Talking Tall Rounds®: Non-atherosclerotic Lower Extremity Arterial Disease

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular andThoracic Institute at Cleveland Clinic.

Scott Cameron, MD, PhD:

Very good morning to you. My name's Scott Cameron. I serve as the Section Head of Vascular Medicine at the Cleveland Clinic. We have a really exciting Tall Rounds session to present to you today where we're going to discuss nonatherosclerotic arterial disease, particularly in the lower extremities. One of the strengths of the vascular medicine physician is that we're continuously looking at every organ system since every organ system has a blood vessel. Every now and again, we'll actually pick up on some really rare diagnosis, but as I think you're going to find out sometimes these diagnoses are not quite as rare as we would like to think and they're very, very easily missed. One of the reasons we chose this session is that many of the diseases we're going to discuss today are actually found in the certification exam by the American Board of Internal Medicine and Cardiovascular Disease. With that, I would just like to open and introduce our first speaker, who's Dr. Medhat Chowdhury. I will invite him to the podium.

Medhat Chowdhury, MD:

Hi everyone. I'm going to start Tall Rounds with a case that was seen on service. The patient is in her early seventies. She has a history of COPD and she had a lung transplant in 2005, a 30 pack year smoking history, and she has antiphospholipid syndrome with a history of thrombotic stroke and dural venous sinus thrombosis and was on chronic anticoagulation for that. She was admitted because of a GI bleed and was being worked up for a source. We were consulted for essentially anticoagulation recommendations.

Medhat Chowdhury, MD:

During the interview, she reported that she was having severe calf pain that had been ongoing for about several months and she had pain even with walking about a hundred feet that resolved with rest. On exam, she had some residual aphasia from her prior thrombotic stroke, but otherwise the exam was unremarkable except for a very diminished dorsalis pedis and posterior tibial pulses bilaterally. Her Doppler tones were also monophasic. At this point, we were suspecting some form of PAD. We went ahead and got PVRs, and initially we had an ABI and then a PVR. As you can see from the PVR, she had very dampened recordings throughout all segments of her legs bilaterally. If you look at the pressures, her brachial pressure was she was normotensive, and normally you expect a much higher pressure compared to the brachial pressure, but here you're seeing it's quite low. At this point, we were suspecting whether she could have some form of inflow disease and we went ahead and got an arterial duplex.

Medhat Chowdhury, MD:

I'll start with the gray scale images here, and as you can see here that there's some heterogeneous plaque adhered to the wall, very minimal athro throughout all the segments on the left side and the right. On color Doppler, as you can see here, there's good filling throughout the vessel. Normally, you expect a nice brisk upstroke and a QRS type pattern on the wave forms, but here you're seeing a very parvus tardus monophasic waveform that is present throughout all the segments. This was also seen on the left side and essentially at this point, given very minimal athro in the iliacs, we were suspecting either some form of disease in the proximal aorta or the heart.

Medhat Chowdhury, MD:

We did a point of care ultrasound and I'll play this cine clips here. We initially noted that there was a thickened septum and there was no significant regurgitation or flux relation in terms of valvular stenosis, so we went ahead and got a dedicated echocardiogram. This apical four chamber view again shows this thickened septum and I'll pull up the peristernal long axis view over here. What you can see coming in and out of view here is the papillary muscle. Normally, we expect the papillary muscle to be a little less apically displaced. Given that there was some suspicion that whether this could be related to the clip itself or the view we were seeing or whether this was apically displaced, we were suspecting outflow tracked obstruction related to the displaced papillary muscle.

Medhat Chowdhury, MD:

We confirmed outflow tract obstruction with amyl nitride as you can recall with the vasodilator and decrease in after load, this worsens outflow tract obstruction in patients with hypertrophic cardiomyopathy or a thickened septum. This shows the classic dagger-like pattern, scene with aortic stenosis. A cardiac MRI was recommended to investigate the source of the outflow tract obstruction, but unfortunately due to non-cardiovascular related illnesses, the patient opted for palliative measures and further workup was deferred.

Medhat Chowdhury, MD:

A few take-home points from this case. It's important to have a very broad differential when evaluating someone with vascular claudication, especially in someone who has dampened wave forms and in someone who has inflow disease. A point of care ultrasound as we showed, is a very helpful tool to delineate further testing and dynamic outflow tract obstruction, although rare can be a cause of vascular claudication. As we'll see in some of the other talks today, inflow disease is not just because of atherosclerosis and there can be many other reasons. With that, I will conclude. Thank you so much for listening.

Scott Cameron, MD, PhD:

The case we just saw was a classic example where a patient has very typical symptoms of claudication, which in most cases is atherosclerotic in origin. But as I think you're about to see, there are many, many causes. We typically think of 12 or 13 different causes of claudication, and one of the challenges is that one needs to retain really strong skills in general medicine in order to make sure we don't miss these. With that, I'd just like to go through a little bit of the pathophysiology and give you kind of the framework that a vascular medicine physician typically will go through that will help us clinch a diagnosis and when it's doesn't seem quite as straightforward as anticipated, no disclosures.

Scott Cameron, MD, PhD:

Good analogies, when I think about peripheral artery disease an emergence in the peripheral vasculature of course is critical limit ischemia is kind of equivalent to STEMI and the coronary vasculature. The superficial femoral artery is akin to the left main because it's the major driver in delivery of blood flow to the lower extremity. The ankle brachial index, as we just saw, is excellent for interrogating the vasculature. Not only can it sometimes tell us with PVRs where the lesion is, it is in fact diagnostic for peripheral artery disease.

Scott Cameron, MD, PhD:

The arterial duplex is also incredibly important because they're dynamic images and it's akin to the echocardiogram where you'll interrogate the valvular function and ventricular function. The only notable difference of course is if you use the angle installation of 60 degrees. As we found out, when you look at the ABI, Dr. Chowdhury showed you that there was a dampening of the typical expected signal. There's loss of the three phases that we would see, the amplitude was decreased in a respectful broadening in this patient. If you look at the duplex, as he clearly showed, there was evidence of atherosclerotic disease, which is not unusual in the patient who's slightly older, but certainly it wasn't to the degree where it would be obstructive, but yet we have this dampened signal by arterial duplex that we must explain the spectral broadening and decreased peak systolic velocity, implying there may a more proximal stenosis.

Scott Cameron, MD, PhD:

When we approach a patient with potential vascular disease, I always keep in mind that common things occur commonly. Common things, when you're going through them, this helps with the diagnostic framework. It'll guide the initial testing and then finally get to the diagnosis. We sometimes think is there a stenosis either locally or upstream? Is it unilateral or is it bilateral? Is there an embolic event? And if there was an embolic event, what was it that precipitated it? Was it an in situ event? Was it dissection? Is there impaired endothelial dysfunction? And then lastly, the thing we think least about, is there an enhanced sympathetic tone to the blood vessels? The smooth muscle that surrounds the blood vessel, certainly in some cases can give claudication in any limb. That's one I’ll tell you that gets missed quite a bit.

Scott Cameron, MD, PhD:

If you look at upstream stenosis on the left, you can see PVRs, and if you just look at them, there's clearly a unilateral discrepancy here with decreased peak amplitude of these PVRs starting at the high thigh cuff propagated all the way down to the toes. By looking at this, I would say there's probably stenosis at the level of inflow and the angiography clearly shows that's the case. The next thing is, is there embolism from a proximal source? Sometimes we see embolic workups maybe a little bit more extensive than could be. We ask ourselves, is there disease in the vasculature upstream? Is there an aneurysm or a dissection that we might need to account for? Or is this an atheroembolic event, which I'll tell you is probably one of the more common things.

Scott Cameron, MD, PhD:

If you look at the popliteal artery, if it happens to be aneurysmal or if you look at the infrarenal aorta, if it happens to be aneurysmal, it's not uncommon for us to see disturbed blood flow. Disturbed blood flow biomechanically activates platelets and it triggers the coagulation cascade, and for that reason, it's not unusual for us to see an intraluminal thrombus in patients with infrarenal aneurysms of the aorta. It's less common in the thoracic aorta in part because it comes from a different part of the body embryologically, but certainly aneurysmal disease or dissection more proximally is something that we think about.

Scott Cameron, MD, PhD:

Is there a dysregulated vascular function? And so if you think about this, it's always important to consider the connective tissue that surrounds the blood vessel. Is there something going on at the level of the connective tissue that's causing remodeling or compression of the artery? Is there enhanced vasoconstriction from a sympathetic overdrive? Is there impaired vasodilation? Is endothelial derived nitric oxide and prostacyclin which contribute mostly to basal vascular tone impaired because of a systemic disease and we sometimes are able to diagnose these. And lastly, is there a medication effect? There are about five or six medications that can markedly decrease blood flow to arteries and if one's obviously not attuned to the way these medications work, it's easy to miss.

Scott Cameron, MD, PhD:

Now lastly, context matters. If you look at an extremity, ask yourself what was the patient doing when this happened? Was the patient resting? What was the clinical context? If you look at this patient's fingers here, clearly you can see decreased blood flow to all of the digits. This was a recurrent event with the patient when they underwent anesthesia. So again, you go through the diagnostic framework, is embolism possible? It's possible but it's not very likely because it's affecting all of the digits. Is thrombosis possible? Is it a proximal source? Certainly if the patient had been instrumented, you could think about atheroembolic showering, but that's typically not the physical examination of embolic showering. This is the physical examination we'd see in a patient who has no blood flow. And so then we go back, is there enhanced sympathetic tone? Well, it turns out that during general anesthesia patients with pheochromocytoma, you can actually precipitate that. This was a patient with extramedullary pheochromocytoma, which is very easy to miss and actually was quite reversible in this patient's case.

Scott Cameron, MD, PhD:

Then finally, the underlying etiology would always determine the treatment. If it's ischemia, we want to remove the obstruction or bypass it, and that's where we work very closely with their surgical colleagues, as you'll hear. If it's inflammation, you treat the inflammation, you don't stent inflammation, you treat the inflammation first and then figure out if the patient needs anything else. If it's external compression, relieve the compression. If it's an embolic event, identify the source. Is there an aneurysm? Is there a dissection? And was there tissue factor released from the sub endothelial compartment triggering the extrinsic level of the coagulation cascade? We see that quite commonly. Then lastly with medications, can we help this by using sympatholytic medications or nitro oxide donors or in some cases antithrombotic medications?

Eric Roselli, MD:

I've been asked to speak about midaortic syndrome. Disclosures are shown here and I don't think any of them are relevant for this talk. We heard Dr. Cameron make the comment that common things happen commonly. At the Cleveland Clinic, uncommon things happen commonly and midaortic syndrome is one of those things that we see. It is essentially an inclusive disease that happens in the descending thoracic or the thoracoabdominal aorta with or without branch vessel involvement. So the syndrome, like all syndromes are really based on the symptoms that are presented.

Eric Roselli, MD:

Oftentimes, these patients will have a combination of upper extremity hypertension and distal hypotension like we see as the topic is appropriate in a lot of our patients with claudication. But the symptoms can be varied depending on where the occlusion occurs and which vessels are being perfused. Claudication is common. You can see renal failure. You can also see heart failure just as you can see in patients with undiagnosed coarctation. But in general, malperfusion of beds downstream with hypertension upstream.

Eric Roselli, MD:

I did a quick PubMed search of this and no surprise, it is rare. I found 96 citations came up when I just put in midaortic syndrome. Almost all of these were case reports. There are some collections of series and there is this paper, which I thought was pretty cool because Pat O'Hara was the senior author on this from 1980. But there is this Hallett classification. I'm not sure that this is a classification that anybody's using very often, just probably because we don't see this disease very often. But the importance of it is that it's important to characterize the patients with regards to where the occlusive disease is involving the aorta and whether any branch vessels are involved.

Eric Roselli, MD:

The etiology is mixed. It can be amongst some of the things that we've heard about like Takayasu's arteritis or giant cell arteritis, atherosclerosis, although I know that's the topic of today, is nonatherosclerotic a claudication. This study is the largest one in the literature. It comes from the group in FUI in Beijing where they describe 143 patients with segmental stenosis, and their definition was that they had to have a gradient greater than 20 millimeters across the stenosis. You see a nice image from this paper where they show several examples of different patients who present with this.

There's also some congenital causes or mixed diagnoses, some uncommon diagnoses like coarctation, neurofibromatosis, Williams syndrome, Behcet's disease, which is an inflammatory disease that represents a small percentage of the patients with this middle aortic syndrome. The treatment's no surprising are antihypertensives and a combination of the techniques that we use when we find obstructive disease, either stenting or stent grafting, insight to reconstruction with surgical interposition grafting or extra anatomic bypasses.

Eric Roselli, MD:

There was another study from the literature, not quite as big as the one from China, but I thought it was important to point out from the group in Houston. Took them over 20 years to compile a series of 13 patients that ranged in age from two to 67. All these patients were treated mostly open, a few endo, but I like this figure that they showed where they showed which zones of the aorta were involved with the stenotic process, the midaortic syndrome process. Most of these were involving the mid to distal descending aorta and then various segments of the visceral aorta.

Eric Roselli, MD:

These are a few memorable patients of mine that I'm going to show you. This 34 year old lady from Afghanistan with poorly controlled hypertension was found to have a 40 millimeter gradient between her upper and lower extremities. And no surprise because she basically had no descending thoracic aorta as you can see on the image on the right and quite remarkable how her internal thoracic arteries and the collateral network has developed across her abdominal wall and her chest wall to compensate for this lack of a descending aorta. This is a pretty extreme example of midaortic syndrome. It's a lot more than mid, it's like the whole thoracic aorta that was missing.

Eric Roselli, MD:

We were able to reconstruct this aorta and we did it with two incisions. You can see the image on the left. We've got a retroperitoneal incision that allowed us to get down to her abdominal aorta and then a higher thoracotomy that we did, you can see on the upper right side of that upper left image. And then two interposition graphs, one sewn to her arch, one sewn to her abdominal aorta and then connected in between around the level of the diaphragm. You can see on this postoperative image already those collateral networks are starting to be relieved of their duties because she now has a new aorta. This really relieved her symptoms. She went home I think on one really small dose of a beta blocker and previously had really no control of her hypertension.

Eric Roselli, MD:

This is similar to sort of the series of patients that we see with aortic coarctation and we've written about our adolescents and adult patients with coarctation before. I thought it was important to point out in that series of over 110 patients, the indications to operate in only two of them was this long segment coarctation, which is essentially the midaortic syndrome like the lady that I showed a minute ago.

Eric Roselli, MD:

One of these patients, the one on the right had an attempt at stenting. The problem is the stents are only going to get so big in these patients and when it's a log segment of coarctation, it's unlikely that stenting is going to expand that whole aorta. I took this lady in her late thirties to the operating room and did an ascending and descending bypass. You see that nice 3D reconstructed image on the right and a couple intraoperative photos of what this looks like. We sewed a graph to the ascending aorta, we pass a retrocable, and sew it to the descending aorta and we use that quite often in that series we used it 20 times.

Eric Roselli, MD:

This is another really interesting case and I think this is an important one to point out. This young man we just treated a couple of months ago, 29 year old with severe hypertension, claudication and fatigue. I really like this guy because he wanted to get back to work and he just found that he couldn't do it. He was dealing with disability from this. You can see his tiny little aorta on these 3D images on the left. I included this skeleton on the left so you can get a sense of how small his vasculature really was. His root was normally formed, but his ascending aorta is only about 15 or 16 millimeters. Then as we work our way through his aorta, his distal descending aorta is about 11 millimeters. Not a whole lot different than some of the coarctations that we treat. Once we get into the abdominal aorta, it's about eight millimeters. Then you can see he's got some atherosclerotic disease in his common iliacs as well, that are only measuring about four millimeters. We came up with a staged hybrid treatment plan for this gentleman.

Eric Roselli, MD:

We thought the first thing to do was to treat the atherosclerotic components of his iliac disease because claudication was one of his most important symptoms, with some stenting on the right and stenting on the left vessels and had a really nice result in both of those. Then while we were there, we passed some catheters up into his aorta, and this is just a picture from my phone demonstrating you could see that there is quite a big differential between the systolic blood pressure and his proximal aorta, that was 207 and his distal aorta is 150. As we pulled our way through that uppermost aorta, we could see this was a long gradation through his entire aorta. I took him to the operating room or we just switched our plan. We were already in the hybrid operating room. We brought the pump in and did a sternotomy and replaced his ascending aorta.

Eric Roselli, MD:

I thought the most important thing is that we optimized that inflow above his aortic root, so we put an interposition graft in his ascending aorta, turned that 16 millimeter ascending aorta into a 24 millimeter aorta and then used an 18 millimeter graft based off his ascending aorta, passed it behind his inferior vena cava to his descending aorta. You can see we have that real nice reconstruction. Interestingly, he did have atherosclerosis through much of his descending aorta as well, and so the lumen of that descending aorta, not only was it small to start with, but also had disease and he really had no reserve in his entire aortic tract.

Eric Roselli, MD:

So those are some unusual cases, but things to think about and we have lots of great options for our patients. We see more and more patients, especially with congenital disease, living longer that need late treatment. They fare better I think with earlier and proactive treatment versus urgent treatment. There's no doubt about that. We have to appreciate that both endo and open approaches to vascular disease in general are always complimentary and we need to better understand these complex presentations of these diseases. Thank you very much and got to give a shout out to all of you to put this on your calendar. We hope to see you for the next CLE Symposium next fall. Thank you very much.

Announcer:

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