POTS+May-Thurner’s Syndrome: Rare Disease Causes Rare Disease?

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The patient is a younger man in his twenties who began having dizzy spells associated with near syncope and tunnel vision. He was previously an athlete and was fit and never had such episodes -he had a resting heart rate typically in the 60’s or lower. Workup for arrhythmias was ultimately positive for POTS -postural orthostatic tachycardia syndrome and he was referred to Dr. Fredrick Jaeger of our Syncope Clinic. Tilt table testing the demonstrated the reported tachycardia over 140bpm while upright rising from 60bpm while supine. A radionuclide hemodynamic study (Syncope Radionuclide Hemodynamic Test) showed 54% of his blood volume pooled in his left lower extremity and lower abdomen with upright posture. Air plethysmography (PHLEBOTEST) showed abnormal refill and fill times in both legs and a duplex of the legs showed deep venous reflux in both legs. MRV revealed narrowing of left common iliac vein by the overlying right common iliac artery (May-Thurner’s Syndrome, MTS), and this was where the patient came to my clinic.

The MRV, shown above and below showed the typical pathoanatomy for MTS, but the patient had no symptoms related to left leg swelling, DVT, or varicosities. He did have a reducible left inguinal hernia which was quite tender.

preop-mri_1

After some deliberation, while not promising anything regarding his POTS, I agreed to proceed with treating his pathoanatomy. Discussion with Dr. Jaeger revealed this: normally about 20% of blood volume parks in the legs with standing which is rapidly dissipated with normal calf muscle pump action. In a subset of patients with POTS, there is a 30-40% maldistribution of blood volume into the legs which may or may not drive the autonomic responses leading to POTS. He has never seen a study result showing a 54% distribution.

It made physiologic and anatomic sense to me to proceed with a venogram and intervention, but I confess I was dubious about any affects I might have on the patient’s POTS and I informed him of it. Also, I recommended seeing a general surgeon for his hernia.

Venography showed obstruction of his left common iliac vein as evidenced by the filling of pelvic and lumbar collateral veins.

preangio

Intravascular ultrasound showed the narrowing better and more directly (panel below). The right common iliac artery narrowed the left common iliac vein severely.

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A 22mm Wall Stent was positioned across this and dilated with a 22mm balloon in the IVC and an 18mm balloon in the iliac vein. The resulting venogram showed resolution of the obstruction with collateral veins no longer visualized (below).

post-intervention-angio

But again, IVUS demonstrated more directly the result (and illustrates the importance of having IVUS available for venous interventions).

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The patient was discharged after procedure on a baby aspirin only. He subsequently underwent laparoscopic inguinal herniorrhaphy and returned to my clinic about a month later. His followup duplex showed a widely patent stent and normal flows in the left iliac venous system.

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Surprisingly -the patient declared that he was cured of his POTS. He said since the stents went in, he has not had any more episodes of near syncope, dizziness, tunnel vision, nor weakness requiring lying down to rest. His wife confirmed that he was a flurry of activity over the holidays that was surprising considering how debilitated he was before. This is astonishing to me.

But it should not be a surprise given this: if the POTS symptoms were the result of autonomic dysregulation, a breakdown of the feedback control loop, there were only several places this could be a problem.

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The pathology, the MTS, explains the POTS in this instance very nicely. Because the problem was in the cardiovascular system part of the diagram which I can fix and not the autonomic nervous system control element, which I can’t fix yet, a solution could be tried. This was not an asymptomatic compression of the iliac vein which we do encounter as an incidental finding. It seems to be POTS caused by MTS, and cured for now by treatment of the MTS.

 

 

The Cost of Success in Iliocaval Venous Thrombosis: Efficacy is Only One Aspect of Device and Procedural Innovation

preop-venous-duplex The patient is a young woman who three weeks prior to presentation developed sudden low back pain and left leg pain while exercising on an elliptical. This pain worsened through the subsequent weeks and she developed fevers, chills, and night sweats, and she came to the emergency department. There, she was found to have left thigh and leg swelling. Duplex revealed a left iliofemoral DVT starting from the iliocaval tributary and extending to her left femoral vein (figure above). A CT scan revealed a pulmonary embolism to the left lung (below). No precipitating factors were present. Vascular surgery was consulted.

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Plan was for catheter directed thrombolysis. Venography from the patient’s popliteal vein via a short saphenous access revealed thrombotic occlusion from the left common femoral confluence to the iliocaval confluence. The thrombus was crossed, and ballooning showed there was chronicity to the occlusion in the pelvis evidenced by waisting of the balloon on inflation. A multihole infusion catheter was placed across the thrombus from the thigh to the inferior vena cava and recombinant tissue plasminogen activator was infused overnight.

pretpa-catheter-placement

The venogram from the popliteal vein showed a patent popliteal and femoral vein and the goal of this procedure became opening the common femoral  vein  and its confluence of multiple veins from the thigh, to connect it via stents to the vena cava (second image below).

femoral-vein-pre-tpa

pretpa-ivc

Clinically, there was no change overnight and when the patient was restudied next morning, there was still an occlusion starting at the common femoral vein.

post-lysis-cfv-occluded

At this point, I had a choice as to what to do next. First, I could stop, and have the patient start anticoagulation and return several months later -often, the common femoral vein returns to drain into pelvic collaterals. As I had discussed in an earlier post, venous interventions are no different from arterial ones in that inflow, draining vein, and outflow have to be considered. In the case of the veins, I like to think of it as connecting major confluences, and for a leg, the common femoral venous confluence is paramount.Confluences

Intervening from the popliteal vein to the vena cava is inferior to being able to connect draining veins at the common femoral confluence to the vena cava. So getting the common femoral vein to patency is critical, and can sometimes be achieved with anticoagulation and time. The second option is to break out a thrombectomy catheter and try to remove the thrombus by various machinations, ie. gadgets and novel catheter systems of which there are many. I felt that given the three week time course of the thrombus, the best we could get was some clearance of thrombus, leaving behind a complex network of chronic thrombus and fibrinous scar with the overnight lysis. I didn’t even try this second option and the thrombectomy machine stayed unplugged, the fancy (and expensive) catheters left hanging. The third option, surgery, was not indicated as the patient did not have signs of phlegmasia, and for the same reasons that the lysis didn’t work, opening the common femoral vein for an endovenectomy has uneven outcomes.

The fourth option, mechanical aspiration sheath thrombectomy (MAST), is a technique developed by Dan Clair, our former chair. As a concept, it is very simple. A large sheath (>12F) is introduced and the thrombus is aspirated while the bare sheath is advanced over a wire. The sheath is then removed and the contents emptied. For this case, an 18 F sheath was introduced into the femoral vein in mid thigh.

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The blood is ejected into a basin and a cell saver (in non-malignant cases) is used to salvage the whole blood.

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This reopened the common femoral vein. This was for me a very important step as without achieving this, I would have had to stent into the femoral vein, excluding many smaller veins draining into the common femoral vein, and effectively basing my revascularization off the popliteal vein confluence, an inferior inflow source for venous revascularization.

post-mast-cfv
CFV post MAST

With the common femoral vein open, placing stents from the vena cava to the common femoral vein was straightforward and described elsewhere (reference). The iliac vein remained closed due to the chronic thrombosis, which was clinically May Thurner’s Syndrome, and was stented.

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Three things deserve comment: the vena cava and iliac veins need to be dilated up to 18mm, and larger for the cava. This is disconcerting, but size does matter. Second, IVUS is critical in confirming that everything is open. Third, the 14mm nitinol stent placed into the common femoral vein will stay open, unlike a stent placed into the artery across the inguinal ligament. It likely has to do with the deeper position of the vein in relation to the artery which protects the vein from the ligament. We don’t have the large diameter nitinol stents designed for iliocaval venous revascularization yet, but the available stents do a good job.

large-balloon-in-iliocaval-vein

The patient was discharged on anticoagulation with resolving edema in the left leg and thigh. At one month followup, duplex confirmed wide patency of the stents and IVC and no new DVT.

Discussion: MAST illustrates a critical issue for all innovation in the current setting of resource limitation. Innovations must be made with not just a consideration to efficacy and potential market, but also cost. The large sheaths used in MAST are commonly available and cheaper by multiples of tens compared to the thrombectomy systems and catheters. Unpublished data reviewing 13 patients undergoing MAST with a mean followup showed 69% with complete thrombus removal, 31% with subsegmental removal, no operative mortality, and 92% primary patency at an average of 79 days of followup, all with symptom improvement (Clair, correspondence). Other groups have reported similiar results using “large catheters” (reference 2), but nothing can compare to an 18F sheath in clearing the iliocaval system.

The patient can expect to have excellent patency in the short to mid term (reference 1).

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References

  1. Titus JM et al. J Vasc Surg. 2011 Mar;53(3):706-12.
  2. Chung HH et al. Vasc Endovascular Surg. 2016 Jul;50(5):321-7

3D VR Images from CT Data Very Useful in Open Surgical Planning: Popliteal Venous Aneurysm

ct-3dvr-planning

Patient is a middle aged man with history of DVT and PE who in preoperative workup for another operation was found to have a popliteal venous aneurysm affecting his right leg. Unlike the recently posted case (link) which was fusiform, this aneurysm was saccular (CT above, duplex below). Popliteal venous aneurysms have a high risk of pulmonary embolism because: they tend to form clot in areas of sluggish flow and once loaded with clot, will eject it when compressed during knee flexion.

preop-duplex

When I perform open vascular surgery, I tend to get a CTA not just because it is minimally invasive and convenient, but because it gives important information for operative planning. The volume rendering function, which takes the 3 dimensional data set from a spiral CT scan, and creates voxels (3 dimensional pixels) of density information and creates stunning images such as the one featured on the current September 2016 issue of the Journal of Vascular Surgery. But these are not just pretty pictures.

In fact, I use these images to plan open surgery, even to the location of incisions. Vital structures are seen in 3D and injuries are avoided. Take for example the CT Venogram on the panel below. By adjusting the window level, you have first the venographic information showing the saccular popliteal venous aneurysm on the left panel, you can also see where it is in reference to the muscles in the popliteal fossa. The greater saphenous vein and varicose veins below are well seen.

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By adjusting the level, subcutaneous structures are better seen including the small saphenous vein which could be harvested to create a patch or a panel graft from a posterior approach. A final adjustment of the window level on the right shows the skin, and I can now plan the curvilinear incision.

By changing the orientation, I can also recreate the surgeon’s eye view of the leg in the prone position (below).

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And you can see how well it matches up to the actual operation shown below:

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This was treated with plication of the saccular aneurysm and unlike the fusiform aneurysm, I did not sew over a mandrill (a large 24F foley) inserted through a transverse venotomy, but rather ran a Blalock type stitch under and over a clamp.

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The several weeks postoperatively showed no further trace of the saccular aneurysm.

postop-duplex

The volume rendering software grew out of the 3D gaming industry. The voxel data that paints flesh and bone on skeletons and costumes and weapons is far more complex than what is applied for the 3DVR packages that are available. The images shown for this post comes from TeraRecon/Aquarius, but they are also available as open source software from Osirix, Vitrea, and various software packages sold with CT scanners. While those that are tied to the scanners are often tied to dedicated workstations -limiting you to going to Radiology and taking over their workstation, many will work in the cloud for both the DICOM data and for virtual desktop access through mobile. Contrast is not necessary if the patient has kidney dysfunction -the vessels can be manually centerlined -ie. a line can be dropped in the center of the artery to illustrate its course when viewing the VR images.

I will plan the surgery while in the clinic with the patient, actually tracing out the incisions and dissections necessary to achieve success. It is a wonderful teaching tool for trainees. But most critically, it helps me imagine the operation and its successful completion.

Complex femoral pseudoaneurysm with arteriovenous fistula and large hematoma treated with novel hybrid therapy

wide avf and pseudo

The patient is a middle aged man who after an interventional procedure was referred to my clinic with an expanding hematoma due to a pseudoaneurysm complicated by an arteriovenous fistula. He was a week out from his procedure and had grown a hematoma roughly the size of a hard boiled egg in his left groin which caused him pain. A duplex scan showed a pseudoaneurysm (below) with fistula flow.

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On examination, he had this well circumscribed indurated hematoma of hard boiled egg size with tenderness. There was a bruit on auscultation. Duplex showed a small chamber of flow adjacent to the proximal superficial femoral artery emptying into the femoral vein. Doppler in the common femoral vein showed relatively high fistula flow, and this is reported to be associated with failure of thrombin injection. CTA (top) demonstrated flow of contrast from femoral artery to vein through a pseudoaneurysm chamber that laid between. Angulation to an axial orientation showed this better (below).

axial AVF
Contrast flows from femoral artery (right) to the fistula chamber, then into the femoral vein.

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Axial MPR
Operation was planned, but in the days leading up to the operation, I had a thought -the primary reason why ultrasound guided thrombin injection would fail is the AVF. It would be simple to fluoroscopically guide an angioplasty balloon on the arterial side to occlude the fistula inflow. The next step would be to get access to the pseudoaneurysm with a needle under ultrasound guidance, confirm location with a contrast injection. Once confirmed, the balloon is inflated and a small volume of thrombin would be injected. I discussed this with the patient in detail and he was enthusiastic about trying this before proceeding with an open repair.

 

pseudoaneurysm avf procedure sketch
Schematic of procedure
The procedure went as planned. Ultrasound guided access is aided with dual live display of B-mode and color flow (below)

Arteriography showed much of the contrast from injection of the pseudoaneurysm to preferentially go to the artery which made me worry less about creating a DVT/PE. With balloon inflated (below), thrombin was injected and balloon inflation held for about 30 seconds.

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There was resolution of flow in the pseudoaneurysm and in the fistula. Before and after duplexes are composited below.

prepost pseudo chamber

Repeat duplex on the following day showed resolution of the pseudoaneurysm and arteriovenous fistula.

In the days before ultrasound guided thrombin injection of pseudoaneurysms, open surgical repair of these was fraught with complications. First, these patients typically had cardiac disease. Second, they were usually anticoagulated often with multiple agents. And finally, they were  many times obese, making not only the operation fraught with complexity, but the ultimate wound healing a delicate and rare phenomena. Even now, we get emergency repairs when access hemostasis fails, and these patients are typically high risk. With hematoma evacuation, inflammation, lymph leaks, and infections may follow; the patient was correct in his enthusiasm for agreeing to proceed with a minimally invasive effort.

As to the techniques, they are all well established in the vascular surgeon’s toolbox. Ultrasound guided access of the pseudoaneursm should be obtained before arterial occlusion. This was  facilitated by general anesthesia which kept the patient from moving. Having access to excellent ultrasound and angiographic imaging made this possible. The patient felt much better and was discharged home the next day after his confirmatory duplex.

Nutcracker Syndrome: A Simplified Approach With Gonadal Vein Transposition

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The patient is a young woman in her twenties who developed severe right sided abdominal and back pain about 4 months prior to presentation associated with bouts of bloody urine. Activity and standing exacerbated her pain and inactivity and recumbency relieved it. She gained 15 pounds because of her inactivity. Examination was significant for tenderness over her left kidney. Urinanalysis showed positive proteinuria and hemaglobinuria.

Prior to consultation with me she had had an MR venogram showing compression of her left renal vein by the superior mesenteric artery (nutcracker phenomena). The presence of hematuria, proteinuria, and pain (albeit atypically right sided) made it nutcracker syndrome.

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Dilated left gonadal vein and pelvic varices indicate left renal vein (LRV) ouflow obstruction by the superior mesenteric artery (SMA)

I ordered a renal duplex and a CT venogram for procedural planning.

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On the duplex, the proximal left renal vein (LRV) was not visualized. The right kidney had normal parenchymal appearance and blood flows, while the left, the kidney appeared distended and had flows consistent with outflow obstruction.

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Spectral Doppler flows show respirophasicity in right renal vein(RRV), outflow obstruction on left renal vein (LRV)
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The left kidney is swollen and tender.

CT Venography showed the gonadal vein to be an important outflow vessel to the left renal vein with dilated proximal segment and reflux into pelvic varices.

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A left gonadal vein to iliac vein transposition was planned via a left lower quadrant retroperitoneal exposure. On the table, a venogram was performed with selective access of the left renal vein.

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The injection from the LRV showed severe compression of the LRV with a channel only slightly larger than the sheath and avid reflux into the gonadal vein. Selective access into the gonadal vein and venography from a confluence in the pelvis showed that flow was one way from the LRV into the gonadal vein and this filled a large region of pelvic varices.

Venogram19

Venogram23

The gonadal vein was large caliber and refluxed into two large veins in the pelvis. The one that fed the varices was not selected for transposition, but rather the longer straighter tributary. A catheter was left for easier identification during the dissection.

A left lower quadrant incision was made and a retroperitoneal dissection performed exposing the gonadal vein and iliac vein.

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Prior to ligation of the tributaries, a sheath was inserted and through this a LeMaitre valvulotome was brought up to the left renal vein and carefully deployed and pulled back, cutting the valves. This greatly increased the outflow from the vein as evidenced by the height of the blood spout from the vein when the sheath was removed. The varices were ligated at their root -treating them definitively. Transposition was to the external iliac vein, and I could see the feasibility of a laparoscopic or robotic approach to this operation (ref 3).

Completion venography showed excellent flow from the LRV down the gonadal vein into the iliac venous system.

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The patient lost less than 10mL of blood and was discharged on postop day 2. Gratifyingly, all of her preoperative pain resolved and her UA showed no more hemoglobinuria or proteinuria.

Discussion

The described treatment options for nutcracker syndrome include (ref 1):

  1. Medical therapy aimed at decreasing renal venous hypertension (for hematuria)
  2. Renal autotransplantation
  3. Left renal vein transposition
  4. Left renal vein to vena cava bypass (autologous or PTFE)
  5. SMA transposition
  6. Nephrectomy
  7. Gonadal vein to IVC bypass
  8. Exovascular stenting (wrap of renal vein with ringed PTFE graft)
  9. Endovascular stenting

Many of the operations are of historic interest. Stenting deserves some comment. The patient self referred because she had read multiple reports of cardioembolization on internet support group comments. The largest nitinol stent (self expanding) available is 14mm. Wall stents in larger diameters are available, but are stiff, poorly conformable, and will elongate if constrained by a non-dilating stenosis like the external compression by the SMA. While acceptable results have been reported, the long term results (20-70 years) for younger patients is unknown. Migration is highly morbid, and usually to the heart, requiring sternotomy and cardiotomy to retrieve the stent. Optimally, a conforming 16-28mm self expanding stent should eventually become available, but conformability is typically inversely proportional to radial strength, and it is the less conformable stents that migrate. Work is ongoing to bring larger diameter nitinol stents for venous indications. The difference between May-Thurner Syndrome and Nutcracker syndrome isn’t merely the size of the veins and stents. The iliocaval confluence is relatively static with some movement of the lumbosacral joints and well suited for treatment with the relatively nonconforming Wall Stents. The left renal vein under the SMA is a very dynamic environment with motion of the SMA and the kidneys with respiration, ambulation, and activity leaving stents vulnerable early to migration and later to fracture.

The left renal vein transposition to the IVC is a nice operation with a good track record (ref 2). The downside is the long midline incision required with transperitoneal exposure. There is bleeding risk and postoperative complications of ileus, wound infection, and small bowel obstruction. Looking at the CTV, it seems obvious that the gonadal vein crosses over the iliac vein in the pelvis and would be a straightforward, less morbid, less invasive option. A review of the literature reveals only a single reference discussing three cases of left renal vein transposition (ref 3), and it was done with a surgical robot. I think that a laparoscopic approach would be simpler and less invasive and will consider developing this if volumes justify it. That said, the open retroperitoneal approach is very straightforward and well used exposure. Using venography to set up and then confirm the results of the transposition was helpful. I don’t think that measuring pressures and diameters and taking calipers to calculate stenoses is all that useful and in some instances a harmful method of justifying endovascular treatment of nutcracker phenomena in the absence of serious symptoms and a careful deliberate workup which includes a good history and physical, a UA, a duplex and CTV.

Intervening on the gonadal vein to iliac vein anastomosis should be straightforward from a groin or thigh venous access on the ipsilateral side. This operation doesn’t preclude any future interventions on the LRV. The pelvic varices were treated with direct ligation. The patient’s pain was successfully relieved in the short term.

Conclusion: Open retroperitoneal left gonadal vein to iliac vein transposition with gonadal vein valvulotomy is effecting in treating nutcracker syndrome.

References

  1. Kurklinsky AK, Rooke TW. Mayo Clin Proc. 2010 Jun; 85(6): 552–559.
  2. Reed NR et al. J Vasc Surg. 2009 Feb;49(2):386-93;
  3. White JV et al. J Vasc Surg Venous Lymphat Disord. 2016 Jan;4(1):114-8.

 

Drainage: the sewer guy knows more about veins than you would think

preintervention

Being a homeowner, you are sometimes stuck negotiating a repair with various workmen whose knowledge of building esoterica is only exceeded by their subliminal contempt of a man who can’t rip out flooring and drywall to renovate a kitchen or bathroom. I can only hope that I don’t come off that way when discussing human plumbing. It was a year into my ownership of my current home that I noticed that many of the drains in the window wells were clogged. A very unpleasant afternoon was spent digging out soil and leaves while trying to snake a coat hanger (access wire), and when I gave up, I tried to call a plumber. Only it was the wrong specialist. “You want a sewer guy.”

The sewer gentleman was a meticulously groomed Italian immigrant who walked about the house after inspecting the drain in question. After some harumphing, he declared he needed to do some tests which included running dye through the various downspouts around the house and drains in the house. Contrast drainography! To top it off, he wanted to run a camera on a flexible tube through to check out the drains. Endoscopy! Plumbing, he sniffed, was easy, but drains were an art.

For the record, our basement was dry, but I could see the money meter whirring away. It was only a few weeks removed from a spring storm where several homes a few blocks away had catastrophic flooding when rains overwhelmed the capacity of their drainage –Drainage Insufficiency!

The testing was fine, but he ended up recommending resealing the entire East side of the house and rebuilding the window wells, because while the house was dry, it was compensating by rerouting a lot of drainage down gutters and the downsloping lawn to the street –Collaterals! and he couldn’t promise the house wouldn’t flood with a torrential month of rain which Shaker Heights is prone to being downwind of the Lake.

And it is with this wisdom that I see the increasing numbers of chronic venous occlusions. For example, the patient whose venogram is pictured above initially complained to her obstetrician of persistent heaviness in the pelvis and swelling of the legs after delivering a healthy baby. MRV showed abundant pelvic collateral veins and she was referred to me.

Our first test in our clinic is a venous duplex of both legs and the abdominal veins. There was an occlusion of the inferior vena cava below the renal veins extending the the iliac veins bilaterally. I am about to give a talk on this and I composited the ultrasound.

duplex

She had iliocaval occlusion, chronic. Her symptoms were over two years, and were ever worsening. She hadn’t developed permanent skin changes of chronic venous insufficiency, but probably would in a decade or sooner. I recommended venography and an attempt at recanalization.

postintervention

The procedure went well, and her symptoms abated. For my trainees, the absence of collaterals in the after image is the sign that hemodynamically, the revascularization is the preferred route of egress. Surprisingly, this has stayed open over two years, but again, my exceedingly well paid sewer gentleman consultant, had something to say about it.

Drainage, he declared, was different from plumbing, because things move slower and there is usually solid matter -poop, leaves, dead birds, etc., to contend with. Larger, high volume drains do best with a direct in-line connection with the city sewer, while downspouts and window wells with their twists and turns and only occasional flushings clog up too well. Wise words.

It gave me a reason why iliocaval venous interventions did so much better than femoropopliteal ones.

Confluences

Venous interventions connect confluences to the main drain, in most cases the suprarenal inferior vena cava. The iliocaval segment drains the common femoral confluence, which even in the worst of chronic lower extremity DVT’s, seems to reopen with several months of anticoagulation. Not the same for the popliteal confluence which, getting much less blood flow to drain, and having a smaller diameter, stents in the femoropopliteal veins just don’t do as well. Plus, it has to drain against a greater hydrostatic pressure. The drain guy’s wisdom seems to apply. It also has implications for the kind of stents we place, and the kinds that are being developed specifically for the venous side.