I’m Aware That I’m Rare: Robert P. Frantz, MD
Robert P. Frantz is the director of the Mayo Pulmonary Hypertension Clinic, which has a robust referral practice of patients with pulmonary arterial hypertension. Dr. Frantz has served as the Mayo site PI on numerous multicenter trials in PH including the majority of trials resulting in FDA approved PH therapies. He also performs complex hemodynamic studies in the catheterization laboratory including right heart catheterizations for patients with pulmonary arterial hypertension and also patients with left heart failure. He also evaluates and manages patients with CTEPH, with particular interest in the role of balloon pulmonary angioplasty.
My name is Dr. Robert Frantz, and I am the director of the Pulmonary Hypertension Clinic at the Mayo Clinic in Rochester, Minnesota and I’ve been here over 20 years. I really spend a lot of time taking care of patients with various forms of pulmonary hypertension. One form of pulmonary hypertension that we’re seeing more often than we used to is what we call chronic thromboembolic pulmonary hypertension [CTEPH].
That can look just like pulmonary hypertension of other causes in terms of having elevated pulmonary artery pressures and normal left heart filling pressures. Then the development of shortness of breath and failure of the right side of the heart leading to fluid retention and poor activity tolerance. But people don’t come waving a flag saying, “Hey, the reason I have pulmonary hypertension is because part of my lung vessels are plugged up with old clots that I didn’t know I had.” So it is a form of pulmonary hypertension that can be overlooked.
We often say that nobody should be diagnosed with idiopathic pulmonary arterial hypertension (or pulmonary hypertension of unknown cause), without making sure they don’t have clots in their lungs. The interesting thing is that many patients could have obstruction of the lung vessels with old fibrotic clots and never have had a clinical history of a clot in their leg veins or having had pulmonary emboli (clots into the lungs) and still have the condition, because it can be silent.
Our lungs are like big filters. So we could have a clot come out of our leg vein during a long airplane ride. It could go flying up to the lungs and plug a lung vessel up. A lot of the times that clot would dissolve, but some of the time, instead of dissolving, it forms a scar that then obstructs that segment of the lung. If enough of those segments get obstructed, finally the cross-sectional area of the lung starts to go down and then it limits flow through the lungs.
The other thing that we know about this condition is that those fibrotic old clots don’t dissolve with blood thinners. You can prevent new ones from developing it, but they’re not really clots in the sense that you think of in terms of a red thrombus that is mushy and will easily move out of the way or dissolve. The body is clever about these things and goes in there sometimes and tries to heal it up, but actually scars it up and it creates an obstruction. That combined with constriction of the lung vessels may be triggered by the lining of the lung vessels not working quite right, and that’s the reason that certain medications that are utilized in chronic thromboembolic pulmonary hypertension actually work, because they can relax the lung vessels to some extent, but they don’t take away the obstruction.
Traditionally, the only good option has been to do open surgery under cardiopulmonary bypass and deep circulatory arrest where you cool down the brain and stop circulation and have a surgeon shell the old fibrotic clot out of the lung vessels, which can be a very effective procedure. But it’s obviously quite invasive. Many patients who have this condition may not be candidates for it because the clots are too far out into the periphery of the lung and can’t be reached, or they have other conditions that make them not a good operative candidate in terms of risk.
So the other options for that are either a medication, and one specific medication called riociguat is approved to relax the lung vessels to try to help that condition, and other medications that we use for other forms of pulmonary hypertension can be useful too. But that medication only takes us so far in somebody who has inoperable or residual thromboembolic disease after prior surgery.
So balloon pulmonary angioplasty is taking techniques as interventional cardiologists we’ve learned to use in the coronary circulation; putting wires and balloons across areas of narrowing and inflating them to make things less narrow. It has been adapted to lung circulation, where if you can get a wire across one of these narrowing in the lung vessels, then you can put a balloon across it and restore flow to that segment and thereby improve the pulmonary hypertension and the efficiency of the lungs. That technique at an expert center in the last number of years has been shown to have relatively low risk, although not zero, and really good results. So we’ve been doing quite a lot of that here at the Mayo Clinic in recent years.
I think it’s like any newer technique that starts in a small number of centers that get very familiar with it, and then depending on how readily the techniques can be learned and applied, will then spread to other centers. So the nature of this procedure at the present time is that a relatively small number of centers are doing significant numbers of these procedures in the United States, but many centers that have interventional cardiology programs are highly interested in it and are often coming to visit here to try to learn how to do it or visiting a couple of other centers in the country that do a fair amount of this to try to learn the technique.
I would say that it’s evolving with it having been in the United States over a decade ago, but maybe not as readily as with current equipment and not maybe quite as successfully. Then, really, the Japanese picked it up and started doing a lot of cases over Japan and demonstrated that it could be done quite effectively. Now the rest of the world is picking it up. Right now in the United States, there’s a handful of centers that are doing substantial numbers of procedures, but there’s intense interest in it. So I think it will continue to spread across other centers overtime.
We try to emphasize the idea of an expert multidisciplinary approach, where somebody who is really familiar with the options of open surgery, medical therapy and balloon pulmonary angioplasty is involved in each patient’s decision making. So the ideal circumstance would be a person who has this diagnosis of chronic thromboembolic pulmonary hypertension is considered at an expert center with regard to whether they’re a candidate for open surgery with regard to whether the vessels that are involved are reachable by a surgeon, and [if] that the person is suitable or not.
If they are not found to be suitable for open surgery, then I think they should really be considered for the balloon procedure, because it has, in my sense, a better opportunity of really taking care of the problem with regard to restoring flow to the obstructive segments as supposed to just relaxing the segments that remain open. So we often end up combining the two things of medical therapy to relax the vessels that are still open, plus balloon work. Then seeing whether we can then takeaway the medications if the balloon work is successful enough to improve the flow to a point where they may not be necessary.
On the other hand, in some patients, if the pulmonary hypertension is not too severe when we start with them, then we might do a balloon work alone and never really need the medications, which is nice in a way, because if you’re going to use a lifelong medication, then that’s going to have potential for side effects and substantial expense, and if you can avoid that, it’s a good thing. So I think every patient should be considered for open surgery, balloon work and medication at a center where those decisions can be made properly. If they’re not candidates for open surgery, they should be considered for balloon angioplasty.
Honestly, there are relatively very few of the patients with chronic thromboembolic pulmonary hypertension that we’ve looked at as potential candidates for balloon angioplasty who felt are not candidates for it. Most of the time, there are vessels that could be crossed and the flow can be improved. If the kidneys are really not in good shape, and especially if they’re diabetic, then the risk of the contrast we need in order to visualize the vessels well might not be worth it.
So the kind of patient I would not do in would be a diabetic patient with kidney impairment, where you know if you give them quite a lot of contrast, you put them at risk at putting them onto dialysis or something because of renal failure. This is a procedure where you usually need to do multiple sessions. You can’t open everything up once. So it might be several sessions of work each one requiring contrast. So if the kidneys are in trouble, you can really hurt them, and maybe those patients are better off just with medical therapy.
I can’t emphasize enough how important a V/Q scan is, which is the nuclear scan where you inhale something that shows where the air is going and you have something injected that shows where the blood is going. Those should match like a hand and a glove, and areas that have ventilation but don’t have good flow are areas that may be obstructed with clot.
The critical issue is that we’re very good at using CT to look for acute clots in somebody who’s in the hospital in the emergency room with shortness of breath and have potential for large clots that are easily seen on CT imaging. But the chronic clots that are often pretty far out are easily missed on a CT scan done with thick sections where the number of cross-sections taken isn’t close enough together to not miss the webs and bands and maybe reviewed by a radiologist that isn’t very familiar with the appearance of chronic old clots that are peripheral.
I’ve seen multiple patients who were felt to have idiopathic pulmonary arterial hypertension sometimes have been treated for years, and that was on the basis having at a CT that had not shown clots. Then they’ve come for a second opinion at some point and I’ve said, “Gosh! They never had a ventilation/perfusion lung scan. Let’s do that,” and find out lo and behold they have chronic thromboembolic pulmonary hypertension, were felt to have idiopathic pulmonary arterial hypertension, because of this issue of the sensitivity of CT scanning being less for findings of chronic clot than a perfusion lung scan.
So if we do a perfusion lung scan that shows evidence of possible clots, then we do an invasive pulmonary angiography, where we put a catheter out in the pulmonary artery and take pictures directly in order to look at the clots in a more distinct way than we can with either CT or with a nuclear perfusion scan. A very important point.
My name is Robert Frantz and I’m aware that I’m rare.
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