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Ann Thorac Surg 2009;88:814-822. doi:10.1016/j.athoracsur.2009.04.071
© 2009 The Society of Thoracic Surgeons
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Nishant D. Patel
Eric S. Weiss
Ashish S. Shah
Luca A. Vricella
John V. Conte
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Right arrow Transplantation - heart

Original Articles: Adult Cardiac

Heart Transplantation for Adults With Congenital Heart Disease: Analysis of the United Network for Organ Sharing Database

Nishant D. Patel, MDa, Eric S. Weiss, MDa, Jeremiah G. Allen, MDa, Stuart D. Russell, MDb, Ashish S. Shah, MDa, Luca A. Vricella, MDa, John V. Conte, MDa,*

a Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
b Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Accepted for publication April 16, 2009.

* Address correspondence to Dr Conte, Chief of Heart and Lung Transplantation, 600 N Wolfe St, Blalock 618, Baltimore, MD 21287 (Email: jconte{at}csurg.jhmi.jhu.edu).

Presented at the Fifty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Austin, TX, Nov 5–8, 2008.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
Background: Congenital heart disease (CHD) in the adult is an uncommon indication for heart transplantation but has been increasing. We assessed survival and predictors of death after heart transplantation for adults with CHD.

Methods: Adult primary heart transplant recipients (aged > 17 years) reported to the United Network for Organ Sharing (1987 to 2006) were reviewed and categorized by diagnosis of CHD vs other diagnoses. Kaplan-Meier survival analysis and Cox regression modeling were performed.

Results: During the study period, 35,334 adults underwent primary heart transplantation, and 689 (2%) had CHD. Adult CHD recipients had longer mean waiting list time (218 vs 195 days; p = 0.004), longer ischemic time (3.5 vs 2.9 hours, p < 0.0001), and were more likely to have pretransplant pulmonary vascular resistance exceeding 4 Woods Units (62% vs 51%, p < 0.0001) vs other recipients. Thirty-day mortality was 16% vs 6% (p < 0.0001), although Kaplan-Meier survival did not differ between groups (p = 0.92) out to 10 years. Ischemic time (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.02 to 1.35; p = 0.02), African American race (HR, 1.9; 95% CI, 1.04 to 3.58; p = 0.03), and pulmonary vascular resistance exceeding 4 Woods Units (HR, 1.5; 95% CI, 1.01 to 2.19; p = 0.04) were predictors of death for adult CHD recipients.

Conclusions: Heart transplantation for adults with CHD is effective and has good long-term prognosis. The 30-day mortality rate is high, but 5- and 10-year survival is not statistically different from patients without CHD.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
Limited treatment options and delayed recognition of children with congenital heart disease (CHD) resulted in staggering infant mortality in the 1950s that approached 70% [1]. Advances in surgical and medical management have led to marked improvement in the long-term survival of patients with CHD. These improvements have lowered infant mortality from CHD, and approximately 75% to 85% of children with CHD are now expected to survive into adolescence and adulthood [2].

Unfortunately, despite surgical treatment, many of these patients will demonstrate progressive decline in cardiac or cardiopulmonary function in adulthood. These patients are particularly challenging due to complex anatomy, prior surgical procedures, and elevated pulmonary vascular resistance (PVR) caused by many years of congestive heart failure. Other patients may present with CHD in adulthood with severe ventricular dysfunction or pulmonary vascular disease not amenable to palliative or corrective repair.

Heart or combined heart-lung transplantation may be the only treatment option for adults with CHD. In fact, some estimate that 10% to 20% of patients with CHD will ultimately require heart or heart-lung transplantation [3]. Previous studies have evaluated outcomes after heart transplantation in adults with CHD, but most have been single-institution studies with a limited number of patients [4–11]. Furthermore, there is a paucity of long-term data. The objective for our study was to analyze early and late survival after heart transplantation for adults with CHD using a large, multicenter national database.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Discussion
 Acknowledgments
 References
 
Study Design and Patient Population
We retrospectively reviewed all data reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) registry for adult patients who underwent primary heart transplantation from January 1987 to December 2006, and 35,334 adult transplant recipients were reviewed. All primary adult heart transplant recipients were grouped according to those with a diagnosis of CHD vs those with other diagnoses. Among adult CHD recipients, we conducted subgroup analyses to assess the effect of PVR, age, and gender on posttransplant survival. As a secondary analysis, we used the UNOS registry to compare survival for adult CHD vs pediatric CHD recipients. The UNOS/OPTN Standard Transplant Analysis and Research (STAR) files provided de-identified data, so waiver of consent was granted by our Institutional Review Board.

Statistical Analyses
Statistical computations were done with STATA 9.0 software (StataCorp, College Station, TX). Continuous variables are presented as mean ± standard error of the mean. Categoric variables are expressed in percentages of the total number of data points available within the database. The t test and {chi}2 analyses were used to compare continuous and categoric variables among groups, respectively. Survival was assessed by the Kaplan-Meier method and compared between groups using the Mantel-Cox log-rank test.

Mortality was first assessed for all risk factors using univariate analysis. Significant predictors of death, among other covariates, were included into a Cox proportional hazards regression model to assess for independent predictors of cumulative mortality for all recipients as well as for the adult CHD group alone. Only well-represented variables (less than 33% missing in the registry) were included in the Cox regression model, including African American race, donor/recipient weight ratio, PVR exceeding 4 Woods Units (WU), recipient gender, age, donor age, ischemic time, pretransplant inotropic requirement, transplant year, human leukocyte antigen mismatch level exceeding 5, pretransplant ventilator requirement, donor to recipient gender match, intensive care unit stay before transplant, extracorporeal membrane oxygenation, transplant type (bicaval vs biatrial technique), and prior operations. Hazard ratios (HR) are presented with 95% confidence intervals (CI).


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Discussion
 Acknowledgments
 References
 
Patient Demographics
During the study period, 35,344 adults underwent primary heart transplantation, and CHD was the diagnosis in 689 (1.9%). The annual number of adults undergoing primary heart transplantation for CHD has steadily increased during the past 2 decades (Fig 1). Data on prior operations were available for 137 of the 689 adult CHD recipients (19.9%). Of those, 119 had prior interventions and 18 did not.


Figure 1
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  		Fig 1. Annual number of adults with congenital heart disease undergoing primary heart transplantation is shown from 1987 to 2006.

 
Pertinent baseline characteristics were dissimilar between groups (Table 1). Of note, the adult CHD transplant recipients were more likely to be women, white, and aged between 18 and 40 years at the time of transplantation than were adult recipients with other diagnoses. Furthermore, adult CHD recipients were more likely to have elevated pretransplant PVR (> 4 WU) and panel reactive antibody (PRA) levels exceeding 10% than adult recipients with other diagnoses.


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  		Table 1 Clinical Characteristics
 
Operative and Postoperative Data
Operative and postoperative data are listed in Table 2. Ischemic time and waiting list duration were both significantly longer for adult CHD patients. The need for posttransplant dialysis and reoperation were significantly higher for adult CHD recipients, and they also had significantly higher risk of posttransplant infection. The incidence of stroke, pacemaker placement, and acute rejection requiring antirejection therapy after transplantation were similar between both groups. The rate of graft failure was lower for adult CHD recipients (38.7% vs 43.1% p = 0.02). Causes of graft failure were primary nonfunction (50.0% vs 47.9%), acute rejection (25.0% vs 22.0%), and chronic rejection (25.0% vs 30.1%). Retransplantation for graft failure was required in 5 adult CHD recipients vs 112 with other diagnoses. Of the 5 adult CHD patients, 1 required retransplantation for hyperacute rejection and 4 for chronic rejection. Of the 112 recipients with other diagnoses, 12 required retransplantation for hyperacute rejection, 22 for acute rejection, and 78 for chronic rejection.


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  		Table 2 Operative and Postoperative Data
 
Survival and Regression Analyses
The 30-day mortality rate was 16.1% for adult CHD patients vs 6.4% for those with other diagnoses, which was significant (p < 0.0001). However, Kaplan-Meier survival was 79.6%, 69.0%, and 57.4% at 1, 5, and 10 years for adult CHD patients vs 86.2%, 71.7%, and 50.9% for patients with other diagnoses, which was not found to be statistically different (Fig 2). Adult CHD recipients were more likely to die from graft primary failure (8.7% vs 3.4%, p < 0.001), stroke (3.7% vs 1.7%, p = 0.03), and multiorgan failure (12.5% vs 6.9%, p = 0.001) than recipients with other diagnoses (Table 3).


Figure 2
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  		Fig 2. Kaplan-Meier curve shows survival of adults with congenital heart disease (ACHD) undergoing transplantation (dashed line) vs adults with other diagnoses (solid line).

 

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  		Table 3 Causes of Death
 
Kaplan-Meier survival conditional on surviving the first 30 days after transplantation was 92.9%, 80.5%, and 67.0% for the adult CHD group at 1, 5, and 10 years, which was higher than the 91.3%, 76.0%, and 53.9% for recipients with other diagnoses (p < 0.0001). Survival conditional on surviving the first year after transplantation showed improved survival of 86.7% and 72.2% at 5 and 10 years for adult CHD recipients vs 83.2% and 59.0% for transplant recipients with other diagnoses, respectively (Fig 3).


Figure 3
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  		Fig 3. Kaplan-Meier curve shows survival of adults with congenital heart disease (ACHD) undergoing transplantation (dashed line) vs adults with other diagnoses (solid line) conditional on surviving the first year after transplantation.

 
Subgroup analyses for adult CHD recipients showed that those who had pretransplant PVR exceeding 4 WU had significantly higher operative mortality of 20.7% vs 8.5% for those with PVR of 4 WU or less (p < 0.0001); however, Kaplan-Meier survival was not significantly different out to 10 years on the log-rank test (Fig 4). Similarly, operative mortality was significantly greater for adult CHD recipients with PRA levels exceeding 10% before transplant vs less than 10% (21.3% vs 9.1%, p = 0.001), although 10-year Kaplan-Meier survival was not statistically different (log-rank p = 0.42). Operative mortality and Kaplan-Meier survival were also similar between men and women CHD recipients (p = 0.44), and when adult CHD recipients were divided by age (Fig 5).


Figure 4
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  		Fig 4. Kaplan-Meier curve shows survival of adult transplant recipients with congenital heart disease stratified by pulmonary vascular resistance (PVR) > 4 (dashed line) and ≤ 4 Woods Units (solid line).

 

Figure 5
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  		Fig 5. Kaplan-Meier curve shows survival of transplant recipients with congenital heart disease stratified by age 18 to 40 years (solid line), 40 to 60 years (dashed line), and > 60 years (dashed-dotted line).

 
We also assessed survival for adult CHD vs pediatric CHD recipients. Operative mortality was significantly greater for adult CHD patients than pediatric CHD patients (16.1% vs 13.1%, p = 0.04), but Kaplan-Meier survival was not found to be significantly different on log-rank analysis (Fig 6).


Figure 6
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  		Fig 6. Kaplan-Meier curve shows survival after transplantation of adults with congenital heart disease (solid line) vs pediatric patients with congenital heart disease (dashed line).

 
When predictors of death for all adult transplant recipients were assessed, recipient African American race (HR, 1.4; 95% CI, 1.35 to 1.57; p < 0.0001), donor age (HR, 1.01; 95% CI, 1.008 to 1.01; p < 0.0001), ischemic time (HR, 1.06; 95% CI, 1.03 to 1.09; p < 0.0001), transplant year (HR, 0.98; 95% CI, 0.97 to 0.99; p = 0.03), human leukocyte antigen mismatch exceeding 5 (HR, 1.07; 95% CI, 1.01 to 1.12; p = 0.009), pretransplant ventilator support (HR, 1.7; 95% CI, 1.4 to 1.9; p < 0.0001), donor-recipient gender match (HR, 0.94; 95% CI, 0.89 to 0.99; p = 0.03), recipient age (HR, 1.01; 95% CI, 1.004 to 1.01; p < 0.0001), PRA level exceeding 10% (HR, 1.13; 95% CI, 1.03 to 1.24; p = 0.008), and a diagnosis of adult CHD (HR, 1.25; 95% CI, 1.02 to 1.52; p = 0.03) were significantly predictive of death. A diagnosis of adult CHD was not an independent predictor of death on Cox regression analysis when excluding patients who died during the first 30 days (HR, 0.9; 95% CI, 0.7 to 1.2; p = 0.51), the first year (HR, 0.8; 95% CI, 0.6 to 1.1; p = 0.1), and the first 5 years (HR, 0.7; 95% CI, 0.5 to 1.2; p = 0.2) after transplantation.

For adult CHD recipients, pretransplant creatinine level (HR, 1.1; 95% CI, 1.04 to 1.26; p = 0.003), pretransplant ventilator support (HR, 2.1; 95% CI, 1.16 to 3.92; p = 0.003), ischemic time (HR, 1.2; 95% CI, 1.04 to 1.31; p = 0.005), donor female gender (HR, 1.4; 95% CI, 1.06 to 1.81; p = 0.01), and recipient African American race (HR, 1.8; 95% CI, 1.20 to 2.81; p = 0.005) were all significantly associated with an increased risk of death on univariate analysis. Cox regression analysis identified that African American race, ischemic time, and PVR exceeding 4 WU were independent predictors of death for adult CHD recipients (Table 4).


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  		Table 4 Significant Predictors of Mortality on Univariate and Cox Regression Analysis
 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Discussion
 Acknowledgments
 References
 
Advancements in medical and surgical management have led to decreased infant mortality from CHD, and most patients now survive into adulthood. So although infant mortality from CHD has decreased, the number of adults presenting with inexorable decline in myocardial and pulmonary function despite surgical palliation or correction has increased. Many of these patients are candidates for heart transplantation. Studies that have analyzed outcomes after heart transplantation for adult CHD [4–11] are limited to institutional studies with relatively low power and limited long-term data. The purpose of this study was to assess outcomes after heart transplantation for adults with CHD using the UNOS database. We found that adults with CHD had a significantly increased risk of operative death, although late survival was comparable with survival for transplant recipients with other diagnoses.

The 2007 International Society of Heart and Lung Transplantation (ISHLT) report on adult heart transplantation [12] found that a diagnosis of adult CHD was a powerful risk factor for death at 1 year, increasing the risk of death by twofold to threefold over patients with cardiomyopathic diagnoses. Despite the increased risk, the authors appropriately cautioned that adult CHD cases represented less than 3% of transplants performed between 2002 and 2005.

Our findings concur with the ISHLT report. In our study, adult CHD was a significant risk factor for death on Cox regression analysis, with a HR of 1.25. Interestingly, conditional analyses showed a diagnosis of adult CHD was no longer a significant predictor when excluding patients surviving less than 30 days, less than 1 year, and less than 5 years. These data suggest that a diagnosis of adult CHD carries with it an increased operative risk but has little effect on late survival. In fact, our Kaplan-Meier analysis conditional on surviving the first 30 days or the first year after transplant indicate a survival benefit for adult CHD recipients vs recipients with other diagnoses. The reason for this is somewhat unclear, but is likely due to the variability in CHD diagnoses in the adult CHD group, recipient age, and comorbid conditions.

CHD is a heterogeneous group of disorders, each with varying operative risk and long-term outlook. The adult CHD group was significantly younger at operation, and despite complex anatomy, higher pretransplant PRA levels, and higher pretransplant PVR, perhaps was less likely to have comorbid conditions like diabetes and hypertension. On the other hand, because the adult CHD group was younger at the time of operation, more adult CHD patients may eventually require retransplantation for chronic rejection, which caries a poorer prognosis than primary heart transplantation.

Prior studies have also found increased operative risk for adults with CHD. Both Lamour and colleagues [5] and Coskun and colleagues [6] reported operative mortality rates of approximately 20%, and Izquierdo and colleagues [7] reported an operative mortality approaching 25%, all of which are higher than the operative mortality rate of adults with diagnoses other than CHD. Pigula and colleagues [4] also reported increased operative mortality of 23% for adults undergoing heart-lung transplantation for CHD.

The adult CHD recipients in our study had an operative mortality of 16% vs 6% for adults with other diagnoses. This increased operative risk can be attributed to the complex anatomy of the patient, which may present challenging obstacles to reconstruction due to difficulties with sternal reentry, potential risk of donor right-sided heart failure owing to pulmonary vascular disease and elevated PVR, and overall debilitated condition.

The mean ischemic time was longer for adult CHD patients than recipients with other diagnoses, and prolonged ischemic time in the adult CHD group was a significant predictor of death on univariate and Cox regression analyses. This was likely due to the factors noted previously and the technical challenges of preparing the native structures for implantation. Others have also reported on the effect of ischemic time on outcomes after heart transplantation. Some have demonstrated poorer long-term survival for patients with longer ischemic times [13, 14], whereas others have found no association between ischemic time and survival [15–17].

A recent study from Russo and colleagues [18], which used the UNOS database, found that the effect of ischemic time on survival depends on donor age. They argued for a more conservative approach to ischemic time with adult-aged donors. Their findings supported the use of younger donor hearts when extended ischemic times were required. Their recommendation probably reflects what happens in the real world. Surgeons appear to wait for the perfect donor in younger patients with higher PVR, and as a result, their waiting times are longer.

Although prior operations may make reentry into the chest more challenging and may increase the risk of bleeding and other complications after transplantation, data from prior operations were available for only 20% of adult CHD patients.

We do not have data on blood transfusion requirements; however, it would not be unreasonable to expect the need for more blood transfusions in these patients and increased morbidity associated with these transfusions, which includes elevated PVR and primary graft failure. This may also lead to right heart dysfunction, renal failure, infection, and death by multiorgan failure. This study found adult CHD recipients were significantly more likely to die from multiorgan failure and primary graft failure. They also had a higher risk of posttransplant infection and dialysis, as well as increased incidence of reoperation vs adults with other diagnoses.

Yet another important consideration is PRA levels. Prior studies, including one from our own institution, have found that elevated PRA is a risk factor for inferior early heart transplant outcomes [19–21]. In this current study, adult CHD patients were more likely to have PRA values exceeding 10% vs adults with other diagnoses. Furthermore, among adult CHD recipients those with PRA values exceeding 10% had a higher operative mortality rate than those with values lower than 10%, although Kaplan-Meier survival showed no difference on log-rank analysis.

Adult CHD recipients may have been more likely to develop sensitization as a result of blood transfusions from previous operations. Unfortunately, previous surgery is not a well-represented variable in the UNOS database, and a history of blood transfusions is not a variable captured by the UNOS registry. However, we do recognize that at the very minimum, 119 patients with adult CHD had prior operations, so it is plausible that increased sensitization may have contributed to the increased operative mortality rate for adult CHD recipients.

More adult CHD patients had elevated PVR than patients with other diagnoses. As could be expected, elevated PVR owing to long standing congestive heart failure was a significant predictor of late death among adult CHD patients, and those with pretransplant PVR exceeding 4 WU had significantly higher operative mortality (20%) than those with PVR of 4 WU or less. Some patients with irreversible pulmonary vascular disease and elevated PVR may require combined heart-lung transplantation. Single institution studies have shown good short-term and midterm outcomes after combined heart-lung transplantation and heart transplantation in patients with elevated PVR [4, 8, 22, 23].

Pigula and colleagues [4] also used a strategy of cardiac repair and lung transplantation for those patients with adequate cardiac reserve and function. They argue that although cardiac repair may increase the complexity of lung transplantation, a distinct advantage includes expanding the donor pool. The authors found no differences in survival for adult CHD recipients who underwent combined heart-lung transplantation vs combined cardiac repair-lung transplantation, although the number of patients in the study was small. Many in the field considered combined heart-lung transplantation to be the best procedure for patients with CHD and severe pulmonary vascular disease. Combined cardiac repair and lung transplantation has been used in the pediatric population by Huddleston and colleagues [24], but this strategy has yet to be fully adopted for adults with CHD.

Recipient African American race was a significant predictor of late death on univariate and multivariate analysis for the adult CHD group. Previous studies have analyzed the effect of recipient and donor race on heart transplant outcomes, with varying results [25–29]. Further studies are needed to fully understand the effect of race on outcomes and need to include data on access to care and socioeconomic factors.

This study has limitations consistent with retrospective analyses and the use of a national multicenter database. Considerable data were missing for some important variables that prevented their incorporation into our Cox regression analyses. We avoided including variables that were less than two-thirds complete to avoid misrepresentation of the patient population in the database.

One of the more important variables missing in the UNOS registry was CHD diagnosis. Approximately 80% of adult CHD recipients had no data about prior surgical operations. For those with a prior operation, the type of surgical repair performed was not known. Unfortunately, this prohibited us from analyzing the effect of single-ventricle anatomy and a failed Fontan operation on outcomes after transplantation.

Lamour and colleagues [5] found that 4 of 5 early deaths in their study occurred in adults with single-ventricle anatomy, of which 3 had a failed Fontan procedure. They indicate that this group seems to be at increased risk for death vs those with double-ventricle anatomy. Single-ventricle patients are at risk for developing pulmonary arteriovenous malformations, which may lead to cyanosis, and also aortopulmonary collateral arteries, which were present in 25% of their patients and likely contributed to worsening heart failure and higher risk of mortality. Although we agree with the authors in principle, this current study cannot shed light on the matter because of the absence of data regarding CHD diagnosis and prior cardiac surgical procedures.

The UNOS/OPTN registry has allowed us to report a large cohort of adult CHD transplant recipients. Adult CHD recipients have an increased risk of operative death compared with adults with other diagnoses that is likely due to the unique operative and perioperative challenges of this patient population. Improving coordination between health care providers to ensure adequate time to prepare the recipient's anatomy for implantation is critical to minimizing allograft ischemic time and operative risk in these patients. The operative mortality rate was especially higher among adult CHD recipients with elevated PVR; for this group in particular, pretransplant pharmacologic efforts to lower PVR using phosphodiesterase inhibitors such as sildenafil may reduce operative risk and the risk of right heart failure, primary graft failure, and other complications after transplantation. Despite the increased operative risk, heart transplantation is safe and effective in the long-term and should be considered a surgical option for adults with CHD.


   Discussion
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
Acknowledgments
 References
 
DR CHARLES HUDDLESTON (St. Louis, MO): Congratulations on a very nicely presented paper. Adults with congenital heart disease now outnumber children with congenital heart disease. As such, they offer additional opportunities for reoperation for a variety of disorders that come in the course of their follow-up as adults and really represent the growth industry for congenital heart surgeons. It is only logical that they should now take on a little bit greater percentage of the transplant population for the adult transplant group as well, which you have shown here.

The nice thing about having this UNOS [United Network for Organ Sharing] database is that you have got large numbers and can provide nice statistics in terms of survival, et cetera. The unfortunate part of it, you address a little bit, is that there are details that are missing. One of the major details, I think, is not only the presence or absence of an operation beforehand but also the diagnosis leading to their transplant.

One group in particular that I think is interesting is the single-ventricle group. I think it is illogical to think that a patient with single-ventricle anatomy is going to have a normal life expectancy, even with good surgical care. Just as far as the numbers are concerned, there were a total of 316 patients undergoing a Fontan operation that were entered into the congenital heart disease STS [Society of Thoracic Surgeons] database for the year 2007; 98% survived their operation. That is a lot of patients to follow, that is a lot of patients that are going to reach adulthood, and, again, how long they are going to live is unknown. Most of them will develop heart failure, it will be a progressive problem, and they probably will be listed for transplantation. That is 316 patients just from the STS database who were entered; it does not cover the entire United States. And that is only one diagnosis, really. I think that they are going to begin to take on a much bigger percentage, as many as 30% to 40% of all the adults receiving transplants in the future. Those are particularly challenging operations.

My questions you addressed a little bit in your conclusions. Since the ischemic time seems to be very closely tied to the mortality and the ischemic time was higher in these groups, I think you can make a case for taking only local donors for these patients and wondered what your thoughts were about this. The actual stroke incidence in the two groups was similar, but death due to stroke was higher in the patients with congenital heart disease, and I wonder if you might comment on that. Again, congratulations on a very nicely presented paper.

MR PATEL: Thank you very much, Dr Huddleston. We absolutely agree with the limitations of the UNOS registry. For 80% of the patients with adult congenital heart disease in this database, there was no history of diagnosis or surgery in the registry, which clearly is one of the drawbacks. One of the things we commented about in the manuscript was looking at the issue of single ventricles, and there was a study that we cited in the paper from Lamour and colleagues from 1999, a Circulation paper. Of their patients that died in hospital, 80% of them had single-ventricle anatomy, and up to 25% to 30% of them ended up with collateral formation and pulmonary AV [arteriovenous] malformations.

With the issue of local donors, I can't speak for Dr Conte, but it seems like a very logical argument to use local donors, especially in the setting where ischemic time is very important. There was a study recently that utilized the UNOS registry from Columbia that showed perhaps that age is really the variable to look at when we are talking about ischemic time. So for patients that are younger, you can get donors from further distances versus those that are older and require shorter ischemic times.

In terms of stroke, we did not see a difference in the incidence of stroke between the two groups.

DR ANDREW C. FIORE (St. Louis, MO): Nishant, very nice presentation. Let me ask you a question about the ischemic time. When you looked at the Cox regression analysis, what number did you come up with for ischemic time that differentiated between higher or lower mortality?

MR PATEL: That is an excellent question. When we included ischemic time into the multivariate analysis, we included it as a continuous variable. So we haven't gone back and actually set specific time limits to see if we can find a cutoff that would increase the risk of death.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
 Acknowledgments
References
 
This work was supported in part by Health Resources and Services Administration contract 231-00-0115. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Dr Weiss is an Irene Piccinini Cardiac Surgery Research Fellow and Dr Allen is a Hugh R. Sharp Cardiac Surgery Research Fellow.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 

  1. MacMahon B, McKeown T, Record RG. The incidence and life expectation of children with congenital heart disease Br Heart J 1953:121.
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