Editor's Choice - Carotid Stenosis Treatment: Variation in International Practice Patterns.

OBJECTIVES: The aim was to determine current practice for the treatment of carotid stenosis among 12 countries participating in the International Consortium of Vascular Registries (ICVR). METHODS: Data from the United States Vascular Quality Initiative (VQI) and the Vascunet registry collaboration (including 10 registries in Europe and Australasia) were used. Variation in treatment modality of asymptomatic versus symptomatic patients was analysed between countries and among centres within each country. RESULTS: Among 58,607 procedures, octogenarians represented 18% of all patients, ranging from 8% (Hungary) to 22% (New Zealand and Australia). Women represented 36%, ranging from 29% (Switzerland) to 40% (USA). The proportion of carotid artery stenting (CAS) among asymptomatic patients ranged from 0% (Finland) to 26% (Sweden) and among symptomatic patients from 0% (Denmark) to 19% (USA). Variation among centres within countries for CAS was highest in the United States and Australia (from 0% to 80%). The overall proportion of asymptomatic patients was 48%, but varied from 0% (Denmark) to 73% (Italy). There was also substantial centre level variation within each country in the proportion of asymptomatic patients, most pronounced in Australia (0-72%), Hungary (5-55%), and the United States (0-100%). Countries with fee for service reimbursement had higher rates of treatment in asymptomatic patients than countries with population based reimbursement (OR 5.8, 95% CI 4.4-7.7). CONCLUSIONS: Despite evidence about treatment options for carotid artery disease, the proportion of asymptomatic patients, treatment modality, and the proportion of women and octogenarians vary considerably among and within countries. There was a significant association of treating more asymptomatic patients in countries with fee for service reimbursement. The findings reflect the inconsistency of the existing guidelines and a need for cooperation among guideline committees all over the world.

Direct measurement of arteriovenous anastomotic blood flow in the septic canine hindlimb.

Absolute blood flow through hindlimb capillaries and arteriovenous anastomoses (AVA) was determined by the radioactive microsphere technique of relative shunt measurement combined with direct (electromagnetic) measurement of femoral artery blood flow. Studies were performed before and 72 hours after infection was created in six dogs by implanting fecal-contaminated wicks in one hindlimb. Three control dogs had sterile wicks implanted. Septic dogs demonstrated decreased arterial pressure and increased core temperature with no change in mean cardiac index. Infected legs had increased total femoral blood flow, decreased peripheral resistance, decreased arteriovenous (A-V) O2 difference, but unchanged oxygen consumption, Paw temperature increased in both infected and normal contralateral limbs. Muscle blood flow (MBF) (Xe133 clearance) increased only in infected legs. A-V shunting increased five-fold and AVA flow increased seven-fold in infected hindlimbs, significantly more than that in contralateral or control limbs. Increased A-V shunting correlated highly (r=0.95) with increased total femoral blood flow in infected legs, but increased MBF was not correlated (r=0.05). Despite increased MBF, increased AVA flow occurs in septic canine hindlimbs and contributes to the low-resistance, high-flow, but unchanged oxygen consumption described in this model.

Hemodynamic effects of sympathectomy in ischemic canine hindlimbs.

One week after unilateral distal superficial femoral artery ligation, 15 anesthetized dogs were studied before and after bilateral lumbar sympathectomy. Total hindlimb capillary (THC) flow and arteriovenous anastomotic (AVA) flow were determined by microsphere arteriovenous (A-V) shunt measurement combined with electromagnetic femoral artery blood flow measurement. Muscle capillary blood flow (MBF) was measured by xenon133 clearance. Baseline femoral blood flow in ischemic (I) hindlimbs was only 53% of contralateral control (C) hindlimbs (I = 56, C = 105 ml/min, P less than 0.01). Ischemia was manifest in I limbs by reduced O2 consumption (I = 1.68, C = 2.53 ml of O2/min, P less than 0.01). After sympathectomy, total blood flow increased significantly in I limbs, but no improvement in O2 consumption occurred. This was due to increased A-V shunting, with increased AVA flow (from 3 to 20 ml/min. P less than 0.01) but unchanged THC flow. Neither resting nor reactive hyperemic MBF improved after sympathectomy. Control limbs showed similarly increased AVA flow, but decreased O2 consumption, suggesting a detrimental effect of sympathectomy. The major hemodynamic consequence of sympathectomy in ischemic canine hindlimbs was increased nonnutritive A-V shunting, with no improvement in total capillary flow.

Direct measurement of arteriovenous anastomotic blood flow after lumbar sympathectomy.

Absolute blood flows through hind limb capillaries and arteriovenous anastomoses (AVA) were determined by the radioactive microsphere technique of relative shunt measurement combined with direct (electromagnetic) measurement of femoral artery flow. Hemodynamic parameters were measured before and after laparotomy, after unilateral lumbar sympathectomy, during reactive hyperemia, and during alpha adrenergic blockade in normal and sympathectomized hindlimbs of six anesthetized dogs. After sympathectomy arteriovenous (A-V) shunting increased from 3.8 to 32.1% (p less than 0.05). AVA flow increased from 4 to 54 ml/minute (p less than 0.01), while capillary flow was unchanged. Nonsympathectomized limbs did not demonstrate these changes. During reactive hyperemia, capillary flow increased more than 100% (p less than 0.03) in both normal and sympathectomized limbs, while AVA flow was unchanged. After phentolamine (5 mg, intravenously), AVA flow increased from 2 to 19 ml/minute (p less than 0.01) only in nonsympathectomized limbs. Phentolamine mimicked surgical sympathectomy effects in nonsympathectomized limbs, with paw temperature, femoral flow, A-V O2 difference, A-V shunting, AVA flow, and capillary flow equal to sympathectomized limbs after phentolamine administration. In the acute canine model, increased blood flow after sympathectomy is due to increased nonnutritive AVA flow, with no change in total hindlimb capillary flow, both at rest and during reactive hyperemia.

Endothelial cells modulate smooth muscle cell morphology by inhibition of transforming growth factor-beta 1 activation.

BACKGROUND: We have previously demonstrated in a coculture model that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) morphology. This study was performed to test the hypothesis that ECs inhibit transforming growth factor-beta 2 (TGF-beta 1) activation through the release of plasminogen activator inhibitor (PAI-1). METHODS: Bovine SMCs were cultured on a thin, semipermeable membrane, either alone or opposite ECs in coculture (SMC/EC). Conditioned media and cell lysates at 1, 5, and 21 days were assayed for TGF-beta 1 and PAI-1 by enzyme-linked immunoabsorbent assay. Cell proliferation rates, protein, and DNA content were measured and compared with SMC morphology. RESULTS: Activation of TGF-beta 1 was significantly decreased (1.2% versus 18.9% active TGF-beta 1 p < 0.05) and PAI-1 was increased (659 pg/ml versus 343 pg/ml p < 0.05) in SMC/EC medium on day 1, compared with the medium of SMC alone. Significantly higher levels of PAI-1 were measured in cell lysates of cocultured ECs (128 pg/micrograms DNA) than in cocultured SMCs (5.8 pg/micrograms DNA, p < 0.05). SMC/EC coculture prevented the SMC hill-and-valley growth morphology seen in SMCs cultured alone. CONCLUSIONS: In a model designed to study SMC/EC interactions, it was seen that ECs can alter growth characteristics of SMCs by producing PAI-1, which interferes with the plasminogen pathway of TGF-beta 1 activation. This suggests that reduced EC PAI-1 production could play a role in alteration of SMC phenotype in vivo.

Aortoiliac occlusive disease in women.

Seventy-five women with aortoiliac (A-I) occlusive disease requiring vascular reconstruction during the past 4 years were reviewed. They represented a growing proportion (39%) of all patients with A-I disease And presented at the same meAn age (57 years) as males. Standard cardiovascular risk factors were high in this group and cigarette smoking was especially predominate (93%). Women presented with elevated triglyceride levels as opposed to increased cholesterol, with frequent type IV hyperlipoproteinemia. An operative mortality rate of 0%, a 4-year graft limb patency of 94%, and a 4-year life-table survival of 93% were observed. Good or excellent long-term relief of symptoms occurred in 96% of patients despite tandem ((superficial femoral) disease in 42% but only 4% superficial femoral reconstruction. A definition of women with "small vessels" was established by using aortic diameter > 1 SD below the overall mean (> 1 cm diameter at the aortic bifurcation). Women in this subgroup presented at a younger age with less severe symptoms, fewer risk factors, and more localized disease. An emphasis on postoperative reduction of cigarette smoking and dietary modification among hyperlipidemic patients probably contributed to the satisfactory results achieved in this increasing percentage of women with A-I occlusive disease.

Prostacyclin treatment of ischemic ulcers and rest pain in unreconstructible peripheral arterial occlusive disease.

The efficacy of prostacyclin (PGI2) treatment was assessed in 26 patients with surgically unreconstructible atherosclerotic arterial occlusive disease of the lower extremity manifested by nonhealing ulcers and rest pain. Patients were randomized to receive a 72-hour intravenous infusion of PGI2 (6 ng/kg/min, n = 13) or placebo (n = 13). Ulcer size was measured by photographic planimetry, and rest pain was graded by blinded objective scoring at monthly intervals for 6 months. Ulcer size increased 64% in PGI2-treated patients and 22% in placebo-treated patients by 1 month after infusion. Rest pain decreased slightly in both PGI2 and placebo groups. At the conclusion of the study, 54% of placebo-treated patients and 31% of PGI2-treated patients had a positive treatment response, indicated by at least a 20% decrease in ulcer size and a 33% decrease in rest pain. PGI2 infusion did not improve the high-placebo response rate seen in these patients with severely ischemic extremities. These results emphasize the importance of placebo-controlled studies, even in patients with unreconstructible arterial disease.

Chronic total renal artery occlusion: effects of treatment on secondary hypertension and renal function.

Chronic total occlusion of 42 main renal arteries was documented by arteriographic studies in 25 female and 15 male patients being evaluated for drug-resistant hypertension. Arteriosclerotic lesions affected 35 patients, and fibrodysplastic obstructions occurred in five. Hypertensive urographic studies showed lateralization to the affected kidney in all 31 studies obtained. Renal vein renin activity lateralized with a mean ratio of 3.88 in the 24 patients studied. In 15 patients, mean renal: systemic renin indices (RSRI) of 2.39 confirmed ischemic kidney renin hypersecretion, and a mean RSRI of 0.03 confirmed contralateral suppressed secretion. Affected kidney lengths averaging 9.4 cm were significantly smaller than the 13.0 cm length of kidneys without occluded arteries. Thirty patients with 31 occluded arteries underwent renal artery bypass (18), endarterectomy (2), or nephrectomy (11). There were two perioperative deaths. Eighty-nine percent of survivors benefited in regard to hypertension control, and 47% exhibited improved renal function. Nonoperative treatment of 10 patients was associated with frequent progression of renal failure and inadequate blood pressure control. This experience documents the appropriateness of surgical therapy for secondary hypertension caused by chronically occluded renal arteries.

Limb-threatening potential of arteriosclerotic popliteal artery aneurysms.

Eighty-eight popliteal artery aneurysms were diagnosed in 59 men and two women (mean age 67 +/- 10 years). Bilateral aneurysms affected 27 patients (44%). Aneurysm diameter ranged from 1.3 to 12 cm (mean 4 +/- 2.6 cm). Most aneurysms were symptomatic (55%). Dominant symptoms included rest pain (19%), claudication (14%), local pain (13%), and gangrene (9%). The remainder of the aneurysms were asymptomatic (45%). Aneurysm thrombosis occurred in 24% of extremities. Associated aneurysms involved the abdominal aorta (62%), iliac artery (36%), and femoral artery (38%). Aneurysms that caused local pain were larger (6.2 +/- 1.9 cm) than asymptomatic aneurysms (2.9 +/- 2.1 cm, P less than 0.01). Aneurysms smaller than 2 cm were more likely to be asymptomatic than larger aneurysms (P less than 0.05). Operative intervention was undertaken for 56 aneurysms, with aneurysmal exclusion or excision with arterial reconstruction performed most often. Four primary and five secondary major amputations were associated with thrombosed aneurysms, compared to no amputations with asymptomatic aneurysms (P less than 0.01). Thirty-two aneurysms were not treated surgically. Limb loss resulted from ischemic complications which developed in 18% of aneurysms treated without operation. The duration of follow-up for patients who had operation and those who did not averaged 62 months and 25 months, respectively. Operative treatment for all bland popliteal artery aneurysms appears justified if complications leading to major amputation are to be avoided.

Abdominal aortic aneurysm rupture: statistical analysis of factors affecting outcome of surgical treatment.

One hundred sixteen patients underwent surgery for ruptured abdominal aortic aneurysms with intraoperative and overall mortality rates of 20.7% and 51.7%, respectively. The correlation of multiple factors to morbidity and mortality was assessed with detailed statistical analysis. Eight preoperative factors were identified as predictors of mortality. Increased intraoperative mortality rates were associated with heart disease (29%), hypertension (30%), flank ecchymoses (57%), and pulsatile abdominal mass (24%). Increased intraoperative and overall mortality rates were associated with preoperative hypotension (39%, 78%) and BUN levels higher than 30 mg/dl (47%, 82%). Increased overall mortality rates were associated with creatinine levels higher than 3 mg/dl (71%) and a hematocrit of 30.0 to 32.5 vol% (75%) (P less than 0.05). Seven intraoperative factors were identified as predictors of mortality. Increased postoperative mortality rates were associated with a duration of operation of more than 400 minutes (100%), hypotension lasting longer than 110 minutes (88%), estimated blood loss more than 11,000 ml (75%), blood transfusion more than 17 U (68%), fluid administration in excess of 7000 ml (70%), and a blood pressure lower than 100 mm Hg at the conclusion of the operation (88%). Cardiac arrest was associated with increased intraoperative and overall mortality rates (77%, 82%) (P less than 0.05). In general these factors cannot be controlled by the surgeon, and future significant reduction in the operative mortality rate may be possible. These findings support the general concept of aggressive elective resection of abdominal aortic aneurysms.

Discriminant arteriographic criteria in the management of forearm and hand ischemia.

Fifty-five patients (33 male and 22 female), 3 to 73 years in age, underwent aortic arch and selective upper extremity arteriography for the evaluation of forearm and hand ischemia from 1971 to 1980. Fifty-one patients had organic occlusive lesions (12 subclavian, 15 axillobrachial, 17 radial-ulnar, and 7 palmar-digital), including distal forearm and hand emboli, as a consequence of proximal occlusive disease in nine patients (5 subclavian, 2 axillobrachial, and 2 radial-ulnar). The remaining four patients had vasospastic disease. Major arteriographic findings of obstructive disease were defined by: morphology of lesions, symmetry or asymmetry of obstructions, segmental versus tandem lesion distribution, and the resultant pattern of collateral circulation. Vasodilatory pharmacoangiography with magnification technique frequently facilitated evaluation of digital and collateral vessels. Therapeutic interventions were dictated by clinical data heavily weighed by the arteriographic examination. Limited arteriographic studies would have been misleading in the evaluation of many patients.

Actuarial analysis of variables associated with rupture of small abdominal aortic aneurysms.

This study identified risk factors associated with rupture of small abdominal aortic aneurysms in patients initially selected for nonoperative management. Sixty-seven patients, 53 men and 14 women, 50 to 91 years of age (mean 72 years) were followed 3 to 99 months (mean 36 months). All patients underwent serial aortic ultrasonography. The annual rate of aneurysm rupture was 6%, with an annual mortality rate caused by rupture of 5% and an annual mortality rate caused by coexistent disease of 6%. Thirty potential risk factors, including blood pressure, aneurysm size measured by ultrasonography, rate of aneurysm expansion, smoking, serum cholesterol levels, and cardiac, pulmonary, and renal risks, were analyzed by Cox proportional hazards regression to identify variables related to rupture. Aneurysm anteroposterior expansion rates varied from 0 to 1.5 cm/year but were not different in aneurysms that ruptured. Only diastolic blood pressure, initial aneurysm anteroposterior diameter, and degree of obstructive pulmonary disease were independently predictive of rupture (p less than 0.05, Wald test). With these data, actuarial rupture rates were predicted for patients with selected values of these three covariates. Predicted 5-year rupture rates varied from 2% when these risk factors were absent to 100% when all three risk factors were significant. Obstructive pulmonary disease, initial aneurysm size, and diastolic hypertension must be evaluated prospectively to assess their accuracy in predicting small aneurysm rupture.

Effect of prolonged intra-arterial prostaglandin E1 infusion on canine arterial graft patency.

This study examined the effect of long-term intra-arterial prostaglandin (PG) E1 infusion on the patency of canine femoral-artery grafts made of polytetrafluoroethylene and measuring 4 X 90 mm (diameter X length). An infusion catheter was placed proximal to one of the bilateral femoral-artery grafts and connected to a subcutaneously implanted infusion pump to continuously infuse PGE1 (1 ng/kg/min) in seven experimental dogs and vehicle alone in seven control dogs. Two-week graft patency was significantly higher in both infused (86%) and noninfused (100%) limbs of PGE1-treated dogs than in control dogs (29%). Although hind-limb blood flow was increased twofold to threefold by PGE1 infusion, graft patency did not improve. Prostaglandin E1 infusion did not significantly alter systemic platelet aggregation but did cause considerable hind-limb edema. Improved early graft patency, which did not persist beyond four weeks, was apparently related to systemic effects of local PGE1 infusion.

Effect of a selective thromboxane synthase inhibitor on arterial graft patency and platelet deposition in dogs.

This study examined the effect of selective thromboxane synthase inhibition and nonselective cyclooxygenase inhibition on vascular graft patency and indium 111-labeled platelet deposition in 35 mongrel dogs undergoing carotid artery replacement with 4 mm X 4 cm polytetrafluoroethylene (PTFE) (one side) and Dacron (opposite side) end-to-end grafts. Aspirin-dipyridamole therapy improved one-week graft patency, from 46% in untreated dogs to 93% in treated dogs. Thromboxane synthase inhibition (U-63557A) improved graft patency in these dogs to 81%. Both drug treatments reduced platelet deposition on Dacron and PTFE grafts by 48% to 68% compared with control dogs. Dacron grafts accumulated significantly more platelets than PTFE grafts but had comparable patency rates. Low-dose aspirin therapy had no significant effect on either graft patency or platelet deposition. All treatment groups showed a 60% to 76% reduction in serum thromboxane B2, but only thromboxane synthase inhibitor treatment increased plasma 6-keto-prostaglandin F1 alpha by 100%. Selective thromboxane synthase inhibition improved small-caliber prosthetic graft patency to the same extent as did conventional cyclooxygenase inhibition in this preliminary study.

The effect of sympathetic innervation on canine muscle and skin blood flow.

Two microsphere techniques were used to measure skin and muscle capillary blood flow, plus blood flow through arteriovenous anastomoses (AVAs), before and after unilateral lumbar sympathectomy in 12 anesthetized dogs. Sympathectomy did not alter capillary flow to tibial muscle, thigh, or lower leg skin, whereas paw skin capillary flow decreased, from 28 to 13 mL/min/100 g. However, total extremity blood flow increased after sympathectomy, because of the rate of AVA flow, which increased from 7 to 30 mL/min. Transient nerve stimulation of the cut distal end of the lumbar sympathetic chain immediately and reversibly decreased the AVA flow rate, from 30 to 10 mL/min. The rate of total hind-limb capillary flow also decreased during nerve stimulation, from 86 to 46 mL/min. The only significant effect of sympathectomy in anesthetized dogs was to redistribute distal hind-limb capillary blood flow to AVAs, which are anatomically located in this region. In contrast to capillaries, AVAs have little intrinsic myogenic tone and are highly dependent on adrenergic innervation.

Aneurysms of extracranial carotid arteries.

Twenty-three extracranial carotid artery aneurysms were encountered in 19 patients. Arteriosclerosis was evident in 16 aneurysms. Severe arterial hypertension affected all patients with arteriosclerotic lesions. Trauma, penetrating neck injury once, and blunt neck injury three times caused four aneurysms. Three aneurysms resulted from earlier carotid artery operations. All 19 patients were symptomatic. Neurologic symptoms affected 13 individuals. Local symptoms referable to the aneurysmal mass troubled 15 patients. Twenty-one aneurysms were treated operatively. There was no operative mortality. Aneurysmectomy with arterial reconstruction was performed 16 times. Aneurysmorrhaphy was undertaken on four occasions and carotid ligation once. Two strokes and multiple cranial nerve injury accounted for three operative complications. No neurologic complications occurred during follow-up totaling 360 man-months. These lesions may be successfully treated by a carefully performed, properly selected operation.

Cost-effectiveness of intra-arterial thrombolytic therapy.

We reviewed the clinical course of 23 patients who received 24 intra-arterial infusions of either streptokinase or urokinase to treat 14 arteries and ten arterial grafts that were occluded due to primary thrombosis (22) or artery-artery embolism (two). Time from symptom onset to treatment was one to 28 days (mean, 11 days). Five infusions (21%) were completely successful since symptoms were eliminated without subsequent operation. Seven infusions (29%) were partially successful since thrombolysis aided, limited, or postponed subsequent surgery. Six infusions (25%) were failures since thrombolysis or clinical improvement did not occur and surgery was required. Six infusions (25%) were associated with thrombolytic complications that required urgent operation (less severe complications occurred in an additional 17% of cases [4/24]). Of the 19 patients without complete success after thrombolytic therapy, 16 underwent surgery during the same admission, two were not operable due to distal disease, and one declined operation. Of the 16 operations, 15 (94%) were successful in restoring graft or artery patency and achieving limb salvage, whereas one failed. In the 12 patients with failure or major complications of thrombolytic treatment, all had successful surgical outcome without morbidity. The actual mean cost of thrombolytic treatment was $8200 per patient and was comparable with the actual mean cost of subsequent surgical treatment in the 16 patients who required operation ($8900 per patient). The effective cost of thrombolytic and surgical treatment was calculated by dividing the actual costs by the proportion of successful cases. The effective cost of thrombolytic therapy per complete success was $39,200 and per complete or partial success was $16,500. This was significantly more than the effective cost of $9400 per complete success of surgical therapy.

Limb salvage despite extensive tissue loss. Free tissue transfer combined with distal revascularization.

Extensive lower-extremity tissue loss may preclude limb salvage despite successful arterial reconstruction. We attempted to avoid limb loss in such patients by combining arterial bypass with microvascular free tissue transfer. Fourteen patient (12 diabetic), 33 to 74 years of age, presented with extensive tissue loss in 15 lower extremities, exposing bone or tendon on the heel, ankle, lower part of the leg, or hindfoot. Mean ulcer size was 5 X 8 cm. Four patients had had previous contralateral below-knee amputations. Femorodistal (seven), popliteal-distal (three), or femoropopliteal (four) bypass, or tibial angioplasty (one), was performed to provide sufficient inflow for free tissue transfer. Serratus anterior, scapular, latissimus dorsi, rectus abdominis, gracilis, ulnar, or temporalis free flaps were used. One free flap failed due to venous thrombosis and was corrected with a second flap. Limb salvage was achieved in 14 (93%) of 15 limbs during a mean follow-up of 24 months. The single amputation occurred due to severe foot ischemia in a patient whose femorodistal bypass remained patent only to the viable free flap. The remaining 13 patients (14 limbs) became ambulatory, including those with free flaps to weight-bearing regions.

Intermittent claudication. Current results of nonoperative management.

We reviewed the clinical course of 91 men with mild intermittent claudication who had been followed up for at least six months without operation. During 2.5 years' mean follow-up, 60% of the patients had more severe claudication. Actuarial analysis revealed an annual mortality of 4.5% and an annual operation rate of 9%. Historical factors, including age, race, smoking, exercise, diabetes, hypertension, and the ankle-brachial index (ABI), were analyzed to determine if these variables could predict clinical outcome. Only cigarette smoking, exercise, and the ABI were significant in this regard. Patients who had smoked at least 40 pack-years had an operation rate 3.3 times higher than those who smoked less. Major daily exercise was associated with stable claudication. The initial ABI did not correlate with clinical outcome. A subsequent decrease in the ABI of at least 0.15, however, was associated with an operation rate 2.5 times higher and a symptom progression rate 1.8 times higher than patients without this change in the ABI. When regression analysis was used, the preceding variables were only 63% to 79% accurate in predicting the clinical outcome of individual patients. Careful follow-up of patients with intermittent claudication is therefore recommended to allow timely operative intervention when required.