July 26, 2007
Study points to new way to predict death risk for patients who suffer a tear in the body's largest blood vessel
Partial clotting in torn aorta is associated with much greater risk; could be detected using current MRI scans and used to guide decisions about surgery
ANN ARBOR, MI – Each year, 10,000 Americans suffer a sudden tear in the lining of their body’s largest blood vessel, the aorta. It’s often misdiagnosed, and it can kill if not treated immediately. Actor John Ritter died of such a tear in 2003.
These three cross-sectional illustrations of the aorta illustrate the different states of blockage that might occur within the "false lumen" or secondary channel created by an aortic dissection. In each case, the false lumen is in purple, and the "true" aorta is red. At left, the channel is clear (also called patent), a state that was associated with lower risks of post-hospital death in the new study. In the middle, the false lumen is partially blocked by clots, a state that was associated with a much higher risk of death. At right, the false lumen is entirely thrombosed, or filled with clots. This state was associated with an intermediate risk of death. ( Copyright 2007 NEJM. Used with permission. May not be used for other purposes without seeking specific permission.)
The New England Journal of Medicine has created an animation that illustrates the aortic dissection model proposed by the researchers in the new paper.
Better medical imaging and treatments such as medication, surgery and catheter-based procedures are now giving more patients a chance to survive this crisis, called aortic dissection. But once they leave the hospital, patients face a one-in-four chance of dying within a few years. And doctors don’t have a reliable way of predicting who is most at risk of dying, and who might benefit most from surgery or other treatment.
Now, a study published in the July 26 England Journal of Medicine by an international team of researchers may offer hope for aortic dissection survivors, and give guidance for their physicians. The researchers, led by University of Michigan Cardiovascular Center experts, propose a new way to predict post-hospital death risk for aortic dissection patients, and a new model for the mechanism behind that risk.
Their model focuses on a phenomenon that can easily be seen on modern medical-imaging scans: the presence of blood clots in the channel created when the layers of the aorta separate like two layers of an onion. This channel, called the “false lumen,” runs alongside the “true” lumen, which is the hollow middle area of the aorta that acts as the pipeline for blood to flow out of the heart and down through the abdomen.
As blood enters the false lumen from the top of the tear in the aorta, it gets trapped inside the new channel. Often, small openings at the bottom of the newly formed channel will allow the blood to flow out. But if the openings aren’t large, blood flow inside the false lumen is slowed down, pressure increases, and clots begin to form.
The study shows that the risk of post-hospital death is more than two-and-a-half times greater for patients who experience partial clotting (thrombosis) of the false lumen, than for those whose false lumen is clear of clots, or patent. Patients whose false lumen is totally filled with clotted blood — which happens quite infrequently — have an intermediate risk of death.
“It appears that this may be a new predictor of which patients are most at risk — knowledge that might help guide decisions about when it’s wise to proceed with more aggressive treatment and when we can hold off. But more research is needed,” says lead author Thomas Tsai, M.D., M.Sc., a U-M fellow in cardiovascular medicine.
The study involves data from 201 patients with dissections in their descending aortas, who were discharged from the hospital after treatment and followed for up to three years or until death as part of IRAD, the International Registry of Acute Aortic Dissection.
IRAD, which is headquartered at the U-M CVC and supported in part by the U-M Medical School, the Mardigian Foundation, and the Varbedian Fund for Aortic Research, includes data from 22 large medical centers in 11 countries. It pools data on treatment and patient outcomes for this relatively rare condition, to allow researchers to draw more scientific conclusions based on larger amounts of data than can be gathered at a single center.
Senior author Kim Eagle, M.D., FACC, is a primary IRAD investigator. He says, “I believe that we are beginning a new era of scientific discovery in aortic diseases at U-M and in IRAD. By taking advantage of advances in imaging studies and genetic associations of aortic diseases, correlations with this entire care area will be transformed.” Eagle is the Albion Walter Hewlett Professor of Cardiovascular Medicine at U-M and a director of the U-M Cardiovascular Center.
In addition to the IRAD data, Tsai and colleagues at U-M Biomedical Engineering are studying a false lumen model of dissection using an artificial material that simulates conditions inside the aorta.
Blood pressure within the false lumen, and the properties and responses of the torn aortic wall, may all play a role in the higher death risk that appears to be associated with partial thrombosis. Data suggest that in a partially thrombosed false lumen, the systolic pressure is lower than the systolic pressure in the aorta, but that the diastolic pressure is higher – leading to a higher average (mean) pressure in the false lumen as compared to the false lumen in patients with a patent or completely thrombosed false lumen.
U-M interventional radiologist David Williams, M.D., has studied the false lumen, and that U-M vascular surgeon Ramon Berguer, M.D., has studied the dynamics of endoleaks in a similar model of abdominal aortic aneurysms treated with stent grafts. This research and work by others around the world lends further weight to the model proposed from the new data. Still, Tsai says, only prospective research and other validation efforts will tell if the false-lumen model is accurate.
The NEJM paper is based on retrospective clinical data from 114 patients who had a patent false lumen when they were admitted to an IRAD hospital, 68 patients who had a partially thrombosed (clot-filled) false lumen, and 19 who had a completely thrombosed false lumen.
By the end of the three-year follow-up period, nearly 25 percent of the patients had died. But the difference in death risk was striking: 13.7 percent of the patients with patent (clear) false lumens had died, compared with 31.6 percent of the partially thrombosed patients and 22.6 percent of the completely thrombosed patients. The difference held up after other factors were corrected for.
In addition to the importance of the false lumen, the researchers found that patients with a history of atherosclerosis and of aortic aneurysm were also more likely to die during the follow-up period. Aortic aneurysms are different from aortic dissections because they involve a bulge in the aorta formed by a weakened area of blood vessel, but the layers of the vessel wall stay together.
The patients were mostly male and in their 60s. Nearly all the patients were diagnosed within a day of arrival at the hospital, using cross-sectional imaging techniques such as CT, MRI or transesophageal echocardiogram (TEE). The patients were all initially treated between 1996 and 2003; in recent years, medical imaging has progressed even further to allow rapid scans to rule out, or rule in, aortic dissections, pulmonary embolisms, and heart attacks for patients who complain of sudden chest and back pain – symptoms that can occur with all three conditions.
In the hospital, all the patients received medications to normalize their blood pressures and heart rates, and for nearly 73 percent of the patients, medications were the only treatment given. Nearly 18 percent had surgery to repair the tear, and 9.5 percent had an endovascular procedure – either a stent graft that blocked blood from entering the false lumen, a fenestration to create more openings in the lower part of the false lumen, or both.
Tsai notes that the current trend toward increased use of endovascular stent-grafts in aortic disease is based on a belief that blocking the flow of blood into the false lumen will lead it to clot completely, thereby decreasing pressures within the channel and possibly leading to gradual healing.
But neither endovascular nor surgical treatment is risk-free for these patients – they carry a risk of paralysis and other problems. And clinical trials comparing stent grafts to best medical therapy in aortic dissection have suggested similar outcomes for both, so they are not to be entered into lightly.
If the false-lumen thrombosis risk model pans out as a useful tool for physicians, it might be recommended that an examination of the extent of thrombosis with special imaging protocols be added to the regular advice that aortic dissection patients be monitored with regular MR scans or CT scans every six to 12 months after diagnosis.
The U-M team is now conducting prospective studies of aortic dissection patients that will follow them over time to see how the false lumen changes as part of its multidisciplinary Cardiovascular Center program in aortic diseases. It is also pursuing the identification of blood markers that might permit an earlier diagnosis both early in the course of a dissection and later on, and working to further refine long-term risk prediction, says Eagle. U-M surgeons G. Michael Deeb, M.D., Himanshu Patel, M.D., and Gilbert Upchurch, M.D. are studying how refinements in open surgery or stent grafting can improve survival and reduce complications.
The journal has prepared an animation of the proposed model of false lumen thrombosis and its impact on pressures within the false lumen. It is available online.
Reference: NEJM, Volume 357, No. 4, pp. 349-359, July 26, 2007
Written by: Kara Gavin
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