ENCORE-VT Takes Noninvasive VT Ablation to Next Level

Patrice Wendling

November 14, 2018

CHICAGO — The nascent field of stereotactic radiation for ventricular tachycardia (VT) took a significant step forward with the prospective phase 1/2 ENCORE-VT study confirming remarkable case series results.

Targeting arrhythmogenic scar tissue with a single fraction of 25 Gy radiation for a median of just 15 minutes reduced VT and premature ventricular contraction episodes 94% at 6 months among 18 evaluable adults with treatment-refractory VT — over half of whom presented with VT storm.

The median number of VT episodes dropped from 119 to three (P <.001), Phillip Cuculich, MD, Washington University in St. Louis, reported at the American Heart Association (AHA) 2018 Scientific Sessions and published online November 10 in Circulation.

Although stereotactic body radiation therapy (SBRT) has been used for decades to target various cancers, Cuculich and colleagues made headlines in 2017 after reporting a 99.9% reduction in VT burden with cardiac SBRT in a case series of five patients. All had retractable VT and together had suffered more than 6500 episodes in the 3 months before treatment.

Following the AHA presentation, an audience member rose to say the results were "ground breaking," and electrophysiologist Suneet Mittal, @drsuneet, tweeted: "ENCORE-VT at #AHA2018 - will be most important study presented this year! VT ablation done faster than an oil change!!!"

From a patient-safety standpoint, this is very much of a leap forward for patients, Cuculich told theheart.org | Medscape Cardiology.

"These are patients who have typically gone through 8-hour procedures with extended recovery times," he said. "The last patient we treated on the protocol worked in the morning, came in on his lunch break for his VT ablation, and did a job in the afternoon. He's a plumber. It's a very different way of thinking."

Electrophysiologist Dhiraj Gupta, @DhirajGuptaBHRS, from the Liverpool Heart and Chest NHS Foundation Trust, United Kingdom, tweeted "ENCORE VT may be the most important study in EP since Bordeaux 's description in 1998 of PV triggers for AF. The excitement in the field is palpable."

Reached for comment, Gupta said nearly 100% reduction in VT burden in the original five patients "was nothing short of extraordinary" and "what's very encouraging is that the results are very similar" among the 19 patients treated in ENCORE-VT.

"Not only was the procedure very successful in reducing the VT burden significantly, it also appears to be safe; certainly safer than what one might expect VT ablation in this very sick group of patients to be," he said.

Among the 19 patients (median age, 66 years; 89.5% male), three-quarters had New York Heart Association class 3/4 disease, 58% had ischemic cardiomyopathy, and their median ejection fraction was 25%.

No acute toxicity occurred during or immediately after SBRT. Grade 1 and 2 adverse events included transient fatigue and hypotension, dyspnea, nausea, radiation pneumonitis, and pericardial effusions.

Within 90 days of treatment, two patients developed grade 3/4 severe adverse events: pericarditis that resolved with oral prednisone and heart failure admission in a patient with NYHA class 4 disease that was treated with diuretics. One patient died at day 17 after an accident in a nursing home and was not included in the efficacy end point.

Overall survival was 89% at 6 months and 72% at 12 months. Dual antiarrhythmic medication use fell from 59% to 12% (P < .008). Quality of life improved in five of nine domains on the Short Form-36 questionnaire at 6 months.

Questions and Concerns

The researchers are actively trying to understand what the cardiac radiobiology is, but the antiarrhythmic effect seen within days of treatment suggests it is unlikely to be a longer-term destruction, like fibrosis or apoptosis, Cuculich said.

"There's something happening on the short term and it's likely a modulation of the electrophysiology," he said. "There's more to learn here because if we do learn more, we learn ways to modulate the effect, to minimize risks, and potentially deescalate dose."

A randomized phase 2 trial, ENCORE-MULTI, being planned with roughly 70 patients and 10 to 12 centers, is expected to start in early 2019, said Cuculich.

Replication of the results outside a single center and in more patients is necessary and will require close collaboration between electrophysiology (EP) and radiation oncology, Gupta said.

"One of the biggest limitations, I think, is that they used noninvasive ECG surface mapping to identify the VT exit sites, and this is not technology that is commonly available in most EP centers," he said. "Going forward, it will be interesting to see whether anatomical delineation of scar will be enough for SBRT prescription, or whether we really do need the multielectrode surface-based ECG mapping that has been used in this study."

The same concern was raised in a related editorial by Paul Zei, MD, PhD, Brigham and Women's Hospital, Boston, who also reported success with SBRT VT ablation, but used a combination of prior mapping with invasive ECG and noninvasive anatomical substrate imaging with proprietary software.

"The role of noninvasive mapping tools in this process remains unclear," write Zei and radiation oncologist Raymond Mak, MD, Brigham and Women's Hospital/Dana-Farber Cancer Institute. "That being said, given what we know about conventional catheter-based mapping and ablation of VT, a completely substrate-based approach to ablation is unlikely to be the optimal approach. Not only will there be the potential for missing the clinical substrate, but excessive ablation may be delivered, particularly given the ability of SBRT to deliver therapy to significant portions of myocardium."

"The limitation will likely not be whether the target can be adequately treated but rather whether paring back delivery will succeed without overtreatment."

Zei and Mak point out that the aggregate experience with SBRT ablation amounts to just 27 patients, "a mere starting point." Basic questions remain about long-term efficacy of the therapy and, as only the 25 Gy-dose has been evaluated, dose-finding studies for optimizing safety and efficacy will clearly be important.

"Despite concerns and unknowns, history points toward gradual growth and maturation of this new field," the editorialists write. "The almost ubiquitous presence of SBRT devices across the United States and the world will almost certainly lower the barrier to eventual widespread adoption."

Financial support for the study was supplied by Washington University and Barnes-Jewish Hospital Foundation competitive grants. Support for ECGI processing and analyses were provided by a grant from the National Institutes of Health. No industry-related support was used. Cuculich reports receiving consulting honoraria from Medtronic. Gupta reports no relevant financial conflicts of interest. Zei reports research and consulting support from Cyber Heart, Biosense Webster, and Abbott/St. Jude Medical. Mak reports research and consulting support from AstraZeneca and speaker fees from NewRT.

American Heart Association (AHA) Scientific Sessions 2018: Session LBP.02. Presented November 10. 2018.

Circulation. Published online November 10, 2018. Article, Editorial

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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