Cover Story

Innovations in Endovascular Limb Salvage

New approaches are saving limbs and lives.

In the past, patients in need of limb salvage due to critical limb ischemia or other forms of peripheral artery disease were likely to need surgical bypass if they had any hope of relief of symptoms or even avoiding amputation. Now, as a result of new technologies, better techniques and increased multidisciplinary collaboration, many of these patients are able to achieve reperfusion via a less invasive percutaneous endovascular approach.

“The endovascular approach has changed the way we treat these patients and now allows us to do revascularizations that were not at all possible just a few short years ago,” Jihad A. Mustapha, MD, FACC, FSCAI, director of cardiovascular catheterization laboratories at Metro Health Hospital, Wyoming, Michigan, told Cardiology Today’s Intervention. “The majority of patients with critical limb ischemia can benefit from an endovascular approach. However, there still remain a subset of patients that require a non-endovascular approach.”

However, not all critical limb ischemia (CLI) cases have the same characteristics and risk factors, so not all patients needing limb salvage can be treated with an endovascular approach, experts said. The ongoing BEST-CLI trial, which is comparing optimal endovascular therapy vs. optimal surgical therapy in patients with CLI eligible for either approach, is expected to better define which patients are best suited for an endovascular intervention and which are best suited for surgical bypass.

‘Marker of Bad Vascular Disease’

CLI affects approximately 1.4 million people in the United States, with about 320,000 new cases every year. About 25% of newly diagnosed patients require amputation within 1 year, with an average survival after diagnosis of approximately 2.5 years. Often, many patients die of causes related to MI or stroke, and the rate of CV death within the year after a CLI diagnosis is high.

Douglas E. Drachman
Douglas E. Drachman

“CLI is a marker of bad vascular disease throughout the body,” Douglas E. Drachman, MD, director of the cardiology and interventional cardiology fellowship programs at Massachusetts General Hospital, said in an interview with Cardiology Today’s Intervention. “In patients with extensive atherosclerosis in the legs, there is high likelihood of disease in other territories such as the heart and brain, with associated risk for MI, stroke and death. Identifying people with CLI and recognizing the risk conferred for systemic adverse events, provides an important opportunity to focus on risk factor modification to protect the heart, brain and limb alike.”

Common risk factors in patients with CLI are diabetes, smoking and advanced age, according to Gary M. Ansel, MD, FACC, system medical chief for vascular at OhioHealth in Columbus, Ohio.

Those who receive endovascular treatment for limb salvage do not differ much from those who receive surgical treatment for it, Ansel said.

In many cases, the distinction comes down to the preferred practice at local institutions.

“Although data demonstrate that endovascular techniques now make up the majority of procedures, there is wide variation in practice, with some hospitals doing little endovascular treatment and others doing little surgery,” said Ansel, a member of the Cardiology Today’s Intervention Editorial Board.

Choosing the Optimal Approach

Despite wide variations in practice, there are effective strategies to select which patients would benefit from an endovascular approach to limb salvage, experts said.

“An endovascular approach is particularly well-suited for patients with comorbidities that elevate the risk of open surgical bypass, those with lack of venous conduit and patients with diffuse tibial disease and lack a target for the graft,” Ansel said.

Conversely, he said, “patients who are nonambulatory or have such advanced tissue destruction that the lack of perfusion is only part of the issue may not be acceptable candidates for any vascular procedure.”

The decision must be made based on an individual patient’s characteristics because CLI is a complex disease that does not lend itself to one-size-fits-all solutions, Sahil A. Parikh, MD, FSCAI, FACC, assistant professor of medicine at Case Western Reserve School of Medicine, Cleveland, told Cardiology Today’s Intervention.

“Truly, the best approach for any individual patient is tailored to that patient’s clinical comorbidities, functional goals and anatomy,” he said. “Where are their blockages and how bad are they? Do they have targets for bypass surgery? Are they candidates for surgery?”

However, endovascular advances aside, there are still some cases in which amputation is the only option.

Patients who are nonambulatory; those who have intense neurologic pain that reperfusion would not help; those who are sick and have been through multiple endovascular and surgical procedures; and those with significant osteomyelitis with unsalvageable tissue are a few examples of those for whom amputation may be the best option, Ansel said. He noted, however, that improved endovascular and surgical techniques are enabling reperfusion in patients with poor distal vessels, a condition previously considered unsalvageable.

More direction on this may be provided by the outcomes of the BEST-CLI trial. The trial is expected to enroll approximately 2,100 patients, with a completion date of December 2018.

In a paper on the BEST-CLI trial design published in Techniques in Vascular and Interventional Radiology,Alik Farber, MD, from the division of vascular and endovascular surgery at Boston Medical Center, and colleagues described that “BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using (1) a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available; (2) a novel primary endpoint that includes limb amputation rates, repeat intervention and mortality; (3) a multidisciplinary structure that fosters cooperation among interventional cardiologists, interventional radiologists, vascular surgeons and vascular medicine specialists; and (4) novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the two treatment strategies being tested.”

Rapid Technological Advances

The standard endovascular approach for CLI uses catheters, guidewires and balloons to re-establish blood flow.

But within that paradigm, an operator has many options, and many of them borrow techniques from treatment of CAD because below-the-knee arteries are about the same size as coronary arteries.

Sahil A. Parikh
Sahil A. Parikh

“We have better devices that are designed for this specific space, but in limb salvage, most of the work is below-knee intervention in the tibial vessels, which are parenthetically the same size as coronary vessels. And so we use a lot of techniques borrowed from the coronaries,” Parikh said.

Depending on patient and lesion characteristics, below-the-knee limb salvage procedures may at times benefit from the use of the latest-generation drug-eluting stent technologies employed to treat CAD, Drachman said.

However, this may not always be the best choice, according to Mustapha.

“My biggest pet peeve is when tibial arteries are compared to coronary arteries,” he said. “I believe they are completely different. Tibial preclinical research is underdeveloped and should be a primary focus to advance the CLI field on solid ground.”

When a patient has a long obstruction below the knee, “often using balloon angioplasty alone can be effective, and may maintain patency long enough to restore tissue integrity at the site of an ulcer,” Drachman said.

Devices for dedicated pedal access, including one made by Cook Medical, and long balloons designed for tibial and pedal intervention are now available from many companies, according to Ansel.

For above-the-knee limb salvage procedures, innovation in stent design “has continued to make stents more supportive, more flexible and more resistant to fractures, which is necessary in light of the extrinsic forces that are such as flexion, muscle contraction and vessel torsion, which may wreak havoc on vascular scaffold integrity,” he said.

Gary M. Ansel
Gary M. Ansel

Drug-coated balloons are also becoming more widely used in these areas because they have been shown to greatly reduce restenosis risk, experts said. Two, the Lutonix 035 Drug-Coated Balloon PTA Catheter (Bard/Lutonix) and the IN.PACT Admiral Drug-Coated Balloon (Medtronic), have been approved by the FDA, and more may be in the near future.

“However, it must be noted that data on use of these devices for CLI is still lacking; most of the data for these devices has been for patients with claudication,” Ansel said.

Atherectomy, a technology used to reduce or remove plaque that is heavily calcified, bulky or otherwise resistant to angioplasty and stenting, is also being used in some limb salvage procedures, Drachman said.

Ansel noted that Cardiovascular Systems Inc., a manufacturer of atherectomy devices, has established the Liberty 360° registry, intended for more than 1,200 patients, to compare outcomes of orbital atherectomy vs. other approaches for treating PAD.

Innovative Strategies

Perhaps even more important to the improvement in endovascular procedures for limb salvage is new techniques that operators are using to treat challenging lesions.

Totally occluded leg arteries, once thought to be impossible to treat with an endovascular approach, are now routinely treated that way.

“In my opinion, the best limb salvage technique is an antegrade/retrograde approach for complex chronic total occlusions, which are a typical obstacle for patients with CLI,” Mustapha said. “We all must master this technique to continue to be successful in advancing the CLI field.”

Jihad A. Mustapha
Jihad A. Mustapha

Traditionally, endovascular limb salvage procedures have been performed using femoral access, but in recent years, radial access, which is associated with fewer vascular complications, and pedal access, which may be the best approach for certain difficult lesions, have become more common.

“Now, there are balloons long enough to reach from the radial approach,” Parikh said. “Interestingly, we’re now attacking disease from below, accessing the pedal vessels in the ankles and working north instead of south. By implementing an approach that goes up and down, we are able to more commonly succeed in opening a [CTO]. But, there is a learning curve to employing these techniques, and we must respect the risk of complications as well.”

Strategies adopted in recent years have improved outcomes for patients with CTO in a peripheral artery, Drachman said.

Figures

Figures. A case study of a patient with critical limb ischemia and a BMI of 42 kg/m2. The case was completed via a single ultrasound-guided tibial access (top, left) while the patient remained on the table at a 45-degree angle. This tibial access and minimally invasive retrograde intervention (TAMI) procedure (bottom, left) was performed using low-profile devices (top, right). Hemostasis was obtained and the patient was ambulatory and discharged home 1 hour post-successful procedure (bottom, right).

Figures courtesy Jihad A. Mustapha, MD, FACC, FSCAI; reprinted with permission.

“One strategy involves the international passage of a wire in the subintimal plane — outside of the vessel lumen — to cross the total occlusion antegrade, with re-entry of the lumen downstream of the obstruction,” Drachman said. “Another strategy is focused on retrograde or transpedal arterial access from the foot. Ordinarily, when you’re working from the groin downward, the point of occlusion of an artery may have a chronic, solidified or ambiguous plaque that is hard to address no matter how stiff or sharp a wire you use. But when you approach the same obstruction from the foot upward, the characteristics of these plaques are different. They may be softer or less ambiguous to cross with a wire from the retrograde approach. And, once crossed, the interventional wire may be snared and pulled out through an access site at the level of the groin, where the intervention may then be performed conventionally in antegrade fashion over that same wire. The transpedal access approach has helped improve the likelihood of success even with some of the most challenging lesions.”

One strategy that still needs refining is balloon sizing, Mustapha said.

“Unfortunately, operators who are performing CLI work continue to undersize the angioplasty balloons, affecting the acute luminal gain and increasing acute luminal loss,” he said. “If an operator is not confident about the size of the target tibial artery, IVUS should be used for confirmation.”

Goal to Save Limbs and Lives

Endovascular approaches for limb salvage have come a long way in recent years, sparing many patients with CLI, foot ulcers and other conditions from surgery and amputation.

Experts said, however, that it is important to remember that patients in need of limb salvage are very sick, often malnourished, and need to be treated for more than just their limb.

“A key point is to identify whether ischemia is playing a role in the development of an ulcer and whether revascularization could help that individual to heal the ulcer,” Drachman said. “Recognizing that patients with vascular disease anywhere in the body are prone to have vascular disease everywhere in the body, and need to be on optimal medical therapy to reduce risk for stroke and MI, is absolutely critical.”

What is needed, Parikh said, “is to study in a controlled way the management of wounds, assessing what are the endpoints we care about. For one practitioner, success is the artery staying open. For another, it’s that the patient is able to walk again. We should be holistic. We should save lives and limbs, not just do one in isolation.” — by Erik Swain

Sidebar: Management of CLI Requires Comprehensive Program, Multidisciplinary Team

Disclosures: Ansel reports receiving royalties on sheaths, support catheters and balloons from Cook Medical; serving on advisory panels for Abbott Vascular, Boston Scientific, C.R. Bard, Medtronic and W.L. Gore; and receiving research grants from Cardiovascular Systems Inc. Drachman reports serving on advisory panels for Abbott Vascular and Corindus Vascular Robotics; receiving research grant support from Atrium Medical and C.R. Bard/Lutonix; and consulting for St. Jude Medical. Mustapha reports consulting for Bard Peripheral Vascular and Medtronic. Parikh reports receiving research support and serving as a consultant/speaker for Abbott Vascular, Boston Scientific, C.R. Bard/Lutonix and Medtronic; he is also an investigator for the BEST-CLI trial.

In the past, patients in need of limb salvage due to critical limb ischemia or other forms of peripheral artery disease were likely to need surgical bypass if they had any hope of relief of symptoms or even avoiding amputation. Now, as a result of new technologies, better techniques and increased multidisciplinary collaboration, many of these patients are able to achieve reperfusion via a less invasive percutaneous endovascular approach.

“The endovascular approach has changed the way we treat these patients and now allows us to do revascularizations that were not at all possible just a few short years ago,” Jihad A. Mustapha, MD, FACC, FSCAI, director of cardiovascular catheterization laboratories at Metro Health Hospital, Wyoming, Michigan, told Cardiology Today’s Intervention. “The majority of patients with critical limb ischemia can benefit from an endovascular approach. However, there still remain a subset of patients that require a non-endovascular approach.”

However, not all critical limb ischemia (CLI) cases have the same characteristics and risk factors, so not all patients needing limb salvage can be treated with an endovascular approach, experts said. The ongoing BEST-CLI trial, which is comparing optimal endovascular therapy vs. optimal surgical therapy in patients with CLI eligible for either approach, is expected to better define which patients are best suited for an endovascular intervention and which are best suited for surgical bypass.

‘Marker of Bad Vascular Disease’

CLI affects approximately 1.4 million people in the United States, with about 320,000 new cases every year. About 25% of newly diagnosed patients require amputation within 1 year, with an average survival after diagnosis of approximately 2.5 years. Often, many patients die of causes related to MI or stroke, and the rate of CV death within the year after a CLI diagnosis is high.

Douglas E. Drachman
Douglas E. Drachman

“CLI is a marker of bad vascular disease throughout the body,” Douglas E. Drachman, MD, director of the cardiology and interventional cardiology fellowship programs at Massachusetts General Hospital, said in an interview with Cardiology Today’s Intervention. “In patients with extensive atherosclerosis in the legs, there is high likelihood of disease in other territories such as the heart and brain, with associated risk for MI, stroke and death. Identifying people with CLI and recognizing the risk conferred for systemic adverse events, provides an important opportunity to focus on risk factor modification to protect the heart, brain and limb alike.”

Common risk factors in patients with CLI are diabetes, smoking and advanced age, according to Gary M. Ansel, MD, FACC, system medical chief for vascular at OhioHealth in Columbus, Ohio.

Those who receive endovascular treatment for limb salvage do not differ much from those who receive surgical treatment for it, Ansel said.

In many cases, the distinction comes down to the preferred practice at local institutions.

“Although data demonstrate that endovascular techniques now make up the majority of procedures, there is wide variation in practice, with some hospitals doing little endovascular treatment and others doing little surgery,” said Ansel, a member of the Cardiology Today’s Intervention Editorial Board.

Choosing the Optimal Approach

Despite wide variations in practice, there are effective strategies to select which patients would benefit from an endovascular approach to limb salvage, experts said.

“An endovascular approach is particularly well-suited for patients with comorbidities that elevate the risk of open surgical bypass, those with lack of venous conduit and patients with diffuse tibial disease and lack a target for the graft,” Ansel said.

Conversely, he said, “patients who are nonambulatory or have such advanced tissue destruction that the lack of perfusion is only part of the issue may not be acceptable candidates for any vascular procedure.”

The decision must be made based on an individual patient’s characteristics because CLI is a complex disease that does not lend itself to one-size-fits-all solutions, Sahil A. Parikh, MD, FSCAI, FACC, assistant professor of medicine at Case Western Reserve School of Medicine, Cleveland, told Cardiology Today’s Intervention.

PAGE BREAK

“Truly, the best approach for any individual patient is tailored to that patient’s clinical comorbidities, functional goals and anatomy,” he said. “Where are their blockages and how bad are they? Do they have targets for bypass surgery? Are they candidates for surgery?”

However, endovascular advances aside, there are still some cases in which amputation is the only option.

Patients who are nonambulatory; those who have intense neurologic pain that reperfusion would not help; those who are sick and have been through multiple endovascular and surgical procedures; and those with significant osteomyelitis with unsalvageable tissue are a few examples of those for whom amputation may be the best option, Ansel said. He noted, however, that improved endovascular and surgical techniques are enabling reperfusion in patients with poor distal vessels, a condition previously considered unsalvageable.

More direction on this may be provided by the outcomes of the BEST-CLI trial. The trial is expected to enroll approximately 2,100 patients, with a completion date of December 2018.

In a paper on the BEST-CLI trial design published in Techniques in Vascular and Interventional Radiology,Alik Farber, MD, from the division of vascular and endovascular surgery at Boston Medical Center, and colleagues described that “BEST-CLI aims to provide urgently needed clinical guidance for CLI management by using (1) a pragmatic design comparing the effectiveness of established techniques while allowing for the introduction of newer therapies as they become available; (2) a novel primary endpoint that includes limb amputation rates, repeat intervention and mortality; (3) a multidisciplinary structure that fosters cooperation among interventional cardiologists, interventional radiologists, vascular surgeons and vascular medicine specialists; and (4) novel techniques to evaluate the cost-effectiveness and quality-of-life outcomes of the two treatment strategies being tested.”

Rapid Technological Advances

The standard endovascular approach for CLI uses catheters, guidewires and balloons to re-establish blood flow.

But within that paradigm, an operator has many options, and many of them borrow techniques from treatment of CAD because below-the-knee arteries are about the same size as coronary arteries.

Sahil A. Parikh
Sahil A. Parikh

“We have better devices that are designed for this specific space, but in limb salvage, most of the work is below-knee intervention in the tibial vessels, which are parenthetically the same size as coronary vessels. And so we use a lot of techniques borrowed from the coronaries,” Parikh said.

Depending on patient and lesion characteristics, below-the-knee limb salvage procedures may at times benefit from the use of the latest-generation drug-eluting stent technologies employed to treat CAD, Drachman said.

However, this may not always be the best choice, according to Mustapha.

“My biggest pet peeve is when tibial arteries are compared to coronary arteries,” he said. “I believe they are completely different. Tibial preclinical research is underdeveloped and should be a primary focus to advance the CLI field on solid ground.”

When a patient has a long obstruction below the knee, “often using balloon angioplasty alone can be effective, and may maintain patency long enough to restore tissue integrity at the site of an ulcer,” Drachman said.

Devices for dedicated pedal access, including one made by Cook Medical, and long balloons designed for tibial and pedal intervention are now available from many companies, according to Ansel.

For above-the-knee limb salvage procedures, innovation in stent design “has continued to make stents more supportive, more flexible and more resistant to fractures, which is necessary in light of the extrinsic forces that are such as flexion, muscle contraction and vessel torsion, which may wreak havoc on vascular scaffold integrity,” he said.

Gary M. Ansel
Gary M. Ansel

Drug-coated balloons are also becoming more widely used in these areas because they have been shown to greatly reduce restenosis risk, experts said. Two, the Lutonix 035 Drug-Coated Balloon PTA Catheter (Bard/Lutonix) and the IN.PACT Admiral Drug-Coated Balloon (Medtronic), have been approved by the FDA, and more may be in the near future.

“However, it must be noted that data on use of these devices for CLI is still lacking; most of the data for these devices has been for patients with claudication,” Ansel said.

PAGE BREAK

Atherectomy, a technology used to reduce or remove plaque that is heavily calcified, bulky or otherwise resistant to angioplasty and stenting, is also being used in some limb salvage procedures, Drachman said.

Ansel noted that Cardiovascular Systems Inc., a manufacturer of atherectomy devices, has established the Liberty 360° registry, intended for more than 1,200 patients, to compare outcomes of orbital atherectomy vs. other approaches for treating PAD.

Innovative Strategies

Perhaps even more important to the improvement in endovascular procedures for limb salvage is new techniques that operators are using to treat challenging lesions.

Totally occluded leg arteries, once thought to be impossible to treat with an endovascular approach, are now routinely treated that way.

“In my opinion, the best limb salvage technique is an antegrade/retrograde approach for complex chronic total occlusions, which are a typical obstacle for patients with CLI,” Mustapha said. “We all must master this technique to continue to be successful in advancing the CLI field.”

Jihad A. Mustapha
Jihad A. Mustapha

Traditionally, endovascular limb salvage procedures have been performed using femoral access, but in recent years, radial access, which is associated with fewer vascular complications, and pedal access, which may be the best approach for certain difficult lesions, have become more common.

“Now, there are balloons long enough to reach from the radial approach,” Parikh said. “Interestingly, we’re now attacking disease from below, accessing the pedal vessels in the ankles and working north instead of south. By implementing an approach that goes up and down, we are able to more commonly succeed in opening a [CTO]. But, there is a learning curve to employing these techniques, and we must respect the risk of complications as well.”

Strategies adopted in recent years have improved outcomes for patients with CTO in a peripheral artery, Drachman said.

Figures

Figures. A case study of a patient with critical limb ischemia and a BMI of 42 kg/m2. The case was completed via a single ultrasound-guided tibial access (top, left) while the patient remained on the table at a 45-degree angle. This tibial access and minimally invasive retrograde intervention (TAMI) procedure (bottom, left) was performed using low-profile devices (top, right). Hemostasis was obtained and the patient was ambulatory and discharged home 1 hour post-successful procedure (bottom, right).

Figures courtesy Jihad A. Mustapha, MD, FACC, FSCAI; reprinted with permission.

“One strategy involves the international passage of a wire in the subintimal plane — outside of the vessel lumen — to cross the total occlusion antegrade, with re-entry of the lumen downstream of the obstruction,” Drachman said. “Another strategy is focused on retrograde or transpedal arterial access from the foot. Ordinarily, when you’re working from the groin downward, the point of occlusion of an artery may have a chronic, solidified or ambiguous plaque that is hard to address no matter how stiff or sharp a wire you use. But when you approach the same obstruction from the foot upward, the characteristics of these plaques are different. They may be softer or less ambiguous to cross with a wire from the retrograde approach. And, once crossed, the interventional wire may be snared and pulled out through an access site at the level of the groin, where the intervention may then be performed conventionally in antegrade fashion over that same wire. The transpedal access approach has helped improve the likelihood of success even with some of the most challenging lesions.”

One strategy that still needs refining is balloon sizing, Mustapha said.

“Unfortunately, operators who are performing CLI work continue to undersize the angioplasty balloons, affecting the acute luminal gain and increasing acute luminal loss,” he said. “If an operator is not confident about the size of the target tibial artery, IVUS should be used for confirmation.”

Goal to Save Limbs and Lives

Endovascular approaches for limb salvage have come a long way in recent years, sparing many patients with CLI, foot ulcers and other conditions from surgery and amputation.

Experts said, however, that it is important to remember that patients in need of limb salvage are very sick, often malnourished, and need to be treated for more than just their limb.

“A key point is to identify whether ischemia is playing a role in the development of an ulcer and whether revascularization could help that individual to heal the ulcer,” Drachman said. “Recognizing that patients with vascular disease anywhere in the body are prone to have vascular disease everywhere in the body, and need to be on optimal medical therapy to reduce risk for stroke and MI, is absolutely critical.”

What is needed, Parikh said, “is to study in a controlled way the management of wounds, assessing what are the endpoints we care about. For one practitioner, success is the artery staying open. For another, it’s that the patient is able to walk again. We should be holistic. We should save lives and limbs, not just do one in isolation.” — by Erik Swain

Sidebar: Management of CLI Requires Comprehensive Program, Multidisciplinary Team

Disclosures: Ansel reports receiving royalties on sheaths, support catheters and balloons from Cook Medical; serving on advisory panels for Abbott Vascular, Boston Scientific, C.R. Bard, Medtronic and W.L. Gore; and receiving research grants from Cardiovascular Systems Inc. Drachman reports serving on advisory panels for Abbott Vascular and Corindus Vascular Robotics; receiving research grant support from Atrium Medical and C.R. Bard/Lutonix; and consulting for St. Jude Medical. Mustapha reports consulting for Bard Peripheral Vascular and Medtronic. Parikh reports receiving research support and serving as a consultant/speaker for Abbott Vascular, Boston Scientific, C.R. Bard/Lutonix and Medtronic; he is also an investigator for the BEST-CLI trial.