Robyn Barst, MD |
Pulmonary Hypertension
Roundtable
Pulmonary Arterial
Hypertension in Congenital Heart Disease: Controversies
and Consensus
Four physicians discussed current and future
strate-gies for the assessment and treatment of
pulmonary arterial hypertension (PAH) related
to congenital heart disease. The roundtable discussion
was moderated by Robyn Barst, MD, Professor of
Pediatrics, Columbia University College of Physicians
and Surgeons, New York, New York, and included
David Wessel, MD, Professor of Pediatrics and
Anesthesia, Harvard Medi-cal School, and Senior
Associate in Cardiology and Anesthesia at Children’s
Hospital, Boston; Nancy Bridges, MD, Chief of
the Clinical Transplantation Section, National
Institute for Allergy and Infectious Disease,
National Institutes of Health, Bethesda, Maryland;
and Dunbar Ivy, MD, Associate Professor of Pediatrics,
Chief and Selby Rickenbaugh Chair of Pediatric
Cardiology, Director of the Pediatric Pulmonary
Hypertension Program, University of Colorado,
and Denver Children’s Hospital.
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David Wessel, MD |
Nancy Bridges, MD |
Dunbar Ivy, MD |
PAH is a known complication of congenital heart dis-ease,
particularly congenital heart defects characterized by
chronic left-to-right shunting. In 1897, Viktor Eisenmenger
described the clinical features of a patient with PAH
and a right-to-left shunt. Paul Wood subsequently used
the term “Eisenmenger syn-drome” for patients with PAH
that appeared to result from a systemic-to-pulmonary shunt.
In 1998, the World Health Organization symposium on pulmonary
hypertension (PH) reclassified various conditions seen
in association with PH, with one of the five broad categories
designated “PAH.” This classifica-tion emphasizes the
similarities between primary pul-monary hypertension (PPH)
and PAH associated with other diseases, including congenital
systemic-to-pulmonary shunts as well as PAH related to
collagen vas-cular disorders, toxins, drugs, portal hypertension,
and HIV. The World Health Organization reclassifica-tion
reflects recent advances in the understanding of pulmonary
hypertensive diseases and attempts to address the similarities
between PPH and PAH associated with certain disorders
(as stated above). Indeed, advances in the understanding
of the mech-anisms underlying the vascular changes in
PAH have contributed to the development of successful
thera-peutic strategies. It appears that some of the medical
therapies for the treatment of PPH may benefit patients
with PAH associated with congenital heart disease. In
this regard, although there is diversity in the etiology
of PAH, the therapeutic literature sup-ports some uniformity.
It is our hope today to discuss the similarities between
PPH and PAH related to congenital heart disease with respect
to diagnosis and assessment of PPH and PAH related to
congeni-tal heart disease as well as current and future
strate-gies for the treatment of PAH related to congenital
heart disease. In addition, in some cases, it becomes
extremely difficult to differentiate if a patient with
a congenital heart defect has Eisenmenger syndrome as
opposed to PPH with a clinically and hemody-namically
insignificant congenital systemic-to-pulmonary shunt.
Dr Barst: Perhaps we can
start with what I think is a very difficult question:
what are the similarities and differences between PPH
versus PAH associated with congenital heart disease versus
Eisenmenger syn-drome? How would you classify a child
who has PAH with a small ventricular septal defect (VSD),
or PAH in a toddler who has an atrial septal defect (ASD)?
Are these cases of Eisenmenger syndrome or should they
be considered PPH with a clinically and hemo-dynamically
insignificant shunt? Perhaps Dr Wessel could start. What
are your thoughts on PPH versus what I refer to as PPH
related to congenital heart dis-ease and how do you distinguish
that from Eisenmenger syndrome?
Dr Wessel: We occasionally
see a disease that looks very similar to PPH but is found
in association with the small and hemodynamically insignificant
congen-ital heart lesions, such as an ASD or a VSD. In
my mind I still think of that disease as primary pul-monary
hypertension provided there is no reason to believe the
defect was much larger in the past. However, I have been
impressed over the years that there seems to be an abundance
of ASDs in particu-lar, that are found in conjunction
with what we are otherwise viewing as PPH. So, I suspect
that at some level there is a genetic or physiologic link
between certain small defects and PPH. Nonetheless, I
don’t have a conceptual difficulty viewing PH in a child
with a relatively small ASD or VSD as a variant of PPH.
However, I think there are lots of other kinds of PH that
I would not refer to as PPH because I believe in some
fashion it is related to the underlying con-genital heart
disease and is therefore secondary to it. For example,
we have all seen patients with some degree of mitral valve
stenosis or abnormality of the mitral valve who have a
left atrial pressure of only 9 or 10 or 11 mmHg and yet
have half or greater than half systemic pressure in the
pulmonary artery. So, I think those are ambiguous etiologies
in some circumstances. The diseases include truncus arteriosus,
transpo-sition of the great arteries, and certain forms
of double outlet right ventricle. Patients who have a
physiologic abnormality associated with their defect for
many weeks or months or even years but are viewed as repairable,
may still have persistence of PH as part of that postoperative
illness. I view this as secondary, not primary pulmonary
hypertension.
Dr Barst: If we step back
for a moment with regard to the clas-sic Eisenmenger syndrome
and your third category which is closest to Eisenmenger
syndrome, I still think there is contro-versy. Do we say
patients have Eisenmenger syndrome if they have an unrestrictive
defect? If a patient has a post-triscuspid shunt that
is unrestrictive, is that Eisenmenger syndrome? And then
we have the other two categories that we should separate.
I think it is important to try and define these three
groups if we want to study these patients, particularly
now that we have many more therapeutic options available.
All drugs have some risk and toxicity and I think that
we do our patients a disserv-ice to demonstrate that drug
x, y, or z is safe and efficacious for PPH and then start
using these therapies for all patients with PH and congenital
heart disease.
Dr Bridges: I think it is
difficult to come up with a robust diag-nostic classification
as long as we are stuck with these syn-dromic, phenotypic
categorizations. If we really could diagnose the disease
we would be closer to knowing what to do with it. If one
wants to use the term “Eisenmenger syndrome,” it seems
most reasonable to take our definition from the two-part
article by Paul Wood (British Medical Journal, 1958).
He described it as “resulting from lesions that have an
unrestrictive communi-cation with exposure of the pulmonary
bed to arterial pressure.” So he specifically left out
things like partial veins or ASDs in his definition of
Eisernmenger syndrome. It doesn’t advance our understanding
to call something “Eisenmenger’s, but with this,” or “PPH,
but with this.” Terms like “Eisenmenger syndrome” or “primary
pulmonary hypertension” are arbitrary terms with standard
definitions and they have to be used accordingly. One
hopes that one day we will learn enough to know that they
don’t exactly describe a specific physiologic entity.
Dr Barst: I agree. Paul
Wood did not include pre-tricuspid shunt lesions in the
definition of Eisenmenger syndrome. If we look at our
experience with continuous intravenous epoprostenol in
patients with PAH and a small VSD or ASD, ie, congenital
heart defects that do not meet the definition of Eisenmenger
syn-drome, in general these patients have done better
than when we have treated a patient with epoprostenol
who has classic Eisenmenger syndrome, eg, unrepaired truncus
arteriosus.
Dr Ivy: Robyn, I would agree.
I think our patients who might be considered to have classic
Eisenmenger syndrome, such as a large VSD, who are treated
with epoprostenol do not show the same response as patients
who have PPH or may have a small ASD or a small VSD. I
would also agree with your comment that we may define
Eisenmenger syndrome as a large post-tricuspid shunt (VSD,
truncus arteriosus, or unrepaired large PDA). The effectiveness
of therapy in patients with classic Eisenmenger syndrome
is different from that in patients with a small defect
and maybe a PPH component.
Dr Barst: I think this is
very important for us to discuss. Nancy, do you want to
comment on this?
Dr Bridges: Yes I would.
With regard to what Dave was saying about how he categorizes
children who have both structural heart disease and pulmonary
vascular disease, I would say that the way I look at it
is very similar. Even within that group, where they clearly
have significant structural heart disease associated with
PH, there are still two subgroups because there are those
in whom the pulmonary vascular disease can be reversed
or halted by doing away with the hemodynamic derangement
and then there are others where you can completely normalize
their plumbing, but the pulmonary vascular disease continues
to progress. So, even in this category of people who have
signifi-cant structural disease, they don’t all have the
same pulmonary vascular disease.
Dr Barst: I agree. And the
most recent hypothesis for the patho-biology of PAH is
a “genetic predisposition” and a “vascular injury,” with
the vascular injury highly variable. Before we move on
to some specific treatment strategies, I would like Dunbar
to comment on his experience with large unrestricted defects
at high altitude compared with when the patients go to
sea level.
Dr Ivy: With regard to the
effects of altitude on pulmonary hypertension, each patient
has to be individualized in terms of treatment. Our general
recommendation is that altitude may be detrimental in
the presence of pulmonary vascular disease. As a rule
we recommend that patients with significant pulmonary
hypertension move to sea level to see if the pulmonary
hyper-tension improves. If the pulmonary hypertension
improves, we recommend that they stay at lower altitude.
The response to altitude in the child with pulmonary hypertension
is not pre-dictable. The degree of pulmonary hypertension
in some patients is not different between sea level or
at moderate alti-tudes of 5,280 feet in Denver. However,
some children with pulmonary hypertension may have clinical
worsening on travel to altitude. We try to discourage
patients from living at altitude with pulmonary vascular
disease, but some families are not able to move and if
there is no difference in their hemodynamics at sea level
versus Denver, then we treat them as best we can. We strongly
discourage our patients from traveling or living above
7,000 feet elevation.
Dr Barst: Thank you. Let’s
move on to treatment strategies, which probably will also
be controversial. I’d like to start by ask-ing Dave his
recommendations for the perioperative manage-ment of PAH.
Although we used to perform cardiac catheteri-zations
on all patients before surgery, we now rarely perform
preoperative cardiac catheterizations unless it is an
interven-tional cardiac catheterization. What do you think,
Dave?
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