clinical research
Transforming
Healthcare Through Reducing Amputations
Reducing Amputations in Chronic Limb Threatening Ischemia Patients
Chronic limb threatening ischaemia (CLTI) is a critical form of end-stage peripheral arterial disease characterized by severe arterial blockage in the legs leading to pain during rest, severe tissue loss (ulcers or gangrenes), and potential limb loss. Associated with increased mortality and poor quality of life, CLTI currently affects nearly two million adults over 40 in the United States. Notably, one-fifth of CLTI patients experience a lack of revascularization options which leads to major lower extremity amputations.
Typically, CLTI affects the geriatric population with multiple risk factors like diabetes, kidney disease, hypertension and a history of smoking. Emerging treatment options that might help avoid amputations in CTLI patients include gene therapy and percutaneous deep venous arterialization (DVA). Trisha Roy, BASc, MD, PhD, FRCSC,FACS, Assistant Professor of Cardiovascular Surgery, provided insights on DVA based on histology and magnetic resonance imaging which could provide revascularization options for the “no-option” CLTI patient and reduce the incidence of amputations in CLTI patients. The details are published in a brief report in the European Journal of Vascular and Endovascular Surgery Vascular Forum.
As a surgeon-scientist, Roy uses novel imaging techniques to transform endovascular techniques. With limb preservation as her clinical focus, Roy delivers precision medicine tailored to her patients’ needs.
Arterial blood flow needs to be urgently restored via endovascular or open-surgical techniques to prevent limb loss in CLTI patients. However, there are no revascularization options for a subset of CLTI patients (commonly referred to as the “no option” sub-group).
Trisha Roy
BASc, MD, PhD, FRCSC,FACS
DVA is a safe and minimally invasive treatment option that plays an important role in amputation prevention in CLTI patients, in cases without the option of conventional revascularization.
Specifically, DVA creates a vein-to-artery connection to deliver oxygenated blood to the venous arch and ischemic tissue to enable wound healing in an attempt to prevent amputation. Selecting the right patients for DVA is a crucial step. However, it is not clear which patient subgroups are good candidates for DVA. The mechanism of action of DVA is also poorly understood.
“Our research program is dedicated to developing imaging techniques to personalize our treatments for critical limb ischaemia. The type of devices or techniques that succeed depends on the unique vascular anatomy of each patient. This is a very new area because what makes a deep venous arterialization procedure possible depends on the venous side of the patient’s circulation. Not much is known about venous disease and anatomy,” said Roy.
A 53-year-old patient with diabetes mellitus underwent a percutaneous DVA that led to improved blood flow to the foot. However, this patient had to undergo a below the knee amputation a few weeks later due to infection.
This occurrence led Roy and her team to wonder what kind of histological alterations took place in the limb post-DVA.
Hallmarks of venous arterialization were found in the blood vessels harvested from the amputated leg for a histological analysis, which included smooth muscle cell proliferation and neointimal hyperplasia. Unexpectedly, these histological changes were also observed in the paired posterior tibial vein that did not undergo DVA in this patient.
“This type of study is challenging because we don't have many patients that undergo deep venous arterialization. Ideally, this approach is for end-stage patients who have no options for revascularization, and it’s really the last option before amputation. It’s not something we do all the time; however, the more we do, the more participants we can enroll in the study, which provide more insights that will reduce the chances of amputation. The goal is to reduce amputations,” Roy commented.
Percutaneous deep venous arterialization is emerging as a potential game changer for no option CLTI; however, its pathophysiological mechanisms are not yet fully understood. This report offers a framework for exploratory studies aimed at understanding the histological changes critical for successful venous arterialization and tissue oxygenation. It’s anticipated that the insight from this research will play a pivotal role in refining patient selection criteria for DVA and optimize the technique, ultimately leading to improved clinical outcomes.
Trisha Roy, BASc, MD, PhD, FRCSC
Assistant Professor, Cardiovascular Surgery
DVA comes with its risks. It’s an extremely involved process that entails a great deal of maintenance procedures and wound care. Additionally, the commitment from the patient and their families is also critical. Hence, it is only recommended for patients who meet these criteria and will benefit from this approach.
“Percutaneous deep venous arterialization is emerging as a potential game changer for no option CLTI; however, its pathophysiological mechanisms are not yet fully understood. This report offers a framework for exploratory studies aimed at understanding the histological changes critical for successful venous arterialization and tissue oxygenation,” explained Roy. “Such investigations are currently underway at Houston Methodist, involving histological analysis of vascular tissues from amputated specimens obtained from patients undergoing planned transmetatarsal and toe amputations following DVA. It is anticipated that the insight from this research will play a pivotal role in refining patient selection criteria for DVA and optimize the technique, ultimately leading to improved clinical outcomes.”.
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Bright Benfor, Judit Csore, Deborah C Vela, Miguel Montero-Baker, Trisha L Roy. Magnetic Resonance Imaging and Histological Insights Into Deep Venous Arterialisation. EJVES Vasc Forum. 2024 Apr 29:61:121-125. doi: 10.1016/j.ejvsvf.2024.04.003.
This research was funded by the Jerold B. Katz Academy of Translational Research of the Houston Methodist Research Institute. (Grant #MRI0001501; Awarded to Trisha L. Roy).
Abanti Chattopadhyay, PhD
February 2025
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