Ganesh Ramaswami

Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography

PURPOSE The North American and the European Symptomatic Carotid Endarterectomy Trial investigators reported a conclusive benefit of carotid endarterectomy for patients with symptomatic 70% to 99% internal carotid artery (ICA) stenosis. However, it has been suggested that plaque structure may be an even more important factor in producing stroke than the degree of stenosis. The aim of this study was to test the hypothesis that the ultrasonic characteristics of carotid artery plaques were closely related to symptoms and to the prevalence of cerebral infarcts on computed tomography (CT). METHODS One hundred five carotid artery plaques causing greater than 70% stenosis in the ICA in 83 consecutive patients who underwent brain CT were characterized into four ultrasonic types: echolucent plaques, predominantly echolucent plaques, predominantly echogenic plaques, and echogenic plaques. Patients with permanent neurologic deficit were excluded. RESULTS There was a significant ipsilateral association between type 1 plaques and symptomatic hemispheres (p < 0.002). Twenty-six of the 105 cerebral hemispheres assessed by CT had infarcts. There was an increased incidence of brain infarcts in type I plaques (37%) compared with 18% in types II, III, and IV combined (p < 0.02). CONCLUSION Our results support the hypothesis that echolucent plaques are more frequently associated with symptoms and cerebral infarctions and provide further evidence that these plaques are unstable and tend to embolize. Studies on the natural history of asymptomatic carotid artery stenosis should investigate whether plaque characterization could identify a high-risk group.

New insights into the pathophysiologic condition of venous ulceration with color-flow duplex imaging: Implications for treatment?

PURPOSE This study was conducted to investigate the distribution of reflux in the veins adjacent to or within the venous ulcer (local) and to correlate it with the pattern of disease of the axial veins (all veins away from the ulcer area) of the affected limb. METHODS Forty-three ulcers in 34 legs of 33 patients were examined with color-flow duplex imaging. The veins in the area of the ulcer were scanned with a sterile technique. RESULTS In 17 legs (50%) there was documented past deep venous thrombosis. All of the 34 limbs had reflux in the superficial or deep axial veins either alone or in combination. Fifteen of these limbs (44%) also had perforating vein incompetence, but none had perforator incompetence alone. Six ulcers showed no evidence of reflux in the local veins when scanned through the ulcer bed despite the presence of reflux in the axial veins of the limb. In 13 limbs with 17 ulcers, either the superficial axial veins alone or the deep axial veins alone were affected (with or without associated perforator incompetence). Examination of the local veins associated with these 17 ulcers revealed a similar pattern of reflux to that seen in the axial veins in 13 cases, with the remaining 4 ulcers showing no local venous abnormality. The pattern of reflux was less predictable at the local ulcer level in limbs where both superficial and deep venous incompetence coexisted in the axial veins. Only 7 of the 26 ulcers (27%) in these limbs had similar evidence of combined superficial and deep reflux in the local ulcer veins, whereas 10 ulcers (39%) were associated with local reflux in the superficial or deep veins alone. CONCLUSIONS These data show that 86% (37/43) of the ulcers has some degree of reflux in the local area, the pattern of which may differ from the axial vein disease. Treatment of the local hemodynamic abnormalities may be an important factor in the healing of the ulcers and in the prevention of their recurrence.

Duplex controlled angioplasty

Duplex examination was carried out to assess lesions in peripheral arteries amenable to angioplasty. With the help of a special catheter, angioplasty of these lesions was performed under Duplex control. Sixteen patients presenting with claudication were examined by Duplex and 38 lesions were identified (31 stenoses, seven occlusions) and all the findings except one (vessel E1) were confirmed by subsequent angiography. Sixteen lesions were considered amenable to angioplasty and 13 lesions (in 10 patients) were selected for Duplex controlled angioplasty. A new catheter system which has a piezo-electric transducer at the centre of the balloon and integrated to a Duplex scanner via a catheter system interface, was used for the procedure. This allows the exact position of the balloon to be represented on the screen. Thirteen lesions (seven superficial femoral artery (SFA), three external iliac, two common iliac and one graft) were subjected to angioplasty under Duplex control. In one patient, the SFA was punctured directly under ultrasound control as the profunda was diseased. The guide wire was visualised in all cases and in the majority of cases, balloon size for the angioplasty was chosen by measurement of the arterial diameter by Duplex, which was also used for haemodynamic evaluation before, during and after the procedure. Eleven lesions (85%) underwent angioplasty entirely under Duplex control and additional X-ray control was needed in only two cases. In conclusion, Duplex allows the monitoring of both anatomical and haemodynamic parameters during angioplasty. It also reduces the risk of ionising radiation. Our initial experience has been encouraging as angioplasty was performed in the majority of lesions purely under Duplex control.

ANGIOPLASTY OF LOWER LIMB ARTERIAL STENOSES UNDER ULTRASOUND GUIDANCE : SINGLE-CENTER EXPERIENCE

PURPOSE To examine the feasibility and utility of ultrasound-guided angioplasty for treating lower limb stenoses. METHODS Duplex ultrasonography was employed to guide 55 balloon dilation procedures (27 iliac, 26 superficial femoral, 1 profunda, and 1 vein graft) with the help of a special ultrasound catheter (EchoMark). Ultrasound was used to determine balloon size, monitor guidewire passage, direct the dilation, and judge procedural success. Angiography was performed prior to the procedure to confirm preprocedural ultrasound findings and afterward to compare with duplex visual and hemodynamic parameters of success (peak systolic velocity ratio < 2.0). RESULTS The balloon size determined from duplex measurements correlated in all cases with sizes selected based on the angiographic image. Guidewire visualization was possible in 95% of the cases. Angioplasty using ultrasound alone was feasible in 84%; inability to obtain a satisfactory image owing to vessel tortuosity, calcification, and bowel gas accounted for the failures. Against the duplex success criterion, initial completion angiograms had an accuracy of 76%, sensitivity of 76%, and specificity of 100%. The additional time for ultrasound guidance averaged 42 +/- 12 minutes for all cases. CONCLUSIONS Our results show that ultrasound guidance is feasible in routine clinical practice. In this series of well-selected cases of arterial stenoses, angioplasty was performed safely using ultrasound guidance alone in over 80% of the cases. Fluoroscopic monitoring is needed when ultrasound visualization is suboptimal.

PGE 1 Treatment of Severe Intermittent Claudication (Short-Term Versus Long-Term, Associated with Exercise) Efficacy and Costs in a 20-Week, Randomized Trial

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe inter mittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 ±10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 μg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE 1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 μg, afternoon 40 μg; second day morning and afternoon 60 μg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 μg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p < 0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p < 0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p < 0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p < 0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was ~ 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p < 0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE 1 treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabili tation, and may be easily used in a larger number of nonspecialized units.

Shock waves in vascular diseases: an in-vitro study.

Three human aortic specimens were used for this in-vitro study on the effects of shock waves on the arterial wall. Specimen one was from a normal (for age) healthy aorta. The full abdominal lengh was used (including mesenteric and renal arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The pieces were placed and fixed into degassed water. Shock waves (SW) were focused onto the aortic wall by means of a B-mode ultrasound imager. An SW generator (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces (excluding piece 1, placed in water and left untreated as control) were treated with SW at increasing energy levels. A second aortic specimen of a man with arteriosclerotic plaques was also used and the experiment repeated at energy levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were selected from theoretically destructive levels to minimal levels known not to alter vascular tissues. High-resolution ultrasounds of the aortic segments were performed with a 10 MHz high- resolution, broad-band (ATL 3000, USA) probe in water before and after SW applica tion to detect structural changes in the wall after SW. Histology was performed with a standard hematoxylin-eosin staining. (Abstract continued) Results: The aortic pieces did not show macroscopic damages at visual examination, and at the ultrasound examination no visible changes were observed even at higher levels of SW energy. Also no effects were seen by histology. In conclusion, no damaging effects were observed, visually, by ultrasound, or by histology. At these energy levels SW appear to be safe and do not produce any damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging procedure for potential treatment (ie, thrombolysis) in which vessel walls could be involved. Theoretically it is possible that functional changes could be observed in vivo including cell permeability modifications and other alterations (including changes in the potential of the cells in SW fields to modify themselves and to divide). At the energy levels described in this study SW could, theoretically be, safely used for vascular applications (ie, treating venous and arterial thrombi or in arterial plaques modification) without altering major, structural, arterial wall characteristics. Lesions or alterations that have a different density from the normal wall (thrombi or plaques) could be differently sensitive to the same dosage of SW. These differences in acoustic impedance characteristics could be used for potential treatments with SW without damaging the arterial wall.

Peripheral Transluminal Angioplasty under Ultrasound Guidance: Initial Clinical Experience and Prevalence of Lower Limb Lesions Amenable to Ultrasound-Guided Angioplasty

PURPOSE Currently, endovascular techniques require monitoring by radiographic imaging for accurate catheter placement. The aim of this study was first to determine the feasibility of angioplasty under ultrasound guidance using a special catheter system. Based on this outcome, the second goal was to investigate the prevalence of lesions amenable to ultrasound-guided angioplasty. METHODS A balloon catheter system (Echomark) has been developed, which allows accurate catheter guidance by ultrasound imaging. An ultrasound-sensitive piezoelectric sensor positioned in the middle of the balloon portion of the angioplasty catheter is interfaced to an external duplex scanner via the catheter system. The exact position of the balloon relative to the transducer is calculated and reproduced on the screen of the duplex scanner to guide balloon positioning. In the feasibility assessment of the procedure, 16 patients with disabling claudication and rest pain were selected for balloon angioplasty under ultrasound guidance based on arteriographic and hemodynamic lesion criteria of > 50% stenosis with a peak systolic velocity ration > 2.5 in a lesion < 4 cm long that could be imaged by duplex ultrasonography. A fall in the peak systolic velocity ratio below 2.0 was selected for a procedural endpoint corresponding to < 30% residual stenosis on the completion angiogram. In the second part of the study, the prevalence of stenoses amenable to ultrasound-guided angioplasty was studied in 80 patients presenting with symptoms of peripheral arterial disease. RESULTS In the feasibility study, 20 stenoses (5 common iliac, 6 external iliac, and 8 superficial femoral arteries and 1 graft) meeting the inclusion criteria were subjected to ultrasound-guided angioplasty with confirmation by completion angiography. The procedure was possible in 18 (90%) of the 20 stenoses. The two failures occurred in iliac arteries that could not be imaged by duplex scanning due to obesity, bowel gas, and/or vessel wall calcification. In one case, the peak systolic velocity ratio exceeded 2.5 despite a satisfactory control arteriogram; redilation was performed, and the ratio fell below 2.0. In the second part of the study, 21 (26.2%) of the 80 patients had 29 stenoses that were amenable to angioplasty according to angiographic criteria (> 50% stenosis and < 4 cm length). All these stenoses were evaluated with duplex scanning to determine their suitability for angioplasty under ultrasound guidance. Twenty-three (79%) of the 29 lesions selected for angioplasty were well visualized by duplex, and angioplasty would have been possible based on our initial clinical experience. CONCLUSIONS Angioplasty under ultrasound control is a feasible technique for peripheral lesions. Ultrasound allows monitoring of both anatomical and hemodynamic parameters during angioplasty and thus provides a procedural endpoint that correlates to the control angiogram. A large proportion (79%) of stenoses deemed suitable for angioplasty can be well visualized by ultrasound, but obesity, vessel wall calcification, and bowel gas may limit the ability to obtain a satisfactory ultrasound image. Ultrasound-guided angioplasty is a potentially useful procedure that warrants further investigation.

Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a ten-year follow-up study (the CAFES-CAVE study)

BACKGROUND Subclinical arteriosclerotic lesions at the carotid and femoral bifurcations may be related to the occurrence of future cardiovascular events and of occult arteriosclerotic coronary disease. B-mode ultrasound of carotid and femoral arteriosclerotic bifurcation lesions may provide a simple screening method to select asymptomatic subjects at risk of future events. METHODS AND RESULTS 13221 low-risk, healthy, asymptomatic individuals were included in a 10-year, prospective, follow-up based on carotid and femoral bifurcation morphology defined by B-mode ultrasound. Four classes were considered at inclusion (I: normal wall, II: wall thickening, III: non-stenosing plaques, IV: stenosing plaques). When 10000 subjects (75.6% of included subjects; 6055 males, 3945 females) completed the 10-year follow-up the study was concluded. At 10 years there were 10 events (out of 7989 subjects) in class I and 81 events in II (930 subjects; incidence=8.6%); 239 events were observed in class III (611 subjects; 39.28%) and 381 events (470 subjects; 81.06%) in IV; 61 deaths occurred in classes III+IV (1081 subjects) producing a death rate within these two classes of 5.5% (51 out of 61=81.5% in class IV). The increased event rates in classes III and IV were significant (log rank; P<0.02) in comparison with I and II. CONCLUSIONS Carotid and femoral morphology identified 2011 subjects (20.1% of the population) in classes II,III,IV including 98.6% of cardiovascular events and deaths in the following 10 years. A higher (P<0.05) rate of progression in classes III and IV in comparison with I and II was also observed. The ultrasound carotid and femoral classification was useful in selecting subjects at very low risk of cardiovascular events (class I), those at limited risk (class II) and a group at moderate risk (class III). A subpopulation at high risk of cardiovascular events (IV) was identified.

Nomograms Used to Define the Short-Term Treatment with PGE1 in Patients with Intermittent Claudication and Critical Ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study

Infusional, cyclic PGE 1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical condi tions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67 ± 12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 ± 11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.