Introduction

Critical limb ischemia (CLI) represents the final stage in peripheral vascular disease (PVD). It is estimated that 1% of Americans above the age of 50 years will eventually face CLI.¹ The current ever-growing epidemic of obesity and diabetes (thanks to calorie-rich diets) and the aging population are expected to exponentially increase this prevalence to an estimated 2.8 million patients by the year 2020. The presentation of patients with CLI has traditionally, albeit mistakenly, been stratified by the Rutherford (RF) classification, which upon its inception excluded all patients with diabetes. Patients classified as RF IV-VI are considered to have CLI, and in recent years, their treatment has shifted towards a more aggressive approach, based on performance of early endovascular revascularization.^2-5 Overall, the treatment of CLI is complex and multifaceted, which mirrors its pathophysiologic nature. This article intends to outline a road map towards the establishment of an efficient and cutting-edge CLI program. The main goal of such a program is to prevent unnecessary amputations, while improving quality of life. At the authors' institution, this idea has been put into motion with the creation of the StAMP (Stop AMPutations) program. It is a hospital-based, physician-led, comprehensive program in which health care providers coordinate the patient's care amongst the multiple specialties involved, such as primary care physicians, infectious disease specialists, podiatric specialists, orthopedic specialists, vascular medicine specialists (interventional cardiologists, radiologists, and vascular surgeons), as well as wound care and orthotics specialists (Figure 1). The program focuses on the clinical outpatient evaluation and its integration with noninvasive and invasive testing, revascularization procedures, and appropriate follow up, including rehabilitation services.

Figure 1: Departments Involved in Building a CLI Team

Revascularization constitutes the main pillar in the treatment of patients with CLI. Historically, this used to be achieved by surgical means. However, the number of infrapopliteal bypasses currently performed is comparatively small and continues to decline. Recent studies on the performance of femorotibial bypasses in the Medicare CLI population have determined that this procedure is only performed between 700 and 800 times per year,⁶ reflecting the significant comorbidities and limitations that surround the performance of this type of surgery. This phenomenon coupled with CLI's mortality rate (40-50% at two years⁷), has lead to an ever-significant increase in the number of endovascular procedures that are being performed across multiple disciplines, including vascular surgery, interventional radiology, and interventional cardiology.

Currently, investigators involved in the Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia (BEST-CLI) trial are attempting to resolve the clinical conundrum of whether open surgical bypass or endovascular revascularization will lead to better outcomes in the treatment of CLI patients. Moreover, this dilemma will likely be funneled into an equally challenging determination: are all physicians and centers equally qualified to deliver state-of-the-art CLI therapy? The quality and adequacy of the treatment provided to CLI patients cannot be solely assessed based on an individual physician's technical skills and his/her ability to perform revascularization procedures. The nationwide establishment of comprehensive CLI programs (such as StAMP) is a necessity and should come to the forefront of the health care system in order to guarantee that these complex patients are treated and followed using uniform protocols guided by quality initiatives geared towards improving outcomes, instead of by isolated health care providers and anecdotal experiences.

CLI Programs: Practical Challenges

Endovascular procedures continue to become mainstream in the management of this complex entity, and technological advances and innovations continue to flood the market. A question rapidly arises when one thinks of the multiple layers and aspects that need be considered in order to provide the highest quality care for these patients: should every hospital have a CLI program?

To answer this question, one must consider some of the challenges:

• CLI patients tend to present with multiple and complex comorbidities, such as heart failure, cardiomyopathy, diabetes, and renal failure.
• CLI patients typically have multilevel and multivessel disease, which requires the performance of multiple procedures in both lower extremities to establish direct in-line blood flow to the feet in patients with ulcers.⁷
• Revascularization procedures to treat complex, severely calcified, and long chronic total occlusions (CTOs) tend to be time-consuming and require experienced operators to lead a highly qualified team. Operators and the team must be proficient and master a highly refined set of skills (retrograde tibial pedal access, ultrasound-guided access and interventions, antegrade CFA access, use of the different available devices to cross and treat these long occlusions, etc.) in order to achieve successful clinical outcomes.
• The creation of a CLI program requires the identification of all the team members (who share the same passion) across the different specialties that need to be involved.
• The interventional team must be conformed by highly motivated nurses, catheter lab techs, physician assistants, nurse assistants, and ultrasound technicians, who will develop the expertise after a long training process. Needless to say, these individuals are rare and, therefore, difficult to recruit.

CLI Centers: Leadership and Champions

To create a successful CLI program, the first step is to identify the physician leader or champion who will be at the heart of this initiative and performing these procedures. Clinicians who work within large institutions will have the added responsibility to help their administration and colleagues understand the impact of the disease in their community in order for them to be willing to provide the resources needed to build such a program. It is important for all the stakeholders to understand that the appropriate management of CLI represents an unmet need in the community in which up to 50% of patients continue to undergo amputations without a previous and proper vascular evaluation.⁶ Figure 2 shows the main blocks recommended as the first step in initiating a CLI program. The CLI physician champion must be almost exclusively dedicated to treating these patients. This individual must be able to plan the multiple procedures that these patients will require and what should occur with them in between procedures, as well as coordinate the patient's follow up with the different members of the team and manage the input of data generated by each team member to elaborate new recommendations. To be able to efficiently perform all of these tasks, this physician must develop the needed expertise, which is unlikely to occur while performing only one to two procedures per month. The future CLI therapist must constantly be driven to learn new technologies and techniques, stay abreast of the wealth of data that continues to emerge, and continue to improve the talents that he or she has already acquired.

Figure 2: The Main Blocks Required to Start a CLI Program

Attending and networking at advanced courses should be part of the job description because attendance will foster operators to continue to learn about the constant development of new devices, techniques, and approaches. Finally, a metric of success of such a program should rely on the establishment of an institution-based program in which this physician leader trains other physicians to master the previously mentioned skills in order for the program to operate independently.

Protocols

The standard of care for CLI patients should mandate an immediate referral to a CLI program with an evaluation by a vascular specialist within 24-48 hours from the first contact with the system upon detection of a new wound. The authors' institution has developed protocols and algorithms that govern timing of clinical evaluation (depending on the severity and acuity of presentation), noninvasive and invasive imaging, as well as planning of the revascularization strategy. One of the most important aspects of the care of CLI patients is the creation and institution of follow-up protocols that control how often these patients need to be seen and objectively re-evaluated with noninvasive testing. A high index of suspicion with immediate referral for selective repeat angiography and/or intervention should be the center of this follow-up strategy and represents an essential part of the StAMP program.

Figure 3 shows our follow up protocol for a CLI patient. This standardized algorithm is followed by all the members of the team, which guarantees that all patients will be approached in the same fashion, regardless of the health care provider that evaluates them at each particular visit. It is essential to have trained office staff members who organize these appointments and help guide patients through the complex process.

Figure 3: Peripheral Vascular Follow-up Protocol for CLI Patients

Currently Proposed Criteria to Establish a CLI Program

In an effort to guarantee quality and improved outcomes, standards should be set; therefore, the following criteria are felt to be the minimum necessary to start a successful CLI program:

• Institutional volume of 400 peripheral vascular procedures per year, with a minimum of 100 CLI procedures.
• Operator volume of at least 75 CLI cases per year.
• Establishment of a CLI revascularization team, which should include at least two operators to provide 24-hour coverage around the year. The team must include endovascular and surgical vascular specialists, as well as highly-trained personnel in the catheterization lab with nurses, catheterization lab and ultrasound technicians, and physician assistants.
• Establishment of an outpatient CLI team, conformed by nurses, nurse assistants, schedulers, and physician assistants who monitor patient flow and progress in the outpatient setting. This unique group of individuals needs to be trained in CLI-related protocols in order to understand the urgency and need to prioritize CLI patients. Also, their training in the evaluation of wounds and performance of basic bedside testing, such as the ankle-brachial index, is of paramount importance.
• A peripheral vascular program coordinator is essential in order to oversee the workflows related to CLI care, which can only be accomplished if all the departments involved are able to work in a symbiotic environment. This person will also be responsible for establishing and updating protocols designed to improve efficiency by early detection and correction of problem areas. This individual will also be responsible for instituting screening and educational programs for the community and the physicians in and out of the center's network, in an effort to permanently increase awareness and promote amputation prevention.
• A scientific review committee should exist in order to review CLI cases, which could be done under the format of a vascular conference during which the clinical, noninvasive imaging, and invasive imaging data are discussed among the team members in order to elaborate a therapeutic plan. Decisions about endovascular versus open versus hybrid approaches occur in this setting. This forum is also intended to review short-term outcomes (to correct any detected deficiencies in the system), and to incorporate emerging technologies in an educational environment designed to foster a continuous learning model.
• A quality committee should track mid-to-long-term outcomes, as well as adverse events with the purpose of creating mechanisms designed to introduce the necessary corrections in a timely fashion. Examples of the quality metrics being measured include rates of blood transfusion and incidence of contrast-induced nephropathy.
• Establishment of a proctorship program through which experienced physicians can train newer generations of CLI therapists.

The rationale to establish criteria based on number of cases performed is founded on the need to identify adequate practice patterns, maximize physician skills, decrease complications, and improve outcomes. While the number of procedures performed does not necessarily translate into successful outcomes, there have been a number of studies suggesting a relationship between improved outcomes and increased physician case volume (for patients undergoing coronary angioplasty).^8,9 The rate of CTOs in patients with CLI is unknown. Based on the authors' experience, patients with CLI tend to have multilevel and multivessel CTOs with complex anatomy and heavily calcified vessels, which explains the level of experience required to successfully treat these patients. As a CLI operator, physicians have to dedicate a significant portion of their time in treating these patients. Perseverance is a key component for success in these complex cases. However, knowing when to stop can be as or more important. Unfortunately, knowledge and experience cannot be gained without actually performing these challenging cases. It is the authors' opinion that current trials evaluating treatment modalities for CLI patients should consider adhering to the aforementioned proposed criteria. History shows that previous trials that ignored physician experience had inferior outcomes to those for which operator experience was a requisite.¹⁰ This will likely increase the reliability of the results and reflect the influence of the available expertise in providing these patients with the best possible care.

The establishment of "hard stop" rules while performing procedures is another way to enhance safety. For example, 60 minutes of fluoroscopy time is agreed upon among the authors' operators as the time to stop. Cases extending beyond a total of four hours make it difficult to maintain focus and lead to staff, operator, and patient fatigue. In an effort to reduce radiation and contrast usage, the authors instituted a policy that incorporated the use of extravascular ultrasound (EVUS) to guide arterial access in different vascular beds (including tibials) and to guide the crossing of long CTOs. In addition to the use of ultrasound, the authors have also incorporated new techniques such as the tibiopedal arterial minimally invasive retrograde revascularization (TAMI) technique, which basically refers to endovascular revascularization via pedal access.¹¹ Figure 4 shows the authors' unpublished experience before and after incorporating EVUS and the TAMI technique. Reporting these findings will be important to expand scientific knowledge about CLI. The Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME) Registry is an ongoing prospective registry documenting endovascular revascularization approaches and procedural and long-term outcomes for patients with advanced PVD or CLI. PRIME aims at involving centers with dedicated CLI programs to provide the scientific community with a uniform understanding of the efficacy of the multiple available treatment modalities in experienced hands at experienced centers. As such, the authors monitor all of our outcomes (including amputation rates) on a yearly basis (Figure 5).

Figure 4: Average Fluoroscopy Time After Incorporating EVUS and the TAMI Technique in Endovascular Procedures

Figure 5: Amputation Rates in a CLI Program

Conclusion

CLI is a complex disease that is unfortunately expected to rise. Building a CLI center with experienced operators requires the creation of a significant infrastructure that goes beyond the physicians themselves. This includes administrative support in addition to training staff members that will care for this population. There are still a significant number of unanswered questions for the CLI population. The combination of data in studies, such as PRIME and BEST-CLI, from high-volume centers of excellence combine will impact patient care in the right direction. Hopefully, future trials evaluating CLI therapies will not overlook the importance of physicians' experience, centers' volumes, and quality metrics before passing judgment about the best modality to treat these complex patients.

References

1. Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996;94:3026-49.
2. Al-Omran M, Tu JV, Johnston KW, Mamdani MM, Kucey DS. Use of interventional procedures for peripheral arterial occlusive disease in Ontario between 1991 and 1998: a population-based study. J Vasc Surg 2003;38:289-95.
3. Anderson PL, Gelijns A, Moskowitz A, et al. Understanding trends in inpatient surgical volume: vascular interventions, 1980-2000. J Vasc Surg 2004;39:1200-8.
4. Egorova NN, Guillerme S, Gelijns A, et al. An analysis of the outcomes of a decade of experience with lower extremity revascularization including limb salvage, lengths of stay, and safety. J Vasc Surg 2010;51:878-85, 885 e1.
5. Goodney PP, Beck AW, Nagle J, Welch HG, Zwolak RM. National trends in lower extremity bypass surgery, endovascular interventions, and major amputations. J Vasc Surg 2009;50:54-60.
6. Goodney PP, Travis LL, Nallamothu BK, Holman K, Suckow B, Henke PK, et al. Variation in the use of lower extremity vascular procedures for critical limb ischemia. Circ Cardiovasc Qual Outcomes 2012;5:94-102.
7. Shiraki T, Iida O, Takahara M, et al. Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia. J Vasc Surg 2014;60:383-9.
8. Strom JB, Wimmer NJ, Wasfy JH, Kennedy K, Yeh RW. Association between operator procedure volume and patient outcomes in percutaneous coronary intervention: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2014;7:560-6.
9. Moscucci M, Share D, Smith D, et al. Relationship between operator volume and adverse outcome in contemporary percutaneous coronary intervention practice: an analysis of a quality-controlled multicenter percutaneous coronary intervention clinical database. J Am Coll Cardiol 2005;46:625-32.
10. Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23.
11. Mustapha JA, Saab F, McGoff T, et al. Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: The TAMI technique, original case series. Catheter Cardiovasc Interv 2014;83:987-94.
12. Conte MS. Understanding objective performance goals for critical limb ischemia trials. Semin Vasc Surg 2010;23:129-37.

Keywords: Advisory Committees, Algorithms, Amputation, Angiography, Angioplasty, Ankle Brachial Index, Blood Transfusion, Cardiomyopathies, Catheterization, Comorbidity, Diabetes Mellitus, Diet, Endovascular Procedures, Fluoroscopy, Heart Failure, Lower Extremity, Medicare, Obesity, Outpatients, Peripheral Vascular Diseases, Physicians, Primary Care, Prevalence, Prospective Studies, Quality of Life, Radiology, Interventional, Referral and Consultation, Registries, Renal Insufficiency, Reproducibility of Results, Specialization, Surgeons, Ulcer, Vascular Surgical Procedures

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