(1)
Interventional Cardiology, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA, USA
Electronic supplementary material:
The online version of this chapter (doi:10.1007/978-3-319-31991-9_38) contains supplementary material, which is available to authorized users. Videos can also be accessed at http://link.springer.com/chapter/10.1007/978-3-319-31991-9_38.
Keywords
EndovascularThrombolyticTreatmentAcuteLimbIschemiaIntroduction
Definition
This chapter focuses on the endovascular treatment options for acute limb ischemia (ALI) of the upper and lower extremities, namely, endovascular and thrombolytic therapies. ALI is associated with a high risk of loss of limb and life and thus requires prompt diagnosis, which can be challenging [1]. ALI is defined as a vascular emergency characterized by an abrupt loss of limb perfusion that threatens tissue viability presenting within 14 days of symptom onset [2].
Prevalence
More than 200,000 patients suffered from lower extremity ALI in the USA in 2000. Estimated hospital mortality was 10 % and >1 in eight underwent in-hospital amputation [2]. Using Medicare claim data from 1998 to 2009, Baril et al. showed that there has been a decrease in the incidence of hospitalization for lower extremity ALI from 45.7 to 26 per 100,000. The percentage of patients undergoing surgical intervention decreased from 57.1 to 51.5 %, and those undergoing endovascular intervention increased from 15 to 33.1 % [3]. ALI of the upper extremities is rare and has been reported as 1:4–5 ratio of upper to lower extremity ALI [4].
Clinical Classification of ALI
There are four clinical categories of ALI. Table 38.1 reveals the differences between various clinical limb scenarios and their prognoses, which serves as a helpful guide to type of intervention [5]. Rutherford proposed an algorithm for ALI; after history and physical and Doppler exam confirm an ALI diagnosis and heparin is initiated, patients in categories I (if early intervention is appropriate) and IIA should undergo diagnostic angiography. These patients may undergo catheter-directed thrombolysis (CDT) with or without mechanical thrombectomy or surgical thrombo-embolectomy. For category IIB and III (if early) patients, one must consider emergent surgery and late category III, delayed amputation [5].
Table 38.1
Clinical categories of acute limb ischemia
Category | Prognosis | Sensory loss | Motor deficit | Arterial Doppler | Venous Doppler |
|---|---|---|---|---|---|
I: Viable | No immediate threat | None | None | Audible | Audible |
IIA: Marginally threatened | Salvageable if promptly treated | Minimal (toes) or none | None | Inaudible | Audible |
IIB: Immediately threatened | Salvageable if immediately revascularized | More than toes, rest pain | Mild/moderate | Inaudible | Audible |
III: Irreversible | Major tissue loss, permanent nerve damage inevitable | Profound, anesthetic | Profound, paralysis (rigor) | Inaudible | Inaudible |
Clinical Presentation
A meticulous history should be taken to identify the onset of symptoms (14 days or more), which may dictate indication for intervention and screening for possible embolic source. This may include a cardiac source, such as arrhythmia, recent percutaneous intervention, trauma, connective tissue disease, and cancer [4–7]. A complete physical exam should be done with focus on the symptomatic extremity (pallor, pulses, sensory, motor) as mentioned in Table 38.1.
Investigations
According to the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Guidelines for Management of Patients with Peripheral Arterial Disease (PAD) , the recommendations are as follows (Table 38.2) [8]:
Table 38.2
ACCF/AHA 2013 guidelines for management of patients with PAD
Level of recommendation | |
|---|---|
Class I (Level of Evidence: B) | Patients with ALI and a salvageable extremity should undergo an emergent evaluation that defines the anatomic level of occlusion and leads to prompt endovascular or surgical revascularization |
Class III (Level of Evidence: B) | Patients with ALI and a nonviable extremity should not undergo an evaluation to define vascular anatomy or efforts to attempt revascularization |
Etiology
There are numerous etiologies for ALI in the lower extremity (LE) and upper extremity (UE) [4, 5]:
Thrombosis (in situ)
Embolic
Cardiac : atrial fibrillation, left atrial appendage thrombus, left ventricular thrombus, myocardial infarction
Paradoxical : patent foramen ovale and deep venous thrombosis
Atherosclerotic : aortic atheroma, thrombosed popliteal aneurysm (LE)
Vasculitis
Trauma
Iatrogenic
Malignancy
Thoracic outlet syndrome (UE)
Subclavian aneurysm (UE)
Treatment
There are three treatment options for ALI, which depend on multiple factors, including duration of symptoms, ALI clinical category, patient comorbidities/functional status, and availability of treatment options per institution [5].
Catheter-directed thrombolysis (CDT)
CDT with percutaneous mechanical thrombectomy (PMT)
Surgical thrombo-embolectomy (Table 38.3)
Table 38.3
Treatment strategy according to ALI clinical categories by Rutherford
Category
I: Viable
Endovascular (CDT ± PMT) or surgical
IIA: Marginally threatened
Endovascular (CDT ± PMT) or surgical
IIB: Immediately threatened
Surgical (but operating room availability may be delayed) so consider endovascular
III: Irreversible
Amputation
Three large randomized trials have evaluated thrombolysis versus surgery for acute limb ischemia of the lower extremity [1, 9]:
Rochester trial [14]
Surgery versus Thrombolysis for Ischemia of the Lower Extremity (STILE) (1994)
ALI <14 days
Ischemia >14 days
STILE subanalysis (1996)
Occluded bypass
Native artery occlusion
Thrombolysis or Peripheral Arterial Surgery (TOPAS) (1998)
Ouriel et al. (Rochester trial) randomized patients to surgery (revascularization or amputation as required, n = 57) versus thrombolysis (with urokinase 4000 IU/min, n = 57) [9, 14].
There was a survival benefit in the thrombolysis group (84 %) compared to surgical group (58 %), p = 0.01.
In-hospital complications were 16 % and 41 % in the thrombolysis and surgical groups, respectively, p = 0.001.
There was no difference in limb salvage.
At 30 days, stroke rates were 1.8 % and 0 %, and hemorrhage rates were 10.5 % and 1.8 % in the thrombolysis and surgical groups, respectively.
The STILE trial included 393 patients from 31 centers and randomized them to surgery versus thrombolysis as the initial treatment for ALI [9]. Two different thrombolytic regimens were used (rt-PA 0.05 mg/kg/h or urokinase 250,000 IU bolus followed by 4000 IU/min, in addition to heparin 5000 IU bolus intravenously then infusion 1000 unit/h + ASA 325 mg).
The trial was stopped early due to adverse events in the thrombolysis group at 1 month (in both bypass and native artery subgroups).
At 6-month follow up:
Patients with <14 days’ duration of symptoms:
Thrombolysis group had significantly reduced rate of death and amputation (15.3 % versus 37.5 %, p = 0.01).
Patients with >14 days’ duration of symptoms:
Thrombolysis group had reversed (increased) trend of death and amputation (17.8 % versus 9.9 %, p = 0.08) that did not reach significance.
Hemorrhage occurred in 5.6 % and 0.7 % in the thrombolysis and surgery groups, respectively.
Catheter placement failed in 28 % of patients in the thrombolysis group.
Patients divided into <14 days’ duration and >14 days’ duration was a post hoc division not stratified in the original protocol.
Over 80 % of patients had symptoms >14 days.
The STILE subgroup analyses at 12 months (low number of patients):
Comerota (bypass grafts):
Reduced amputation rate (<14 days’ duration group).
Overall, the thrombolysis group had higher rate of continued ischemia, claudication, or critical limb ischemia (73 % versus 50 %, p = 0.01).
Increased morbidity in prosthetic grafts compared to autogenous grafts (p = 0.038).
Weaver (native artery):
Recurrent ischemia (64 % versus 35 %, p = 0.0001) and major amputation (10 % versus 0 %, p = 0.0024) were higher in the thrombolysis group.
Very few patients were included in subgroup analysis.
Some patients failed to receive a catheter, but were included in the thrombolysis group.
The TOPAS trial included 213 patients from 79 centers. All patients had class II ischemia for <14 days. Three different urokinase thrombolysis regimens were used (2000 IU/min versus 4000 IU/min versus 6000 IU/min for first 2 h). All regimens were followed by 2000 IU/min.
Comparison between thrombolysis (optimal dose 4000 IU/min) and surgery was done.
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