CHICAGO – Transcatheter aortic valve implantation using the CoreValve system improved hemodynamics with a very low incidence of stroke in 1,015 consecutive patients with severe aortic stenosis in the real-world ADVANCE study.

The 30-day stroke rate was 2.9% (1.2% major and 1.7% minor), and 3.4% at 6 months (1.6% major and 1.8% minor). Transient ischemic attack rates were 0.4% and 1.2%, respectively, as adjudicated by an independent neurologist.

Mean aortic valve gradient decreased from 45.6 mm Hg at baseline to 9.3 mm Hg at 30 days and to 9.5 mm Hg at 6 months, while effective orifice area increased from 0.7 cm² at baseline to 1.7 cm² at both 30 days and 6 months.

"The CoreValve ADVANCE study, which is the largest, multicenter, prospective, fully monitored TAVI study, shows that treatment of real-world inoperable and frail high-risk patients with the Medtronic CoreValve is safe and associated with an improvement in aortic valve function and low stroke and mortality rates at 1 month and 6 months follow-up," principal investigator Dr. Axel Linke said at the i2 Summit, a conference sponsored by the American College of Cardiology.

Medtronic’s transcatheter CoreValve System, which features a porcine pericardial tissue valve that is sutured into a self-expanding nitinol frame, is currently limited to investigational use in the United States.

The 1,015 patients, mean age 81 years, were considered inoperable or high risk and were enrolled from March 2010 to July 2011 at 44 centers in 12 countries in Western Europe, Asia, and South America. All centers had conducted at least 40 TAVI procedures prior to the study and had a heart team in place. Clinical end points were reported according to Valve Academic Research Consortium (VARC) criteria.

Among the 996 patients in whom implantation was attempted, the procedural success rate was 98%, said Dr. Linke, professor of medicine at the University of Leipzig (Germany) Heart Center.

The study’s primary end point of major adverse cardiac and cerebrovascular events occurred in 8.3%, with all-cause mortality at 4.5%, myocardial infarctions 0.2%, and emergent cardiac surgery or percutaneous reintervention 1.7%. MACE events were adjudicated by an independent clinical events committee consisting of TAVI-experienced interventional cardiologists and cardiac surgeons, Dr. Linke pointed out at the meeting, also sponsored by the Cardiovascular Research Foundation.

Additional 30-day VARC end points included cardiovascular mortality at 3.4%, major bleeding in 9.7%, life-threatening bleeding in 4%, major vascular complications in 10.7%, and acute stage III kidney injury in 0.4%.

New pacemaker implantation was required in 26.3% of patients, due largely to significant bradycardia or higher grade AV block. The timing of the implantation was left to the discretion of the surgeon, with some implantations occurring during TAVI and others at postoperative day 1 or 2. Although the pacemaker placement rate is consistent with what has been reported in European registries, Dr. Linke noted during a press briefing at the meeting that rates in the study varied widely among countries, from 8% to 30%.

Survival rates were high at both 30 days (95.5%) and 6 months (87.2%). A prespecified subgroup analysis by logistic EuroScore revealed a 6-month survival rate of 95.7% for those with a score of 0-10, 92.4% with a score of 10-20, and 88.1% with a score greater than 20.

Session co-moderator Dr. George Dangas of the senior cardiology faculty at the Mount Sinai Medical School in New York, said the consensus is that bleeding rates with TAVI have improved over time, but remarked that "a 10% bleeding rate is still not that small."

Dr. Linke said further investigation is still needed, but that "despite the fact we have relatively high bleeding rates, they have lost their impact on mortality in the latest registries.

"I believe we still have bleeding, but we have gained so much experience to get control of the bleeding, therefore we have fewer cases of bleeding related-death."

Audience members also questioned what may have contributed to the low incidence of stroke in ADVANCE. Dr. Linke said they don’t yet have an explanation for the very low stroke rates, but that valve expansion may be at play.

One contributor may be "really aggressive oversizing with the cobalt rim that might crush the calcium and release the calcium into those bloodstream," he said. "Here, it’s a rather passive expansion and it might be that the calcium is still covered by fibrotic tissue and endothelium and not exposed to the bloodstream. This might be one reason, but we are still in the process of understanding what is going on."

At baseline, 31% of ADVANCE patients were diagnosed with diabetes, 20% had peripheral vascular disease, and 21% had undergone previous CABG. Their mean logistic EuroSCORE was 19.2. Roughly 80% were New York Heart Association class III and IV. At 6 months post-TAVI, 1% were class IV, 12% class III, 44% class II, and 43% class I.

This study was sponsored by Medtronic Bakken Research Center. Dr. Linke reported serving as a proctor for and receiving customary travel and expenses from Medtronic. Dr. Dangas serves as a consultant to AstraZeneca and Cordis.

CoreValve Excels in 'Real-World' Study