Implications of Contemporary Clinical Trials Transcatheter Aortic Valve Implantation The Interventionist Vision

Percutaneous catheter-based interventions are an emerging area in the treatment of valvular heart disease. Percutaneous aortic balloon valvuloplasty was initially introduced by Cribier et al1 in 1985 for patients with severe calcific aortic stenosis. This technique results in moderate hemodynamic improvement and significant clinical improvement, but it is associated with significant periprocedural morbidity and mortality and with a very high hemodynamic and clinical restenosis within 6 to 12 months after the procedure.2 Today, this technique is used mainly as a bridging technique to surgical aortic valve replacement (AVR) or to transcatheter aortic valve implantation (TAVI).2–4 The early results of percutaneous catheter-based valve replacement are promising. The first percutaneous heart valve replacement was performed by Bonhoeffer in 2002 in the pulmonary position5,6 and by Cribier in 2002 in the aortic position.7,8 Nowadays, TAVI has evolved to become a valid therapeutic option for patients with severe aortic stenosis who are inoperable or are at very high risk for surgical AVR.7–10 Recently, TAVI has been offered to select patients with good results. In Europe, TAVI is now an established, evidencebased alternative to open AVR in patients with aortic stenosis who are unsuitable for conventional cardiac surgery. Recent reported studies from the United States have demonstrated that for patients with severe aortic stenosis who are not candidates for surgery, TAVI with the Edwards SAPIEN valve significantly reduced mortality compared with standard treatment (Placement of Aortic Transcatheter Valves [PARTNER] trial, cohort B).9,10 Currently, there are 2 first-generation percutaneous valves in clinical application, a balloon-expandable Edwards SAPIEN and a self-expandable valve (CoreValve), with several other second-generation new players achieving first-inhuman application. Since 2002 when the first TAVI in a human was reported by Cribier et al,7 percutaneous heart valves have already undergone several modifications from the first-generation devices. Nonetheless, it is inevitable that as technology develops to overcome the present limitations and to result in safer and more effective techniques, percutaneous heart valve replacement will undoubtedly increase in frequency. Other meticulously designed clinical trials must be performed to definitively determine the shortand long-term results of TAVI compared with the gold standard of open surgical replacement and to define the appropriate patient population who will benefit the most. The pivotal PARTNER trial is the first randomized (1:1), controlled, multicenter study assessing the effectiveness and safety of TAVI in patients with severe, symptomatic aortic stenosis who are at high risk for conventional surgery. The study device (Edwards SAPIEN) is available in 23and 26-mm valve sizes and is delivered via a 22F or 24F sheath for the transfemoral approach or a 26F sheath for the transapical route. The balloon-expandable bioprosthesis is composed of a stainless steel frame inside of which a trileaflet bovine pericardial valve is mounted. In the PARTNER trial, the criteria used to define severe degenerative aortic valve stenosis were an aortic valve area of 0.8 cm (or aortic valve area index 0.5 cm/m), a mean aortic gradient of 40 mm Hg, or a peak aortic jet velocity of 4 m/s. All patients had a New York Heart Association functional class 2. Some of the exclusion criteria included recent acute myocardial infarction ( 1 month), recent stroke or transient ischemic attack (within 6 months), congenital unicuspid or bicuspid aortic valves, a preexisting prosthetic heart valve in any position, severe ventricular dysfunction (left ventricular ejection fraction 20%), renal insufficiency (creatinine 3 mg/dL), and a life expectancy 12 months. Subjects enrolled in the PARTNERS I trial were separated into 2 groups, and each cohort was separately powered and analyzed. In the first group, called cohort B, which was composed of patients who were deemed to be unsuitable candidates for surgery, TAVI was compared with standard medical therapy. Inoperability was judged by a cardiac interventionist and 2 separate surgical investigators and was based on a 30-day probability of death or serious, irreversible condition 50% after surgical valve replacement. In cohort A, TAVI was compared with surgical AVR in high-risk surgical candidates who were characterized by a Society of Thoracic Surgeons risk score 10% and the presence of comorbidities resulting in a 15% predicted 30-day mortality as assessed by a cardiac surgeon. Depending on their eligibility for transfemoral access, cohort A patients were further assigned to either the transfemoral or transapical arm of the trial. Within each arm, patients were randomized between TAVI and surgical AVR. The primary end point was all-