M. Griffin

Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects : a 10-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: 13 221 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 10 000 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,xa0III,xa0IV 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.

Foam-Sclerotherapy, Surgery, Sclerotherapy, and Combined Treatment for Varicose Veins: A 10-Year, Prospective, Randomized, Controlled, Trial (VEDICO Trial)

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclero therapy ; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclero therapy ; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occur rence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. Standard, low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.

'Real' epidemiology of varicose veins and chronic venous diseases: the San Valentino Vascular Screening Project.

The aim of this study was to evaluate the prevalence and incidence of venous diseases and the role of concomitant/risk factors for varicose veins (VV) or chronic venous insufficiency (CVI). The study was based in San Valentino in Central Italy and was a real whole-population study. The study included 30,000 subjects in eight villages/towns evaluated with clinical assessment and duplex scanning. The global prevalence of VV was 7%; for CVI, the prevalence was 0.86% with 0.48% of ulcers. Incidence (new cases per year) was 0.22% for VV and 0.18% for CVI; 34% of patients with venous disease had never been seen or evaluated. The distribution of VV and CVI in comparison with duplex-detected incompetence (DI) indicates that 12% of subjects had only VV (no DI), 2% had DI but no VV, 7.5% had DI associated with VV, 2% apparent CVI without DI, 3% DI only (without CVI), and 1.6% both CVI and DI. VV associated with DI are rapidly progressive and CVI associated with DI often progresses to ulceration (22% in 6 years). VV without significant DI (3%) and venous dilatation without DI tend to remain at the same stage without progression for a lengthy time. New cases per year appear to have a greater increase in the working population (particularly CVI) possibly as a consequence of trauma during the working period. In older age (> 80 years), the incidence of CVI tends to decrease. Ulcers increase in number with age. Only 22% of ulcers can be defined as venous (due to venous hypertension, increased ambulatory venous pressure, shorter refilling time, obstruction and DI). Medical advice for VV or CVI is requested in 164 subjects of 1,000 in the population. In 39 of 1,000, there is a problem but no medical advice is requested and in only 61 of 1,000, the venous problem is real. In VV in 78% of limbs, there is only reflux, in 8% only obstruction, and in 14% both. In CVI, 58% of limbs have reflux, 23% obstruction, and 19% both. In conclu sion, VV and CVI are more common with increasing age. The increase with age is linear. There was no important difference between males and females. These results are the basis for future real, whole population studies to evaluate VV and CVI.

Prevention of Venous Thrombosis in Long-Haul Flights with Flite Tabs: The LONFLIT-FLITE Randomized, Controlled Trial:

The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treat ments ; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 throm botic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p<0.05). Events were asymptomatic. In conclusion, Flite Tabs were effective in reducing thrombotic events and in controlling edema in high-risk subjects in long flights.

Prevention of Venous Thrombosis with Elastic Stockings During Long-Haul Flights: The LONFLIT 5 JAP Study

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in longhaul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibial veins were scanned before and within 90 minutes after the flights. Of the 205 included subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p<0.0025; six times greater in the control group). Intention-to-treat analysis counts 18 failures in the control group (12 lost to follow-up + six thromboses) of 112 subjects (15.8%) versus eight failures (7.3%) in the treatment group (p<0.05). The tolerability of the stockings was very good and there were no complaints or side effects. All events were asymptomatic. Considering these observations, Scholl Flight Socks are effective in reducing the incidence of DVT in high-risk subjects.

Prevention of Venous Thrombosis and Thrombophlebitis in Long-Haul Flights with Pycnogenol®

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol® per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol®group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol® treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Two-week topical treatment with Essaven gel in patients with diabetic microangiopathy--a placebo-controlled, randomized study.

The pulmonic valve is the least commonly involved valve in infective endocarditis. Pulmonic valve endocarditis is usually associated with tricuspid valve endocarditis, and isolated pulmonic valve endocarditis is exceedingly rare. The predisposing factors for developing pulmonic valve endocarditis include a congenitally anomalous pulmonic valve, intravenous drug abuse, and the presence of indwelling intravenous or flow-directed pulmonary artery catheters. More cases of group B streptococcus endocarditis are being reported. The risk factors for group B strepto coccus endocarditis include diabetes mellitus, cancer, alcoholism, malnutrition, immunocom promised status, intravenous drug abuse, postpartum and postabortion states, and underlying valvular disease. The vegetations of this type of endocarditis are usually large and have a higher tendency to result in embolism. The presentation of group B streptococcus endocarditis is usually acute and may result in rapid valve destruction if not treated promptly. A case of isolated pulmonic valve endocarditis caused by group B streptococcus, Streptococcus agalac tiae, is presented that was diagnosed with multiplane transesophageal echocardiography in a 40-year old, alcoholic, malnourished man, who was successfully treated with intravenous peni cillin G. The literature on the isolated pulmonic valve endocarditis caused by group B strepto coccus is reviewed.

Effects of Shock Waves on the Microcirculation in Critical Limb Ischemia (CLI) (8-Week Study)

Shock waves (SWs) are used to control and decrease pain in several clinical conditions (eg, painful elbow and shoulder, etc). This clinical effect may be due to cellular stunning of the tissues (particularly nervous components) in the area treated with SW. It may also be the consequence of unknown metabolic actions on tissues, which may include changes in cellular permeability and the liberation of proteins and mediators locally acting on pain and nerve endings. The aim of this study was to evaluate the reduction in pain and the microcirculation improvement induced by SWs treatment in an 8-week study in patients with chronic limb ischemia (CLI). Patients with CLI (15 with rest pain only and 15 with rest pain and limited distal necrosis) were included. The treatment was based on a 30-minute SWs session, three times weekly for 2 weeks. Clinical and microcirculatory evaluation were performed with laser Doppler PO 2 and PCO2 measurements. Pain was measured with an analogue scale line. A Minilith SL1 (Storz Medical, Switzerland) litotriptor was used. The parabolic reflector is coupled to the skin with a silicon water cushion. Focal pressure was adjusted between 6 and 70 Mpa in eight steps. The energy flux density was variable from 0.03 to 0.5 mJ/mm2. Focal diameter and distance were defined (depth of target within the patients foot of about 70 mm). The coded intensity used in this study was between 6 and 8 and the application time was 20 min (at four impulses per second). Twenty-eight of the 30 patients with CLI (15 with rest pain only and 13 with necrosis) completed the study. The treatment was well tolerated. Blood pressure was unchanged after 8 weeks while the increase in laser Doppler flux was significant (p<0.05) (at all measurements after treatment). The ORACLE score at 1 and 8 weeks was decreased (p < 0.05). The same trend was observed with the analogue scale line for pain (p < 0.05). PO2 increased (p < 0.05) and PCO2 decreased (p < 0.05). Tibial pressure did not change. All patients observed an increase in their subjective pain-free walking distance. The improvement was still present after 8 weeks. In a separate subset of 37 patients (mean age 60 ±9 years; males) with CLI, a SWs dose-finding evaluation was performed. Flux changes were measured at the dorsum of the foot. Three treatment plans were used: (a) 20-minute SW treatment only once; (b) 20-minute SWs treatment every 2 days for 1 week; (c) 20 minutes every day for 1 week. Treatments were well tolerated. A different increase in flux was observed on the basis of different treatments. Flux vari ations generally indicated that increased SWs dosage was associated with proportional flux increase. Flux improvement was still present after 4 weeks. SWs treatment in CLI produced changes both in the microcirculation and on pain. These preliminary results are comforting and open new research options to be explored in the near future.

Superficial vein valve repair with a new external valve support (EVS). The IMES (International Multicenter EVS Study).

The aim of this international multicenter trial was to evaluate the effects of a new surgical device (Gore External Valve Support-EVS) and technique for external valvuloplasty of the long saphenous vein (LSV). Patients with superficial venous disease and venous hyper tension due to pure superficial venous incompetence were randomized into two treatment groups, the first treated with conventional treatment (ligation or stripping) and the second with external valvuloplasty with the EVS. Patients with uncomplicated varicose veins within the age range of 35-65 years were included. Incompetence with presence of functional cusps at the saphenofemoral junction (SFJ), with vein dilatation were the main inclusion criteria. The EVS comprised of a GORE-TEX® patch material (including a nitinol frame) that is placed around the vein, producing a reduction in the caliber of the vein. Also the vein section becomes elliptical. These combined actions are aimed to reduce incompetence, allowing a better closure of the cusps. The EVS was placed at the SFJ after limited dissection of the vein and ligation of collaterals. The procedure was randomized as an alternative to simple ligation or stripping (according with the procedure commonly used in the center). The associated ligation of distal incom petent veins was allowed. The main outcome measures of the study were evaluated by color-duplex (morphologic findings and evaluation of reflux) and with ambulatory venous pressure (AVP) or air-plethysmography (APG). Main endpoints of the first year of the study and main subject of this report (mainly concerning safety within the first year of follow-up) were considered presence/absence of reflux; patency of the veins; mobility/function of vein cusps; occurrence of thrombosis; tolerability of the device; and increased complexity and operating time needed for the EVS. At 1 year 30 patients had been randomized (14 EVS implanted, 16 controls). Reflux was absent in all EVS patients, all treated veins were patent, and all cusps were mobile. No thrombosis had been observed and the tolerability of the device was very good. The increased complexity required by placing the EVS was limited (5-12 minutes more). In conclusion results of the first year show efficacy and tolerability of the EVS. In selected patients (superficial LSV incompetence, reflux-dilatation, functional SFJ cusps, incompetence mainly due to enlargement of the vein), the EVS could be an effective alternative to destructive ligation and/or stripping of the vein. Prolonged follow-up will indicate the clinical poten tials of the EVS.

Treatment of Superficial Vein Thrombosis with Standardized Application of Essaven Gel A Placebo-Controlled, Randomized Study

The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 4-week study evaluated the average skin temperature and an analogue symptomatic score. Below-knee SVT was associated with large varicose veins. In patients treated with active EG the decrease in score and in the average, composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage. In conclusion, treatment with EG in SVT improves symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective use of EG in SVT.Beside atherosclerosis, aortic aneurysms can be part of the clinical spectrum of many systemic diseases, including infectious, inflammatory, genetic and, less often, congenital disorders. A 48- year-old white man presented with multiple large aneurysms of the aorta and its main branches. Medical history was unremarkable except for the presence of a softened abdominal mass since he was 28 years old. On the physical examination, an arterial murmur was heard over the left carotid artery and a palpable mass was noted in the whole right side of the abdomen. No skin or joint abnormalities were noted. Aortography, computed tomography, and magnetic resonance angiography showed multiple large aneurysms of the descending thoracic and abdominal aorta. Aneurysms of the innominate, left subclavian, and carotid arteries were also seen. This case resembles those previously reported, in which multiple aortic aneurysms were associated with abnormalities of the type III procollagen gene (COL3A1). Although the classic stigmas of the Ehlers-Danlos syndrome type IV were lacking, this genetic disease may be the cause of the multiple aneurysms in this patient.