"More than 1.2 million people die from coronary artery disease every year, a quarter of them before or soon after arriving at the hospital," says Ik-Kyung Jang, MD, PhD, director of cardiovascular clinical research in the MGH Cardiology Division and lead author of the current study. "The ability to identify dangerous plaques before they rupture and produce a heart attack or sudden cardiac death will be crucial to innovative preventive therapies."
Plaques are deposits of fats, cholesterol and other materials that collect in major arteries, restricting or sometimes blocking blood flow. While some plaques are relatively stable, others are vulnerable to rupture and release their contents into the bloodstream, causing a blood clot to form. Heart attacks and other acute coronary events usually result from the rupture of high-risk, vulnerable plaques in coronary arteries, and the characteristics of those plaques have been determined primarily by autopsy studies.
OCT uses infrared light delivered via fiberoptic catheter to produce high-resolution, cross-sectional images of blood vessels. Study co-authors Guillermo Tearney, MD, PhD, of the MGH Pathology Department and the Wellman Center for Photomedicine at MGH, and Brett Bouma, PhD, also of the Wellman Center, developed the use of OCT to visualize coronary arteries, including vulnerable plaques. The technology developed in their laboratory was used for this first study to examine the structure of plaques in patients with cardiac disease.
The study enrolled patients scheduled to undergo cardiac catheterization for whom angiograms or other imaging techniques had identified the arterial lesion responsible for their symptoms. Participants either had experienced a recent heart attack or had acute coronary syndrome (ACS), a set of symptoms associated with reduced blood supply to the heart muscle. A third group had stable angina, chest pain that occurs with physical or mental stress, which is not usually related to plaque rupture. Clear OCT images of the suspicious lesions were obtained for 20 heart attack patients, 20 with ACS and 17 with stable angina.
Vulnerable plaques are believed to have three major characteristics - a deposit of lipids (fats), a thin cap of fibrous material covering the lipid pool, and infiltration of the immune cells called macrophages. The OCT images showed that the heart attack and ACS patients had more lipid in their plaques and significantly thinner fibrous caps than did the stable angina patients. Overall, vulnerable plaques were identified in 72 percent of the heart attack patients, 50 percent of those with ACS and only 20 percent of stable angina patients.
"This is the first technique that allows us to study the structural changes underlying vulnerable plaques in living patients, and it supports the conclusions of previously reported postmortem studies," says Jang. "We still need to gather more data to confirm these characteristics, and our group will carry out further studies of how plaques develop and rupture. Someday OCT may provide information that will guide treatments to prevent plaque rupture and its disastrous consequences." Jang is an associate professor of Medicine at Harvard Medical School.
Along with the study's senior author Bouma and Tearney, additional co-authors are Briain MacNeill, MD, Masamichi Takano, MD, and Fabian Moselewski, of the MGH Cardiology Division; Nicusor Iftima, PhD, and Milen Shishkov, PhD, of the Wellman Center; Stuart Houser, MD, and Thomas Aretz, MD, MGH Department of Pathology; and Elkan Halpern, MGH Department of Radiology. The study was supported by grants from the Center for Integration of Medicine and Innovative Technology, for development of the imaging system platform; the National Institutes of Health and Guidant Corporation.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.