Pulmonary Hypertension Roundtable
Pulmonary Arterial Hypertension in Congenital Heart Disease: Controversies and Consensus
Robyn J. Barst, MD 
David Wessel, MD
Nancy Bridges, MD
Dunbar Ivy, MD
Four physicians discussed current and future strategies 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 Medical 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.
PAH is a known complication of congenital heart disease, 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 syndrome” 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 classification emphasizes the similarities between primary pulmonary hypertension (PPH) and PAH associated with other diseases, including congenital systemic-to-pulmonary shunts as well as PAH related to collagen vascular disorders, toxins, drugs, portal hypertension, and HIV. The World Health Organization reclassification 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 mechanisms underlying the vascular changes in PAH have contributed to the development of successful therapeutic 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 supports 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 congenital heart disease as well as current and future strategies 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 hemodynamically 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 syndrome? 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 hemodynamically insignificant shunt? Perhaps Dr Wessel could start. What are your thoughts on PPH versus what I refer to as PPH related to congenital heart disease 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 congenital heart lesions, such as an ASD or a VSD. In my mind I still think of that disease as primary pulmonary 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 particular, 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 congenital 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, transposition 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 classic Eisenmenger syndrome and your third category which is closest to Eisenmenger syndrome, I still think there is controversy. 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 disservice 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 diagnostic classification as long as we are stuck with these syndromic, 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 communication 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 syndrome, 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 significant structural disease, they don’t all have the same pulmonary vascular disease.
Dr Barst: I agree. And the most recent hypothesis for the pathobiology 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 hypertension 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 predictable. The degree of pulmonary hypertension in some patients is not different between sea level or at moderate altitudes 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 asking Dave his recommendations for the perioperative management of PAH. Although we used to perform cardiac catheterizations on all patients before surgery, we now rarely perform preoperative cardiac catheterizations unless it is an interventional cardiac catheterization. What do you think, Dave?
Dr Wessel: I think different centers have evolved slightly different strategies for the assessment of patients who they think are at some risk of having elevated pulmonary vascular resistance as a part of their congenital heart disease. In general, if patients come to us with a large lesion that should represent a large left-to-right-shunt, and they have no signs or symptoms of congestive heart failure, that certainly raises a red flag that pulmonary vascular resistance may be elevated. Now how much one investigates that preoperatively in my mind depends in part on the age of the patients. If it is quite a young patient (in the first months of life) with a large defect and no evidence of congestive heart failure, I think the recommendation is still going to be intervene, operate on that patient; it doesn’t necessarily mean that the child is going to have significant PH as a postoperative problem. Cardiac catheterization is not necessarily mandatory. However, in an older patient who comes to us with a larger lesion at the ventricular level or even the ductus level, if one sees PH either indirectly inferred by the echocardiogram or by the absence of signs and symptoms of congestive heart failure, then I think the burden is on us to quantify the pulmonary vascular resistance and the extent of the pulmonary vascular disease because it does have pretty substantial implications for postoperative morbidity, mortality and the long-term outcome. So, I would recommend that after a child gets substantially beyond the first year of life with evidence of elevated pulmonary vascular resistance, then before intervention we catheterize those patients or get a better handle on the quantitative aspects of pulmonary vascular resistance. I believe in testing for vasoreactivity because in PPH we know that these outcomes are related to the vasoreactivity of the patient during testing. I think that carries over to the perioperative period for the child with secondary pulmonary hypertension as well.
Dr Barst: Now what about those patients who have PAH out of proportion to their pulmonary venous hypertension? Is there an age at which you would not operate? Do you do preoperative cardiac catheterizations on these patients or do you just say, “We’re going to operate because we know it is reversible and then we’ll deal with the postoperative issues.”
Dr Wessel: In general we would do a preoperative catheterization in those patients, usually because the disease that causes severe PH is one in which there is other physiologic information or an opportunity for intervention that requires catheterization. It has always been my impression (in children) that if one can repair the left-side heart disease, that the PH will not present a major problem and cause death. In the postoperative period it is treatable and generally worth the risk of intervention. The simplest answer to your question is that we are very optimistic that in children with PH related to left-side heart disease if one can intervene and repair the heart disease, then the PH generally regresses.
Dr Barst: Is there a PVRI that you consider “operable” versus “inoperable”? And if you do, are you calculating the PVRI using measured oxygen consumption or assumed oxygen consumption? Are there some times when you think it is important to leave a small interatrial communication as a “pop-off valve” in the immediate perioperative period?
Dr Bridges: If by doing vasodilator testing I can’t get the PVR somewhere in the neighborhood of six Wood units indexed, I have not sent them for repair. What I have done in several of those cases is referred them for a pulmonary artery band if they have a lesion suitable for banding. So let’s consider a patient with an unrestrictive post-tricuspid valve shunt who has a baseline, indexed PVR of 12 Wood units, which I think we may all agree is not repairable, and with vasodilator testing I can reveal some reactivity, but still not to an indexed PVR below six Wood units. In such cases I have referred the patient for a pulmonary artery band and subsequently brought the patient back for reevaluation for complete repair. That approach has been very successful in some cases, in that the pulmonary artery pressure and PVR falls after the band, and the patient can go on to repair.
Dr Wessel: I think it depends in part on the level of the shunt (ie, atrial or ventricular) as well as the demonstrated reactivity. We might be more liberal with atrial level shunts and accept a higher PVR. Let’s consider children with a large VSD, or truncus arteriosus, or AV canal, and a ventricular level shunt. We are probably a little bit less conservative than Nancy has described, but if we can get the pulmonary vascular resistance to less than 8 units, corrected for body surface area then we would be inclined to have a shunt undergo a surgical repair. If it is between 8 and 12 U/m2, then we want to assess not only their age, because in younger patients we are more likely to want to intervene than in older patients, but also their reactivity. I think to be fixed at 12 U/m2 is a little bit different than to have a pulmonary vascular resistance that may start at 12 but drop down to 8 or 9 U/m2. Above 12 U/m2, I think that we are reluctant to operate. Then again there have been occasional younger children for whom we performed a repair in the operating room or placed a device in the cath lab to close the left to right shunt, even though the PVR was 12 U/m2. What I have tried to incorporate into our evaluation is whether we turn them into a left to right shunt during catheterization with vasodilator testing. So if a young patient has high resistance, but one can demonstrate by pulmonary vasodilator testing that one can turn the shunt into a left-to-right shunt I think that there are more opportunities for intervention and long-term therapy for PH. We do from time to time leave a small atrial septal communication when closing a large VSD in a high-resistance patient. Frankly, I don’t think that helps so much minute to minute in the postoperative perod as it might help during an acute decompensation or even resuscitation. I think that if one can provide an opportunity for blood to fill the left ventricle by going right to left at the atrial level, it provides a better opportunity to get through that acute decompensation or even resuscitation as opposed to being faced with completely separated circuits when there is a very intense pulmonary vasoconstriction and a right heart that just can’t manage through the pulmonary hypertensive crisis.
Dr Barst: I completely agree with everything that has been said, including if a patient has borderline resistance, if we can decrease the shear stress or pressure, we are more aggressive about operating on these patients. We may leave an interatrial communication as a pop-off valve. The next question is since we keep throwing around the term “vasodilator testing”, are you including oxygen as well as inhaled nitric oxide, aerosolized iloprost, intravenous epoprostenol, or intravenous adenosene?
Dr Ivy: We use measured oxygen consumption in all of these patients and we use a combination of oxygen and nitric oxide, as previously shown to be the most effective strategy by Dr Wessel.
Dr Wessel: In preoperative patients we have found that using nitric oxide and oxygen together gives us the best pulmonary vasodilating response.
Dr Barst: How confident are you that using a measured oxygen consumption in room air will be accurate for calculating PVRI with inhaled nitric oxide and supplemental oxygen?
Dr Wessel: PVR is a calculated variable and can have enormous error especially when oxygen consumption is assumed and not measured. That is why we must be flexible when determining operability. If one looks at all of the data that have been accumulated over the years with nitric oxide, it does appear that, in the absence of large changes in cardiac output, inhaled nitric oxide does not change oxygen consumption. There is much experience to substantiate this assumption. So I am reasonably confident that in the absence of extreme right-heart failure and very low cardiac output that giving NO to patients to breathe does not substantially change the oxygen consumption and introduce an error in PVR calculation that is based on a measured oxygen consumption at baseline before nitric oxide.
Dr Bridges: I agree with that. And I think there are two other things that may be worth saying here. One is that even the measured oxygen consumption that one gets in the cath lab is not completely accurate. I think we just have to remember that all of these measurements that we make in the cath lab are just estimates, or snapshots, even after we have done our best to create standardized conditions. And the second thing is that, from my view, almost all of the vasodilator testing that I do in the cath lab is done with very pragmatic endpoints in mind. For example, I know that in some labs, hyperventilation is used to test for pulmonary vasoreactivity. I don’t see what the point of that is, frankly, because it is not a therapy that I am going to use in the postoperative period or for long-term therapy for the patient who is not having surgery. I try to use oxygen, I use nitric oxide, I use calcium channel blockers. I try to test with the same things that I think I might reasonably use for therapy for the patients.
Dr Barst: The therapies that we should discuss include calcium channel blockers, epoprostenol intravenously, treprostinil subcutaneously, oral beraprost, iloprost (which is available in Europe for both intravenous and inhaled administration), inhaled nitric oxide, oral endothelin-receptor antagonists, and oral phosphodiesterase inhibitors.
Dr Ivy: I would just like to start by saying that evaluation of PH is very important before even considering therapy. We have patients who have repaired congenital heart disease, who are later found to have other exacerbating factors for pulmonary hypertension, such as thromboembolic disease, ulcerative colitis, or thyroid dusease. The treating physician shouldn’t assume that because the child has congenital heart disease, the congenital lesion is the only cause of the patient’s pulmonary hypertension. With regard to therapy, we do not use calcium channel blockers in patients who are not reactive to short-acting vasodilators at cardiac catheterization, have low or borderline cardiac output, or have high right atrial pressure. We don’t test calcium channel blockers in those patients. So, I think it is important for the general pediatric cardiologist who is going to perform vasoreactivity testing to use calcium channel blockers only in patients who are reactive.
Dr Bridges: I agree precisely with every single thing that Dunbar just said. That is exactly the way I approach patients. I still find it alarming how many pediatric cardiologists in the community are starting calcium channel blockade in the clinic after an echo. That is still a big, common practice and I think we really need to emphasize that that is not an appropriate practice. I think the other problem is that there are occasional patients who have a paradoxical response to calcium channel blockade. I haven’t seen many, I think I have seen 3 in the last 10 years, but I have seen 3 patients whose PA pressure went up, whose PVR went up, and whose cardiac output went down when treated with calcium channel blockade. These were all patients who had a very nice response to nitric oxide. Dunbar, have you seen this?
Dr Ivy: Yes. I would agree. In patients reactive to acute vasodilator testing, we test the response to calcium channel blockers in the cath lab. We usually use IV diltiazem instead of nifedipine, just for ease of administration.
Dr Barst: OK, let’s turn our attention to the various treatment options. We have soft retrospective and prospective data in PPH that anticoagulation prolongs survival in adult patients. We don’t have those data in children. If we start off saying a very small percentage will respond favorably to calcium channel blockers, for those children that is wonderful, but let’s discuss the other 80 to 90% of patients. Do you want to touch on anticoagulation, and then move on to other therapies with vasodilator and perhaps antiproliferative effects?
Dr Bridges: I generally anticoagulate my patients unless I have a very good reason not to. And that is regardless of the etiology of their PH, as long as we are talking about PAH. The only exception that I make to this is in the case of young toddlers because of the risk of a bleeding event in association with a fall, and the difficulty of monitoring their anticoagulation. I will wait until they are a little older before I anticoagulate them.
Dr Barst: You are right. We don’t have data. But I think all of us are seeing patients who are having significant episodes of hemoptysis. So I think we need to be careful about “assuming” that we should use anticoagulation in patients with PAH associated with congenital heart disease the same way we do with PPH.
Dr Bridges: Assuming that they have appropriate levels of anticoagulation, an INR of 2 to 21⁄2, do we really think that is a cause of any of the hemoptysis? Hemoptysis is a part of the disease.
Dr Barst: Yes, absolutely, but if a child has hemoptysis, are you continuing them on low-dose anticoagulation, since we think that the hemoptysis is part of their underlying disease, or are you doing something else?
Dr Wessel: We certainly study patients who are having acute hemoptysis to investigate whether there are collaterals that can be identified that are contributing to the symptoms. I think it is a little bit hard when you actually get there and you start looking at collaterals and deciding which ones to embolize. I’d like to outline an algorithm for the care that we are gradually evolving for patients with PPH or perhaps repaired congenital heart disease where there’s still persistence of PH. First we test them in the cath lab and look for vasoreactivity. If they are very good responders we put them on a calcium channel blocker and evaluate them closely over the next few months to see if there is a sustained reduction in pulmonary artery pressure. If they’re not dramatic responders, then we go to the other therapies. I think there is a reasonable basis now for discussing the use of continuous IV prostacyclin that could be offered to the child. If there were a reason not to use a central venous line and continuous IV epoprostenol, then we would consider some of the other alternatives. The next option usually is other FDAapproved therapies for certain kinds of adult PH disease. Bosentan is an example but our experience is mixed and preliminary. Beyond that we get into more investigational therapy and we have offered families inhaled nitric oxide for long-term administration or I think we may see emerging the opportunity to use phosphodiesterase inhibitors in outpatients. Most of these patients who are not in the infant or toddler group we anticoagulate. We may modify that in Eisenmenger patients with hemoptysis.
Dr Barst: Are we helping these patients with these treatments, particularly Eisenmenger patients who have an 80% 5-year survival and a 40% 25-year survival without treatment? Are there subgroups that we need to evaluate to determine the overall risk-benefit considerations for these various treatments versus no treatment?
Dr Wessel: As everyone knows, the majority of advances in the treatment of PH in adults have been a result of properly designed clinical trials. We do not have placebo-controlled trials to guide our therapy in patients with Eisenmenger syndrome. We extrapolate in part from adult PPH work and studies by Dr Barst. So I would say that we don’t know if we are helping. It would be crucial, especially in most pediatric diseases, that we start proper trials because we’re taking clues from our adult patients but we’re not certain that children will react the same way. I am pleased to say that trials with sildenafil, endothelin-receptor blockers, and inhaled nitric oxide are under way in children.
Dr Barst: I would remind everyone that for the FDAapproved therapies, even though several, i.e., treprostinil and bosentan, are approved for the broad category of PAH, epoprostenol and bosentan were not evaluated in patients who have PAH associated with congenital heart defects. And I think that’s very unfortunate. It behooves us to make sure we are doing “no harm” using these therapies in PAH patients with associated congenital heart disease.
Dr Bridges: I think one thing that we have to be conscious of in making individual treatment decisions for patients who have residual significant structural lesions and pulmonary vascular disease is that if they’re getting worse because of myocardial failure rather than increasing cyanosis, they are not, in my opinion, candidates for vasodilator therapy. In other words, if I do a heart catheterization on one of these patients who, say, has an unrepaired VSD or an unrepaired canal and they have a right atrial pressure of 15, a QP/QS less than one, and low systemic cardiac output, I don’t really think that vasodilator therapy of any sort is going to be helpful for any of those patients. I think that sort of myocardial failure is really a harbinger of very end-stage disease in such patients.
Dr Wessel: I want to underscore the comments that were made about the true Eisenmenger population in patients who have right-to-left shunting and a significant degree of cyanosis. This is a patient population that has not been well studied and we need to be most cautious about these new therapies in that patient population. The subgroup that Nancy has just described with significant heart failure in association with it is one in which we should be especially cautious about these therapies because we do have a bit of natural history data for Eisenmenger syndrome that I think may be a little bit different from the adult or PPH. We know that historically one can survive several years with Eisenmenger’s physiology and we have to be very cautious about introducing new therapies that are systemic vasodilators when we have an open unrestricted defect and the potential to go right to left.
Dr Barst: We haven’t seen any clinically significant right-to-left shunting but I agree that we need to be cognizant of this potential adverse effect with vasodilator therapy in patients with Eisenmenger syndrome. We must remember that without treatment(s), Eisenmenger patients often live into their 20s, 30s and beyond. Nancy, would you address timing of transplantation and outcome?
Dr Bridges: There are two issues when you’re looking at thoracic organ replacement in people with coexisting congenital heart disease and pulmonary vascular disease. First is the technical set of issues. It’s obviously much more straightforward when you’re considering lung transplantation for a person with PPH; these patients rarely need heart replacement. You need to be sure that you have a good understanding of the technical risks associated with transplantation for this particular patient and make a very careful decision about what sort of thoracic organ replacement will be done, heart and two lungs, heart and one lung, or heart repair plus one or two lungs. It’s a very individualized decision. And then there are the physiological considerations: at what point have patients with Eisenmenger syndrome definitively failed all the available medical therapies, making it appropriate to go on to transplantation? I still pretty much use the hallmark in most cases of progression of heart failure. If we have tried all of the available vasodilator and anticongestive therapies and demonstrated that they are not useful for the patient or that they were useful and the patient is no longer responding and I start to see the progression of heart failure, I think that is the appropriate time to list the patient. If you have a patient you know is going to need replacement of both the heart and the lungs, then obviously you need to list earlier because the waiting time will be longer.
Dr Ivy: In discussing a pediatric algorithm, treatment of patients who are not responsive to acute vasodilator testing depends on clinical status and functional class. My algorithm would continue that if a child presents with congestive heart failure with a nonreactive pulmonary vascular bed, I think that epoprostenol is the standard of care for that patient and we would consider listing for transplantation. If the patient is nonreactive but with normal cardiac output and right atrial pressure and no sign of congestive heart failure, then other therapies may be considered, such as treprostinol, sildenafil, bosentan, or perhaps long-term inhaled nitric oxide. I would agree with Dr Bridges entirely.
Dr Barst: Would each of you like to comment on where you think we should be headed in the future? I think we do these patients a disservice when we treat all patients with PAH and associated congenital heart defects the same, regardless of age, congenital heart defect and its associated physiology, as well as how symptomatic the patient is from his or her PAH. We still don’t know if the “disease” is the same or different in various patients with PAH and associated congenital heart disease.
Dr Ivy: I would reiterate that it is very important that we start multicenter randomized trials in children with these newer agents.
Dr Wessel: As we move forward I think it’s important that we have a more aggressive attitude toward intervening with these patients. We are now seeing treatments for patients referred to us as “Do Not Rescuscitate” status because there is thought to be no therapy. Yet they’ve had sometimes spectacular results from existing lines of therapy for treatment of their pulmonary hypertension. It is our obligation to really exhaust all those forms of medical treatment and then consider more heroic efforts like transplantations. It is also important to inform the medical and patient communities that trials and treatments do exist for them.
Dr Bridges: I agree with everything that’s been said and I would add that it’s important both for those of us who are more specialized in seeing patients with PH and the general pediatric cardiologist to view each patient with an open mind. As I’ve had more patients with PH referred to me, I’ve found that there are more variations of the disease than I originally recognized and it’s easy to be too quick to categorize the patient. That’s a mistake. We need to start out with the view that we do not know the disease and make sure the evaluation is complete and the approach to therapy is flexible. Given how much ignorance we still have about the patients we are treating, we need to remain humble when faced with this disease.
Dr Barst: I think it is also important for us to collaborate with our colleagues in adult cardiology as more and more children with congenital heart disease are surviving into adulthood. Each patient with pulmonary vascular disease deserves an individualized evaluation and treatment approach.