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Catheter ablation for AF: Debate continues over benefit
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The debate on the use of catheter ablation in patients with atrial fibrillation has intensified among cardiologists after results of the anticipated CABANA trial demonstrated that the procedure conferred better outcomes in patients with AF compared with medical therapy in per-protocol and on-treatment analyses, but not in an intention-to-treat analysis.
CABANA was initially presented at the Heart Rhythm Society Annual Scientific Sessions in May 2018 and, nearly a year later, two reports from the trial were published in JAMA. In the main results, catheter ablation did not significantly reduce the primary composite endpoint of disabling stroke, death, cardiac arrest or serious bleeding compared with medical therapy in the intention-to-treat analysis. However, the catheter ablation group had lower rates of secondary endpoints including death or CV hospitalization and AF recurrence. Although the rate of all-cause mortality was lower in the catheter ablation group compared with the medical therapy group, it did not reach statistical significance.
In a quality-of-life analysis, patients with symptomatic AF assigned catheter ablation had improvements in quality of life compared with those assigned medical therapy, as shown in the Atrial Fibrillation Effect on Quality of Life summary score (86.4 points vs. 80.9 points), the Mayo AF-Specific Symptom Inventory frequency score (6.4 points vs. 8.1 points) and the Mayo AF-Specific Symptom Inventory severity score (5 points vs. 6.5 points).
“There were some issues in CABANA, and that is that the event rates were lower and there were crossovers,” CABANA principal investigator Douglas L. Packer, MD, professor of medicine and consultant in the division of heart rhythm services in the department of cardiovascular medicine at Mayo Clinic, told Cardiology Today. “Whenever there are crossovers for lower event rates, an intention-to-treat [analysis] may not give you the full understanding of the trial because it affects the precision with which any statement can be made. With the number of patients we had and with the crossovers, we couldn’t say to any absolute certainty that one [strategy] was better than the other.”
Despite the mixed results, the CABANA trial confirmed that catheter ablation is safe compared with medical therapy for the treatment of AF.
“The data from CABANA reassures physicians that we are not harming patients by choosing to pursue catheter ablation over antiarrhythmic drug therapy,” Christine M. Albert, MD, MPH, founding chair of the department of cardiology in the Smidt Heart Institute at Cedars-Sinai, said in an interview. “The trial results reinforce our current practice with regards to ablation for atrial fibrillation. In general, we perform ablations for the purpose of improving symptoms and quality of life in symptomatic patients rather than to improve longevity.”
The CABANA trial can also be viewed as a jumping point for future research, experts said.
“The biggest mistake clinicians and the scientific community can make is to hastily conclude that CABANA is a negative trial,” Cardiology Today Editorial Board Member Jonathan P. Piccini, MD, MHS, FACC, FAHA, FHRS, associate professor of medicine and director of the Duke Center for Atrial Fibrillation at Duke University Medical Center, said in an interview. “There are a lot of important findings from CABANA that have great relevance to our patients with AF. There are also some important findings that require further investigation.”
Advantages, drawbacks of ablation
Catheter-based ablation of myocardial tissue via radiofrequency technology or cryotherapy, almost always including pulmonary vein isolation and sometimes including ablation of other areas, was first documented in 1998 as a treatment that could reduce recurrence of paroxysmal AF better than antiarrhythmic drug therapy, Packer and colleagues wrote in JAMA. In CASTLE-AF, a smaller study than CABANA which was published in 2018, catheter ablation was associated with lower rates of death or hospitalization for worsening HF compared with medical therapy. Catheter ablation was also linked with better outcomes compared with medical therapy in a meta-analysis published in September and in a retrospective study of patients from a U.S. administrative database published in April.
In CABANA, all patients assigned ablation received pulmonary vein isolation, and additional ablation techniques were performed at the discretion of the operators. Operators could use any ablation catheter approved in their country. Clinicians treating patients assigned medical therapy were advised to begin with rate-control medications such as beta-blockers, calcium channel blockers or digoxin, though rhythm-control medications (seven of which were specified in the study protocol) could be used in patients who had previously failed rate control. Both groups received oral anticoagulation in accordance with guideline recommendations.
Catheter ablation maintains several advantages over medical therapy, including that it is a more definitive strategy for treating patients with AF.
“Catheter ablation obviates the need for antiarrhythmic drugs and rate-controlled medications, which themselves in turn can cause side effects and impact the quality of life in patients with AF,” Cardiology Today Editorial Board Member Jagmeet P. Singh, MD, DPhil, associate chief of the cardiology division at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said in an interview.
Catheter ablation serves as superior maintenance of sinus rhythm and symptom control in patients, experts said. The CABANA results suggested patients with HF with reduced ejection fraction may have substantial improvements in CV outcomes if they undergo ablation.
A major advantage of the procedure is the improvement in quality of life, especially since patients are typically asymptomatic.
“These episodes can be disruptive to your usual day-to-day activities with symptoms,” Andrea M. Russo, MD, director of electrophysiology and arrhythmia service and program director of the clinical cardiac electrophysiology fellowship at Cooper University Health Care in Camden, New Jersey; professor of medicine at Cooper Medical School of Rowan University in Camden; president of the Heart Rhythm Society; and Cardiology Today Editorial Board Member, said in an interview. “You can also have side effects from medications and this can impact quality of life. Catheter ablation improved quality of life presumably due to lower recurrence rates of AF.”
However, there are some disadvantages to the procedure, including its invasive nature and the use of general anesthesia.
“While I agree that catheter ablation has many advantages in terms of symptom reduction, it must be remembered that the principal goal of CABANA was to determine if catheter ablation would save lives and prevent hard outcome events like stroke. That primary endpoint was not met, and so other endpoints are ‘exploratory.’ In addition, there are drawbacks that must be carefully explained to the patient. One is that catheter ablation is a procedure that carries risk, so you’re putting catheters in the heart and delivering heat energy through a catheter that has the potential for harm,” Cardiology Today Arrhythmia Disorders Section Editor Peter R. Kowey, MD, the William Wikoff Smith Chair in Cardiovascular Research at the Lankenau Institute for Medical Research, Chairman Emeritus of Cardiology at Main Line Health and professor of medicine and clinical pharmacology at Jefferson Medical College, said in an interview. “Having said that, we were all impressed by the low complication rate in CABANA. The second caveat is that it’s not always effective. In some patients, catheter ablation is ineffective for its purpose, and late recurrences are not uncommon.”
Ablation vs. medical therapy
Whether a patient with AF should be treated with catheter ablation or medical therapy is an individualized decision that is made between the cardiologist and the patient.
“I wouldn’t look at patients with atrial fibrillation with broad brush strokes and paint them with all the same brush,” Packer said. “CABANA gives a lot of information that parses out the nuances of atrial fibrillation in specific patients. If that’s the case, then it gives you information for a specific patient that is imminently pragmatic, and if it’s imminently pragmatic, then you can apply it to particular patients.”
Currently, there are no recommendations on which patients should receive catheter ablation and which should receive medical therapy, but there are several groups that may benefit from the procedure. Some of these target populations include relatively young patients with minimal heart disease who do not have very large left atrial cavities and do not have AF for a long period of time and those with paroxysmal AF or HF.
In contrast, some patients may not be appropriate candidates for catheter ablation, such as very old patients with longstanding AF or those with minimal AF who are not bothered by their symptoms.
If medical therapy is the appropriate treatment option for a patient, the decision must then be made whether to follow a rate control strategy or a rhythm control strategy.
“If the atrial fibrillation has been relatively shorter duration and the atrium is not significantly remodeled, it’s a no-brainer that we should go down the rhythm control strategy, especially if the patient is symptomatic,” Singh said. “On the flip side, if the patient is mildly to not symptomatic and the atrial fibrillation has been going on for several years before it was detected and the left atrium is now remodeled significantly, then just a rate control regimen to control the heart rate is probably the best strategy because the ablations are probably not going to bring back sinus rhythm, or the patient may require multiple ablations.”
Even with this approach, cardiologists should not strictly define which conditions should be treated with certain medications, experts said.
“I wouldn’t make sweeping generalizations about what the optimal regimen is,” Packer said. “The optimal regimen is going to be that which best improves the patient’s quality of life, without side effects.”
In addition, Packer said, catheter ablation should not be viewed as an option to reduce mortality risk.
“When we have a patient with atrial fibrillation, it is very rare for us to be treating them with ablation to reduce mortality in any regard,” Packer said. “The absence of the recurrence of atrial fibrillation and the improvement in quality of life is probably substantially more important.”
Questions of trial design
After results from the CABANA trial were made public, questions circulated as to whether a sham-controlled trial would ever be conducted to assess catheter ablation in patients with AF. Most experts say that it is very unlikely that a trial of that kind would be conducted due to numerous concerns and other issues.
“From a trialist point of view, it’s a great thing to do, and it has been done for other invasive procedures,” Albert said. “It’s not impossible, [but] it would be incredibly difficult to recruit patients for such a study.”
The problem, Piccini said, is that “sham trials, particularly interventional sham trials, have a lot of challenges, including ethical and safety concerns, cost, and limited ability to randomize large numbers of patients, which is important in order to evaluate uncommon but important events like stroke or death. Sham trials will probably be done, but will be largely be limited to evaluating symptoms and AF reduction. Many clinicians doubt the value of a sham trial since we have a lot of good evidence with robust monitoring that shows AF ablation leads to superior and durable AF reduction in many patients.”
It may be difficult to recruit enough patients and physicians to participate in such a trial, experts said.
“I was speaking to about 300 people with atrial fibrillation, and we talked about sham procedures,” Packer said. “I asked them, ‘Would you be willing to undergo a sham procedure to help us learn more about ablation?’ There was not a single patient that was willing to even consider that trial. The same is true for most physicians.”
Further research
Although the CABANA trial answered some outstanding questions about catheter ablation, more long-term data are needed, in addition to insights on potential benefits in subgroups of patients such as those with HF with reduced ejection fraction or persistent AF.
“I’ve had patients who were ablated in the early 2000s, were doing great, and then after 15 years had some AF,” Russo said. “I would consider that a successful ablation procedure. You can only follow patients in the study for a certain period of time. CABANA had a good length of follow-up. We don’t have this length of follow-up in clinical trials. It just isn’t realistic.”
Those interviewed by Cardiology Today also called for more research on whether there is an optimal time, if any, after catheter ablation to take patients off of guideline-directed anticoagulation therapy for thromboembolic prevention. It would be helpful for cardiologists to know when to stop non-vitamin K antagonist oral anticoagulants in patients who received the therapy after ablation, especially in those who may be at risk for complications.
In addition, more insight is needed on how to potentially improve outcomes after catheter ablation through lifestyle improvements. Albert said such research does not need to occur in the form of a randomized controlled trial, but rather a practical study.
“It’s really important for us to be able to integrate lifestyle management into the treatment of patients with atrial fibrillation, either as an adjunct to ablation and antiarrhythmic drug therapy or as primary therapy,” she said.
Several analyses from the CABANA trial will be presented and/or submitted for publication in the future, focusing on AF recurrence, the impact of a patient’s age, effects of the different types of AF, the importance of sinus rhythm in patients with HF, and findings from MR and CT imaging, Packer said.
“What we’re hoping for is that the technology progresses; that is, we understand a bit more about the pathophysiology and that we come up with better techniques to ablate patients in a safe fashion,” Kowey said.
How to counsel patients on options
Discussing treatment options should be the starting point for all patients with AF, especially if catheter ablation is a potential strategy.
“All patients with recurrent symptomatic AF should know that they have several options to reduce their AF burden and improve their quality of life,” Piccini said. “For many patients, this means an attempt at drug therapy. If that fails, then catheter ablation should be considered. However, a small minority of patients, who are concerned about the side effects or safety of long-term antiarrhythmic drug therapy, may prefer catheter ablation as first-line therapy.”
It is important to discuss treatment options and the available data, which may help in the decision-making process. Although it may be a fairly belabored conversation with the patient, especially when discussing the potential risks and benefits of all options, it is essential to educate the patients to help them make the right decision for their goals.
“Patients often know what they want,” Albert said. “They often know whether they want to take lifelong medical therapy or whether they want to try an ablation and potentially see if they could achieve a cure with it or at least a suppression of atrial fibrillation for some time. Often the patient will drive part of that conversation.” – by Darlene Dobkowski
- References:
- Asad ZUA, et al. Circ Arrhythm Electrophysiol. 2019;doi:10.1161/CIRCEP.119.007414.
- Mark DB, et al. JAMA. 2019;doi:10.1001/jama.2019.0692.
- Marrouche NL, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1707855.
- Noseworthy PA, et al. Eur Heart J. 2019;doi:10.1093/eurheartj/ehz085.
- Packer DL, et al. JAMA. 2019;doi:10.1001/jama.2019.0693.
- For more information:
- Christine M. Albert, MD, MPH, can be reached at christine.albert@cshs.org.
- Peter R. Kowey, MD, can be reached at koweyp@mlhs.org; Twitter: @peterkowey.
- Douglas L. Packer, MD, can be reached at packer.douglas@mayo.edu.
- Jonathan P. Piccini, MD, MHS, FACC, FAHA, FHRS, can be reached at jonathan.piccini@duke.edu; Twitter: @jonpiccinisr.
- Andrea M. Russo, MD, can be reached at russo-andrea@cooperhealth.edu.
- Jagmeet P. Singh, MD, DPhil, can be reached at jsingh@mgh.harvard.edu; Twitter: @jagsinghmd.
Disclosures: The CABANA study was funded by Biosense Webster, Boston Scientific, Medtronic, the NIH and St. Jude Medical. Albert reports no relevant financial disclosures. Kowey reports he was on the steering committee for CABANA, has equity interest in BioTelemetry and consults for numerous pharmaceutical and device companies in drug and device development. Packer reports he has financial ties with numerous device companies. Piccini reports he is a consultant for Abbott, Boston Scientific, Medtronic and Philips and received research funding from Abbott, American Heart Association, Boston Scientific, Johnson & Johnson and the NHLBI. Russo reports she is president of the Heart Rhythm Society and participated in studies for Boston Scientific without financial honoraria. Singh reports he consults for Abbott, Biotronik, Boston Scientific, Impulse Dynamics, LivaNova, Medtronic and Toray.