Look More Closely at the Valve

Abstract

Clinical trials of medical therapy to prevent progression in calcific aortic valve disease (CAVD) are hampered by the lack of sensitive measures of disease activity in the valve leaflets. Although the long-term goal of therapy is to prevent adverse cardiovascular outcomes, including mortality and aortic valve replacement, these end points have several limitations. First, the hard end point of mortality is frequently affected by comorbid conditions. Patients with CAVD typically are elderly, with a high prevalence of coronary and noncardiac disease, so that isolating the effect of valve obstruction on survival is problematic. Second, the end point of valve replacement for symptom onset reflects considerable physician variation in the threshold for intervention, as well as patient preferences. In addition, some patients are not promptly referred for valve replacement at symptom onset, sometimes inappropriately but often because of concerns about surgical risk or patient factors such as extreme age, dementia, or a severely reduced life expectancy due to coexisting conditions. Inclusion of these end points in clinical trials might obscure any benefit of medical therapy. Finally, clinical outcomes provide limited information about the mechanism of benefit; for example, medical therapy might improve outcomes by effects on coronary disease or ventricular function rather than affecting the disease process in the valve leaflets. Article see p 76 Hemodynamic measures of aortic stenosis (AS) severity provide some insight into the disease process. Noninvasive Doppler velocity, gradient, and valve area measurements have provided the foundation of our knowledge about CAVD progression and are useful measures for evaluating the effects of therapy on valve obstruction in clinical trials. Yet even hemodynamic assessment is not the ideal measure of disease because stenosis occurs late in the clinical course, may not be a sensitive marker of changes in the leaflets once significant disease is present, and is not …