Medtronic initiates study evaluating potential of combination of pulmonary vein isolation and renal denervation for atrial fibrillation

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Medtronic has announced the start of a clinical study using Medtronic technologies to determine whether paroxysmal and persistent atrial fibrillation can be treated with a combination of two ablation procedures targeting different anatomical locations—specifically, the pulmonary veins and the renal arteries. Study patients will also receive an implantable cardiac monitor to track their heart rhythm on an automatic and continuous basis.

SYMPLICITY AF is a prospective, randomised, multicentre, feasibility clinical study investigating pulmonary vein isolation and renal denervation compared to pulmonary vein isolation alone, for the treatment of paroxysmal or persistent atrial fibrillation in patients with both atrial fibrillation and hypertension. Pulmonary vein isolation will be performed with the Arctic Front Advance Cardiac Cryoablation system, and renal denervation will be performed with the Symplicity Spyral catheter and Symplicity G3 radiofrequency generator. The Symplicity Spyral catheter and G3 generator are investigational in the USA.

Patients in both arms of the trial also will receive a Reveal Linq Insertable Cardiac Monitor to automatically and continuously detect and record the net recurrence of abnormal heart rhythms after therapy randomisation. This more comprehensive method of cardiac monitoring will provide greater detail and accuracy about the treatment effect of combination therapy with pulmonary vein isolation and renal denervation versus pulmonary vein isolation alone. Emile G Daoud, at The Ohio State University Wexner Medical Center, USA, enrolled the first patient in the trial.

“Hypertension is one of the most prevalent risk factors for developing atrial fibrillation, but we have seen that it is also potentially the most modifiable risk factor for halting the progression of the disease,” says principal investigator Larry Chinitz, director, Heart Rhythm Center, NYU Langone Medical Center in New York. “As we continue to look for ways to prevent atrial fibrillation recurrence and improve outcomes for patients with atrial fibrillation, this trial may reveal a potential new treatment path for patients.”

Studies have shown that an overactive sympathetic nervous system contributes to the development of both hypertension and atrial fibrillation. Current therapies do not specifically address sympathetic nervous system over activity and historically have focused on maintenance and regulation of rate and rhythm as well as anti-coagulation to prevent stroke. Renal denervation has been shown to effectively reduce elevated sympathetic nervous system activity, and previous research has signaled that renal denervation combined with pulmonary vein isolation may improve patient response to pulmonary vein isolation in atrial fibrillation patients.

SYMPLICITY AF will enroll up to 245 patients in up to 12 centres throughout the USA. Seventy of these patients meeting all inclusion but no exclusion criteria and thus determined to be eligible for the trial will then be randomised to either pulmonary vein isolation and renal denervation or to pulmonary vein isolation alone; all randomised patients will receive a Reveal Linq insertable cardiac monitor. The primary safety endpoint is comprised of events related to both the pulmonary vein isolation and renal denervation procedures. The primary efficacy endpoint will measure freedom of chronic treatment failure, defined as atrial fibrillation lasting 30 seconds or longer or the requirement for an intervention for atrial fibrillation through a minimum of six months. Heart rhythm data from the Reveal Linq will be reviewed monthly.

Enrollees in the trial include patients with either paroxysmal or persistent atrial fibrillation, and hypertension defined as office-based systolic blood pressure of >=150 mm Hg, despite treatment with two or more antihypertensive medications at the highest appropriate dose.

The study will also gather feasibility outcomes data on the use of the Arctic Front Advance Cardiac Cryoablation Catheter for pulmonary vein isolation in the persistent atrial fibrillation population. The Arctic Front Advance Cardiac Cryoablation system is not approved in the USA for the treatment of persistent atrial fibrillation; therefore, it is considered investigational in this patient population.