My name is Stephen Cook, and I’ll be discussion adults with congenital heart disease, a growing population requiring multidisciplinary cardiovascular care.  For all lesions it’s interesting to recognize that there is a growing prevalence of adults with congenital heart disease compared to children with congenital heart disease.  Specifically looking at adults with severe congenital heart disease there is a growing prevalence by about 85% in severe congenital heart disease since 1985 to the year 2000.  It’s interesting to compare adults with congenital heart disease to children with congenital heart disease as there has only been an increase in the prevalence in this severe group by only about 22% over this same time period.

So how do we explain the changing prevalence in this adult congenital patient population? Well many of us believe that it’s multifactorial in etiology as there’s been a changing birth prevalence rates related to advancing maternal age or perhaps even medication exposure during the first trimester.  Others would propose that it’s related to advanced in fetal cardiac ultrasound, as we are able to maximize the detection of congenital heart disease which would explain our ability to detect less severe forms of congenital heart disease, but I’m not sure if that would explain our ability to explain the increased prevalence of severe congenital heart disease over the last several decades.  But I think we can certainly attribute this to changes in surgical progress because patients with severe congenital heart disease are perhaps the most likely to benefit from improved surgical outcomes.  And now what we are seeing is a greater survival to adulthood that’s now shifting mortality beyond 18 years of age. 

So I think what’s also helped with the look at it is the pediatric to adult congenital heart disease timeline, and look at many factors that explains our now expanding adult congenital heart disease population.  So starting at the incidence of congenital heart disease what else is attributing to this expanding patient population, and you can see yes, we’ve had advances in fetal diagnoses but we’ve also had advances in neonatal care. We now have improved surgical techniques, earlier complete repair, lower postoperative and perioperative mortalities. This now leads to increased earlier survival as well as increased midterm survival, and it’s all of these factors that contribute to the expanding adult congenital patient population.

So if we look at the overall prevalence of adults with congenital heart disease and we extrapolate from Canadian patient population data and look at this patient population data and expand this to our US patient population of about 209 million adults in the United States, we expect that in the year 2000 there were somewhere between 650 and about 975,000 adults with congenital heart disease. And it’s clear that this number continued to grow between the year 2000 and 2010. 

Using growth rates from the UK and Canada we continue to expect that there is 9,000 to 15,000 congenital heart disease patients that are expected to have graduated to adulthood each year over the last decade. Thus during that last decade there’s probably 90 to 150,000 new patients that have been added to this growing patient population.  So it’s clear that these demographic changes are going to shift the burden of lifelong care into the adult population and influence the distribution of healthcare service utilization amongst the adult congenital patient population.

Unfortunately the evidence of this impact of adult congenital heart disease care on healthcare utilization remains scarce.  So among this aging population the adequate evaluation of healthcare utilization of adults regarding hospital admissions is critical to prepare us for utilization of healthcare resources. I think it’s important because we need to inform our patients as well, more precisely about how we are going to inform them about healthcare resources that will be available to them. 

So I think probably one of the most important studies to recognize is by Muldar et al, who performed one of the first observational cohort studies using the Dutch CONCOR National Registry to assess the extent and characteristics of hospital admissions in registered adults with congenital heart disease from the time period over 2001 to 2006. This is an interesting study because the CONCOR National Registry is also linked to the Dutch National Medical Registration. During this time period 5,798 were available for analysis. During this time period up to 50% or 2,905 patients were admitted, the median age of the adult congenital patient population that were admitted were 39 years, and you can see the range of admissions were 18 to 86 years of age, and almost half of the patients were male. And it’s interesting to note that among defects, univentricular heart had the highest incidence and duration of admission.

So looking at the adult congenital demographics who are the patients that were studied? Well the 6 most common contenders of patients that were admitted included patients with simple defects and complex defects as well.  The 6 most common were atrial septal defects, ventricular septal defects, aortic stenosis and pulmonary stenosis, but also included complex lesions such as tetralogy of flow and coarctation of the aorta. You can actually see, I’ve actually included the median age of each patient group studied here, and the oldest actually included Ebstein’s anomaly with a median age of 40 years but included a range of 40 to 45 years of age. 

Looking at admission rates for the CONCOR or the adult congenital patients was actually quite interesting.  For each decade studied during the year 2005 the adult congenital patients were much – had a much greater rate of admission for each decade studied.  And beyond age 30 years of age the adult congenital patients had a 2 to 3 times greater risk of admission compared to the general Dutch patient population, which approached almost 68% by age 70 to 80 years of age. 

So what were the adult congenital patients being admitted for?  Looking at just cardiovascular admissions there were a variety of admissions, whether it included pregnancy, evaluation of pacemakers, perioperative care, heart failure and chest pain, but what you can see is most striking, the majority of the patients had admissions related to arrhythmias, most commonly ventricular arrhythmias, but even more common were atrial arrhythmias including super ventricular tachy arrhythmias. 

But what I think is more important to recognize from this study is that these patients also had numerous non-cardiovascular related admissions, whether it was related to hematologic, respiratory, hem-onc, musculoskeletal and again most commonly non-cardiovascular admissions were related to either pregnancy, which accounting for about 45% of admissions to this Dutch registry, either pregnancy and/or delivery related admissions for our adult congenital patients.   

So in summary I think this study really helped us recognize that if this does demonstrate the extent of the emerging burden of disease in terms of hospital admissions in the registered adult with congenital heart disease in a large nationwide population, I italicize the word registered because I think, you know when I think back at looking at patients in the US well what’s happening to the patients who aren’t registered. We are not accounting for any of these patients at all.  Again I think it’s helpful to recognize that if the adult congenital patient has high admission rates at all ages whether they are 30 years of age or 80 years of age, and it was clear in this study that admission rates increase with age, admission rates were 2 to 3 times higher in the adult congenital patient population compared to the general Dutch population.  And finally that I think it’s necessary to develop tertia care centers with expertise for both cardiovascular and non-cardiovascular health problems in the adult with complex congenital heart disease.

So I think this study really truly points out that the adult congenital patient population places increasing demands on all subspecialties of medicine. So I think it’s interesting that three were patients who were undergoing perioperative evaluations that were both cardiovascular and perhaps even non-cardiovascular.  So I think this may place stresses on all forms of evaluation in the hospital and I think it’s important that patients who are undergoing non-cardiovascular surgical evaluation I think or other cardiology, or other non-cardiovascular colleagues are going to require a knowledge of basic physiology and late onset complications that are unique to each form of congenital heart disease and given the extensive variations in anatomy and surgical interventions I think our non-cardiology colleagues are really going to need to develop a perioperative care plan to predict the effects of pharmacologic agents and ventilatory management strategies and fluid administration to safely manage our patients during this time of a non-cardiovascular surgical admission.

So it’s indeed true that our patients are somewhat complex and are at risk for arrhythmias, vascular lesions, residual shunts, valvular disease and heart failure, but I think it’s also true that  you have to think of the adult congenital patient as a whole patient outside of their cardiovascular related complications.  Many of our patients have been told that they have physical limitations and/or restrictions, many of our patients may present with communication challenges, many of our patients have difficulties even coping with their underlying disease. Many women are in the prime of their life and want to discuss pregnancy and contraception and again when I discuss patients are in the prime of their life, it’s also true that they want to have a discussion regarding education and career choices,  how they deal with difficulties relating to unemployment and most importantly how do we overcome challenges regarding health and life insurance.

So I think it’s incredibly important that we discuss and provide quality adult congenital heart disease care as we know that there’s clearly a burden or an increasing number of adults with congenital heart disease, and the purpose of improving quality of care for adults with congenital heart disease patients is to provide healthcare services that increase the likelihood of desired healthcare outcomes that are consistent with professional knowledge.  By doing so we can hope to decrease variations and practice patterns, avoid gaps in patients with lifelong conditions, and provide a currency for dialogue among patients, healthcare providers, the healthcare system and perhaps even policymakers.

So how do we finally do this? Well I think we do this by identifying lesion specific pathology and by creating lesion specific pathways. And I think we do this in a unified manner through the development of 2008 ACC AHA guidelines that were developed specifically for the care of adults with congenital heart disease.  So I think I want to actually walk through one specific lesion and kind of use the guidelines to see how we manage this one patient. So here is an example of a patient with coarctation of the aorta.  You can see that there is a discreet narrowing just distal to the left subclavian artery, it’s kind of a zoomed up view here to see how we kind of surgical address this. This is the first example of an end to end anastomosis as one method of surgical repair of this lesion and then this is another example of a left subclavian flat angioplasty.  But despite surgical repair it’s not uncommon that many of our patients feel that they are fixed or cured and that’s not often the case.  We encounter many late onset complications that include hypertension, re-coarctation, aortic complications such as aortic aneurism or dissection, valvular disease associated with a frequently encountered bicuspid aortic valve and therefore many of our patients may have associated aortic stenosis or aortic insufficiency and numerous intracardiac anomalies associated with coarctation.

In addition it’s not uncommon that many of our patients also have associated late onset causes of late onset complications that may be associated with death in our long term survivors that include myocardial infarction, sudden cardiac death, heart failure, cerebral vascular accidents, as we’ve also already mentioned, rupture of aortic aneurisms, perioperative death, perhaps from poor preoperative planning and other non-cardiovascular causes of death.  So I think it’s important that we kind of collaboratively manage these patients to either avoid or prevent these late onset complications. 

So I’m going to quickly walk through each late onset complication and describe each and the importance of recognizing each late onset complication starting with arterial hypertension, which is a common late onset complication despite even surgical repair.  It’s more frequently encountered in surgical repair that occurs at a later age, it’s often encountered with re-coarctation and it’s an important risk for increased mortality in this patient population as it’s thought to be associated with accelerated coronary atherosclerosis, ventricular dysfunction and perhaps even rupture of aortic or cerebral aneurisms. 

Another late onset complication we’ve discussed is recoarctation or residual coarctation. This is another important cause of morbidity after coarctation therapy as its presence alone may even induce or aggravate systemic arterial hypertension.  This is thought to occur with all surgical techniques with a prevalence ranging anywhere from 3 to 41% and it’s been associated with a smaller patient size, younger age at initial operative repair and transverse arced hypoplasia.  Stent therapy is often required to overcome recoarctation as a result of immediate elastic recoil, so balloon angioplasty is not thought to be helpful enough to treat this lesion, it’s often required for long segments of narrowing or multiple obstructions in the arch.  

Next most patients may also encounter aneurisms, which is thought to be the most lethal complication as it’s associated with life-threatening rupture. Aneurism formation is thought to occur as a result of independent aortic wall changes associated bicuspid aortic valve and/or the presence of arterial hypertension.  All surgical techniques are thought to carry a risk of postoperative aneurism but we think that the lowest incidence of aneurism may be associated with an end, a prior end to end anastomosis. 

Lastly is the bicuspid aortic valve which is found to occur in about 85% of our patients with coarctation of the aorta.  And we know that there’s a increased prevalence of aortic valve stenosis and then secondly aortic valve insufficiency in patients with a bicuspid aortic valve. So we should certainly be screening our patients for these associated complications if we know that they also have a bicuspid aortic valve and there is certainly a worry of dilation of the ascending aorta in both patients with bicuspid aortic valve and certainly if you add on top of this coarctation of the aorta. 

So we know that noninvasive imaging is certainly integral to the long term followup of the adolescent and young adult to detect these late onset complications in this complex population.  So how do we use the guidelines to help us follow these patients with this lesion?  So certainly echocardiography has been added to the guideline, the advantages include that this is a widely available noninvasive technique, it’s certainly available as our initial assessment in the outpatient clinic, unfortunately from a disadvantage standpoint it can have poor image quality in the adolescent or young adult, unfortunately the aortic isthmus is not always readily detected in adolescents or young adults with complex congenital heart disease. 

So if we look at the guidelines they often say to perform suprasternal windows specifically to look at the aortic arch, the transverse arch and the proximal descending thoracic aorta.  We often recommend to combine these windows with color or spectral Doppler to characterize any turbulent flow to really characterize the presence or absence or the site of recoarctation.  It’s important to recognize any pitfalls as the accuracy of the gradient may be scrutinized or should be scrutinized in the presence of significant collateral formation. 

So I think I’d like to just bring up a pertinent case of a 41 year old woman who actually presented to our adult congenital heart disease clinic to establish care.  As you can see here this is – she has limited transthoracic windows in the suprasternal notch, she had a body mass index of 38 kilograms per meter squared. She then proceeded to have a contrast enhanced magnetic resonance angiogram of the arc and you see what’s somewhat concerning is that she has a significant dilated aneurism just distal to the take off of the less subclavian artery that would have been otherwise missed had we only performed transthoracic imaging of the suprasternal notch. 

So cardiovascular magnetic resonance imaging has certainly become the gold standard to assess perhaps not only patients with coarctation of the aorta but all patients with complex congenital heart disease as early recognition of these late onset complications are helpful to avoid subsequent morbidity and mortality in this complex patient population. I think this helps to provide extensive information with regards to complete assessment and anatomy and geometry of the aortic arch, particularly after the arch has undergone remodeling and/or surgical repair. 

We use this technique to determine disease severity, in other words recoarctation.  We use several techniques including velocity encoded semi-MR techniques, we also can use a single examination to look at concomitant valvular disease, whether it’s a simple bicuspid aortic valve or more complex valvular disease seen in a patient with shone complex. And again we can  use this single exam to go on and perceive an assessment of both the left and right ventricles by assessing left ventricular volumes, mass and function and we can character the myocardium with delayed enhancement.

And again is CMR cost effective?  Well unfortunately there are a few studies that are available on the adult congenital population to assess quality metrics.  So Therian, et al actually performed a really interesting study using CMR as the gold standard performed a retrospective analysis to determine the sensitivity and specificity to detect recoarctation or aneurism in a group of coarctation patients who underwent the following screening tools.  She included history, physical exam, EKG, chest x-ray and transthoracic echo.

And in 84 patients they looked at recoarctation and aneurism, and looking at the recoarctation patient population about 87 patients the prevalence of this late onset complication was about 26%.  Using echocardiography alone the sensitivity was only about 87%.  When they included all 7 tests the sensitivity increased to about 100% and using clinical visit, echo and chest x-ray similarly the sensitivity increased to 100% to detect this late onset complication.  Looking for aneurisms there was a prevalence of about 14% in this patient population.  But unfortunately as you can see chest x-ray had the greatest sensitivity for detecting this late onset complication, that being a sensitivity of only 67%, so there is a significant amount of this late onset complication which is a relatively lethal late onset complication that was being missed.  It wasn’t until all 7 tests were incorporated that brought  up the sensitivity to 93%.  And that also included a clinical visit, echocardiogram and chest x-ray that also brought the sensitivity up to 93% as well.

So what were the cost analysis and recommendations? They decide that a clinical visit and CMR was probably their first line testing to detect all late onset complications for this patient population.  Secondly if CMR was not available at their institution they thought the most important or cost effective method for detecting late onset complications was clinical visit and a screening transthoracic echocardiogram.  And if there was concern for late onset complication they recommended a follow-up CMR. And they felt that this approach would identify the most late onset complications in the most cost effective manner.  So I think kind of summarizing with this case will kind of help solidify utilization of all the guidelines and incorporating kind of cost effectiveness at the same time.

So I’d like to present a 28 year old woman who presented for initial evaluation to our adult congenital heart disease clinic.  She has a past medical history of coarctation of the aorta, she underwent balloon angioplasty at 14 years of age. She does have a history of hypertension and is currently being treated with Methyldopa 500 mg twice daily. She was followed by a pediatric cardiologist until about 18 years of age and has been suddenly – and has been unfortunately lost to follow-up. She denies any cardiovascular symptoms and fortunately she’s undergone two successful pregnancies. 

Her physical examination.  Her upper extremity blood pressure is 132/75 and lower extremity blood pressure is 139/80, so she has no evidence of a residual arm/leg blood pressure gradient. Her chest examination demonstrates a normal precordium, she has a systolic click and 1/6 systolic ejection murmur.  Her lungs are clear and again she has no evidence of a radial-femoral delay on her pulse examination as well. 

So what are the current recommendations for clinical evaluation for previously repaired coarctation using the current guidelines? Well the ACC AHA guidelines would recommend initial imaging and hemodynamic evaluation by transthoracic echocardiography as we’ve discussed, including suprasternal notch windows in patients with suspected aortic coarctation.  In addition every patient with coarctation should have at least one cardiovascular MR or CT scan for complete evaluation of the thoracic aorta as well as the intracranial vessels. 

I’ve also reviewed the Canadian guidelines which suggest that all patients should have a periodic MRI following repair of aortic coarctation to document post-repair anatomy and mechanical complications such as restenosis or aneurism and CT is thought to be an alternative only if MRI is not possible. I think it’s interesting to review the Canadian guidelines as well as they actually do not include echocardiography in the initial evaluation in this coarctation patient population. 

So she did undergo echocardiography and as you can see there is no evidence of a significant recoarctation, by continuos Doppler her peak loss is less than 2 meters per second, which is consistent with her physical exam findings. It was unique we did think upon subsequent review that there perhaps may have been a subtle dilation of the proximal descending thoracic aorta just distal to the less subclavian artery, but yet  her echocardiogram was actually interpreted as normal. 

She did go on to a cardiovascular MRI examination as you can see on this horizontal long axis image on the left she has normal biventricular size and systolic function, she had no significant valvular disease and on the vertical long axis image on the right again she has no evidence of left atrial enlargement, she has no mitral valve disease and normal biventricular – normal left ventricular function.  Her volumes were normal and she had normal left ventricular ejection fraction estimated at 66%. 

We then proceed with phase contrast imaging, and it as interesting to note that she did have evidence of a subtle aneurism just distal to the take up of the less subclavian artery, so this did catch our attention and this was what prompted our re-interrogation of her transthoracic echocardiogram after her MRI was completed. 

We then went back and looked at – she then went on to have a contract enhanced MR angiogram and again you can exactly see what on her phase contrast imaging she does have evidence of a significant aneurism just distal to the take off of her subclavian artery, measuring 1.8 by 2.5 cm in diameter.  Again, it is significantly dilated as you can see the proximal descending thoracic aorta measures 1.6 by 1.7 cm and the supraceliac artery measures 1.3 by 1.5 cm in diameter. 

So turning back to the guidelines, what do we now, how do we proceed with this young woman?  Well, the ACC AHA guidelines suggest that for recurrent aortic coarctation, so coarctation after surgical repair that catheter based intervention, whether it’s balloon or stent therapy, is generally safe and the preferred alternative to surgery in the absence of confounding features, in other words aneurism or pseudo-aneurism, so our patient, or significant coarctation that affects adjoining arterial arch branches. So not too helpful for the young woman that we have here.  So I thought perhaps we should turn to our Canadian guidelines perhaps that will be more insightful.

Their recommendations that were complications of surgical repair include aneurism and pseudo-aneurism formation.  So I wasn’t sure as to what to do next for this young woman, so I thought I should turn to the European guidelines, perhaps they will be a little bit more insightful for how to manage aneurism formation after compli – after complication of initial palliation of this young woman.   

The European guidelines tell us that aneurisms of the ascending thoracic aorta or at the intervention site present a risk of rupture and death, patch repairs or a Dacron patch are at particular risk of repair site and aneurisms should be imaged on a regular basis. So I thought after reviewing all the literature I should perhaps turn to my lucky 8 ball for probably the most insightful wisdom which was ask again later.  So then I thought you know why not do an evidence based medicine literature search, and this was probably really helpful because this is probably what’s happening all around us and Gunn et al actually used a Nitinol stent to actually treat a similar patient with a similar late onset complication quite successfully that they were actually able to use a covered stent to wall off this segment of aneurism with a successful repair. 

So what are covered stents? So these are polytetrafluoroethylene covered stents with Platinum iridium in a zig pattern with goal to increase their strength.  They expand anywhere from 12 to 24 millimeters in diameter and the zigs represent the repeating pattern in a row and each zig height is about 5 ½ millimeters. 

So is the case report enough for me to convince one of my patients that this is the way to go?  Fortunately there has been other studies looking at early and intermediate term results.  This is a study that actually looked at 33 covered stents implanted in 30 patients with a follow-up period of approximately 40 months.  Aneurism were utilized in 8 of those patients.  Additional studies looked at covered stents in 38, 37 patients with a median age of about 29.6 years.  In those patients aneurisms included 7 patients.  The conclusions from both of these studies include that covered stents should be used as therapy of choice in patients with complications such as pseudo-aneurism after coarctation repair as this provided a safe and alternative therapy to conventional stent therapy in patients with complex coarctation of the aorta. 

So we actually proceeded and discussed at length with this patient both the results of the study as well as the case report and took this patient to the interventional suite. As you can see from these AP and lateral projections it actually confirmed quite nicely what we had perhaps suspected from her transthoracic echocardiogram confirmed by MRI as well is that she does have evidence of a significant aneurism distal to the left subclavian artery. 

At the time of her cardiac catheterization she had a 3 dimensional rotational angiogram which is a relatively new technique in the cardiac catheterization suite. This procedure can help provide accurate measurements in patients with complex congenital heart disease as well which can be suitable to identify complex lesions in patients with complex congenital heart disease to aid in the assessment and placement of transcatheter stents. 

She then went on to have a 8 zig 45 millimeter covered CP stent successfully walling off that segment of aneurism without any evidence of residual aneurism noted on her final angiogram. And you can see by her hemodynamics she had no evidence of a residual coarctation at the conclusion of her procedure.   Her final 3-D rotational angiogram demonstrates adequate placement of her transcatheter stent that appears well seated.

So in summary what are the key issues in the evaluation of an adult with congenital heart disease? Well I think this case really nicely demonstrates that lifelong cardiology follow-up is clearly recommended for all patients with coarctation, whether they are repaired or not, and this includes an evaluation with cardiologists with expertise in adult congenital care.  In addition, patients who have had surgical or percutaneous intervention for coarctation should also have annual follow-up. And even if the coarctation repair appears to be satisfactory, late post-operative imaging should be performed to assess for aortic dilation or aneurism formation. And I think you can take these three tenets and you can apply them to all forms of congenital heart disease. I think this is specific for this case for coarctation, but I think you can take these three tenets and take them to tetralogy as below transposition of the great arteries, these are patients who are living longer and can certainly run into trouble as they are developing new and late onset complications. 

So how do we organize our care?  I think it’s helpful to kind of think about a regional adult congenital heart disease center and these are full care facilities capable of providing comprehensive services to our adult congenital heart disease patients. I think this is a center that’s going to recognize how do we identify late onset complications, how do we get that patient to the interventional lab to address a late onset complication such as significant recoarctation or significant aneurism to prevent sudden cardiac death, to prevent aneurism rupture?  In addition I think about a regional adult congenital center as a location where we can provide sufficient number of patients that will ultimately facilitate subspecialty training. We certainly have a supply and demand mismatch where there are not enough subspecialty physicians that are available to provide care for this large growing number of patients that are requiring care here in the United States as well as throughout North America.   And finally, we certainly need to have patients at a single location or at regional centers to facilitate research to provide evidence based medicine that was clearly required for this case as well as for this entire unique patient population.

So finally, I think that these advances in transcatheter, surgical and medical care have provided the dramatic increase in the number of adult congenital patients. I think about the development of regional adult congenital centers, where we will certain be following a larger cohort of patients with not just severe as well as moderate but I think even now simple lesions as well because I think it’s time to start thinking about providing therapeutic interventions that prevent rather than treat known complications.  And finally I think that the biggest goal of having these centers in adult congenital heart disease care is to optimize healthcare delivery and we do this through establishing collaborative models between regional adult congenital centers and non-adult congenital heart disease facilities, because our big goal is to reduce errors in care and providing the best care, quality care for our patients.  Thank you.