D. Eugene Strandness

Diagnosis and Treatment of Chronic Arterial Insufficiency of the Lower Extremities: A Critical Review

Atherosclerosis is the most common cause of chronic arterial occlusive disease of the lower extremities. The arterial narrowing or obstruction that occurs as a result of the atherosclerotic process reduces blood flow to the lower limb during exercise or at rest. A spectrum of symptoms results, the severity of which depends on the extent of the involvement and the available collateral circulation. Thus, symptoms may range from intermittent claudication to pain at rest. Intermittent claudication denotes pain that develops in the affected limb with exercise and is relieved with rest. This pain usually occurs distal to the arterial narrowing or obstruction. Since the superficial femoral and popliteal arteries are the vessels most commonly affected by the atherosclerotic process, the pain of intermittent claudication is most often localized to the calf. The distal aorta and its bifurcation into the two iliac arteries are the next most frequent sites of involvement. Narrowing of these arteries may produce pain in the buttocks or the thighs as well as the legs. Epidemiological studies indicate that up to 5% of men and 2.5% of women 60 years of age or older have symptoms of intermittent claudication.1 2 The prevalence is at least threefold higher when sensitive noninvasive tests are used to make the diagnosis of arterial insufficiency in asymptomatic and symptomatic individuals.3 The symptoms of chronic arterial insufficiency of the lower extremities progress rather slowly over time. Thus, after 5 to 10 years, more than 70% of patients report either no change or improvement in their symptoms, while 20% to 30% have progressive symptoms and require intervention, and less than 10% need amputation.4 5 Despite the relatively benign prognosis for the affected limb, however, symptoms of intermittent claudication should be viewed as a sign of systemic atherosclerosis. This explains why, compared with …

Pentoxifylline efficacy in the treatment of intermittent claudication: Multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients

The efficacy, safety, and tolerance of pentoxifylline (Trental, Hoechst-Roussel Pharmaceuticals, Inc.) in the treatment of intermittent claudication associated with chronic occlusive arterial disease (COAD) were evaluated in a double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving a total of 128 outpatients. The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a standardized treadmill test. Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD. Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients. These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD. White the precise mode of therapeutic action requires clarification, pentoxifylline was well tolerated with minimal unwanted effects.

Prospective Study of Atherosclerotic Disease Progression in the Renal Artery

BACKGROUND The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS Subjects with >/=1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, <60% stenosis, and >/=60% stenosis, respectively (P=0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having >/=60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure >/=160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (>60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. CONCLUSIONS Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.

A Comparison of Cilostazol and Pentoxifylline for Treating Intermittent Claudication

PURPOSE We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. PATIENTS AND METHODS We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks. RESULTS Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups. CONCLUSION Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.

Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: A one- to six-year follow-up

PURPOSE This study investigated changes in the deep venous system and the development of the postthrombotic syndrome (PTS) after an episode of acute deep vein thrombosis (DVT). METHODS Seventy-eight patients (41 male patients, 37 female patients) with acute DVT in 83 legs (31 right, 42 left, five bilateral) underwent annual follow-up examinations for 1 to 6 years (median, 3 years) for symptoms and signs of the PTS. A venous duplex scan was performed at each visit to detect obstruction and reflux in the veins, both of which may contribute to the development of the PTS. DVT was primary in 69 limbs and recurrent in 14 limbs. RESULTS When last examined 49 limbs were free of symptoms, and 34 had the PTS (23 edema only, 11 hyperpigmentation). Only two patients had ulcers during the follow-up period; both patients had the ulcers in areas of hyperpigmentation in limbs with recurrent DVT. The extent of disease was similar in limbs with the PTS (79% multisegment, 18% single segment) and those without the PTS (69% multisegment, 12% single segment). In limbs with the PTS the deep veins were normal in only one (3%), six (18%) showed reflux only, five (15%) obstruction only, and 22 had features of both obstruction and reflux (65%). In limbs without the PTS the deep veins showed no abnormality in nine (18%), reflux only in 17 (35%), obstruction only in six (12%), and reflux with obstruction in 17 (35%). In the 11 limbs with hyperpigmentation nine had obstruction and reflux noted, one had obstruction only, and one had reflux alone. CONCLUSIONS After an episode of acute DVT 12% of the limbs returned to normal by duplex criteria. Although only 13% developed skin complications, 41% had features of the PTS. Limbs with the PTS had more than three times the odds of having combined reflux and obstruction than did limbs without the PTS (odds ratio = 3.5, 0.95 confidence intervals = 1.4, 8.6). Continued study of these patients will determine the course of those limbs with venous abnormalities that have not yet developed symptoms and signs of the PTS.

An Electrically Calibrated Plethysmograph for Direct Measurement of Limb Blood Flow

This paper describes an electrically calibrated plethysmograph which may be used with all lengths of mercury-in-rubber strain gauges. Due to the very low resistance of these strain gauges, electrical calibration of previously available plethysmographs has suffered from errors caused by lead-wire resistance. The present instrument eliminates lead-wire errors by a design which effectively places the strain gauge at the corners of the measurement bridge. Linearity of the output for large changes in gauge resistance has been insured by the incorporation of a constant-current bridge supply.

Deep venous insufficiency: The relationship between lysis and subsequent reflux

PURPOSE Although venous valvular insufficiency is well recognized as the most important etiologic mechanism in the development of the postthrombotic syndrome, the factors contributing to valve incompetence after deep venous thrombosis remain obscure. METHODS To establish the relationship between recanalization and valve competence, 113 patients with acute deep venous thrombosis were studied with serial duplex ultrasonography. RESULTS Median lysis times for segments developing reflux (214 to 474 days) were 2.3 to 7.3 times longer than for corresponding segments not developing reflux (65 to 130 days) for all except the posterior tibial vein. In the posterior tibial vein, median lysis times for those with and without reflux were nearly identical (72 vs 80 days). The median time to onset of reflux was significantly less than the median lysis time in the mid and distal superficial femoral veins and was simultaneous with recanalization in all other segments. CONCLUSIONS Early recanalization is important in preserving valve integrity for all but the posterior tibial segment. However, the small number of patients with reflux despite early lysis (< 1 month) or without reflux despite relatively late lysis (> 9 to 12 months) suggests that other factors may also contribute to the development of valvular incompetence. These factors may be particularly important in the posterior tibial vein, in which lysis time has little relationship to the ultimate development of reflux.

Classification and Grading of Chronic Venous Disease in the Lower Limbs-A Consensus Statement-

Classification and grading of chronic venous disease in the lower limbs : A consensus statement

Natural history of atherosclerotic renal artery stenosis: A prospective study with duplex ultrasonography

PURPOSE Although the prevalence of renal artery stenosis in patients with peripheral arterial disease is in the range of 30% to 40%, the role of renal revascularization in patients without severe hypertension or kidney failure is controversial. Duplex scanning is a noninvasive technique that is ideally suited for screening and follow-up of renal artery disease. The purpose of this study was to document the natural history of renal artery stenosis in patients who were not candidates for immediate renal revascularization. METHODS Eighty-four patients with at least one abnormal renal artery detected by duplex scanning were recruited from patients being screened for renal artery stenosis. Of the 168 renal artery/kidney sides, 29 were excluded (15 prior interventions, 6 nondiagnostic duplex scans, 8 presumed nonatherosclerotic lesions), leaving 80 patients with 139 sides for the follow-up protocol. Renal arteries were classified as normal, less than 60% stenosis, 60% or greater stenosis, or occluded by use of previously validated criteria. RESULTS The study group included 36 men and 44 women with a mean age of 66 years who were monitored for a mean interval of 12.7 months. The initial status of the 139 renal arteries was normal in 36, less than 60% stenosis in 35, 60% or greater stenosis in 63, and occluded in 5. Although none of the initially normal renal arteries showed disease progression, the cumulative incidence of progression from less than 60% to 60% or greater renal artery stenosis was 23% +/- 9% at 1 year and 42% +/- 14% at 2 years. All four renal arteries that progressed to occlusion had 60% or greater stenoses at the initial visit, and for those sides with a 60% or greater stenosis, the cumulative incidence of progression to occlusion was 5% +/- 3% at 1 year and 11% +/- 6% at 2 years. The mean decrease in kidney length associated with progression of renal artery stenosis to occlusion was 1.8 cm. CONCLUSIONS Progression of renal artery stenosis, as defined in this study, occurs at a rate of approximately 20% per year. Progression to occlusion is associated with a marked decrease in kidney length. Whether this natural history can be improved by earlier intervention for renal artery stenosis remains to be determined.

Duplex ultrasound scanning in the diagnosis of renal artery stenosis: A prospective evaluation

Since ultrasonic energy can be used to interrogate vessels at great depth, it is only natural that it should be applied to deeply placed arteries in the abdomen. Early studies suggested that high-grade stenoses of the renal artery could be detected by this approach as long as the peak systolic velocity in the renal artery was normalized by that measured in the abdominal aorta. A retrospective study comparing the peak velocity in the renal artery to that from the adjacent abdominal aorta (the renal aortic ratio) showed that if this value exceeded 3.5, it is likely to be associated with a greater than 60% diameter-reducing stenosis. To test this hypothesis, we used duplex scanning to prospectively evaluate 58 renal arteries in 29 patients in whom arteriograms were available. There were 39 renal arteries with 0% to 59% stenosis, 14 with 60% to 99% stenosis, and five occlusions by angiography. Renal duplex scanning accurately diagnosed 38 of 39, 11 of 14, and four of five of these, respectively, giving a sensitivity of 84%, a specificity of 97%, and a positive predictive value of 94% for the detection of a greater than 60% diameter-reducing stenosis. The overall agreement with angiography was 93%. These data show that renal duplex scanning can be used to diagnose renal artery stenosis in patients with hypertension or renal dysfunction, thus providing a rational basis for the selection of patients for angiography.