷ CONVERGE (Convergence of Epicardial and Endocardial Radiofrequency Ablation for the Treatment of Symptomatic Persistent AF), ⁵⁸ and TOP-AF (Staged Transthoracic Approach to Persistent Atrial Fibrillation) ⁵⁹ are currently awaited. Benefits of this approach in the long-standing persistent AF population remain to be seen.

Summary

Considerable effort and research has been expended over the decades and demonstrated generous benefits of CA for AF. Ablation of the PVs has endured as the foundation of CA intervention for AF. Multiple ablative adjuncts to PVI have been tested to improve success, particularly for persistent AF. Aside from posterior wall isolation, no significant improvement has been shown to date. Multiple modes of energy application are available to perform ablation, with radiofrequency and cryo-ablation being the most common. Technologic advancements now appear poised to address the difficulties of obtaining improved durable ablation of the PVs, identifying substrate outside of the PVs potentiating the persistence of AF that will result in improved outcomes, all while doing so in a safer fashion.