Bone and cartilage growth to blame for heart valve disease

Northwestern researcher’s study points to active rather than passive process

Research to be published in the April 18 issue of the Journal of the American College of Cardiology provides the first explanation of an active rather than passive process that leads to heart valve degeneration, furthering a Northwestern researcher’s effort to lead a paradigm shift in the medical community’s beliefs about the cause of valve disease.

Heart valve disease is caused not by a ’wear and tear’ phenomenon, but by an inflammatory process likely triggered by high cholesterol that stimulates certain cells to reprogram into bone cells in the aortic valve and cartilage cells in the mitral valve, says principal investigator Nalini Rajamannan, MD, newly appointed director of the Center for Heart Valve Disease in the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital and assistant professor of medicine, Northwestern University Feinberg School of Medicine, who examined diseased mitral and aortic valves removed during surgery for the study.

“Common wisdom in the medical community has always been that thickening of the mitral valves was part of the aging process as deposits of calcium, a mineral found in the blood, built up on the valves. Therefore, research has never focused on preventing the problem,” says Dr. Rajamannan. “Currently the only option is to surgically repair or replace the damaged valves. Our findings open the door to the idea that medical therapies such as statins may be able to play a role in preventing or slowing the process and curtailing the need for surgery.”

Valvular heart disease is on the rise with the aging of the United States population, and is second only to coronary artery disease as a cause for open heart surgery. Heart valve disease leads to 100,000 surgeries in the U.S. each year to repair or replace damaged valves. Mitral valve disease is a leading cause of atrial fibrillation, which is a major culprit in strokes and heart failure. Aortic valve disease can lead to heart failure, arrhythmia, infections in the heart, and sudden death may occur in 15 to 20 percent of people who have symptoms.

Dr. Rajamannan has focused her research for the past seven years on advancing the knowledge of mechanisms of aortic and mitral valve disease using animal models and human studies. “I wanted to know why diseased valves had were hardened with a glassy whitish appearance – totally different than healthy tissue, which indicated to me that the actual structure of the valves had changed,” she says. Dr. Rajamannan has been awarded over $750,000 in grants from the NIH and the American Heart Association to pursue this research.

Dr. Rajamannan’s laboratory was the first to treat animals with calcifications in heart valves with medications called statins, the same drugs that are currently used to treat high cholesterol. In an early pioneering study, animals treated with statins had significantly less heart valve disease than the control animals that were not treated. The results from the animal studies and now with the human valves demonstrate that valvular heart disease has an active biology which can be treated with medications similar to that of coronary artery disease.

The current wisdom is that mitral valve insufficiency (leaking of the valve) was caused by degenerative changes over the course of time – more or less, wear and tear. Dr Rajamannan’s unique observations indicate that the process of valve degeneration is instead an active process, linked to inflammation and cellular growth, that shares similar risk factors to hardening of the arteries (atherosclerosis).” says Robert Bonow, MD, co-director of the Bluhm Cardiovascular Institute. “This suggests that there may be medical treatments in the future that could either treat this condition or prevent it from developing.”

This research was completed with the support of an American Heart Association Grant-in-Aid (0350564Z) and a grant from the US National Institutes of Health (1K08HL073927-01).

Dr. Rajamannan’s research will be featured at the American College of Cardiology’s 2006 Heart Valve Summit being held June 15-17 in Chicago, which will bring together several of the world’s leading cardiologists and cardiac surgeons to provide a comprehensive review of recent advances in the treatment of valvular heart disease.