Calcific Aortic Valve Disease: Not Simply a Degenerative Process

Abstract

A Review and Agenda for Research From the National Heart and Lung and Blood Institute Aortic Stenosis Working GroupExecutive Summary: Calcific Aortic Valve Disease – 2011 UpdateNalini M. Rajamannan, MD*; Frank J. Evans, PhD; Elena Aikawa, MD, PhD; K. Jane Grande-Allen, PhD; Linda L. Demer, MD, PhD; Donald D. Heistad, MD; Craig A. Simmons, PhD; Kristyn S. Masters, PhD; Patrick Mathieu, MD; Kevin D. O'Brien, MD; Frederick J. Schoen, MD, PhD; Dwight A. Towler, MD, PhD; Ajit P. Yoganathan, PhD; Catherine M. Otto, MDFrom the Division of Cardiology and Pathology: Feinberg School of Medicine, Chicago IL (N.M.R.); National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda MD (F.J.E.); Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.); Rice University, Houston TX (K.J.G.-A.); David Geffen School of Medicine at UCLA, Los Angeles, CA (L.L.D.); Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA (D.D.H.); Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada (C.A.S.); Department of Biomedical Engineering, University of Wisconsin, Madison, WI (K.S.M.); Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada (P.M.); University of Washington, Seattle, WA (K.D.O., C.M.O.); Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.J.S.); Department of Medicine, Washington University, St Louis, MO (D.A.T.); and Georgia Institute of Technology, Atlanta, GA (A.P.Y.).Correspondence to Nalini Marie Rajamannan, MD, Northwestern University Feinberg School of Medicine, 303 E Chicago, Tarry 12 -717, Chicago, IL 60611, E-mail n-rajamannan{at}northwestern.eduaortic valveaortic valve calcificationaortic valve stenosiscalcificationcardiac calcifications Introduction Calcific aortic valve disease (CAVD) encompasses the range of disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal valve function, is termed aortic valve sclerosis, but it is likely that the initiating events in the disease process occur much earlier. Disease progression is characterized by a process of thickening of the valve leaflets and the formation of calcium nodules—often including the formation of actual bone—and new blood vessels, which are concentrated near the aortic surface. End-stage disease, eg, calcific aortic stenosis, is characterized pathologically by large nodular calcific masses within the aortic cusps that protrude along the aortic surface into the sinuses of Valsalva, interfering with opening of the cusps. There is no disease along the ventricular surface. For decades, this disease was thought to be a passive process in which the valve degenerates with age in association with calcium accumulation. Moreover, although CAVD is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated disease process that cannot be characterized exclusively as senile or degenerative. The National Heart, Lung, and Blood Institute convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat, and potentially prevent this complex disease process. Normal Aortic Valve Anatomy and Function Key Structure-Function Correlations Heart valves permit unobstructed, unidirectional forward flow through the circulation. …