Polyester fiber and Dacron // Stainless steel and nitinol // Not biochemistry and genetics // Remain the best way to fix “delicate and intricate plumbing.”
Vascular Disease: Pipe Repair
Even in 2011, there are plenty of ways to die from a breach in the aorta. An aneurysm, a bubble that has formed in a weakened section of the body’s largest artery, may rupture, bringing death very quickly, as blood that is supposed to carry oxygen to every organ pools uselessly in the chest or abdomen. Or in a dissection, layers of the artery wall delaminate and allow blood to seep into side channels within the wall. Penetrating aortic ulcers, caused by plaque burrowing into blood vessel walls, pose still another potentially fatal problem, as do traumatic tears that shear open the aorta following a sudden blow to the chest, such as from the steering wheel during a car crash.
Except for traumatic tears, these aortic pathologies tend to be silent and indolent, growing slowly and asymptomatically over many years. The first sign of an aneurysm may be sudden, excruciating pain as the aorta splits open or bursts. Or someone may simply collapse and die, never knowing what happened. These pathologies are dangerous enough when they affect the lower portion of the aorta in the abdomen, but they are particularly deadly when they occur in the chest. A thoracic aneurysm that reaches six centimeters in diameter has a 10% to 20% chance of tearing open each year, and dissections are prone to break apart. “When they rupture, the odds of making it to the hospital and walking out on your own to your previous life are less than 20%,” says Michael R. Jaff, medical director of the vascular center at Massachusetts General Hospital. Meanwhile, among thoracic tear victims who make it to a hospital, half die within 24 hours.
Those unpalatable statistics describe a situation too little changed from the medical world in 1902, when William Osler wrote that “there is no disease more conducive to clinical humility than aneurysm of the aorta.” Even now, after more than a century of revolutionary advances in most areas of medicine, aneurysms and related pathologies continue to humble the profession. Thoracic aortic aneurysms are common, affecting 10 in 100,000 people each year in the United States. And a ruptured abdominal aortic aneurysm is the 13th leading cause of death in the United States, most often occurring in males 65 and older. Some evidence suggests that their incidence has tripled in the past 30 years.
Recently, though, the odds of surviving aortic disease or injury have gotten better. The improvement hasn’t come from new molecular therapies based on our growing understanding of the human genome, nor have there been any new blockbuster drugs aimed at aortic pathologies (although statins and ACE inhibitors help reduce atherosclerosis and hypertension, two suspected risk factors). Instead, the real gains result from nuts-and-bolts refinements in surgery and in the endovascular-stent-graft devices normally inserted via a small incision in the groin and snaked into position through blood vessels. “Aortic pathologies are basically issues of plumbing, a very delicate and intricate plumbing, and all current therapies are mechanical,” says John Elefteriades, chief of cardiac surgery at Yale–New Haven Hospital. Yet like other, flashier innovations, those plumbing repairs save lives, and researchers continue to expand this low-tech frontier.
The aorta exits the heart’s left ventricle through the aortic valve. In its first stretch, the complex, tortuously shaped thoracic aorta ascends a short way and arcs like a candy cane with branches going off to the brain, lungs and arms. Then it descends through the chest and tapers into the abdominal aorta, which nourishes the stomach, kidneys and other visceral organs. At the navel, the abdominal aorta branches off like trousers into the legs to supply the lower body.
Researchers still don’t know what makes an aneurysm an aneurysm, molecularly speaking, or why different sections of this plumbing system suffer different maladies. It has been widely assumed that atherosclerosis, in which fatty plaques form on the inner walls of blood vessels, can lead to aneurysms, but in many patients the opposite occurs. The proven risk factors are hypertension, smoking and family history—that is, genetics.
“But what genetically predisposes people to develop aneurysms?” asks Jaff. “What is the genetic expression of a cell in an aneurysm? What goes wrong in the aorta wall that causes it to degenerate? What molecules can we target to prevent an aneurysm from forming or growing? We don’t have answers to any of those questions.”
Still, although the biochemistry remains a mystery, the mechanical aspects of aortic diseases are well understood, and therapies boil down to two options. Surgeons can open the chest to cut out the bad part of the pipe and sew in a new section—a graft made of a sleeve of Dacron or polyester fabric. Or, more recently, physicians may snake a self-expanding device from an incision in the groin through the vascular pipes and deploy a graft that reinforces the weak section.