The comprehensive Penn Advanced Limb Preservation (PALP) program at Penn Medicine has the object of preventing amputation and its associated risks in patients with peripheral artery disease (PAD) and its terminal phase, chronic limb-threatening ischemia (CLTI).
In addition, the PALP Program mission includes the resolution of disparities in PAD care; improved detection and treatment of disease; and the integration of new technologies and advances in clinical research for “no-option” CLTI patients. No-option patients are defined as individuals whose peripheral vasculature offers no recourse for medical or surgical intervention. These patients typically have severe ischemia and/or advanced pedal artery occlusive disease, and are at very high risk for amputation.
PAD and CLT: Etiology and Risk Factors
PAD is common in the United States, affecting almost 30 percent of individuals older than age 70 and more than 50 percent of persons with a history of smoking. A condition for which leg pain (claudication) is the chief symptom, PAD has a significant effect on function and quality of life. The disease involves vascular stenosis and ischemia in the calves and feet as a result of occlusive atherosclerosis of the aorto-iliac, femoropopliteal, and infra-popliteal arteries. Beyond pain, early symptoms include cramping, paresthesias, and cold feet.
PAD-associated claudication worsens over time in the absence of treatment. In the final stages, pain is unremitting. In CLTI, the end-stage manifestation of PAD, protracted (>2 weeks) claudication at rest is definitive, and may be attended in advanced cases by diffuse limb ulceration, necrosis, and gangrene. CLTI is particularly concerning for persons with additional contributors to peripheral vascular dysfunction, including those with type 2 diabetes, hypertension, metabolic syndrome, kidney disease, and the triad of smoking, obesity, and sedentary lifestyle. Between 20 percent and 25 percent of individuals with untreated CLTI will lose a limb to amputation at 1 year of diagnosis; rates of mortality for CLTI at five years approach 50 percent.
Therapeutic Approaches to PAD/CLTI at Penn Medicine
Limb preservation at the PALP Program seeks to reverse, treat, or avoid the numerous events and conditions that contribute to amputation, and is distinct from limb salvage, which seeks to rescue limbs from trauma, and interventional radiological procedures for acute thrombotic events.
Conservative and Local Treatments for Early stage PAD
The diagnosis and treatment of early-stage PAD may be prompted by the appearance of claudication on exercise that resolves with rest. When diagnosed at this early stage, lifestyle modification and medications are recommended first-line therapies at the Penn PALP Program. These efforts combine such preventative measures as pediatric foot care with exercise, smoking cessation, and nutritional and diabetic counseling.
More advanced disease, may require wound-care management wherein wounds and ulceration are treated with debridement and antibiotics to preserve limb function and mobility and prevent progression to CLTI, gangrene, and amputation.
Treatment for patients with diagnosed CLTI at Penn PALP has the goal of restoring sufficient peripheral artery perfusion (revascularization) to permit wound healing and avoid the progression of disease. This may be achieved by minimally invasive interventions, including angioplasty, percutaneous stenting, lithoplasty, lower extremity bypass, and open surgery.
Treatment at Penn PALP for “No Option” CLTI Patients
As many as 20 percent of patients with CLTI are at imminent risk for amputation because they have no available targets in the tibial and pedal arteries for revascularization therapy. For these no-option patients, the Penn PALP Program offers the LimFlo System, an FDA-approved technology for percutaneous deep vein arterialization (DVA), available through the PROMISE III clinical trial (NCT05313165) led at Penn Medicine by Elizabeth Anne Genovese, MD, MS, FACS, RPVI.
The LimFlo System combines cannulation, angioplasty, and stenting to divert blood from the tibial artery into the tibial vein to perfuse and revascularize the limb and foot. During the pivotal PROMISE II study, 76 percent of no-option CLTI patients were able to avoid amputation and saw progressive wound healing and significant pain relief following LimFlow treatment.
Clinical Trials in PAD/CLTI
In addition to PROMISE III, the PALP Program offers access to:
MOTIV BTK (NCT05406622), which is exploring the safety and effectiveness of a bioresorbable, drug-eluting device coated with Sirolimus (rapamycin), an agent with applications in stent and scaffold devices to prevent vessel closure.
DEEPER REVEAL (NCT05358353), a study investigating the safety and efficacy of the Temporary Bare Spur Stent System, a retrievable stent system used in the infrapopliteal arteries for the treatment of critical limb ischemia.
About the Penn PALP Program
The Penn Advanced Limb Preservation (PALP) Program has the mission of preventing amputation as a consequence of PAD, CLTI, and other threats to vascular patency in the peripheral limbs. To achieve this objective, the Program integrates specialists in virtually every field associated with the management of peripheral endovascular disease, including podiatry, infectious disease, vascular surgery and endovascular therapy, wound care, endocrinology, and cardiology. Patients also have access to specialists in radiology and rehabilitation, as well as to advanced clinical trials.