It was a year of big results for catheter ablation, continuing the procedure’s steady rise in atrial fibrillation (AF) management. Mark O’Neill, consultant cardiologist and professor of Cardiac Electrophysiology at St Thomas’ Hospital and King’s College London, UK, spoke about new developments in catheter ablation at the Europe AF (London, UK).
Looking at trends in science publishing makes it clear that AF ablation has been rising quickly to the foreground of AF management over the past two decades. In his talk on the year’s most important lessons in AF ablation, O’Neill pointed to the consistent and significant growth in papers published on the topic since the late-1990s. In the past five years, the number of ablation studies is almost equal to that of the preceding 20 years, O’Neill said, adding that in order to navigate and highlight important papers in a mass of data, three questions provide a quick guide to evaluating the impact of a new study: “Is it new? Is it true? And does anyone care?”
Three ablation studies
The MANTRA-PAF trial was a first-line medication vs. ablation study for patients with paroxysmal atrial fibrillation (PAF). Five years out, 245 of 294 patients attended face-to-face clinical follow-up, had an electrocardiogram (ECG), a medication review, and underwent one seven-day Holter. O’Neill called the follow-up “remarkable”, explaining: “This is often a weakness of studies in our field; that we get one- or two-year data and then single centre observational data many years out.” Results showed ablation outperforming drug therapy as a first-line treatment for PAF in terms of freedom from AF as well as from symptomatic AF, based on comparison between the patient symptoms and the seven-day Holter recorder at the five-year follow-up. Other interesting data from the trial included the low rate of progression from paroxysmal to persistent AF, as well as the lack of significant difference in improvement of quality of life between the ablation and medical therapy arms, though improvement was significant for both. O’Neill called the outcomes “a very heartening result” for AF catheter ablation.
The CASTLE-AF study was the big study of the year, O’Neill remarked. Nassir Marrouche (University of Utah, Salt Lake City, USA) presented the data during a late breaking session at the European Society of Cardiology (ESC) congress (26–30 August 2017, Barcelona, Spain).
The trial was a study of catheter ablation vs. conventional treatment in patients who had clear left ventricular dysfunction and atrial fibrillation, with the primary endpoint being mortality. Patients were selected with PAF or persistent AF, a contraindication to antiarrhythmic medication, a left ventricular ejection fraction (LVEF) of less than 35% and New York Heart Association (NYHA) symptoms of class II or greater. All patients had an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronisation therapy defibrillator (CRT-D). In CASTLE-AF, the ablation protocol highlights the changing approaches to AF ablation over the last decade. After undergoing a pulmonary vein (PV) isolation, O’Neill said, patients “could have whatever the operator deemed appropriate. And as we know, what is deemed appropriate has changed dramatically over the last ten years or so, during which CASTLEAF has been recruiting and reporting.” The outcomes of CASTLE-AF demonstrated a mortality benefit for ablation vs. conventional therapy, with a risk reduction of 47% when adopting an ablation strategy. In addition to demonstrating significant mortality benefit, the data also favoured ablation with reduced heart failure admissions as well as cardiovascular hospitalisation. A consistent trend towards ablation outperforming conventional treatment across the population of patients treated in CASTLE-AF ensured Marrouche et al’s findings are relevant for AF ablation.
The third 2017 ablation study O’Neill highlighted was the CAMERA-MRI study, which investigated catheter ablation vs. medical rate control in persistent AF and systolic dysfunction (LVEF≤45%). It tested the hypothesis that restoration of sinus rhythm could improve left ventricular (LV) systolic dysfunction compared with medical rate control in cardiomyopathy of unexplained aetiology. Sixty-eight patients were randomised between continued medical rate control or ablation. AF burden was assessed in ablation patients with an implanted loop recorder, and serial Holters in the medical rate control patients, with the primary endpoint of change in the LVEF on magnetic resonance imaging (MRI) at six months.
“The idea that rate and rhythm control are equivalent strategies if ideal rate control can be achieved is questioned by this study”, O’Neill said, pointing to the group of patients with ablation and restoration of sinus rhythm arm, which showed a much greater increase in ejection fraction than in patients with medical rate control alone. In patients with an abnormality of late gadolinium enhancement on the ventricular MRI there was still an improvement with catheter ablation but that improvement significantly increased in the absence of evidence of late gadolinium enhancement on the MRI scan. O’Neill summarised, “This study demonstrated quite clearly that catheter ablation was associated with an improvement in ejection fraction, that the absence of abnormality on the MRI scan almost pointed out a super-responder for catheter ablation in management of AF, and that clearly the mechanism of cardiomyopathy or ventricular impairment in AF is more complex than simply ventricular rate.
In fact, rather than using the terms “tachycardia-mediated cardiomyopathy”, the authors propose the term “arrhythmia-mediated cardiomyopathy” to explain what is going on in atrial fibrillation with left ventricular impairment.” Study investigators Oussama M Wazni and Mina K Chung wrote in an editorial comment in the Journal of the American College of Cardiology (JACC) that despite the limitations of the study, its positive results “should encourage the rethinking of current guidelines, especially in heart failure patients in whom durable sinus rhythm with minimal use of antiarrhythmic drugs achieved through catheter ablation may be a matter of life and death”.
A study by Milad El Haddad (Ghent University, Ghent and Sint-Jan Hospital, Bruges, Belgium) et al on determinants of acute and late PV reconnection in contactforce-guided PV isolation was published in Circulation: Arrhythmia and Electrophysiology in 2017. El Haddad et al tested the hypothesis that PV to left atrial reconnection is explained by two phenomena: interlesion discontinuity and insufficient lesion depth in the radiofrequency encircling lesion. Looking carefully at each lesion delivered, a point-by-point ablation strategy was used, and the weakest link in the encirclement determined. The study closely analysed each ablation point, showing that PV reconnection in contact force-guided PV isolation can be explained by sub-optimal predicted lesion depth and contiguity within the deployed radiofrequency circle.
These findings led Philippe Taghji (Sint-Jan Hospital, Bruges, Belgium) et al to ask what a meticulous PV isolation might achieve, testing the hypothesis that an ablation strategy which eliminates interlesion discontinuity or incomplete transmurality should result in PV isolation.
Their data, published in JACC: Clinical Electrophysiology, suggested that an ablation protocol respecting strict criteria for lesion depth and contiguity results in acute durable PV isolation followed by a high single-procedure arrhythmia-free survival at one year.
O’Neill also called attention to upcoming research on a high-power and short-duration ablation strategy in order to create similar lesion depth but with greater width, thereby increasing lesion-to-lesion uniformity and transmurality. The strategy which is currently being studied in animal trials is “possibly a game changer in point-bypoint ablation”, according to O’Neill.
Endpoint errors and course correction
Highlighting the debate on appropriate endpoints in catheter ablation, O’Neill turned to a substudy of the STAR AF II trial–a trial which he said “really has made us scratch our heads over the course of the past 12 months”. The trial demonstrated no real difference in outcomes in persistent AF between PV isolation alone, or in combination with either linear ablation or complex fractionated electrogram ablation. This year, a substudy by Simon Kochhäuser (University of Münster, Muenster, Germany) et al published in Heart Rhythm analysed the influence of AF termination and prolongation of AF cycle length on freedom from AF in the trial’s patient population. Kochhäuser et al found that although AF termination was a univariate predictor of success, by multivariate analysis the presence of early sinus rhythm was the strongest predictor of success (hazard ratio 0.67, p=0.004). Indeed, the study concludes that “freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm compared to those without AF termination (63% vs. 44%, p=0.007).” O’Neill remarked that “intraprocedural AF termination may not be an appropriate endpoint” in catheter ablation for persistent AF, as the data from this 2017 substudy suggests.
The final study O’Neill selected for his 2017 lessons in catheter ablation developments was the CASA-AF study, a nonrandomised study on persistent AF and thoracoscopic surgery vs. stepwise left atrial ablation. “This study is a little bit different”, O’Neill explained, “in that an electrophysiologist followed the operating surgeon into the operating theatre.” The electrophysiologist assessed the completion of all surgical lesions, increasing the rate of achieved conduction block by 19%. At one-year follow-up, a single thoracoscopic procedure showed a significantly higher success rate compared to stepwise left atrial ablation (approximately 75% vs. 40%), although with more complications in the former group. “It is food for thought, rather than prescriptive of anything we need to do,” O’Neill said, but added that the study is worth keeping an eye on as it progresses to a randomised multicentre study in the near future.