AF Ablation Gets Boost from Technology & Disease Understanding
- Atrial fibrillation (AF) ablation is increasing and is being offered to sicker patients
- Recurrence post-ablation still plagues the field
- Ballloon technologies promise to reduce procedure time
- Delayed-enhancement MRI could be a game changer
Writing on the wallIn a worldwide survey conducted between 2003 and 2006, Cappato et al found AF ablation to be effective in about 80 percent of patients after 1.3 procedures per patient, with about 70 percent of them not requiring further anti-arrhythmic drugs during intermediate follow-up (Circ Arrhythm Electrophysiol 2010;3:32-38). Noted observations included:
- Ablation is increasingly being offered to patients with AF and to sicker AF patients;
- Proportions of successful cases that are free of anti-arrhythmic drugs appear to increase with experience;
- The proportion of overall successes does not appear to have improved, as better results with catheter ablation only appear to be counterbalanced by poorer efficacy of previously ineffective anti-arrhythmic drugs; and
- Complication rates and incidence of iatrogenic atrial flutter do not appear to be decreased with experience.
“The primary driver for whether to ablate or not is symptoms,” says Edward P. Gerstenfeld, MD, from the division of cardiac electrophysiology at the Hospital of the University of Pennsylvania in Philadelphia, who was not associated with the above study. “Several studies, although not prospective, show a mortality benefit from keeping people in sinus rhythm rather than leaving them in atrial fibrillation, but there is controversy over this idea. One study showed people who stayed in sinus rhythm fared better, but it’s not clear if the improvement was because they were in sinus rhythm or if it was just a marker of being better.”
Interestingly, the approval of dabigatran (Pradaxa, Boehringer Ingelheim) in 2010 to reduce the risk of stroke could actually decrease the number of ablations, according to John D. Day, MD, director of Heart Rhythm Services at Intermountain Healthcare in Murray, Utah. “No one likes to use warfarin and to a certain degree, procedures are being driven by patients wanting to avoid this drug. Dabigatran may lessen the incredible drive to get off warfarin.”
Day also cautions that many patients are moving to higher deductable health plans and may not be able to afford the more effective ablation treatment because of the high out-of-pocket expenses.
First-line therapy?Several factors play a role in ablation success including younger age, less duration time, paroxysmal versus persistent or permanent and fewer comorbidities. In a recent study, Leong-Sit and colleagues found that patients younger than 45 years had a lower major complication rate and a comparable efficacy rate, with a greater chance of being AF free without anti-arrhythmic drugs compared with older patients (Circ Arrhythm Electrophysiol 2010;3:452-457). Current U.S. and European guidelines and consensus documents indicate that ablation is a second-line therapy for all categories of patients or only in rare clinical situations. However, Gerstenfeld, a co-author of the study, says, “These findings suggest that it may be appropriate to consider ablation as a first-line therapy in this age group.”
There is currently momentum to make AF ablation a first-line therapy. Years ago, patients with supraventricular tachycardias had to have failed several medications before undergoing a three- to four-hour ablation procedure. Now, the procedure is offered as a preferred, first-line therapy, typically taking 90 minutes, says John M. Mandrola, an EP with Louisville Cardiology in Louisville, Ky. “Atrial fibrillation is not there yet. However, AF patients previously had to have failed two drugs and now it is one. For young people with paroxysmal AF, it’s not unreasonable to offer ablation as a first-line therapy, because you know the disease will remain and drugs are often poorly tolerated.”
With advances in technology, including imaging, mapping and catheters, physicians don’t need so much to ask “can I ablate this patient, but should I,” Mandrola notes. The decision to ablate or not is easier for the extreme cases of drug refractory, symptomatic patients, but the intermediate cases can be challenging to call, he says.
Balloon technologyGenerally, a successful first-time AF ablation is not a guarantee. Whereas simple arrhythmias carry a 98 percent initial success rate, that figure drops to 75 percent for AF. “The guidelines for AF ablation actually approve multiple ablations to achieve success. I perform repeat procedures, but I don’t like it,” says Nassir F. Marrouche, MD, executive director of the Comprehensive Arrhythmia Research and Management Center at the University of Utah Health System in Salt Lake City. Marrouche has been conducting studies to determine how to use delayed-enhancement MRI to triage patients for first-time success based on the amount of fibrosis in the left atrium, and the technique shows promise (see sidebar page 6).
Part of the problem with AF ablation is the use of a focal catheter to create hundreds of lesions. This method worked well in the early days of ablating simple arrhythmias, but the dot-to-dot method for AF contributes to long procedures, as well as the high rate of recurrence.
Newer technologies such as cryo- and laser balloons are designed to reduce the number of lesions required. The balloons are inflated against the surface area of the atrial tissue of the pulmonary vein and the tissue is ablated at once either via heat or extreme cold. In the STOP-AF trial, the Arctic Front (Medtronic) cryoballoon proved better than drug therapy in paroxysmal AF patients. Results presented at ACC10 showed that first procedure success rate with the cryoballoon was 74 percent and 54 percent for two ablation procedures. The Arctic Front cryoballoon is CE marked and Medtronic hopes to launch the device in the U.S. this spring.
“The cryoballoon has made some in-roads in Europe, but nowhere near the initial impact of the irrigated catheter tip, which flipped the whole market overnight,” says Day. He adds that the first-generation cryoballoon has limitations. “The ideal cryoballoon would be one-size-fits-all and have very uniform cooling to produce effective lesions.”
Dukkipati and colleagues showed that with visual guidance, 100 percent of targeted pulmonary veins could be isolated using a variable-diameter, compliant balloon with the capability of real-time endoscopic visualization during ablation using laser energy (CardioFocus) (Circ Arrhythm Electrophysiol 2010;3:266-273). Endoscopically, regions of the balloon in contact with blood appear red, and regions in contact with tissue blanch white.
“Ultimately, this device will shorten the time it takes to ablate paroxysmal AF, but more importantly, it will improve the success rate of the procedure by improving the durability of pulmonary vein isolation,” says senior author Vivek Y. Reddy, MD, director of the EP labs at Mount Sinai Medical Center in New York City. He adds that for patients with persistent or permanent AF, “once we can reliably achieve durable pulmonary vein isolation, there will likely be many chronic AF patients that will be treatable with pulmonary vein isolation alone.”
Researchers noted that their findings compared favorably with the cryoballoon. However, “often more than one cryoballoon is used in conjunction with another catheter for ‘spot ablation’ to achieve isolation of all the pulmonary veins,” they wrote. In addition, the cryoballoon is associated with reversible right phrenic nerve palsy (in STOP-AF, 11 percent in the cryo arm experienced phrenic nerve paralysis, of which nearly all resolved at 12 months), whereas the laser balloon was associated with no major adverse events, including phrenic nerve injury. The CardioFocus laser balloon is CE marked, but not yet FDA approved. A pivotal U.S. study to evaluate the device will start in the first quarter of this year, Reddy says.
He adds that this balloon technology will improve efficacy, make it easier to perform AF ablations and, therefore, increase the number of physicians performing the procedure, while also enabling more patients to be considered for ablation.
The Cardiac Ablation System (Medtronic), a circular multi-electrode catheter that allows EPs to selectively ablate a broader area of tissue rather than single-point ablation, is being tested in the U.S. in the TTOP-AF trial for patients with persistent AF. Enrollment has recently been completed. The device is CE marked and approved in Canada. European investigators have found an 80 percent success rate, with an average time of less than two hours.
GenesIt is likely that genomic discoveries will play a role in future AF treatment and prevention. Lubitz et al at Massachusetts General Hospital in Boston noted that researchers have identified rare gene variants underlying familial AF and mutations associated with atrial action potential duration. In addition, genome-wide association studies have “implicated novel biological pathways responsible for AF” (Circ Arrhythm Electrophysiol 2010;3:291-299).
While large gaps still exist between discovery and “evidence-based practice of genotype-guided patient management,” balloon and imaging technologies hold promise to reduce procedure time, as well as recurrence. It’s no wonder that EPs are all aflutter.
|Pre-, Intra & Post-MRI for AF Ablation Could Be Game Changer|
The group has devised a scoring system based on left atrial enhancement of gadolinium contrast, an indication of the amount of fibrotic or scarred tissue, which Marrouche says is prognostic of first-time ablation success, as well as the success of rhythm control strategies. The scoring stages are: Utah I: 0 to 5 percent of fibrosis; Utah II: 5 to 20 percent; Utah III: 20 to 35 percent; and Utah IV: 35 percent or more (see image).
Used prior to ablation, DE-MRI can identify regions of significant structural remodeling or fibrosis. All potential ablation patients at CARMA undergo a DE-MRI. About 5 to 12 percent of them are not good candidates for ablation (Utah IV). Conversely, about 40 percent with persistent or permanent AF and minimal scarring (Utah I-III) are good candidates. “The success rate in these patients is 99 percent,” Marrouche says, “which goes against commonly accepted wisdom.”
“Right now we use very gross measures to determine AF ablation success,” says John M. Mandrola, an EP with Louisville Cardiology in Louisville, Ky. “Often, we think an ablation won’t work and it does or we think it has limited chance of success and it succeeds beyond our expectations. We want to do the procedure in patients that it will benefit the most. If MRI can help in that regard, it would be great.”
DE-MRI also allows for ablation lesion characterization, according to Marrouche. Acute edema, defined as enhancement on T2-weighted MRI, immediately post-AF ablation correlates with low voltage areas, but not with DE-MRI-defined scar. In a recent study, Marrouche and colleagues found that only 6.9 percent of 149 patients had complete and contiguous circumferential scarring of all four pulmonary vein antrum (Circ Arrhythm Electrophysiol 2010;3;249-259). DE-MRI accurately depicted the location and extent of scar lesions and identified the location of breaks in ablation lesions. Such knowledge can help EPs plan repeat procedures, he says.
In another study of 144 patients, Marrouche et al found no recurrences in Utah I patients, 28 percent in Utah II, 35 percent in Utah III and 56 percent in Utah IV (J Cardiovasc Electrophysiol 2010; online Aug. 30). They noted that circumferential pulmonary vein scarring in Utah II and overall left atrium wall scarring in Utah III predicted recurrence, while Utah IV had no recurrence predictors. They concluded that since more atrial tissue is involved in creating the AF substrate, “going outside the pulmonary vein antral region to modify this substrate leads to improved ablation outcomes.”
In May, Marrouche opened an EP-MRI clinical and research lab and is currently experimenting with intra-operative MRI guidance. His group has developed MRI-compatible mapping and ablation catheters and is awaiting FDA approval of the devices. Marrouche anticipates using the intra-operative system in patients later this year. In one preclinical study, his group achieved real-time visualization of lesion formation in 30 percent of ablations performed under 3T MRI guidance (Heart Rhythm 2010; online Oct. 26). In the other cases, the lesion either was formed outside the imaged region (25 percent) or was not created (45 percent) “presumably due to poor tissue-catheter tip contact.” In addition, intra-operative MRI can provide real-time data regarding structure and function that when merged with electrophysiological data, can help guide the catheter and avoid potential complications.
Despite there being only a handful of institutions conducting this type of research, Marrouche envisions using DE-MRI to screen those at risk for AF, as 30 percent of the AF population is asym–ptomatic. If scarring is found, these patients can be monitored for AF every six months or so. The official rate for AF-related stroke is between 15 and 20 percent, he says. However, neurologists target it at 38 to 40 percent, because they are generally the first specialists to assess these patients. Interestingly, preliminary studies suggest that more than 20 percent of fibrosis is predictive of stroke risk, he says.
MRI has the potential to save costs by reducing unnecessary and repeat procedures, as well as lowering complication rates, Marrouche says. In addition, “If we can catch asymptomatic patients before their disease worsens, we can markedly improve their quality of life and potentially cure the disease, saving dollars and time in downstream tests and procedures.”