The Hopkins findings, published in last week's edition of the journal Circulation, are believed to be the first to tie specific "remodeling" changes in heart mass and volume to early and growing signs of trouble in any specific region of the muscle, specifically, the anterior wall (or front part) of the left ventricle, the heart's main pumping chamber.
"Making new use of magnetic resonance imaging technology, we have been able to gather the first visual clues of how heart disease develops regionally and possibly spreads to different parts of the heart and cardiovascular system," says senior study investigator and cardiologist João Lima, M.D., associate professor of medicine and radiology at The Johns Hopkins University School of Medicine and its Heart Institute.
According to Lima, cardiologists are aware of many diseases that lead to deformations in the heart's shape, both big and small, but this is the first experiment to have traced or mapped these changes in great detail. In problems such as enlarged hearts and hypertension, he says, "there are disproportionate increases in heart muscle mass to volume of blood being pumped."
The results of the Hopkins-led study of adults 45 to 85 are among the first to emerge from the Multiethnic Study of Atherosclerosis, called MESA for short, which is monitoring nearly 7,000 men and women of different ethnic backgrounds and with no existing signs of heart disease to determine who develops coronary artery disease and who does not.
All participants in the MESA study had cardiac MRIs performed at enrollment, but in this smaller group study, equal numbers of men and women were randomly assigned to have tagged-MRI analysis. To minimize any bias in interpretation of results, some scans was analyzed twice and by any one of three cardiologists.
For every scan, calculations were made for more than a dozen parameters of heart function, including thickness of various heart walls, pumping volume, ejection fraction (the percentage of blood pumped from the left ventricle during a heart beat), and shortening fraction (how much each muscle shortens during contraction), blood pressure (an indicator of the workload or stress on the heart), and body mass index. For logistical reasons, however, measures were only taken for regional mass in the left ventricle, the largest of the heart's four chambers, limiting the study's implications to this one particular chamber.
To calculate total changes in heart shape, which is three-dimensional, the researchers relied on a previous model that used MRI scans to calculate a ratio of muscle mass to volume of pumped blood. The greater the ratio, the greater the amount of concentric heart remodeling that has occurred.
When the researchers compared changes in heart shape to changes in heart function, statistical analysis showed that pumping function deteriorates as hearts increasingly change shape or remodel. Changes in heart shape often involved gains in mass and wall thickening.
The results confirmed for both men and women that changes in one particular region of the heart, the anterior wall of the left ventricle, were linked to the greatest declines in heart function.
In men with the greatest percentage of remodeling, for example, heart function also declined, as measured by shortening fraction (how much the muscle contracts during a heart beat). Study results showed men with a normal-sized heart, weighing 150 grams, with a remodeling ratio of 0.7 grams per milliliter, had a shortening fraction of 17.5 percent less. But, men with more remodeling and, for instance, a higher mass of 190 grams, had a remodeling ratio of 1.4 grams per milliliter and a shortening fraction of 15 percent less. This proves, the researchers say, that remodeled heart muscle was not able to contract as much as normal heart muscle.
The Hopkins researchers also found that particular patterns of remodeling and related heart function differ between men and women. In men, increased remodeling and decreased heart function appear to be gradual and steady over time. In women, initial results showed a temporary benefit to remodeling: Their heart function slightly improved during the heartbeat, before a steep decline in heart function ensued.
While the study was not comprehensive enough to offer conclusions as to why these gender difference occurred, the researchers speculate that it may be related to the fact that women develop cardiovascular disease later in life than do men, and that a women's deteriorating heart function may also be delayed.
"Our results raise the possibility that early treatments for regional heart problems could eventually be used to prevent or suppress larger problems from developing, which could affect the entire cardiovascular system," says lead study author and cardiologist Boaz Rosen, M.D., a senior research fellow at Hopkins. "We have also shown that it is now possible to map changes of the heart in an early stage of their development, increasing the diagnostic and predictive applications of MRI as a key tool in combating cardiovascular disease."
While the researchers were not able to conclude that these early signs of heart deformation and regional dysfunction were the cause or trigger of congestive heart failure or other fatal heart conditions, they do believe that they have created the first pictures needed to make such predictions in the future.
"Because the MESA study follows participants for 10 years, this will be an ideal study to further investigate the health consequences of this remodeling process," says radiologist David Bluemke, M.D., Ph.D., an associate professor and director of MRI at Hopkins. Bluemke was a co-author of the study.
MRI is a noninvasive technique that produces high-quality images of structures and other internal organs inside the body. Unlike X-rays, MRI does not involve radiation, but instead uses large magnets and radio-frequency waves to produce "real-time," two- dimensional images. The specific MRI technique used in this study was developed at Hopkins by radiologist Elias Zerhouni, M.D., and further improved by radiology engineer Nael Osman, Ph.D. Because of the large size of an MRI machine, taking pictures requires that patients lie down on a platform that is moved within the magnets' coils. The technology's applications and image quality have grown steadily since MRI was introduced into medicine in the 1990s.
Funding for this six-center trial, which will study patients for six to eight years, comes from the National Heart, Lung and Blood Institute, a member of the National Institutes of Health.
Other MESA investigators involved in this study were Michael Jerosch-Herold, Ph.D., and Donna Arnett, Ph.D., from the University of Minnesota, in Minneapolis; Sinha Shantanu, Ph.D., from UCLA; John Crouse III, M.D., from Wake-Forest University, in Winston-Salem, N.C.; and Richard Kronmal, Ph.D., and Susan Heckbert, M.D., from the University of Washington, in Seattle. Other members of the Hopkins team were Thor Edvardsen, M.D., Ph.D.; Shenghan Lai, M.D., Ph.D.; Ernesto Castillo, M.D.; and Li Pan, M.S.