Each year, more than 30,000 people in the U.S. die from thoracic aortic aneurysms that rupture or lead to aortic dissection. While the incidence of such confirmed aneurysms is fairly modest—5.9 per 100,000 person-years—estimates place the number of enlarged and potentially undiagnosed aortas in the population in the hundreds of thousands.
Current size-based guidelines for aortic intervention do not always identify patients before dissections occur. But many patients do well with just medications and monitoring, so providers understandably do not want to expose them to unnecessary surgeries or procedures. How best then to determine who needs which approach? When does aortic enlargement cross into a potentially dangerous aortic aneurysm and when does it just bear watching?
At the Penn Aorta Center, physicians and scientists are working to provide referring providers and their patients with answers.
"We want to be on top of that and not see patients when they're already at, or past, the point of recommended intervention," says Victor Ferrari, MD, a cardiologist and imaging specialist who sees referrals at the center. "Beforehand, we can evaluate them and confirm the proper diagnosis."
Finding the Line Between Aortic Dilation and Thoracic Aortic Aneurysm
With aortic enlargement, it is important to use accurate language with patients, the Penn team says. Rather than an aneurysm, patients may have less severe dilation—enlargement that often warrants evaluation and may need intervention but typically poses less imminent risk.
"Otherwise, we spend time walking them back from that what seems like a really scary diagnosis to something that is still unsettling but not so acute," says Katherine Fisher, a senior clinical nurse at the Penn Aorta Center.
Only when the thoracic aorta reaches twice the expected size is an aneurysm present, according to joint guidelines from the American Heart Association and the American College of Cardiology. In practice, though, that determination is not so simple, as patients typically do not come with baseline measurements of their aortas before expansion. Diameter also varies by age—the aorta naturally widens as we grow older—body size and location, as the artery gradually tapers as it gets farther from the aortic valve.
Often, clinicians have used benchmarks for intervention in national guidelines as a lodestar—specifically, the broad recommendation that a diameter of 5.5 centimeters or more in the ascending aorta triggers surgery or endovascular repair.
But here, too, uncertainty arises. A national, randomized clinical trial seeks to determine if the 5.5-centimeter standard should be lowered to 5 centimeters. It will compare outcomes for patients undergoing aortic repair to those receiving close monitoring.
"This has major ramifications for the future," says Penn Aorta Center director Nimesh Desai, MD, who helped design the trial and serves as Penn's principal investigator. "Emerging evidence shows that the risk of having an aortic rupture or dissection or having rapid growth is actually somewhere between 5 and 5.5."
Beyond that, Penn physicians continue their leading work to show that several other factors also need consideration, starting with the fact that larger people tend to have larger aortas. In other words, relying solely on absolute size is outdated.
"Like much of life, it is more complicated than that," says Wilson Szeto, MD, the cardiac surgeon who oversees the Penn Aorta Center's efforts at Penn Presbyterian Medical Center. "We're trying to get the field better answers on when to intervene."
Determining When to Treat Aortic Aneurysms
A more sophisticated approach to aortic enlargement starts with body size, Szeto says. He and other aorta center colleagues promote the idea of adjusting, or indexing, aortic diameter, whether simply by height or with a more complex measure such as body surface area (BSA).
Stratifying risk—and potentially intervening sooner or at smaller aortic diameters—then takes in other factors at Penn. Aortas growing at more rapid rates warrant particular concern, as do aneurysms at the aortic root.
Patients with bicuspid aortic valves often develop aortic aneurysms and may need earlier intervention. Marfan syndrome, Loeys-Dietz syndrome and the vascular form of Ehlers-Danlos syndrome—connective tissue disorders tied to inherited or de novo genetic variants—also raise risk, as does Turner syndrome. These genetic conditions can weaken the aorta without causing it to expand.
"One of the areas that the Penn Aorta Center team is most excited about is our research, both clinical and basic, into the causes of syndromic aortic conditions and the issues they create," says center founder Joseph Bavaria, MD. The recent expansion of the aorta center's efforts means an even greater focus on determining why aneurysms form, how they progress and which ones are likely to eventually turn dangerous, Dr. Bavaria says.
Other inherited variants tied to aortic aneurysms and aortic dissections running in families may also trigger a recommendation for earlier intervention. These variants include changes to the genes ACTA2, MYH11, MYLK and PRKG1. (Other genetic variants tied to familial thoracic aortic aneurysm and dissection, or FTAAD, are clinically significant but not as potent.)
Given the complexity, the Penn team encourages referral for any patient with a thoracic aorta larger than 4 centimeters, especially those with additional risk factors. It is definitely better to evaluate the aorta sooner, says Joshua Grimm, MD, a cardiac surgeon at the Penn Aorta Center—even if the patient ends up not needing further care.
"I would never fault a referring physician for someone that shows up in the clinic with an aorta that I think is stable," Dr. Grimm says.
Evaluating Aortic Enlargement in Patients Before Referral
Depending on their effect on other bodily structures, thoracic aortic aneurysms can cause pain between the shoulder blades or in the shoulders, neck, jaw or chest. They can also lead to hoarseness, dyspnea or dysphagia.
The bulk of patients are asymptomatic, though, with potential aortic enlargement often spotted through imaging given for other reasons. When evaluating patients, the Penn team has found that following certain steps works best:
- Include the brain, heart, mesentery and extremities during physical examination.
- Ask about hypertension, smoking and inflammatory conditions—while much of thoracic aortic disease seems connected to genetic variants, these risk factors can also play a role.
- Take a detailed family history of siblings, parents and grandparents, including incidence of aortic dissection, aortic aneurysm or cerebral aneurysm or presence of bicuspid aortic valve, connective tissue disorder or known genetic variant tied to aortic disease. (Patients with a family history typically present at a younger age, though not as early as those with connective tissue disorders.)
- Look for physical signs of Turner syndrome or one of the three main connective tissue disorders that can affect the aorta.
- Start with transthoracic echocardiography at multiple spots along the aorta—measure from outer aortic edge to outer edge under updated guidelines—but then move on to computed tomography for confirmation of suspicious findings.
- Assess the aortic valve when the aortic root or ascending aorta are enlarged—while TTE offers a starting point, transesophageal echocardiography provides more detail.
- Continue to monitor patients who do not need immediate intervention via CT or MRI, with shorter intervals for higher risk, per national guidelines.
With imaging, the Penn team advises providers to watch for pitfalls that skew results. Each genetic syndrome has its own requirements, such as which segments of the aorta to measure or what other features to evaluate. With both CT and echo, aortic diameter must be measured perpendicular to blood flow. And when drawing comparisons to previous scans, the same aortic location must be referenced and the length of the segment noted. The same protocols should be followed, accounting for breath holding, slice thickness and gating, for example.
"Otherwise, you may not be comparing apples to apples," Dr. Ferrari says. "That variability can be important in making a decision."
Providing Referring Physicians with a Resource for Aortic Enlargement
The Penn aorta team is working with referring physicians from around the region and the country to serve as consultants when significant aortic enlargement is suspected. Patients receive individualized recommendations and can access the services they need in one location, from genetic testing to interpretive expertise and consistency with multimodality imaging.
That imaging could soon include spectral CT for much greater detail at the same radiation dose and 7-Tesla MRI to gauge heart metabolism and damage from aortic disease, both efforts currently in the research phase. Penn already offers cardiac MR with 4D flow, to see how changes in blood movement from unusual aortic valves can affect the aorta.
"We can actually image the stress that's on the wall of the aorta," Dr. Desai says. "We can determine if there are reasons why someone might be at unique risk."
Patients who need intervention get treated by Penn's aortic surgeons, national leaders in bicuspid aortic valve repair, valve-sparing root surgeries and endovascular aortic repair.
Penn also offers surveillance clinics that see nearly 2,000 patients a year for bicuspid aortic valves, aortic enlargement and aortic dissections—one of the largest volumes in the country. Some patients just need ongoing monitoring, while others have continued follow-ups after surgery or endovascular procedures. Even with successful intervention for a thoracic aneurysm, another aneurysm can develop elsewhere in the aorta. And type A dissections often leave residual effects despite repair.
"We follow these folks for life," Dr. Grimm says. "We are looking at subtle changes that can really affect someone's life in a deleterious way, and we try to mitigate the condition before it gets to that point."
Additional Resources from the Penn Aorta Center