AHA Outlines Diagnosis, Treatment Options for Underrecognized Critical Limb Ischemia

Critical limb ischemia (CLI)—evidenced by ischemic rest pain, a nonhealing wound/ulcer, or gangrene for more than 2 weeks with signs of poor blood flow—remains underrecognized by clinicians and patients, but a new scientific statement from the American Heart Association (AHA) addresses this lack of awareness, as well as the uncertainty over the best means of patient management.

Published online today in Circulation, the paper aims to add clarity by cataloging current options for diagnosis and treatment, identifying gaps to be filled by future technologies, and highlighting patient populations that merit added attention to reduce disparities.

CLI is “a debilitating disease with increased mortality in the first year of diagnosis, greater than what we see for coronary artery disease,” said writing group chair Sanjay Misra, MD (Mayo Clinic, Rochester, MN). Still, “healthcare providers in the cardiovascular space really don’t understand the importance of it and are really missing an opportunity to help patients.”

The scientific statement is aimed broadly at clinicians taking care of patients who might be at risk for developing vascular disease. “I think there will be something there for everyone,” said Misra, who stressed to TCTMD that the document stemmed from a multidisciplinary, team effort.

Michael R. Jaff, DO (Newton-Wellesley Hospital, MA), told TCTMD that Misra and colleagues capture “what an unmet clinical need [CLI] is.”

“We don’t really have a way to determine whether or not you need to do a revascularization in patients who have an ulcer,” he explained. “We don’t have a way to determine if you’ve revascularized enough so that the wound will heal. We don’t even have an ability to assess whether if you amputate a toe, that the toe amputation will heal or if you’re better off doing a below-the-knee amputation. I have to [say], this is no different than it was when I was a fellow in the early 1990s.”

Ultimately, for patients diagnosed with CLI, “you do the best you can” in terms of revascularization and wound care, Jaff stressed.

The Technology

The AHA statement outlines the pros and cons of diagnostic tools already in use, including ankle brachial index (and ankle systolic pressure), toe brachial index (and toe pressure), transcutaneous oximetry, and skin perfusion pressure. Experimental technologies to diagnose poor lower-extremity perfusion, such as indigo carmine angiography, CT perfusion, MRI, contrast-enhanced ultrasound, and hyperspectral imaging, are also explored.

“The goal of an ideal perfusion assessment test for CLI, unlike claudication, is to identify whether adequate blood is supplying the extremity to prompt timely wound healing and reduce major and minor amputations. Accurate noninvasive limb perfusion assessment will likely allow timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with venous, neuropathic, or pressure ulcers,” Misra et al advise.

[CLI is] a debilitating disease with increased mortality in the first year of diagnosis, greater than what we see for coronary artery disease. Sanjay Misra

Additionally, assessment of regional perfusion or oxygenation can inform where revascularization is most needed and whether an intervention has been successful.

Also on the horizon are implantable biosensors to detect oxygen levels in the extremities. One example is the Lumee Oxygen Platform (Profusa), which has received CE Mark approval in Europe but is an investigational device in the United States.

Biosensors “give the patient or their provider a signal that this person has some subclinical findings of oxygen levels running low and may warrant additional tests [or] potential intervention,” Misra said, adding that the devices may be particularly good for rural patients who have a hard time getting to a doctor’s office. But in the setting of PAD, usability is key; socks, different types of shoes, and unusually high or low room temperatures might lead to false readings, he noted.

The Patient

Demographic disparities in PAD detection and treatment are a problem, the AHA statement indicates, noting that there are also differences in patient comorbidities and CLI presentation.

“Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain,” Misra and colleagues note. “Alarmingly, black patients are 78% more likely to receive lower-extremity amputation for CLI than their white counterparts, even after adjustment for comorbidities, socioeconomic status, and access to facilities with revascularization capacity. These findings have been replicated when adjusting for disease severity. Black patients also experience the lowest rates of revascularization.”

Women, meanwhile, are more likely than men “to be hospitalized emergently for PAD, more likely to present with CLI, and have higher mortality rates after lower-extremity revascularization or amputation. [They also] have increased risk for femoropopliteal lesions, multilevel disease, and occlusive lesions compared with men,” they write.

You do the best you can. Michael R. Jaff

As pointed out by Jaff, the diagnosis can be clear-cut when “you can’t feel a pulse in the foot and [patients have] gangrene in the toe—that’s critical limb ischemia. You don’t have to go through a series of machinations.”

More challenging, he commented, is a diabetic patient with chronic kidney disease who presents with an ulcer on their big toe but also with noncompressible vessels and borderline results on noninvasive testing. “Then, the question is: would revascularizing that heal the wound faster than if you just did wound care? And honestly, the decision on that depends on who the patient sees first,” said Jaff. “If they go to a vascular surgeon or an interventional cardiologist, they would likely end up getting revascularization. If they went to a podiatrist, they would likely get wound care.”

Nor is disease progression uniform. “Sometimes these wounds are slow and indolent and they don’t really worsen or get better. People just kind of keep going to their doctor for wound care. Others within a week can go from a small ulcer to a deep foot infection and would need hospitalization or surgery,” he said.

Proper wound care requires seeing patients in the office two or three times per week to monitor healing, Jaff emphasized. Where the problem lies is when patients “don’t come back for a month. It’s pretty common. And then, by the time they get in to see somebody, the cat’s out of the bag. Not only will they need revascularization but they’ll likely [need amputation].”