Outcome of catheter-directed thrombolysis for lower extremity arterial bypass occlusion☆☆☆★

Materials and methods 

This study was undertaken because two of the authors, Drs Nehler and McLafferty, trained at an institution performing graft replacement for LEAB occlusion and became vascular faculty at institutions performing CDT for LEAB occlusion. Because of these practice patterns, this review does not have a comparable graft replacement arm but will use series from the surgical literature as controls. With vascular surgery databases at the Denver Veterans Affairs Medical Center and Southern Illinois University in Springfield, Ill, all patients undergoing CDT for acute (≤14 days) LEAB occlusion from January 1, 1988, to December 31, 2001, were identified. Patient records were reviewed for demographic variables including age, gender, and the following risk factors: diabetes, hypertension, coronary artery disease, prior coronary artery bypass surgery, congestive heart failure, and dialysis-dependent renal disease. The number of prior lower extremity vascular interventions and the primary indication for the patient's initial lower extremity revascularization were recorded. The duration of LEAB patency before CDT was recorded.

Technique of CDT was intraarterial within the thrombus and consistent with other reports.9, 11 After pulse spray, urokinase was dosed at 150,000 to 200,000 units per hour. Tissue plasminogen activator was dosed 0.3 mg/kg in 75 mL normal saline solution. This volume was pulsed in 2-mL to 3-mL increments, followed by a 0.05-mg/kg drip. Concomittent heparin drip was frequently used with urokinase but not with tissue plasminogen activator. Data regarding CDT for LEAB occlusions included: LEAB conduit (vein or prosthetic), LEAB anatomic configuration (aortofemoral, extraantomic, femoropopliteal above-knee, femoropopliteal below-knee, or femorotibial), duration of CDT; the number of subsequent follow-up angiographic studies per CDT, duration of CDT, success of CDT at achieving LEAB patency, the presence of any residual LEAB lesions identified after CDT, whether any endovascular procedures were performed for residual lesions, and information regarding any bleeding or thromboembolic complications of CDT.

Information recorded after CDT included: hospital stay, subsequent surgical revascularization procedures performed, 30-day mortality, and major nonfatal morbidity. Long-term data included: secondary graft patency, limb salvage, survival, recurrent graft occlusions, management of recurrent graft occlusions, additional hospitalizations for complications related to CDT, incidence of graft infection, and incidence of graft replacement.

Results 

One hundred four patients (mean age, 65 ± 13 years; range, 41 to 90 years) underwent CDT for 109 acute LEAB occlusions. Table I shows patient demographics, risk factors, and pertinent surgical history.

Table I. Demographics and risk factors for 107 patients undergoing CDT for LEAB occlusion

	Demographic or risk factor	%
	Male gender	77
	Diabetes	32
	Coronary artery disease	54
	Prior CABG	27
	Congestive heart failure	10
	Hypertension	46
	Dialysis dependence	5
	Smokers total (current)	89 (48)
	Contralateral BKA/AKA	12
	Two or more prior revascularizations	60
	Three or more prior revascularizations	34
	Known first revascularization for claudication	40
	Limb threat on LEAB occlusion presentation	88

CABG, Coronary artery bypass grafting; BKA, below-knee amputation; AKA, above-knee amputation.

Table II. Characteristics of 112 LEAB occlusions undergoing CDT

		No. (%)
	Suprainguinal	14 (13)
	Aortic	6 (6)
	Extraanatomic	8 (7)
	Infrainguinal	95 (87)
	Above-knee popliteal	22 (20)
	Prosthetic	19
	Autogenous	3
	Below-knee popliteal	30 (27)
	Prosthetic	6
	Autogenous	24
	Tibial	43 (39)
	Prosthetic	8
	Autogenous	35

One hundred seven of 109 CDT procedures (98%) were completed/abandoned within 48 hours. Median number of angiographic studies during CDT was 2.8 (range, 1 to 5). Urokinase was used in 103 CDT procedures (94%) and tissue plasminogen activator was used in the remainder of CDT procedures. CDT was successful in restoring patency in 84 LEABs (77%). Thirty-three LEABs had no demonstrable lesions after successful CDT, but two needed tibial embolectomy for distal embolization and two others were replaced during the same hospitalization. Fifty-one LEABs had residual lesions after CDT. Table III lists the anatomic location of these lesions.

Table III. Anatomic location of lesions in 51 LEABs after successful CDT

	Location of lesion	No. (%)
	Inflow	10 (20)
	Outflow	27 (53)
	Intragraft	4 (8)
	Inflow and outflow	10 (20)

The median hospital stay was 8 days (range, 2 to 73 days). Complications are described in Table IV.

Table IV. Complications associated with CDT

	Complication	No. (%)
	Death	3 (2.8)
	Bleeding	14 (13)
	Thromboembolic	15 (14)
	Myocardial infarct	4 (4)
	Renal failure	1 (1)
	Compartment syndrome	1 (1)

The mean follow-up period after CDT was 45 ± 36 months. The secondary graft patency rates (± standard error) on an intention-to-treat analysis were 32% (±4.9%), 25% (±4.7%), and 19% (±4.7%), at 1, 3, and 5 years, respectively (Fig 1).

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Fig. 1. Secondary patency for 109 LEABs after CDT.

Table V. Relationships between gender, graft anatomy, conduit, days of symptoms CDT and initial CDT success and secondary patency in those patients with infrainguinal grafts

	Variable	Immediate success	Secondary graft patency
	Gender	P = .42	P = .69
	Graft anatomy	P = .73	P = .25
	Conduit	P = .85	P = .75
	Days of symptoms	P = .39

One hundred forty-nine additional hospitalizations were necessary for recurrent lower extremity ischemia or complications during the follow-up period. Twenty-five of the 54 LEABs (46%) that eventually failed after initial successful CDT had two or more reocclusive episodes, and 10 (18%) had three or more reocclusive episodes. Thirty-three additional CDT procedures were performed to manage recurrent LEAB occlusion. Thirty-three operative graft thrombectomies with or without revision were used to manage recurrent LEAB occlusion. Twenty-three additional LEAB surgical revisions were performed to manage graft stenoses uncovered after additional CDT or graft surveillance. Seven of 84 LEABs (8.3%) initially salvaged with CDT eventually became infected (six requiring major amputation). Six of these grafts were prosthetic, all had had multiple occlusions with need for repeat surgery, and most had associated wound complications. Twenty of 84 LEABs (24%) initially salvaged with CDT were eventually replaced (four immediately and 16 after episodes of recurrent ischemia). Two patients died during repeat hospitalizations for recurrent lower extremity ischemia and subsequent complications. Limb salvage rates (± standard error) were 73% (±4.6%), 63% (±5.3%), and 55% (±5.9%) at 1, 3, and 5 years, respectively (Fig 2).

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Fig. 2. Limb salvage for 105 limbs after CDT for LEAB occlusion.

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Fig. 3. Survival in 104 patients undergoing CDT for LEAB occlusion.

Discussion 

The management of LEAB occlusion represents a clinical enigma for the modern vascular surgeon. Moreover, this problem will increase in the future because of an aging population and the exponential increase of endovascular technology for infrainguinal occlusive disease. Our experience with CDT for LEAB occlusion yields several observations regarding this patient cohort. Ninety percent of patients had limb salvage indications at the time of LEAB occlusion at a mean age (65 years) that was approximately 5 years younger than typical limb salvage series.16, 17, 18, 19 Perhaps because these were younger patients, at least 40% had their first vascular intervention for claudication. Before CDT, 60% and 34% of these patients had undergone at least two and three prior revascularizations, respectively. Finally, these LEABs had early failure before CDT with 20% constructed of nonautogenous conduit in the infrageniculate position. In general, this is a younger vascular population with an escalation in their vascular disease over time.

The immediate success and durability of CDT for LEAB occlusion in our analysis is similar in our report to previous series and randomized trials.2, 7, 8, 9, 10, 11 Three quarters of the LEABs had patency restored. One quarter had bleeding or thromboembolic complications, and roughly half needed surgical therapy, which shows the technical difficulties of catheter-based interventions in patients with multiple prior revascularizations. Approximately two thirds of LEABs salvaged with CDT had residual lesions. Most of these lesions were managed with endovascular methods. The long-term performance of these salvaged LEABs was disappointing. Secondary patency dropped off markedly by 6 months (40%), with a slower attrition rate up to 5 years (20%). No difference was seen in secondary patency rates for any subgroup examined, which may represent a type II error. Limb salvage rate decreased at a fairly steady rate to approximately 50% at 5 years. The amount of morbidity accrued during the follow-up period was concerning. A large number of reocclusions/interventions occurred, with one in 10 salvaged grafts eventually infected and almost one in four of salvaged grafts eventually replaced.

Our data neither prove nor disprove that surgical therapy for LEAB occlusion is preferable to CDT. There is every reason to speculate that the short-term and long-term morbidity in a population undergoing redo LEAB would be substantial owing to perioperative mortality, reoperations for thrombotic, bleeding, and wound complications for open surgery comparable with complications of CDT.16, 20, 21, 22, 23 Long-term morbidity with regards to wound complications, lower extremity edema, graft surveillance/revision, graft failure/replacement, and modest limb loss over time may have been similar.13, 14, 16, 21, 22, 23 Of note, immediate amputation may play a role in a subset of patients as a result of age, comorbidities, minimal arterial outflow for reconstruction, or marginal function.

Given that therapy alternatives for LEAB occlusion appear relatively dismal, can measures be taken to reduce this disadvantaged population of patients? It appears clear that a subset of patients with initial intervention for claudication will eventually progress to limb threat after revascularization failure. Standard clinical patterns of progression would include: 1) patients with iliac angioplasty/stenting followed by failure or aortofemoral bypass followed by limb occlusions, with an eventual crossfemoral reconstruction necessary18; and 2) patients with an above-knee femoral popliteal bypass with failures eventually resulting in a femorotibial reconstruction.24, 25 Although the actual percentage of these difficult cases created with intervention in the claudication population is unknown, it is clear to every vascular surgeon that once this clinical course had started, misery is the rule rather than the exception. Therefore, one of the clear messages of these data is to proceed with caution when intervening for claudication.

Currently, we individualize the management of LEAB occlusion on the basis of patient age/comorbidities, available conduit, and arterial runoff. Younger patients with prior prosthetic infrainguinal grafts for claudication and available saphenous conduit undergo arteriography with or without CDT to define arterial outflow followed by saphenous vein graft replacement. Older patients or those with compromised or limited autogenous conduits available undergo CDT. If successful, lesions are managed with endovascular methods if possible. Although half of CDT salvaged LEABs will reocclude in 6 to 12 months, half will remain patent. Unfortunately, the number of patients in our series was insufficient to provide reliable subset analyses to determine which patients/grafts/lesions/conduits might perform best. Those patients with early reocclusion after CDT should undergo graft replacement or amputation. This strategy takes advantage of the patients who do well with CDT and minimizes the long-term morbidity of repetitive LEAB occlusions.

Modern LEAB occlusions represent a difficult vascular cohort with frequent multiple revascularization failures. Many of these patients are younger, with initial interventions for claudication, and now face limb-threatening ischemia with significant deterioration in their antecedent vascular anatomy. Although no subsequent course appears ideal and some may conclude the poor secondary patency rates are unacceptable, we believe an initial attempt at CDT in many patients with liberal use of graft replacement for failures or as an initial strategy in those with favorable remaining conduit offers the potential to minimize the long-term morbidity in a population with a poor natural history.