Victor F. Tapson, MD |
Pulmonary Hypertension
Roundtable
Surgically Curable
Pulmonary Hypertension: A View From the Experts
Five physicians addressed important issues in
the diagnosis and management of patients with
pul-monary thromboembolic disease. The roundtable
dis-cussion was moderated by Victor F. Tapson,
MD, Associate Professor of Medicine, Division
of Pul-monary and Critical Care Medicine, Duke
University Medical Center, Durham, North Carolina,
and includ-ed William Auger, MD, Professor of
Clinical Medicine, University of California, San
Diego, Medical Center, San Diego, California;
Peter Fedullo, MD, Clinical Professor of Medicine,
University of California, San Diego, Medical Center;
Eckhard Mayer, MD, Professor of Thoracic Surgery,
Department of Cardio-Thoracic Surgery, University
Hospital, Mainz, Germany; and Christopher McGregor,
MD, Professor of Surgery, Consultant in Cardio-Thoracic
Surgery, and Director of the Mayo Clinic William
J von Liebig Transplant Center, Rochester, Minnesota.
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William Auger, MD |
Peter Fedullo, MD |
Eckhard Mayer, MD |
Christopher McGregor, MD |
Dr Tapson: Let’s start with
a general statement. If we start with the US, how many
centers can do throm-boendarterectomy for chronic pulmonary
embolism?
Dr Auger: It’s hard to get
a handle on that. It seems some groups are trying to perform
thromboen-darterectomies on an irregular basis. If you
look at the centers that are set up to do these surgeries
on a regular basis, one thinks of the Mayo Clinic, and
I would probably include the Cleveland Clinic, and the
UCSD Medical Center—about three to four centers in the
United States.
Dr Tapson: Dr Mayer, how
about in Europe? How many centers do this and would you
be able to name them?
Dr Mayer: I think there
are approximately five to seven centers all over Europe.
There is an active cen-ter in Paris, one in northern Italy,
one in Austria, one in England, and three centers in Germany.
In Europe, I think we have the largest experience in Mainz,
with approximately 300 cases over the last 12 years, although
these numbers are not comparable to the experience in
San Diego.
Dr Fedullo: Now that you’ve
raised that question, Vic, I think it raises another question
and that is, how many centers should be doing this procedure
and how do the other members of the panel feel about the
minimum number of cases that are required on an annual
basis to optimize outcome? There are good data regarding
other high-risk procedures that volume is related to outcome.
The issue is, can the procedure be done with optimal safety?
There’s a huge learning curve with this procedure. Perhaps
Dr Mayer could comment on what he thinks about the volume
of pro-cedures and its relationship to outcome.
Dr Mayer: We had a very
significant learning curve during the first 5 years of
our program when we start-ed in 1989. The results were
much worse compared with the last 5 to 8 years. I do believe
that a center should have a multidisciplinary team and
there should be at least 20 operations per year. That
means 30 to 40 patients are referred for surgery and at
least 20 patients per year should be operated on to gain
enough experience. Even with 20 patients a year, it will
take a little time until the results can reach a level
comparable to the San Diego results.
Dr Tapson: What do you think
about that, Chris?
Dr McGregor: I think I agree
with what people have said. Clearly, there is a learning
curve. For the first patients, the mortality for us was
around 19% and in the subsequent 42 patients it fell to
less than 4.6%. I think there are two aspects to this
operation in terms of outcomes. I agree totally with Dr
Mayer that this operation should be part of a pulmonary
hyper-tension multidisciplinary group. In terms of surgical
outcomes, there are multiple reports where people have
not gotten over that early learning curve and have a mortality
rate of anywhere from 20% to 40% and there’s no point
in people doing that unless they’re going to see it through
so that patients down the line benefit from that learning
curve. Regarding the number per year, one could argue,
but I would say that the minimum of one a month or 12
per year— that kind of number, although the more the better.
There is a second issue: once there is significant experience
with this surgery the mortality you achieve is dictated
by patient selection and how aggressive you will be in
accepting patients with distal disease for surgery. There
will always be a mortality for this surgery if you are
going to be very aggressive in the pursuit of distal disease.
I would be interested in what Professor Mayer thinks about
that.
Dr Mayer: I totally agree
with that. During the first phase of our learning curve
we had a mortality rate of approximately 20% to 24%. There
was a lot of criti-cism and all the cardiologists and
respiratory physi-cians told us this procedure is too
risky for our patients. Therefore, we changed the patient
selectionfor a phase of 2 or 3 years and we accepted only
patients with proximal disease who were considered surgically
accessible. We were able to reduce our mortality rate
to less than 5%. But with increasing experience we started
to accept patients with very distal disease during the
last couple of years and those patients do have a higher
risk than 5%. So it’s really true that you can influence
the mortality rate by changing the patient selection.
However, the patients with very distal disease do not
have good surgical or medical alternatives so I think
someone with adequate surgical experience should also
do the high-risk operations in patients with very distal
dis-ease.
Dr McGregor: And I would
add that if you’re not occasionally—and I’m talking about
mortality of less than 5% here—if you’re not occasionally
having a suboptimal outcome, maybe you’re not going to
help a large number of people with relatively distal disease
who could be helped. So I think there’s a balance that
could be reached here.
Dr Fedullo: I agree completely.
There are always those cases that really surprise us in
terms of suspecting that the patient had distal disease
during their evaluation phase and who have just a wonderful
hemodynamic outcome.
Dr Auger: It certainly has
been one of our challenges as diag-nosticians in selecting
appropriate patients to have surgery. What constitutes
distal disease? Those of us who see these patients on
a regular basis are occasionally surprised by what we
have assessed as distal disease turns out to be resectable
while patients who we feel have accessible disease can
some-times be very difficult cases. So there are still
some diagnostic problems for us in this patient population.
Dr Fedullo: Absolutely.
The correlation between the angio-graphic and hemodynamic
findings is a critical part of the refer-ral process.
A procedure in someone with distal disease with a PVR
of 1500 carries a much higher risk than one in a patient
with a PVR of 500, who would probably tolerate the procedure,
even if very minimal amounts of clot were removed at the
time of surgery.
Dr Tapson: How do you define
distal disease? Is it a relative term or fairly absolute?
Dr McGregor: Therein lies
the problem, Vic, as Bill just out-lined. As a surgeon,
I go in sometimes to what is billed as dis-tal disease
and it’s surprisingly amenable to surgery. At other times
I go in expecting to be able to have a good surgical out-come
and it turns out to be very difficult, with more distal
dis-ease than anticipated. I think there’s a certain sort
of art to defining distal disease and I don’t think diagnostically
we’re as good as we’d like to be.
Dr Mayer: I completely agree.
Even if you think you have a lot of experience it sometimes
happens that the operation is a real surprise in a good
way and also in a bad way. Sometimes the operation and
the postoperative course are very dif-ficult in patients
who were considered very good candidates preoperatively
while other patients con-sidered to have very distal peripheral
disease are easily operable. Even with a lot of experience
and good diagnostic tools we are never sure before we
are at the end of the operation.
Dr Fedullo: It raises two
points. First, it’s a shame that angioscopy is not more
widely available because we find it useful in determining
operability and we’ve been having a problem obtaining
angio-scopes. The other issue is that in certain patients
this is clearly both a medical and surgical disease. We
thought of it somewhat simplistically in the early years
as nothing more than mechanical obstruction of the major
pulmonary arteries—but it’s clear that there can be a
small-vessel component to the dis-ease process and the
future approach to the disease under that circumstance
may involve both surgical and medical therapy.
Dr Auger: I want to underscore
what Professor Mayer and Peter have said, that there still
remain a number of challenges for us, even in the evaluative
or preoperative phase. Peter and I have changed our thinking
about how these patients develop pul-monary arterial hypertension
over the years. What we once thought was just progressive
thrombotic obstruction of the pul-monary vascular bed
may indeed not be the major determinant of the severity
of pulmonary hypertension over the years. In the unobstructed
vascular bed, small-vessel pathology seems to develop
over time, eventually leading to a significant rise in
pul-monary vascular resistance and cor pulmonale/RV dysfunction.
Consequently, our preoperative preparation may sometimes
include pulmonary vasodilator therapy for a period of
time to improve the hemodynamic profile prior to committing
patients to the operating suite.
Dr McGregor: When one has
a patient with longstanding throm-boembolic primary pulmonary
hypertension with a PVR in excess of 1200 or 1300 and
one has achieved what you would think is a textbook surgical
resection and does not have signif-icant reduction in
pulmonary artery pressure—it doesn’t hap-pen that often
but does occasionally—what do you think is hap-pening
under those circumstances? Are those secondary changes
in the normal vessels?
Dr Fedullo: I agree with
Bill’s point of view entirely. I think these people develop
a substantial distal pulmonary arteriopathy and despite
a good surgical specimen, some of these patients have
considerable postoperative pulmonary hypertension.
Dr McGregor: Peter, what
happens to the small vessels distal to the obstructive
material we remove? Have those vessels been protected
or are they subject to the same secondary arterio-pathic
changes as the unobstructed vessels?
Dr Fedullo: You would think
they would be protected but in the series that Ken Moser
did a number of years ago, looking at this, he found the
arteriopathic changes in both the involved and the uninvolved
parts of the lung. Is that correct Bill?
Dr Auger: What you’re stating
is absolutely correct, but there were problems with that
study. It was very difficult to correlate accurately the
areas from which the lung was biopsied to the areas that
were angiographically obstructed by chronic throm-boembolic
disease versus the areas that were unobstructed. In that
study small-vessel arteriopathy occurred in both the obstructed
and the unobstructed lung regions. What we would have
liked to have seen is a difference, more small-vessel
changes in the unobstructed vascular bed versus the obstruct-ed
vascular bed. However, I think if you look at preoperative
and postoperative lung perfusion scans in patients with
major-ves-sel chronic thromboembolic disease, the increase
in perfusion in lung regions that have been endarterectomized
relative to those that were not endarterectomized would
suggest a lesser degree of small-vessel disease in the
obstructed vascular bed.
Dr Tapson: What’s the latest
in the theory of in situ thrombosis? Do we think that
a lot of these cases start as embolic disease and then
in situ thombosis develops? What’s the theory now?
Dr Fedullo: It’s almost
impossible to say but the data that we have based on sequential
lung scan findings is that progressive pulmonary hypertension
occurs in the absence of new perfusion scan defects. This
suggests that in situ thrombosis isn’t a major problem
in the progression of the pulmonary hypertension. Ac-tually
the progression is felt to be due to progressive small-ves-sel
changes.
Dr Tapson: Along those lines,
do you all have a fairly consistent approach to evaluating
somebody for surgery? In terms of eval-uating severity,
is it fair to say that everyone undergoing this procedure
should at least have an angiogram? What about the CT scan?
Are we finding cases where the CT is clearly mislead-ing
or misrepresenting what’s going on? I guess that would
be one of the issues, right?
Dr McGregor: We do ultra-fast
CT as well as pulmonary angiog-raphy in all the patients,
and I would not see them as compar-ative investigations
but rather as additive in terms of the infor-mation they
give. By that I mean the nature of the disease will determine
which test is more useful. In other words, if you have
a thin transparent veil occluding a segmental pulmonary
artery. If that’s the nature of the pathology, an ultra-fast
CT will miss it totally because of the distance between
the cuts. On the other hand, a pulmonary angiogram, if
there is circumferential dis-ease, may look better than
it should be, considering the extent of the disease and
the ultra-fast CT cutting across those vessels at right
angles. You will see intimal thickening. So you get dif-ferent
kinds of information from the two tests but I do not believe
the ultra-fast CT in any way replaces the necessity of
doing a pulmonary angiogram.
Dr Fedullo: I agree completely
and also agree completely with the point that the two
studies provide complementary informa-tion and can be
very useful when used together.
Dr Auger: I also agree that
the CT angiogram can be very useful. There have been cases
of pulmonary hypertensive patients with clearly defined
disease on CT angio and major perfusion defects on lung
perfusion scans, in whom we feel it was not necessary
to do pulmonary angiography. However, there’s an increasing
tendency to have it replace conventional pulmonary arteriography.
I do not believe it has that power as yet. There are still
some unanswered questions as to how useful it is in establishing
surgically accessible disease. And I would under-score
Chris’s statement that this disease can appear very dif-ferent
in the pulmonary vascular bed from one patient to the
next. This is a surgically heterogeneous disease.
Dr Mayer: Regarding the
diagnostics, I completely agree that the combination of
CT and angiography is the standard at the moment. However,
within the last 2 years we were operating on approximately
30% of our patients without conventional angi-ography
and we do have very good magnetic resonance (MR) angiographies
that are comparable to conventional angiogra-phies in
most cases. I believe that 2 or 5 years from now MR techniques
will replace angiography and CT scanning in many CTEPH
patients. MR function tests of the right ventricle can
give us even more information than echocardiography. I
do believe that there is a future for MR technology in
the diagno-sis of these patients.
Dr McGregor: I agree totally
with that. One of the advantages of MR as well as ultra-fast
CT is that one can get an estimate of right ventricular
ejection fraction that is much more quantita-tive and
reproducible than that achieved with echocardiography
because of geometric considerations. It’s very useful
to know what the right ventricular ejection fraction is
going in. We’ve just completed a series of 30 or 40 consecutive
patients where we did right ventricular ejections before
and after PTE. All patients were measured while off of
vasodilators. It is interest-ing that as a group the right
ventricular ejection fraction (RVEF) improves highly significantly
from before to after, verifying that we’ve achieved something
positive. But also what was very interesting to me was
that it didn’t matter where you started in terms of EF.
In other words, even if your EF was 15 or 10 you improved
as much as if it was 30. So that’s very encouraging that
we did see improvement in the low EF and the higher EF
groups preoperatively.
Dr Tapson: Would it be fair
to say then that there isn’t really an RVEF lower limit
with which you couldn’t operate? I guess you have to look
at the whole patient and the level of other under-lying
disease, weight, etc. If it were just the RV alone, would
an RVEF that was absolutely dismal in a class IV patient
ever keep you from doing the procedure?
Dr McGregor: My current
take on the thing is that I don’t care what the pre-op
RVEF is, depending on what the likelihood is of getting
a good surgical result. In other words, if the EF is 12%
but I’m confident that I can get a good outcome surgically,
then the EF does not affect my selection. But if I see
an RVEF of 10% or 12%, and the disease is “questionable,”
I’m a little anxious, and maybe I shouldn’t be but I still
am.
Dr Fedullo: I couldn’t agree
more. That is where experience iscrucial to the evaluation
of these patients. The anatomic findings must be correlated
with the hemodynamic findings. There’s no blueprint but
you have a sense that the patient with poor RV function
and distal disease will not do well. On the other hand,
someone with poor RV function and very accessible disease
is much more likely to do well. But it takes a certain
experiential base to be able to make that determination.
Dr Mayer: I think there’s
no lower limit of right ven-tricular function. If the
endarterectomy is successful and the findings correlate
with the severity of pul-monary hypertension, the preoperative
RV function doesn’t really make a difference.
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