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Mississippi Delta Miracle: Angiographic Screening Yields Dramatic Reduction in Amputations

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Peripheral artery disease (PAD) is a circulatory deficiency prevalent among the aging global population, with an estimated 202 million cases worldwide and 18 million in the United States in 2010.1,2 To identify patients with PAD, early screening is absolutely crucial, allowing timely and appropriate treatment to commence. Delays in treatment, as well as insufficient therapeutic methods, lead to a greater risk of amputation and significantly higher economic costs. As of 2015, the annual economic burden of PAD in the U.S. exceeded diabetes, coronary artery disease, and cancer.3 Contrary to recent U.S. Preventative Services Task Force (USPSTF) recommendations4 declaring insufficient evidence for the benefit of ankle-brachial index (ABI) screening, research worldwide over two decades has shown that PAD is a commonly neglected condition, is effectively detected by ABI, and is strongly correlated with and an independent predictor of mortality in coronary artery disease (CAD) patients.5–9

Among patients with PAD in their lower limbs, 1-3% will likely develop critical limb ischemia (CLI), the most advanced and deadly form of the disease.2 The burden of PAD is growing with increased life expectancy: 21 million Americans are predicted to have the disease by 2020, and in Europe, Germany reports not only an increase in the number of PAD-related hospitalizations, but also in the proportion of PAD cases becoming CLI.2,6,10 This rising trend of PAD progression to CLI reflects a long-recognized failure of the medical community to utilize aggressive risk factor modification as therapy. In 2001, the PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) study revealed that, despite the prevalence of PAD among primary care patients, it was routinely underdiagnosed by U.S. providers and undertreated relative to the proactive measures taken for other cardiovascular diseases.9,11 These PAD patients were less intensively treated for lipid disorders and hypertension, even though atherosclerosis risk factors were prevalent.9 Similarly, in Germany, PAD was shown to be widespread among elderly diabetics in primary care, but those patients were less likely to be treated with antiplatelet therapy than were CAD and cardiovascular disease patients.8

These phenomena of failure to screen at-risk populations and suboptimal medical management of patients allow PAD to progress to CLI. Defined clinically as continuous rest pain for at least two weeks12, CLI patients who do not undergo revascularization risk the progression of gangrene13 and the development of sepsis, which often leads to mobility loss, amputation, or even fatal cardiovascular complications.14,15 Without effective revascularization, over one-fifth of patients with CLI will have a major amputation within one year.16 Among CLI patients who had no other intervention, primary amputation was performed as the index procedure in 19-67% of cases, despite the fact that most of these patients had undergone no diagnostic angiogram.17,18 Within one year, 22% of untreated CLI patients will die.19

Amputation Trends and Guidelines

At the turn of the millennium, best practices suggested that 15-16% of CLI patients should undergo amputation as their primary treatment procedure.20,21 Now, according to the 2016 AHA/ACC Guideline on the Management of Patients with PAD22, amputation is no longer acceptable as a first-line PAD therapy, even in patients with below-the-knee (BTK) disease. Instead, endovascular revascularization is recommended in CLI patients with comorbidities such as congestive heart failure, cardiomyopathy, severe lung disease, and chronic kidney disease. In all CLI cases, the AHA/ACC insists an evaluation for revascularization options should be performed by an interdisciplinary care team before amputation is considered.23 In spite of these modern guidelines, it is estimated that in the past decade, 160,000-180,000 amputations were performed annually in the U.S.15 The most current data available from the U.S. government reveal that lower extremity amputation procedure volume increased 5.0% from 2013 to 2014 and 8.8% from 2014 to 2015.24 In terms of major amputations, recent U.S. studies indicate 25-33% of CLI patients undergo major amputation as a primary procedure, leading to 65,000-75,000 such amputations per year.20

The lack of adherence to guidelines persists beyond the U.S. In South Africa and Algeria, 6-7% of the entire population require an amputation.15 In Europe, it is estimated that 40,000-50,000 major and minor amputations occur yearly. A current review of nationwide studies in Germany revealed that more than 50,000 ischemic limb amputations are performed each year, with the rate of minor amputations on the rise.25 This review showed that at 4-year follow-up, the risk of limb amputation was 35.5% in Rutherford 5 patients and 67.3% in Rutherford 6 patients.25 Also in Germany, a recent retrospective study analyzed data from the nation’s largest public health insurer.10 The authors found that the in-hospital performance of revascularization and angiography decreased as PAD progressed, concomitant with an increase in amputations and death. They concluded that, “[d]espite overwhelming evidence for reduction of limb loss by revascularization, CLI patients still received significantly less angiographies and revascularizations.”10 They further noted the alarming fact that 37% of the amputated CLI patients had received no angiography or revascularization during their index hospital stay or in the 2 years prior.10

Similarly, in the U.S., Medicare databases disclose that over 50% of patients who underwent major lower extremity amputation had no prior arterial evaluation and no vascular procedure performed in the year prior to amputation, with only 35% having their ABI measured and 16% undergoing angiography.13,15 These deficient practices persist despite the fact that many established predictors for major amputation risk, such as tibial artery calcification (TAC) score, require arterial evaluation to assess.26 The percentage of CLI patients who undergo amputation with no prior revascularization attempt is even higher: 60-71% in the U.S. and close to 50% in Germany.20

The Amputation Approach

Why is amputation performed so frequently in lieu of peripheral vascular intervention (PVI)? There appear to be several underlying reasons, chief among them a lack of awareness on the part of physicians regarding predictive factors and alternatives. One common misconception regards the utility and appropriateness of PVI for advanced-stage CLI disease. Particularly in Rutherford Classes 5 and 6 patients, it is largely believed that amputation as a first-line therapy is the only effective treatment option. However, the results of the LIBERTY 360 trial demonstrated, as far out as 18 months post-PVI, a freedom from amputation rate of nearly 82% for Rutherford 6 patients.27 Extensive, multi-level disease is also frequently considered resistant to any treatment option short of amputation. In a 2018 review of lower extremity PAD interventions published in Nature, however, Hiramoto et al concluded that, “in the hands of skilled operators, even the most extensive aortoiliac lesions can be successfully treated by an endovascular approach.”16

Other obstacles to PVI therapy are based upon sociodemographic factors. Patients who are African-American or Native American have a much higher chance of undergoing major amputation than a lower extremity revascularization procedure.28 In fact, percutaneous angioplasty was not performed at a Native American hospital until 2014, nearly 37 years after the first such procedure was offered worldwide.29 For Native Americans, the likelihood of having a leg amputated (18.5%) or any lower limb amputated (14.9%) is significantly higher than that of non-Hispanic whites.30 In the Southwest, Native Americans are three times more likely to undergo a major amputation than are non-natives.29 When considering the significant patient subset of diabetic veterans, the amputation risk for Native Americans is relatively substantial: 74% higher than that of non-Hispanic whites, which exceeds the risk for both African-Americans and Hispanics.30

The racial disparities are even more pronounced when one takes into account regional effects. For census purposes, the U.S. is divided into four regions: Northeast, Midwest, South, and West. Native Americans are much more likely to be treated at West, South, rural, small, and non-teaching hospitals.30 The West region contains a preponderance of Indian Health Service (IHS) facilities, and the predicted rate of amputation for Native Americans, specifically in this region, is more than twice as high as for non-Hispanic whites.30 Peculiar to this region is an inability to attribute causes that contribute to these racial disparities. Only around half of the variation can be explained by observed factors like patient demographics and comorbidities. One theory attempting to address this discrepancy purports that the concentration of IHS facilities in the West drives the tendency to amputate, implying that a treatment algorithm of amputation-first is in effect. Another theory suggests that statistical discrimination is at play, the idea that “physicians decide upon a course of treatment based on their perception of an individual patient’s likely candidacy for that treatment and the past course of treatment for patients sharing similar characteristics (such as race).”30 Why this bias would only exist in the West region, however, is not immediately apparent.

If statistical discrimination is to blame for racial disparities, its effects are not limited to the treatment of Native American populations. While PVI options are routinely offered to white patients in the U.S., the same cannot be said for African-American patients. In part, this is due to the fact that a significant discrepancy exists between these patient groups when it comes to the prevalence and severity of PAD.31,32 As African-Americans tend to present with greater comorbidities, such as chronic renal disease, obesity, and diabetes, they typically face an increased risk of amputation, repeat intervention, and mortality.31–33 However, it has also been shown that African-American patients are less likely to be evaluated with an angiogram than are white patients.28 It is commonly believed that African-Americans are not as likely to benefit, in terms of quality of life, from PVI as are their white counterparts.31 This was shown to be false in a study published in 2017, investigating quality of health (QOH) in PVI patients. Although the African-American study cohort had more comorbid conditions at baseline than the white subject cohort, significant and similar improvements were seen in both racial groups in all QOH measures, from physical limitations to symptoms to quality of life.31 The study authors concluded that physicians should not be dissuaded from treating African-American patients with PVI when appropriate.

A New Approach

Today, the goal of many in the medical community is to avoid amputation as a first-line treatment for CLI patients.13,17 To facilitate this goal, it is necessary to elucidate the predictors of amputation risk in order to design an effective, alternative treatment algorithm. A holistic approach to identifying such risk factors, both physiological and socioeconomic, affords the greatest opportunity for the medical community to recognize and intervene for these patients.

In 2011, Henry et al reported a diversity of factors informing the possibility a patient would undergo a major amputation index procedure. Unsurprisingly, lower income bracket, increasing age, emergent as opposed to elective hospital admittance, and public (Medicaid) insurance all predicted elevated risk of major amputation, as did PAD comorbidities such as complicated diabetes mellitus, renal failure, and congestive heart failure.28 Based on the results of their multivariate analysis, these researchers came to the striking conclusion that “[p]atients evaluated with an angiogram were at 90% lower odds of having an amputation.”28 Their investigation further revealed that women are more likely to undergo a diagnostic angiogram and less likely to have a major amputation than are men.

In recent years, percutaneous transluminal angioplasty (PTA) has been established as the primary therapeutic intervention for CLI patients with infrapopliteal disease.34 While PTA enjoys high procedural success rates in focal lesions, the first line of therapy for the elderly, diabetic, end-stage renal disease (ESRD) patient population still tends to be amputation.17 A recently published, systematic review of the literature revealed that age and diabetes are predictive factors for amputation-free survival or limb salvage in CLI patients who undergo PTA.35

In November 2018, a new set of Global Vascular Guidelines was jointly released by the Society for Vascular Surgery, European Society for Vascular Surgery, and World Federation of Vascular Societies.36 Currently in draft form, these guidelines seek to address the management of CLTI (chronic limb-threatening ischemia) by focusing primarily on physiological markers. In agreement with our work here, the joint societies emphasize the importance of vascular imaging in all patients with suspected CLTI. The guidelines incorporate both the established wound, ischemia, and foot infection (WiFi) staging (limb threat assessment) system37 and a newly proposed GLASS (GLobal Anatomic Staging System) methodology for anatomic assessment. Together, the goal is to provide physicians with a set of standards to assess the appropriateness of endovascular intervention and likelihood of limb salvage.

Keep in mind, however, that just because a patient is considered unsuitable for revascularization does not mean her or his only option is amputation. As shown by Martini et al, even highly comorbid, elderly patients with poor run-off vessels may have a salvageable limb when the patient is treated by a dedicated team with a robust treatment plan.12

Our Story

With all of this in mind, how does one apply an understanding of socioeconomic and physio/medical factors to best treat CLI patients? While many medical practitioners and working groups purport that CLI management requires both high-level institutional support and the efforts of a large, multidisciplinary team of experts, the success story reported herein will show otherwise.14

Cardiovascular Solutions of Central Mississippi (CVSCM) is located in the Mississippi Delta. In 2017, according to conservative estimates, PAD in Mississippi was present in 168,000 people and CLI was present in almost 19,000 people.38,39 While known for its poverty, the Mississippi Delta is also a region of the U.S. defined by Medicare as having one of the lowest revascularization rates for PAD in the year prior to amputation.13 By dividing the nation into hospital referral regions (HRRs), Medicare data reveals which areas have the most intensive vs the least aggressive vascular care. The proportion of patients undergoing a diagnostic endovascular procedure in the year prior to amputation ranges from 30% in the “very low intensity” HRRs to 54% in the “very high intensity” HRRs.13 The Mississippi Delta is among the HRRs in which patients were least likely to undergo a vascular procedure, including diagnostic-only angiography, in the year prior to amputation.13

The data from Bolivar Medical Center (BMC) in Cleveland, Mississippi reflect these regional trends. Prior to the affiliation of a peripheral interventional cardiologist within BMC, the institution performed zero peripheral angiograms and 56 major amputations (Figure 1). In just a few short years, CVSCM facilitated an 87.5% decrease in the institution’s amputation rate. How was this accomplished without hospital support or a large, multidisciplinary medical team?

The CVSCM algorithm involves a holistic approach and comprehensive assessment from the beginning:

  1. A patient’s first point of contact in medicine determines whether she or he lives or dies. It also determines whether or not a patient loses his or her limbs. At CVSCM, every patient has socks off during every visit, regardless of the presenting chief complaint. The strength of pulses is inspected and ulcers/wounds, hair loss, poor nail growth, and temperature of feet bilaterally are inspected. Most patients turn out to be atypical presenters, but not asymptomatic.
  2. Elicit symptoms by asking the patient to describe any abnormal sensation or events (e.g., legs give out, or legs/feet burn, or fatigue) using words at an appropriate literacy/scientific level.
  3. By doing the above, and addressing risk factors, a physician may prevent the patient/disease severity from progressing from early to late stages of the disease spectrum. This has both a clinical (reduction in cardiovascular morbidity/mortality) and significant economic impact by reducing cost to the patient, hospital, and community.
  4. Once a patient is diagnosed with PAD, perform screening for CAD and other polyvascular diseases. As a consequence of doing this at CVSCM, there has been a significant reduction in the number of patients presenting to emergency rooms with acute coronary syndromes.
  5. Recognize and aggressively target modifiable risk factors. Does the patient smoke or otherwise have nicotine exposure?40 Be aware of and sensitive to the community. Especially in economically depressed regions such as the Mississippi Delta, the majority of patients chew, dip, vape, or snuff nicotine products.
  6. Order ultrasounds on all abnormal findings. All studies are read at CVSCM unless the ultrasound is performed at a hospital, in which case it is read by a radiologist. Most patients with infrapopliteal disease will typically have ABI diagnostic readings misinterpreted.41 The limitations include falsely elevated or normal readings in patients who have calcified disease, for example, diabetics (who tend to have infrapopliteal lesions)42,43, the elderly, and those with renal disease. Therefore, other supplementary modalities, like duplex ultrasound, are more reliable in the aforementioned population.
  7. Immediately implement guideline-recommended therapy once a diagnosis is made. As evidenced by the PAD literature, medical and other recommended therapies are significantly underutilized worldwide.10,42
  8. Advocate for patients with CLI to seek a second opinion and delay recommendation for amputation after successful endovascular revascularization. It is not uncommon for some surgeons to recommend amputation days or a week after successful PVI — such practices must be discouraged. There should be sufficient time for healing while the patient undergoes aggressive wound care treatment with appropriate antibiotics based on culture and sensitivities.
  9. Participate in community educational outreach to raise awareness of risk factors that contribute to PAD disparities. This is done at CVSCM primarily through churches (faith-based), where it is reiterated that the burdens are amenable to medical treatment within the context of supportive behavioral and lifestyle changes. The faith-based platform is a unique venue to effectively communicate with all the community stakeholders in hopes of reducing disease burden, improving access to quality care, and dealing with some of the challenges for improving regional care.

What cannot be captured in any algorithm is the importance of establishing trust between the provider and the patient population. Respectfully cognizant of our African American-predominant market, we have successfully communicated through the faith-based approach that CVSCM is the antithesis of statistical discrimination. We have found that patients are able to discern this unspoken value and understand that their candidacy for a treatment plan or procedure will not be biased by preconceived notions. Whether these preconceptions are provider opinions that are based on shared characteristics (race) or on a patient’s prior course of treatment, they must be eliminated from the care algorithm. Regardless of race, our experience has shown the importance of providing cardiovascular disease information at the appropriate literacy and scientific level. In addition, we stress the significance of medication adherence as well as explain the angiogram procedure, emphasizing that it is performed on an outpatient basis.


In 2018, very few valid reasons exist to pursue an amputation-first approach in the treatment of CLI. The often-shared excuses of practicing in an economically disadvantaged area with limited physician referrals, lack of institutional support, challenging patient populations, and the absence of multidisciplinary team involvement have all been met with great success at CVSCM. In reality, the lack of reimbursement for PAD screening and suboptimal medical management of an at-risk, diverse population (older age, nicotine exposure, diabetes, obesity, racial/ethnic minority) are the true barriers to effective treatment of PAD. This failure to treat risk factors and inadequate implementation of current practice guidelines allow the progression of the disease to CLI, which ultimately leads to major adverse cardiac and lower extremity events. This both increases economic costs to the healthcare system and greatly increases the risk of harm to the patient by amputation and/or death.

Our approach of aggressive screening and compassionate care has resulted in a tremendous decline in amputations performed, and a concomitant increase in quality of life for our patients. Consider that within 1 year of undergoing a lower-extremity amputation, 9.1% of amputees have died, and within 5 years, that rate jumps to 25.6%.45 Beyond the obvious benefits to our local population, the screening, diagnosis, and treatment of PAD in its early stages reduces the macroeconomic cost of CLI by shifting treatment from a more expensive inpatient setting to a less expensive outpatient setting — saving Medicare/Medicaid dollars. Many others have also demonstrated that treatment at less severe disease stages is less costly.10,21

In addition to the advantages of treating less advanced PAD in general, the economic cost to society is substantially impacted by reducing amputations in particular.45 The median yearly healthcare cost for one CLI patient to undergo a major amputation exceeds $39,50046, while cumulatively, the national hospital costs are greater than $9 billion47. At a single University of California – Los Angeles (UCLA) Medical Center, amputation-related hospital costs over 7 years surpassed $47 million.45 The consequence to local communities is even more significant. While many assume an inordinate disposable income exists among the California population, this state actually ranks highest in the country for its poverty rate when considering supplemental factors, such as medical costs.48 On the other hand, the state of Mississippi has the highest poverty rate in the country based on standard census considerations49, and it further holds the number-one rank as the state with the lowest number of physicians50,51. Reducing amputations is therefore impactful both in economically depressed regions like the Mississippi Delta and in economically prosperous regions like central California, where cost-of-living expenses essentially push the state into poverty.

How have we accomplished these transformations at CVSM? We have found that trust facilitates care-seeking behavior, and promotes honesty and adherence among the patient population. Traditionally, minority community members do not take advantage of accessible healthcare education due to a lack of trust and the Mississippi Delta is no exception. Our faith-based coalition and collaborations, not advertising dollars, have re-established that trust. We have educated and informed our patients, so they can be transformed into community navigators fighting for a healthy oasis with a preventative mindset. Our approach speaks to the total mind, body, and spirit.

Engendering hope and loyalty is determined by the interpersonal and technical competence of local physicians, with a sprinkle of humility; this is where we think our team of nurses and the peripheral interventionalist at CVSCM have made the largest impact in the Delta. In addition to affording access to quality and consistent, comprehensive cardiovascular care, we treat our patients as family members. Since accessibility to affordable healthcare limits the type of quality treatment that is rendered, we have taken this out of the equation at CVSCM, despite the fact that we are located in a poverty-stricken, underserved region. Not only do we treat the minority population with compassion and competence, we ensure that they receive quality care, including diagnostic angiograms, PVI, and other medical interventions.

Our experience is encouraging in light of national data, which reveals many of the negative factors that predispose an amputation decision can be mitigated by our approach. Henry et al showed in their 2011 report, for example, that once the protective effect of undergoing a diagnostic angiogram is incorporated into the analysis, “hospital LER [lower extremity revascularization] procedure volume” no longer predicts a patient’s odds of major amputation.28 Thus, even in economically depressed regions, inclusion of angiography in the CLI treatment algorithm can potentially overcome facility deficiencies. Our group successfully reduced the amputation rate, not only without hospital support, but also in a challenging patient population.

The likelihood of amputation for African-Americans is approximately twice as high as for Caucasians, a fact that the medical community largely attributes to patients being admitted when they are sicker and in emergency circumstances.32 However, the literature suggests that the odds of undergoing a major amputation are not fully accounted for by these medically-founded factors. Approximately 30-50% of racial and ethnic disparities in amputation rates remain unexplained by observed causes such as health care access.32 In fact, the Henry et al 2011 subanalysis of patients with diagnostic angiograms revealed that race, income, and insurance status persisted as factors driving major amputation.28 This again points to the phenomenon of statistical bias.30 In spite of these substantial barriers, we have defined an effective treatment algorithm at CVSCM to avoid amputation in high-risk CLI patients, which can plausibly be replicated in any region of the U.S. and beyond. 

1Cardiovascular Solutions of Central Mississippi, Bolivar Medical Center, Cleveland, Mississippi; 2Scientific Affairs Associate, Cardiovascular Systems, Inc., St. Paul, Minnesota; 3President, The SAGE Group, Beaufort, South Carolina; 4Director of Scientific Affairs, Cardiovascular Systems, Inc., St. Paul, Minnesota

The authors can be contacted via Dr. Foluso A. Fakorede at

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