Clinical Studies Assessing Transcatheter Aortic Valve Replacement

IntroductionDegenerative aortic stenosis is the most common acquired valvular heart disease in the developed countries, affecting more than 300,000 people in the United States alone.1 Symptoms of aortic stenosis are latent until there is critical narrowing of the aortic valve that results in left ventricular hypertrophy, increased left ventricular diastolic pressure and left ventricle mass, and increased myocardial oxygen demand causing subendocardial ischemia.2 Once symptoms develop, the prognosis changes dramatically unless the aortic stenosis is corrected.2Surgical aortic valve replacement (sAVR) is the recommended therapy for patients with symptomatic aortic stenosis. The most recent American College of Cardiology and American Heart Association (ACC/AHA) guidelines for sAVR are found in Table 1.3 It is important to note that none of these recommendations are based on evidence from large-scale, randomized clinical trials but instead rely on the expert opinion of experienced clinicians. The Society for Thoracic Surgery Predicted Risk of Mortality (STS-PROM) has been used to estimate 30-day mortality operative risk. Other surgical risk scores, such as the logistic EuroSCORE, while correlated with overall prediction of risk, are poorly calibrated to estimate precise sAVR mortality rates.4Many patients cannot undergo sAVR due to excessive surgical risk, including porcelain aorta,5, 6 hostile mediastinum, severe lung or liver disease, frailty, renal failure,7-9 advanced age, and prior CABG,10 among other factors,11, 12 many of which are not included in current surgical risk assessment algorithms. In patients who are deemed unsuitable for sAVR due to comorbidities, transcatheter aortic valve replacement (TAVR) has been used as an alternative to relieve symptoms and extend life. Almost 50,000 patients have been treated worldwide with one of the two commercially approved TAVR devices, including the balloonexpandable Edwards SAPIEN Transcatheter Heart Valve (Edwards LifeSciences, Irvine, California) and the self-expanding CoreValve Revalving System (Medtronic, Minneapolis, Minnesota). A number of additional transfemoral and transapical devices are under evaluation.The purpose of this report is to review the clinical trials used to evaluate TAVR in patients who are at higher risk for sAVR. The clinical evidence base includes both prospective registries and randomized clinical trials. Future trial designs evaluating TAVR in intermediate populations will also be discussed.