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 suggest that the number of enlarged and potentially undiagnosed aortas in the population is in the hundreds of thousands.
One concern is that current size-based guidelines for aortic management do not always identify patients before dissections occur. Given the expense and potential consequences of surgery and because most patients do well with medications and monitoring, providers are understandably wary of unnecessary interventions for dissection. However, unanswered questions remain for the at-risk population: 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?
Physicians and scientists are working to provide referring providers and their patients with answers at the Penn Aorta Center.
"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
When communicating with patients, it’s crucial to use precise language in discussions of aortic enlargement, says the Penn team. “By managing the way we discuss the condition, we can walk patients back from 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. It’s important, she adds, that clinicians recognize that patients may have a less severe dilation that requires evaluation and may need intervention but generally poses a lower immediate risk.
The fallibility of universal guideline standards for aortic dilation
Traditionally, when the ascending aorta gets above 5.5 cm, surgery is recommended to replace the aorta. Often, clinicians have used such benchmarks for intervention in national guidelines as a lodestar—but here, uncertainty arises, and a national, randomized clinical trial is currently seeking to determine if the 5.5-centimeter standard should be lowered to 5 centimeters. The study compares 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 this, 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. Diameter also varies organically—the aorta widens naturally as individuals age and gradually tapers as it gets farther from the aortic valve.
"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 better answers on when to intervene."
Determining when to treat aortic aneurysms
A more advanced approach to understanding aortic enlargement begins with body size, according to Dr. Szeto, who is Chief of the Division of Cardiovascular Surgery at Penn Medicine. He and his colleagues at the Penn Aorta Center advocate for the practice of adjusting, or indexing, aortic diameter either by using a straightforward measure like height or by employing a more complex calculation involving body surface area.
Stratifying risk—and potentially intervening sooner or at smaller aortic diameters—takes in other factors. Aortas growing at more rapid rates warrant particular concern, as do aneurysms at the aortic root.
In addition, 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 weaken the structural stability of the aorta wall without causing it to expand.
"One of the areas that the Penn Aorta Center team is most excited about is our clinical and basic research into the causes of syndromic aortic conditions and the issues they create," says Dr. Szeto. The expansion of the Aorta Center's efforts means a greater focus on determining why aneurysms form, how they progress and which ones are likely to become dangerous over time, he adds.
Other inherited variants tied to aortic aneurysms and aortic dissections running in families may also trigger a recommendation for earlier intervention. These variants include mutations of 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 this complexity, the Penn team encourages referral for any patient with a thoracic aorta larger than 4 centimeters, especially those with additional risk factors.
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 the following steps work 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 syndromes 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—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 transthoracic echocardiogram 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. 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.
"Otherwise, you may not be comparing apples to apples," imaging specialist 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 works 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 Medicine has one of the largest volumes for aorta monitoring and care in the country, with clinics that see nearly 2,000 patients a year for bicuspid aortic valves, aortic enlargement, and aortic dissections. 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. Moreover, type A dissections often leave residual effects despite repair.
"We follow patients for life," says Dr. Grace Wang, a vascular surgeon and researcher at the Center. "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