Bone and Cartilage Growth to Blame for Heart Valve Disease, Northwestern Researcher Finds

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.  Dr. Rajamannan, also an assistant professor of medicine, Northwestern University Feinberg School of Medicine, 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 Va lve 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. 

About Northwestern Memorial Hospital
Northwestern Memorial Hospital is one of the country's premier academic medical centers and is the primary teaching hospital of Northwestern University's Feinberg School of Medicine. Northwestern Memorial and its Prentice Women's Hospital and Stone Institute of Psychiatry have 744 beds and more than 1,400 affiliated physicians and 5,000 employees.  Providing state-of-the-art care, Northwestern Memorial is recognized for its outstanding clinical and surgical advancements in such areas as cardiothoracic and vascular care, gastroenterology, neurology and neurosurgery, oncology, organ and bone marrow transplantation and women's health.

Northwestern Memorial was the sole recipient of the prestigious 2005 National Quality Health Care Award and eight of its medical specialties are listed in this year's U.S. News & World Report's issue of "America's Best Hospitals."  The hospital also has been cited as one of the "100 Best Companies for Working Mothers" by Working Mother magazine six consecutive years and has been chosen by Chicago-area consumers for more than a decade as their "most preferred hospital" in National Research Corporation's annual survey.

About the Bluhm Cardiovascular Institute
The Bluhm Cardiovascular Institute at Northwestern Memorial Hospital is a world-class heart program offering comprehensive services and state-of-the-art surgical treatments in all areas of cardiovascular care.  Recently named by Solucient, an industry-leading healthcare information provider, as the only Chicago hospital on its list of the country's 100 Top Cardiovascular Hospitals, Northwestern Memorial Hospital offers a timely response to referrals and a multidisciplinary approach that joins physicians, nurses and a range of other medical specialists and caregivers from Cardiology, Cardiac Surgery, Vascular Surgery, Cardiovascular Anesthesiology and Radiology
from evaluation to follow-up.  Patients benefit from the latest minimally invasive surgical techniques and are offered the opportunity to participate in a range of clinical research trials. 

Advanced Cardiovascular Care
Patients referred to the Bluhm Cardiovascular Institute experience a healthcare environment in which the most advanced diagnostic and treatment options are supported by state-of-the-art technology and a commitment to medical excellence through research.  Expertise is available in all areas of cardiovascular care, including:

Cardiac Surgery
Valve repair and replacement
MAZE and atrial fibrillation ablation procedures Coronary artery bypass with arterial conduits
LV and aortic aneurysm repair
Congestive heart failure surgery
Ventricular assist devices
Heart transplantation

Vascular Surgery
Thoracic and abdominal aortic aneurysm surgery
Carotid endarterectomy and stents
Endovascular surgery for aortic aneurysms and limb salvage
Lower extremity bypass procedures
Uncommon mesenteric and upper extremity revascularization
Supraaortic trunk revascularization

Cardiology
Primary and secondary prevention
Advanced diagnostic testing including echocardiography, nuclear cardiology, cardiac MRI and computed tomography
Cardiac electrophysiology, including diagnostic EP procedures, catheter ablation and pacemaker and ICD implantation
Heart failure management
Evaluation of heart valve disease
Acute coronary care
Diagnostic catheterization and interventional cardiology

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