Siegburg, Germany - Percutaneous implantation of the self-expanding CoreValve aortic valve bioprosthesis in the first-ever series of patients shows that the procedure is feasible in those deemed too high risk for valve surgery and, when successful, results in marked hemodynamic and clinical improvement at 30 days [1].

However, there was a high periprocedural mortality of 20%, and there are several important lessons to be learned from this first-in-human single-center study, say the researchers, led by Dr Eberhard Grube (HELIOS Heart Center, Siegburg, Germany). They report their findings in the October 10, 2006 issue of Circulation.

Multicenter studies are now under way with a second-generation device, and if these demonstrate a high procedural success rate with acceptably low morbidity and mortality, "the CoreValve prosthesis may represent an important therapeutic alternative for high-risk patients with degenerative aortic valve disease who are poor operative candidates," they conclude.

Dr William O'Neill (University of Miami Miller School of Medicine, FL), who is one of the leaders in this field, said: "This is pioneering work, and the authors are to be commended for the reporting of outcomes for the learning curve of a new device and a new procedure in high-surgical-risk patients."

Grube and colleagues explain that aortic stenosis in Western populations is primarily degenerative, and patients are typically elderly, with multiple comorbid conditions that increase surgical risk. Hence, such patients are often declined for the current standard approach—open-heart surgery with mechanical or bioprosthetic valve replacement—because periprocedural mortality can be up to 50%.

They used a new self-expanding aortic valve prosthesis that was delivered percutaneously and retrograde across the aortic valve at a single study center (Heart Center, Siegburg) in 25 such high-risk patients.

The CoreValve was successfully implanted in 17 of the 25 patients (68%), resulting in immediate marked hemodynamic improvement, with sustained valve performance for 30 days. The reduction in afterload translated into symptomatic relief, with a reduction in NYHA class by one to two grades in all patients.

Importantly, "there were no cases of valve migration, destabilization, or thrombosis; myocardial ischemia from coronary obstruction; or stroke," the researchers note.

Nevertheless, say the researchers, "several important lessons are apparent from this first-in-man single-center study that should improve future results with this device."

First, the periprocedural morality was high (five of the 25 patients died). Two patients died of procedure-related events (one from wire perforation of the left ventricle, one after the inability of the prosthesis to cross a heavily calcified valve). A third patient was not pretreated with clopidogrel and died of disseminated intravascular coagulation, while two others who also did not receive a thienopyridine before the implant developed a severe thrombocytopenia of prolonged duration.

They note, however, that extracorporeal circulatory support was used in the early phase of the trial and that this could have contributed to complications.

O'Neill says the hemodynamic support that appears to be required with this device "is the main drawback."

"The truest test in this regard will be whether thrombocytopenia develops after CoreValve device placement without extracorporeal support," say Grube et al.

In addition, the optimal antiplatelet and antithrombotic regimen to support implantation of the CoreValve device needs to be clarified, they note.

Also, they say, the precise positioning of the device "remains challenging and was responsible for half the procedural failures. In this regard, the role of transesophageal echocardiography to guide placement continues to evolve, and markers are being added to the device to facilitate accurate positioning."

Finally, tracking of the relatively long and high-profile stent valve apparatus can be difficult in small-diameter or noncompliant atherosclerotic aortas, they note, and the current device configuration limits its use to patients with a relatively small valve annulus and narrow ascending aorta.

"As a result, mainly women qualified for this early-stage investigation," they note. "Next-generation devices will include larger-caliber designs to allow treatment of a broader cross section of the patient population with degenerative aortic stenosis."

A second-generation device (the 18F device) is currently being tested in a multicenter study, they note, adding that much longer-term results will be needed—at least five years of follow-up—to assess the long-term durability of this prosthesis (nine of the patients from this trial have encouraging follow-up at six to 12 months).