Using magnetic resonance imaging technology, or MRI, to tag the work ofmillions of individual strands of heart muscle fibers, researchers atJohns Hopkins have successfully mapped the smallest deformations insidethe beating hearts of 441 middle-aged and elderly men and women whohave either silently developed heart disease or remained healthy. Thenovel use of the MRI allowed the researchers to create a gridlike,three-dimensional, computer image of each heart and track gradualdeformations during each heartbeat.
The Hopkins findings, published in last week's edition of thejournal Circulation, are believed to be the first to tie specific"remodeling" changes in heart mass and volume to early and growingsigns of trouble in any specific region of the muscle, specifically,the anterior wall (or front part) of the left ventricle, the heart'smain pumping chamber.
"Making new use of magnetic resonance imaging technology, wehave been able to gather the first visual clues of how heart diseasedevelops regionally and possibly spreads to different parts of theheart and cardiovascular system," says senior study investigator andcardiologist João Lima,M.D., associate professor of medicine and radiology at The JohnsHopkins University School of Medicine and its Heart Institute.
According to Lima, cardiologists are aware of many diseasesthat lead to deformations in the heart's shape, both big and small, butthis is the first experiment to have traced or mapped these changes ingreat detail. In problems such as enlarged hearts and hypertension, hesays, "there are disproportionate increases in heart muscle mass tovolume of blood being pumped."
The results of the Hopkins-led study of adults 45 to 85 areamong the first to emerge from the Multiethnic Study ofAtherosclerosis, called MESA for short, which is monitoring nearly7,000 men and women of different ethnic backgrounds and with noexisting signs of heart disease to determine who develops coronaryartery disease and who does not.
All participants in the MESA study had cardiac MRIs performedat enrollment, but in this smaller group study, equal numbers of menand women were randomly assigned to have tagged-MRI analysis. Tominimize any bias in interpretation of results, some scans was analyzedtwice and by any one of three cardiologists.
For every scan, calculations were made for more than a dozenparameters of heart function, including thickness of various heartwalls, pumping volume, ejection fraction (the percentage of bloodpumped from the left ventricle during a heart beat), and shorteningfraction (how much each muscle shortens during contraction), bloodpressure (an indicator of the workload or stress on the heart), andbody mass index. For logistical reasons, however, measures were onlytaken for regional mass in the left ventricle, the largest of theheart's four chambers, limiting the study's implications to this oneparticular chamber.
To calculate total changes in heart shape, which isthree-dimensional, the researchers relied on a previous model that usedMRI scans to calculate a ratio of muscle mass to volume of pumpedblood. The greater the ratio, the greater the amount of concentricheart remodeling that has occurred.
When the researchers compared changes in heart shape to changesin heart function, statistical analysis showed that pumping functiondeteriorates as hearts increasingly change shape or remodel. Changes inheart shape often involved gains in mass and wall thickening.
The results confirmed for both men and women that changes inone particular region of the heart, the anterior wall of the leftventricle, were linked to the greatest declines in heart function.
In men with the greatest percentage of remodeling, forexample, heart function also declined, as measured by shorteningfraction (how much the muscle contracts during a heart beat). Studyresults showed men with a normal-sized heart, weighing 150 grams, witha remodeling ratio of 0.7 grams per milliliter, had a shorteningfraction of 17.5 percent less. But, men with more remodeling and, forinstance, a higher mass of 190 grams, had a remodeling ratio of 1.4grams per milliliter and a shortening fraction of 15 percent less. Thisproves, the researchers say, that remodeled heart muscle was not ableto contract as much as normal heart muscle.
The Hopkins researchers also found that particular patterns ofremodeling and related heart function differ between men and women. Inmen, increased remodeling and decreased heart function appear to begradual and steady over time. In women, initial results showed atemporary benefit to remodeling: Their heart function slightly improvedduring the heartbeat, before a steep decline in heart function ensued.
While the study was not comprehensive enough to offerconclusions as to why these gender difference occurred, the researchersspeculate that it may be related to the fact that women developcardiovascular disease later in life than do men, and that a women'sdeteriorating heart function may also be delayed.
"Our results raise the possibility that early treatments forregional heart problems could eventually be used to prevent or suppresslarger problems from developing, which could affect the entirecardiovascular system," says lead study author and cardiologist BoazRosen, M.D., a senior research fellow at Hopkins. "We have also shownthat it is now possible to map changes of the heart in an early stageof their development, increasing the diagnostic and predictiveapplications of MRI as a key tool in combating cardiovascular disease."
While the researchers were not able to conclude that theseearly signs of heart deformation and regional dysfunction were thecause or trigger of congestive heart failure or other fatal heartconditions, they do believe that they have created the first picturesneeded to make such predictions in the future.
"Because the MESA study follows participants for 10 years, thiswill be an ideal study to further investigate the health consequencesof this remodeling process," says radiologist David Bluemke, M.D.,Ph.D., an associate professor and director of MRI at Hopkins. Bluemkewas a co-author of the study.
MRI is a noninvasive technique that produces high-qualityimages of structures and other internal organs inside the body. UnlikeX-rays, MRI does not involve radiation, but instead uses large magnetsand radio-frequency waves to produce "real-time," two- dimensionalimages. The specific MRI technique used in this study was developed atHopkins by radiologist Elias Zerhouni, M.D., and further improved byradiology engineer Nael Osman, Ph.D. Because of the large size of anMRI machine, taking pictures requires that patients lie down on aplatform that is moved within the magnets' coils. The technology'sapplications and image quality have grown steadily since MRI wasintroduced into medicine in the 1990s.
Funding for this six-center trial, which will study patients for sixto eight years, comes from the National Heart, Lung and BloodInstitute, a member of the National Institutes of Health.
Other MESA investigators involved in this study were MichaelJerosch-Herold, Ph.D., and Donna Arnett, Ph.D., from the University ofMinnesota, in Minneapolis; Sinha Shantanu, Ph.D., from UCLA; JohnCrouse III, M.D., from Wake-Forest University, in Winston-Salem, N.C.;and Richard Kronmal, Ph.D., and Susan Heckbert, M.D., from theUniversity of Washington, in Seattle. Other members of the Hopkins teamwere Thor Edvardsen, M.D., Ph.D.; Shenghan Lai, M.D., Ph.D.; ErnestoCastillo, M.D.; and Li Pan, M.S.
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