IV – Investigations
Acute venous disease
Chairperson: M. de Maeseneer
Asymptomatic deep vein thrombosis
The term “asymptomatic” could in fact have several meanings – the symptoms (pain or edema) can be truly absent, unrecognized, misinterpreted or masked by another problem. The intensity and character of signs and symptoms depend on how fast the thrombotic process develops and on the location and extent of DVT. The sensitivity of DVT signs and symptoms is much lower in bed-ridden patients than in outpatients. During clinical probability assessment, not only signs and symptoms but also risk factors of DVT should be taken into consideration.
Even iliocaval thrombi might be asymptomatic. Case reports have documented acute massive PE as well as severe PTS as a consequence of preceding undiagnosed DVT. However, larger studies have not demonstrated a high risk of poor outcome in patients with undiagnosed DVT. For example, if the exclusion of the diagnosis of DVT was based on clinical probability assessment solely, some cases of asymptomatic DVT were missed, but the prognosis of the patients was not poor. The problem is whether to screen some at-risk patient groups for asymptomatic DVT and which method should be used. In one study, complete duplex ultrasound had a poor sensitivity for asymptomatic DVT (compared with bilateral venography). Several studies have assessed the prevalence of asymptomatic DVT in various patient groups, eg, in surgical patients. The results have proven the occurrence of DVT despite prophylaxis (the prevalence of 10% and 8% after major abdominal and major orthopedic surgery, respectively), in the great majority of cases DVT was asymptomatic, mostly untreated, but the prognosis was good. Another study has searched for asymptomatic DVT in cancer patients and found the prevalence of 10%.
As to possible long-term sequelae, the published literature has not been conclusive so far. The epidemiological data on PTS prevalence are quite consistent with the known incidence of (diagnosed) DVT, thereby suggesting that PTS as a consequence of a possible prior undiagnosed DVT is probably not too frequent. However, a metaanalysis has found the prevalence of PTS after asymptomatic DVT to be 17%.
In a trial assessing the prophylaxis of VTE after the surgery of a ruptured Achilles tendon, 34% of cases of DVT occurred despite prophylaxis – mostly asymptomatic and most peroneal. The patients were given standard therapy (anticoagulation, compression) and in follow-up no significant clinical consequences were found (though sonographic changes – reflux and/or obstruction – were present).
In conclusion, DVT can occur without any symptoms and asymptomatic DVT may disappear without sequelae, but may cause serious complications as well. If the suspicion of asymptomatic DVT is high (based on clinical probability assessment), further tests should be used (D-dimer, ultrasonography, and even CT if necessary). In cancer patients, routine screening for asymptomatic DVT is discouraged (long-term DVT prophylaxis is recommended). Once asymptomatic DVT has been diagnosed, it should be treated.
Chronic venous disease
Duplex of the deep veins – tips and tricks
It is important to define the distribution and extent of reflux and obstruction for the treatment of chronic venous disease. The author summarized various aspects of detection with duplex ultrasound in chronic venous disease. The author reported that reflux was primary in 65% of patients, secondary in 27%, primary and secondary in 8%, and congenital in <1%. The prevalence of skin damage increased with the extent of reflux and obstruction. Reflux plus obstruction increased 3.5- fold the risk of signs and symptoms. The author highlighted that anatomic variations are very frequent. In a survey of 1000 limbs examined by duplex he observed 834/1000 (83.4%) had anatomic variations. The femoral vein was double in 261 limbs, triple in 12, hypoplastic in 2, and absent in 1, with reflux in one vein in 4% and thrombosis in 5%. Persistent sciatic vein was present in 3 limbs. The popliteal vein was double in 374 limbs and triple in 26, with reflux in one popliteal vein in 7% and thrombosis in 6.1%. The posterior tibial vein was triple in 82 limbs, single in 16, and absent in 3. The peroneal vein was triple in 11 limbs and single in 11. In another study (327 patients with DVT 122 chronic venous disease), a significant asymmetry rate of 84.4% was present.
The author showed the criteria for defining significant central vein stenosis with duplex: peak vein velocity V2/V1 across the stenosis, poststenotic mosaic color, abnormal Doppler signal at the area of stenosis, contralateral asymmetry, vein dilation prior to the stenosis. He indicated the reflux cut-off values: superficial veins > 500 ms, perforator veins > 350 ms, calf veins + deep femoral > 500 ms, femoropopliteal veins > 1000 ms. Finally, he discussed the ultrasound findings in acute thrombosis: noncompressible vein dilation, filling defect on color Doppler, absence of signal, smooth borders, homogenous texture, echolucent. Chronic: decreased diameter, wall thickening, rough borders, heterogenous texture, echogenic, intraluminal webs, reflux. During question time the author suggested several sites to better visualize the calf veins.
Chaiperson: G. Jantet
Chronic Venous Insufficiency – Think Obstruction!
P. Neglen of River Oaks Hospital, Flowood, Mississippi, started his presentation by defining the problems experienced by patients with CVI: leg pain, swelling, discoloration, dermatitis, lipodermatosclerosis, and venous ulceration. Although CVI is recognized to have several contributing pathophysiological factors (failure of calf muscle pump, stiff joints, vein wall stiffness, vein lumen geometry, calf venous volume, etc.), the main emphasis has so far been on valve reflux. CVI has almost become synonymous with venous reflux.
Intravascular ultrasound–guided endovenous stenting of iliac venous obstructions or stenosis has resulted in major clinical improvement, even in the presence of remaining reflux, suggesting that chronic proximal obstructions are an important pathophysiological factor in the clinical expression of CVI. Generally speaking one should initially investigate the patient (duplex scanning, venography, magnetic resonance venography, CT-V or intravenous ultrasound) in order to define the classification of venous dysfunction (advanced CEAP) and afterwards combine conservative treatment with invasive procedures if necessary. P. Neglen emphasized that duplex ultrasound is only a qualitative method: duration of detected reflux does not correlate with clinical severity, peak reflux velocity is better but its high variance prevents clinical use and it is not possible to assess the contribution by individual segment reflux to global hemodynamics. Therefore, duplex findings alone are not enough for targeting and correction of a multi-level and multisystem disease. There is no method of quantifying reflux at a single valve site and in the superficial, perforator or deep system separately. Nor is it known how to quantify hemodynamically venous outflow obstruction (to what degree a venous obstruction is hemodynamically significant, for instance). There is no reliable noninvasive test and here invasive pressure measurements are insensitive. Duplex ultrasound is a test for segmental reflux and obstruction. It is the initial choice for determining morphologic criteria for obstruction and is able to define the severity of reflux and obstruction. Existing routine tests (eg, outflow air or straingauge plethysmography, duplex ultrasound and femoral or other pressure tests) can not be used to exclude significant venous outflow obstruction. When venous outflow obstruction is suspected, ultrasound scanning of the lower extremity has to be complemented by transfemoral venography, magnetic resonance venography, CT-venography or intravenous ultrasound in selected cases. Intravenous ultrasound is superior to all other imaging techniques for diagnosis of the degree and extent of obstruction. It is essential for adequate stent placement in the femoral-ilial-caval venous outflow.
Why do we have to think of obstruction in our practice? Because venous outflow obstruction plays an important role in the clinical manifestation of chronic venous disease, particularly pain. Ulcers occur rarely in the presence of isolated obstruction (4%) and more often in association with reflux (30%). Treatment of obstruction results in impressive clinical relief of pain, swelling, healing of ulcers, venous clinical severity score, venous disability score and quality of life, even when associated reflux is left untreated. Pelvic outflow obstruction is observed frequently following acute DVT, because only 20-30% of the veins completely recanalize. In cases of chronic iliofemoral obstruction, more severe symptoms are present than in femoropopliteal disease. Venous claudication is present in 15-44% of cases, and ulcer in 15% of cases within 5 years. Interestingly, in 80% of proximal postthrombotic cases an underlying compression-type lesion (May-Turner/Cockett syndrome, or iliac vein compression syndrome, intraluminal congenital lesionswebs, spurs, chords) can be identified. Stenting of the underlying stenosis after clot removal improves patency from 27-44% to 86-93%! These “primary”, nonthrombotic iliac vein lesions (NIVLs) (more frequently on the left side) may be more pathogenic than previously thought. In the author’s experience of stenting more than 1000 obstructive limbs, approximately 40% had nonthrombotic blockage. Intravenous ultrasound–positive NIVLs are frequently present in “primary” reflux cases! NIVLs are frequently seen in asymptomatic populations (intraluminal lesions in 22-23% and external compression in 66-88%)! These primary lesions might not become clinically significant until other components of the venous system fail (and reflux is added) and the extremity becomes decompensated. Correction of these permissive iliac lesions alone often results in remission, even when the secondary pathology is not addressed. Intravenous ultrasound should be used in patients with clinical features (pain out of proportion to lesion, proximal postthrombotic disease, no detectable lesions explaining symptoms) and in the presence of positive indicators of obstruction (stenosis/occlusion on imaging techniques, presence of collaterals, positive pressure tests). Intravenous ultrasound–verified stenosis of greater than 50% is considered for stenting. Postprocedural thrombotic complications are rare (1.5-3%), the cumulative primary and secondary patency rate of stenting is quite good and the rate of in-stent restenosis is 1-10%.
As a key message of this exciting presentation we can summarize the following: a comprehensive workup and classification is mandatory prior to treatment; in the case of CVI think of obstruction; an obstructive NIVL on intravenous ultrasound is a frequent finding; complement ultrasound scanning of the lower extremity with transfemoral venography, magnetic resonance venography, CT-V or intravenous ultrasound; venous stenting is an evolving method which is the primary choice in the treatment of iliocaval obstruction; a more aggressive approach to diagnosis and treatment of venous outflow obstruction is justified; attempt minimally invasive procedures before surgery; iliofemoral obstruction should be treated before axial deep reflux in combined disease; superficial reflux should be treated before axial deep reflux; combine iliac venous stenting and endovenous ablation of superficial reflux even in the presence of axial deep vein reflux; deep valve repair should be considered when the above measures fail; percutaneous artificial valve placement may change this paradigm, but at this moment this is not the case.
Diagnostic approach to venous malformations
The author stressed the importance of distinguishing correctly between hemangiomas and venous malformations (VMs). Hemangioma is a “self-limited” vascular tumor of endothelial cells that appears in the neonatal period. Hemangioma has a characteristic initial rapid growth, proliferation phase, followed by a phase of involution with a slow regression before the age 5-10 years, in the majority of cases. The differential diagnosis between VMs and hemangiomas is in general easy on the basis of the clinical history and a careful physical examination. Occasionally, a simple test such as an ultrasound study can confirm the clinical diagnosis.
The Hamburg classification based on the ISSVA (International Society of the Study for the Vascular Anomaly) workshop held in Germany in 1988 was created to classify congenital VMs according to their pathogenesis and clinical course, which are essential for different treatment choices. The classification distinguishes between predominantly arterial malformations, venous, lymphatics and capillary lesions or a combination of them. Every congenital VM is divided into two embryological subtypes (extratruncular or truncular). The identification and confirmation of this embryological subtype is the first step towards proper management, because their prognosis is completely different.
In the second part of the presentation, B-B. Lee emphasized the correct differentiation between VMs and arteriovenous malformations, both being congenital VMs, but with very different prognoses. Congenital VMs present at birth as a vascular defect and continue growing at a rate proportional to the growth of the body. Congenital VMs may be a mix of several vascular defects with several characteristics and behaviors, involving more than one vascular component (arterial, venous, lymphatic, or capillary). Congenital VMs may present as a single predominant component (eg, venous malformations) or a combination of two or more types (eg, hemolymphatic malformation). Arteriovenous, lymphatic, and venous malformations are different forms with different clinical courses and prognoses.
VM is the most common form of congenital vascular malformation. In the majority of cases, a VM presents as an independent lesion but, sometimes, as a combined form with other congenital VMs (eg, Klippel-Trenaunay syndrome; Parkes-Weber syndrome). The identification of the embryological subtype of the VM (extratruncular or truncular) is of pivotal importance. The extratruncular form of VM is characterized by a single alteration: retention of mesenchymal cells (angioblast) during early embryological development. This lesion tends to progress with an unpredictable prognosis and a high rate of recurrence. The defect in the truncular VM appears during the vascular formation of the trunk during later fetal development. It remains as a truncal fetal malformation without a normal involution (eg, sciatic vein, marginal vein), or as a defective vessel trunk formation: obstruction/dilatation of the formed vessels (eg, venous aneurysm), or aplasia, hypoplasia, and/or hyperplasia of the vessel development (eg, agenesis/rudimentary deep vein). Truncular VM has, basically, a hemodynamic effect with better prognosis and less frequent recurrence than extratruncular VM. Unless there is any serious morbidity or complication, the truncular lesion in general should be closely monitored, with conservative/supportive management.
Finally, B-B. Lee explained the management of one VM. Following careful history taking and physical examination, the diagnosis must be confirmed with a noninvasive test such as ultrasound or MRI. More invasive studies (eg, arteriography) can be reserved for the more advanced cases and when surgical/endovenous therapeutic measures are being considered. Because of the high incidence of co-existing lesions, when one congenital VM is confirmed, the presence of others should be checked for.
Chronic Cerebrospinal Venous Insufficiency: diagnosis and treatment
Chairperson: P. Zamboni
Moderator: B-B. Lee
What we heard in this session has the potential to be a revolution in medicine. The hypothesis of P. Zamboni is the following. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown pathogenesis. Magnetic resonance venography and postmortem studies have shown a topographic correspondence between MS plaques and an impaired cerebral venous system. Could impaired cerebral venous outflow, with delayed venous drainage and reflux to the brain, be at least partly responsible for MS?
Chronic cerebrospinal venous insufficiency and multiple sclerosis: theoretical and practical issues
M. Simka further described this hypothesis, suggesting that chronic cerebrospinal venous insufficiency could lead to venous reflux toward to the brain. This might provoke a breakdown of the blood-brain barrier, extravasation of erythrocytes and immune blood cells, and trigger the inflammatory process of MS. The main abnormalities found at ultrasonography in patients with chronic cerebrospinal venous insufficiency are stenoses of the internal jugular veins, inverted valves, absence of flow in the internal jugular or vertebral veins, reflux in internal jugular and vertebral veins, as well as in the deep cerebral vein on transcranial ultrasonography.
Cerebral veins and iron deposits explored by advanced MRI-SWI
M. Haacker reported his use of venous magnetic resonance angiography (MRA) to evaluate iron deposits in the brain. This susceptibility-weighted imaging (SWI) MRA can visualize medullary veins and iron content in the gray matter. He observed a concordance between areas where iron tends to be deposited and venous drainage areas. As compared with controls, MS patients have increased amounts of iron in basal ganglia and the thalamus. In young patients, evaluation of iron content at SWI-MRA had the potential to discriminate between MS and control patients.
Imaging and endovascular treatment of chronic cerebrospinal venous insufficiency
The imaging and endovascular treatment of chronic cerebrospinal venous insufficiency was presented by R. Galeotti. He reported on a series of 65 MS patients with ultrasonographic criteria for chronic cerebrospinal venous insufficiency who all underwent phlebographic examination of main extracranial and extravertebral venous pathways: left femoral access, and imaging of the iliac, iliolumbar, renal, and azygous veins, as well as bilateral imaging of internal jugular and vertebral veins. They found multiple lesions: significant stenoses, annulus and septum, valve malformations, membranous obstruction, vein hypoplasia or agenesis. Uni- or bilateral internal jugular vein stenosis was found in 91% of patients, and azygous lesions were found in 86%. None of the 235 control patients included in the same study had ultrasonographic criteria for chronic cerebrospinal venous insufficiency.
All venous lesions were treated by percutaneous transluminal angioplasty. After 18-month follow-up, 95% of treated azygous veins remained patent, versus only 50% of internal jugular veins. A different distribution of lesion types between the two territories may account for this difference in the long-term success rate. Patients with internal jugular vein restenosis might benefit from redilatation with high pressure and cutting balloon, or open surgery.
Treatment of chronic cerebrospinal venous insufficiency: clinical results on associated multiple sclerosis
F. Salvi described the clinical progression of these 65 MS patients who underwent percutaneous transluminal angioplasty for chronic cerebrospinal venous insufficiency. Whereas those with secondary progressive or primary progressive MS had little change in their MS severity score after 18 months, patients with relapsing-remitting MS exhibiting significant improvement: 50% of them were relapse-free after 18 months. All patients with relapsing-remitting MS who had persistent vein patency at 18 months were relapse-free, whereas all patients with restenosis experienced disease relapse.
The authors concluded that chronic cerebrospinal venous insufficiency and MS might be closely related, and that endovascular treatment may alter the course of MS, though more studies are needed to confirm these results.
Max Ratschow Medal Session (Collegium Internationalis Angiologiae)
Chairperson: E. Rabe
Pelvic venous disorders: the desperate plea of women with the nutcracker syndrome
The Max Ratschow Medal Session (organized by the Collegium Internationalis Angiologiae) was introduced by the UIP president E. Rabe, who presented the main speaker – J-L. Villavicencio, an internationally known vascular surgeon. After paying tribute to M. Ratschow (the first German angiologist), J-L. Villavicencio proceeded to the lecture.
The main symptoms of pelvic venous disorders are chronic diffuse pelvic and flank pain, dyspareunia, dysmenorrhea, dysuria, vulval, intrapelvic and lower extremity varices, hematuria, and proteinuria. The possible etiology is: gonadal vein insufficiency, insufficiency of internal iliac vein and its tributaries, combination of both these – “dumping syndrome”, and nutcracker syndrome.
Nutcracker syndrome is caused by the compression of the left renal vein between the aorta and superior mesenteric artery producing obstruction of the gonadal and left renal venous outflow leading to retrograde flow toward the pelvis and subsequent pelvic congestion, formation of periureteral tortuous collaterals and dilatation of gonadal veins. The diagnosis should be based on clinical and laboratory evaluation (hematuria, chronic left flank pain, proteinuria) and imaging methods – noninvasive (multi-slice 3D CT angiography, duplex ultrasound, MRI) and invasive (direct varicography, retrograde selective renal and gonadal phlebography, retrograde video-angiography with renocaval gradient measurement – normal is 0-1 mm Hg). The differential diagnostics should exclude other gynecologic pathology and urinary or bowel diseases. Treatment options comprise surgical and endovascular procedures: nephropexy, gonado-caval bypass, external Gore- Tex renal vein stents, balloon angioplasty with intraluminal renal vein stenting, left renal vein transposition to a lower caval site, spleno-renal bypass, and gonadal vein embolization alone or with the embolization of internal iliac vein tributaries. The treatment modality should be tailored to the type and severity of symptoms, the patient´s age, and hemodynamic findings.