Calcific Aortic Stenosis: Bringing Discoveries from the Lab to the Clinic
In its seminar series supporting translational research efforts at Northwestern, the Northwestern University Clinical and Translational Science (NUCATS) Institute recently featured Nalini Rajamannan, MD, associate professor of medicine in the Division of Cardiology. Her talk, “Calcific Aortic Stenosis: A Disease Ready for Primetime,” traced how her research observations led to prospective clinical trials to determine whether treating patients with atherosclerosis with cholesterol-lowering drugs reduces their chances of developing valve stenosis.
Translational research refers to “the movement of research findings from one point on the discovery chain to the next—moving from one point to the next until an application is achieved,” said Philip Greenland, MD, NUCATS director. “For basic science research to be translated into clinical applications, it must typically go through research, discovery, clinical testing, and assessment phases.” NUCATS facilitates the translational process through a variety of resources including research discovery programs, technology development, industry outreach, participation in clinical trials, and community engagement.
Dr. Rajamannan, director of the Center for Heart Valve Disease at Northwestern Memorial Hospital’s Bluhm Cardiovascular Institute, has taken advantage of resources available at Northwestern to translate her research findings into a potential treatment for calcific aortic stenosis, a disease that involves the calcification of aortic valves of the heart. It leads to more than 51,000 hospital admissions per year in the United States, and successful treatment usually requires surgical valve replacement. Dr. Rajamannan’s research approach combined population science, phenotypic expression of calcific aortic stenosis in animal models, and clinical trials.
Upon first noting that calcific aortic stenosis was associated with risk factors for coronary artery disease and familial hypercholesterolemia, Dr. Rajamannan corroborated this association with clinical index cases and genetic evidence. Using an animal model of experimental atherosclerosis, she showed that treating the animals with cholesterol-lowering drugs decreased the incidence of calcified valves. With this evidence in hand, Dr. Rajamannan then began a multicenter, retrospective clinical study to determine whether treatment with cholesterol-lowering drugs slow the progression of cardiac stenosis in humans. The evidence suggested a positive effect, which led to the prospective clinical trial now underway at Northwestern
Each step of Dr. Rajamannan’s study involved collaboration with clinicians and basic scientists at Northwestern, which is exactly the idea behind the NUCATS Institute, said Dr. Greenland. “Our vision is to become a major research catalyzing center, facilitating the growth of translational and clinical research across the entire Northwestern enterprise.”