Surgical palliation or primary transplantation for aortic valve atresia

Stackhouse et al

Congenital

Surgical palliation or primary transplantation for aortic valve atresia Kathryn A. Stackhouse, MD, MS,a Brian W. McCrindle, MD,b Eugene H. Blackstone, MD,c,d Jeevanantham Rajeswaran, PhD,d James K. Kirklin, MD,e Leonard L. Bailey, MD,f Marshall L. Jacobs, MD,g Christo I. Tchervenkov, MD,h Jeffrey P. Jacobs, MD,i and G€ osta B. Pettersson, MD, PhD,c for the Congenital Heart Surgeons’ Society ABSTRACT

100 90 80 70 Survival (%)

Objective: The study objective was to describe the surgical pathway progression through adolescence of an inception cohort of neonates with aortic valve atresia managed initially with surgical palliation or primary transplantation, comparing survival and self-reported health-related quality of life.

Primary transplant

60 50 40

Surgical palliation

30

Results: Risk of death was initially high for both treatment strategies. However, compared with initial surgical palliation, survival with primary transplantation, including wait-list mortality, was greater and persisted long-term (65% vs 40% at 15 years; P ¼ .002). Survival after secondary transplantation (48% at 9 years) was lower than after primary transplantation (74%). Health-related quality of life total score was lower overall than that of the general adolescent population (71  16 vs 84  13; P ¼ .0001; normal ¼ 100), but similar to that of adolescents with chronic diseases. It was similar in the surgical palliation and primary transplantation groups (70  16 vs 75  15; P ¼ .3). Patients who received surgical palliation reported more symptoms (76  15 vs 63  18; P ¼ .02). Conclusions: Patients receiving primary heart transplantation for aortic atresia in 1994 to 2000 experienced better survival, fewer symptoms, and equivalent quality of life compared with those undergoing initial surgical palliation. Notwithstanding the limited availability of neonatal and infant donor hearts, primary transplantation may be considered for those neonates with risk factors predictive of exceptionally poor survival after surgical palliation. (J Thorac Cardiovasc Surg 2019;-:1-11)

From the aDepartment of Surgery, Beth Israel Deaconess Medical Center, Boston, Mass; bDepartment of Cardiology, Hospital for Sick Children, Toronto, Canada; Departments of cThoracic and Cardiovascular Surgery and dQuantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio; eDivision of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Ala; fDepartment of Cardiothoracic Surgery, Loma Linda University, Loma Linda, Calif; gDivision of Cardiac Surgery, Johns Hopkins, Baltimore, Md; hDivision of Pediatric Cardiovascular Surgery, Montreal Children’s Hospital, Montreal, Canada; and iJohns Hopkins University, Baltimore, Md. This study was supported in part by member institutions of the Congenital Heart Surgeons’ Society, the Drs Sidney and Becca Fleischer Heart and Vascular Education

20 10 0 0

2

4

6

8

10

12

14

16

Years after Entering CHSS Institution

Survival of an aortic atresia inception cohort (19942000) by initial management strategy. Central Message Notwithstanding the limited availability of donor hearts, primary transplantation may be considered for aortic atresia with risk factors predictive of exceptionally poor survival after surgical palliation.

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Methods: From 1994 to 2000, 565 neonates with aortic atresia were admitted to 26 Congenital Heart Surgeons’ Society hospitals and followed annually for vital status. Initial management included surgical palliation (n ¼ 453) and primary cardiac transplantation (n ¼ 68). PedsQL health-related quality of life questionnaires were sent cross-sectionally to a subgroup of 198 patients alive at previous followup, with 80 responses.

Perspective Among patients born in 1994-2000 with aortic atresia, long-term survival in those managed with primary transplantation was better than in those managed with surgical palliation. For both groups, early-phase hazard was greater than a fairly constant late-phase hazard. Selfreported quality of life scores were similar for both groups and comparable to those of adolescents with chronic diseases.

See Commentary on page XXX.

Chair, and the Peter and Elizabeth C. Tower and Family Endowed Chair in Cardiothoracic Research. Received for publication Aug 7, 2018; revisions received Aug 16, 2019; accepted for publication Aug 25, 2019. Address for reprints: G€osta B. Pettersson, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Ave/Desk J4-1, Cleveland, OH 44195 (E-mail: [email protected]). 0022-5223/$36.00 Copyright Ó 2019 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2019.08.104

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Abbreviations and Acronyms CHSS ¼ Congenital Heart Surgeons’ Society CI ¼ confidence interval

Scanning this QR code will take you to the article title page to access supplementary information.

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Aortic atresia is lethal without neonatal treatment. Innovations in surgical palliation and primary heart transplantation, combined with advances in managing these patients over the past several decades, have led to greatly improved survival. Therefore, more of these patients are living into adulthood.1-5 However, no large multi-institutional studies describe the sequence of treatments from birth through adolescence, and how survival varies according to initial neonatal treatment strategy. Further, with growing numbers of survivors reaching adulthood, caregivers must be prepared to deal with their medical and health-related quality of life issues. The Congenital Heart Surgeons’ Society (CHSS) enrolled an inception cohort of neonates with aortic atresia across North America between 1994 and 2000 and has followed them annually.6,7 This unique cohort provides the opportunity to study survival and healthrelated quality of life through adolescence and explore possible associations between these outcomes and initial management strategies. Therefore, purposes of this investigation were to assess the effect of alternative management strategies on survival and health-related quality of life as these patients approach adulthood, with particular focus on surgical palliation versus primary cardiac transplantation. PATIENTS AND METHODS Patients From 1994 to 2000, 565 neonates born with aortic atresia and concordant atrioventricular and ventriculoarterial connections were admitted to 26 CHSS institutions (Appendix E1), 36% on the day of birth and 95% by day 10.7 All had absence of blood flow across the aortic valve as determined by color Doppler echocardiography. During this era, institutional review boards waived the requirement for written parental consent; thus, the cohort is believed to comprise essentially consecutive patients. The neonates were initially managed by 1 of 4 strategies: surgical palliation (n ¼ 453), listing for primary cardiac transplantation (n ¼ 68), biventricular repair (n ¼ 6), or supportive care only (n ¼ 38) (Figure E1). Management strategy was at the discretion of parents, based on guidance from individual institution’s physicians. Early outcomes of the initial portion of this cohort have been reported.6,7 In this historical cohort, primary transplantation was performed predominantly at 2 institutions (Figure E2). Characteristics of patients from these 2 institutions were

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similar to those at all other institutions, but only a few patients underwent surgical palliation at these institutions.

Data Acquisition Admission, diagnostic, and surgical information were abstracted from institutional medical records and cardiac catheterization, echocardiogram, and surgical reports. Characteristics of patients undergoing surgical palliation and primary transplantation were similar, with the exception that those with associated mitral atresia were more often managed with surgical palliation than primary transplantation (Table 1). Eight patients with a large ventricular septal defect and functional mitral valve underwent primary (n ¼ 6) or secondary (n ¼ 2) biventricular repair after a Norwood procedure; they are all alive but not considered further, nor are the 38 patients managed with supportive care, all of whom died within 2 months. Data are housed at the CHSS Data Center, located in The Hospital for Sick Children in Toronto, Canada. The University of Toronto Research Ethics Board approved use of these data for research.

Follow-up In the early 2000s, institutional review boards required that these patients be consented for continued follow-up. CHSS Data Center personnel contacted the institution and a parent or guardian of each patient annually to ascertain interim details of relevant clinical history, additional investigations, and interventions. Clinical data were complete for 70% of patients within 1 year of the 2013 annual follow-up. From the date of admission, 50% of patients were followed more than 11.8 years, 25% were followed more than 16 years, and 10% were followed more than 17.5 years. At the 2013 follow-up, 249 patients were known to be alive, but 51 of these were not contacted because of lack of institutional review board approval. Two validated questionnaires related to general and diseasespecific health-related quality of life were included in the 2014 follow-up inquiry: the PedsQL and PedsQL Cardiac Module (Appendix E2).8 Of the 198 contactable patients, 80 (40%) completed and returned the follow-up packet. Responders versus nonresponders are compared in Table E1. For this portion of the study, an ‘‘as-treated’’ analysis was performed of 60 patients after surgical palliation and 15 after transplantation.

Data Analysis Analyses were performed using SAS version 9.2 software (SAS Institute, Inc, Cary, NC). Continuous variables are summarized as mean  standard deviation or as equivalent 15th, 50th (median), and 85th percentiles when their distribution was skewed; comparisons were made using Wilcoxon rank-sum or Kruskal–Wallis tests. Categoric data are summarized by frequencies and percentages; comparisons were made using the chi-square test or Fisher’s exact test when frequency was less than 5. Time-to-event estimates are presented with asymmetric 68% confidence intervals (CIs), comparable to  1 standard error. Mortality. All-cause mortality by initial management strategy was estimated nonparametrically by the Kaplan–Meier method and parametrically by a multiphase hazard model,9 the latter used to resolve the phases of time-varying instantaneous risk of death (hazard function), which in most cases was 2. The first phase describes high, early postprocedure risk and the second subsequent ongoing risk. Competing risks. Progression of patients from initial palliation through stages of surgical reconstruction used competing-risks analyses.10 After first-stage palliation (Norwood), competing risks were superior cavopulmonary shunt (bidirectional Glenn), secondary heart transplantation, and death. After second-stage palliation (bidirectional Glenn and occasionally hemi-Fontan), competing risks were Fontan procedure, secondary heart transplantation, and death. Transition into each of these mutually exclusive states was estimated nonparametrically10 and parametrically.9 Health-related quality of life. The PedsQL was reverse-scored and linearly transformed to a 0 to 100 scale (0 ¼ 100, 1 ¼ 75, 2 ¼ 50,

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TABLE 1. Patient characteristics

Characteristic Demographics Female Race White Black Other

n* 559 329

Overall cohort (n ¼ 565) No. (%) or Mean ± SD 201 (36)

n* 453 255

217 (66) 48 (15) 64 (19)

Surgical palliation (n ¼ 453) No. (%) or Mean ± SD 173 (38)

Primary transplant (n ¼ 68) n* No. (%) or Mean ± SD 68 51

175 (69) 38 (15) 42 (16)

15 (22)

P .04 .0007

34 (67) 2 (3.9) 15 (29)

Atria Atrial septal defect Atrial septal defect jet width (mm)

455 289

430 (95) 5.6  1.7

378 228

355 (94) 5.7  1.7

52 39

52 (100) 5.5  1.8

.17 .02

Ventricles LV forms apex LV absent

310 306

7 (2.3) 53 (17)

242 239

3 (1.2) 41 (17)

41 41

2 (4.9) 6 (15)

.06 .7

Ventricular septal defect Present Small Large Multiple

248 41 41 25

50 (20) 21 (51) 20 (49) 6 (24)

179 34 34 20

40 (22) 18 (53) 16 (47) 5 (25)

51 4 4 2

7 (14) 1 (25) 3 (75) 0 (0)

Mitral valve Mitral atresia Tricuspid valve Tricuspid regurgitation grade None Mild Mild/moderate Moderate Moderate/severe Severe Pulmonary valve Pulmonary regurgitation grade None Mild Mild/moderate Moderate Aorta Ascending aorta diameter (mm) PDA diameter (mm)

440

362 297 (68) 99 (23) 34 (7.7) 10 (2.3)

378

284 (75)

454

314

244 (78)

382 199 (44) 162 (36) 54 (12) 29 (6.4) 9 (2.0) 1 (0.22)

360

41

.03

35

2.3  0.83 6.6  1.3

.04

11 (27) 15 (37) 10 (24) 5 (12) 0 (0) 0 (0)

270 (89) 23 (7.6) 8 (2.6) 1 (0.33) 411 217

26 (63)

41

302

2.4  0.84 6.5  1.3

.006 31 (66) 12 (26) 1 (2.1) 3 (6.4)

175 (46) 136 (36) 43 (11) 20 (5.2) 7 (1.8) 1 (0.26)

324 (90) 26 (7.2) 9 (2.5) 1 (0.28) 491 280

47 252 (70) 78 (22) 27 (7.5) 5 (1.4)

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RV dysfunction None Mild Moderate Severe

.9 34 (97) 1 (2.9) 0 (0) 0 (0)

51 40

2.6  0.85 6.4  1.3

.002 .7

SD, Standard deviation; LV, left ventricle; RV, right ventricle; PDA, patent ductus arteriosus. *Patients with data available.

3 ¼ 25, 4 ¼ 0), with higher scores representing better health-related quality of life. Domain scores were calculated as the sum of item scores divided by number of items answered, thereby adjusting for missing data. The Physical Health Summary Score is identical to the Physical Functioning Scale. The Psychosocial Health Summary Score is the mean of items comprising the Emotional, Social, and School Functioning Scales. Scores were standardized as z-values using norms for healthy adolescents (z ¼ 0).8 The PedsQL Cardiac Module was scored in the same

manner, with 3- or 5-point Likert scales reverse-scored and linearly transformed.

RESULTS Surgical Palliation After Norwood palliation and before a bidirectional Glenn, 2 patients underwent biventricular repair (combined

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Norwood-Rastelli) and 7 patients underwent a secondary heart transplant (Figure E1). Most patients transitioned to a bidirectional Glenn between the ages of 3 and 9 months (Figure 1). After bidirectional Glenn and before the Fontan, another 7 patients underwent secondary heart transplantation. Most patients transitioned from bidirectional Glenn to Fontan completion between the ages of 1 and 3 years (Figure E3). After the Fontan operation, 5 more patients underwent secondary heart transplantation. Primary Heart Transplantation Of 68 patients listed for primary heart transplantation, 59 received a heart and 9 died on the waiting list (Figure E1). The likelihood of transplantation within 6 months after listing was 86% (CI, 71-94), and likelihood of death on the waiting list was 13% (CI, 8-21) (Figure 2). The average age at primary transplant was 51 days. After primary transplantation, 1 patient underwent retransplantation.

Secondary Transplantation Of 19 patients who underwent a transplant after a Norwood, bidirectional Glenn, or Fontan procedure, 9 died by the end of follow-up; intermediate-term risk of death was 7.3%/year (CI, 3.5-15) compared with 1%/year after primary transplant (Figure E5), and survival was 46% (CI, 35-58) at 9 years after transplantation (Figure 4). Confidence limits for primary versus secondary transplant separated after 5 years. However, older age at transplantation was a more reliable risk factor for death than the transplant being secondary (Table E2). Health-Related Quality of Life PedsQL scores in all domains were lower for both surgical palliation and transplant groups than those in the general adolescent population (Figure 5, B), but were similar to those for other chronic pediatric diseases, such

100 90

Alive without bidirectional Glenn or transplant

80 Percent in Each Category

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Survival by Initial Management Patients managed by initial surgical palliation experienced high instantaneous risk of mortality in the first weeks after the Norwood procedure, which then decreased to 1.5% to 2.0%/year by age 4 to 5 years, with an inflection point between ages 1 and 2 years (Figure 3, A). Fifteenyear survival was 42% (Figure 3, B).

For patients managed by primary transplantation, risk of death on the transplant wait-list averaged 0.25%/day (Figure E4). Including wait-list deaths, early mortality was not as high as for those initially managed by surgical palliation in this 1994 to 2000 era (Figure 3, B). Fifteenyear survival, including wait-list deaths, was 62%. Longterm risk of death remained constant after 5 years at 1%/ year (CI, 0.8-1.8) (Figure 3, A, difference from surgical palliation P ¼ .002).

Bidirectional Glenn

70 60 50 40

Death 30 20 10 Transplant 0 0.00

0.25

# at risk: 453

257

0.50 0.75 Years after Norwood Operation 129

37

1.00

8

FIGURE 1. Competing risks after Norwood operation in patients with aortic atresia: alive without event (black dots and lines), bidirectional Glenn (yellow triangles and lines), transplantation (red squares and lines), and death before any of these procedures (blue circles and lines). Solid lines represent parametric estimates of being in each category across time. These estimates are enclosed within dashed 68% confidence bands equivalent to  1 standard error. Symbols are nonparametric estimates with 68% confidence bars.

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100 Alive without transplant 90

Transplant

Percent in Each Category

80 70 60 50 40 30 20 Death on transplant waitlist 10 0 0

1

4 2 3 Months after Listing for Primary Transplant

68

44

9

5

6

# at risk:

as asthma and diabetes (Figure E6). Adolescents with aortic atresia had worse school functioning scores than adolescents with diabetes, asthma, and obesity, but scored similarly to adolescents with cerebral palsy, a group that scored lower than those with other chronic diseases in all domains. There were no statistically significant differences between PedsQL scores of transplant recipients compared with those undergoing surgical palliation (Figure 5, A), although transplant recipients scored slightly higher in all domains. In both groups, highest scores were in the social domain (78  19 vs 77  20, P ¼ .8) and lowest in the school domain (67  24 vs 63  22, P ¼ .6). There was large variability among patients in all domains. For the more specific PedsQL Cardiac Module, transplant recipients had fewer symptoms than those who underwent surgical palliation (Figure 6). Patients in both groups scored high in the compliance domain, with a smaller standard deviation than in other domains. The lowest scores for both groups were in the cognitive domain. DISCUSSION Principal Findings Survival. This longitudinal inception cohort study of patients with aortic atresia admitted as neonates to 26 North American institutions from 1994 to 2000 provides new descriptive information regarding their intermediate-term outcomes. In that era, survival was markedly reduced by

high early risk of death, irrespective of initial treatment strategy. But survival for primary transplantation (predominantly at 2 institutions), including wait-list deaths, was better than after initial surgical palliation, primarily because of lower early mortality. Older age at transplantation, such as at secondary transplant after surgical palliation, was associated with lower survival than after primary transplantation in infancy Quality of life. Self-reported health-related quality of life was worse in both surgical palliation and primary transplant groups than in the general adolescent population, but similar to that of individuals with other chronic diseases.11,12 Fewer symptoms were reported after transplantation than after surgical palliation, but otherwise these groups had similar health-related quality of life. Surgical Palliation This CHSS experience occurred in an era when management strategies to stabilize neonates presenting with hypoplastic left heart physiology were evolving to optimize their status before initial surgical intervention. Some strategies were based on lessons learned from transplant centers, where it was often necessary to extend supportive pretransplant care over many weeks.6 Even in this early era, mortality after surgical palliation was similar to that after primary transplantation in some institutions.6 Today, principles of supportive care before and after surgical palliation are well understood and standardized.1

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FIGURE 2. Competing risks after listing for primary cardiac transplant in patients with aortic atresia: alive without transplant (black dots and lines), transplant (red squares and lines), and death on transplant wait-list (blue circles and lines). Solid lines represent parametric estimates of probability of occurrence of competing events, enclosed within dashed 68% confidence bands equivalent to  1 standard error. Symbols are nonparametric estimates with 68% confidence bars.

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10

Death (%/year)

8

6

4

Surgical palliation

2 Primary transplant 0 0

2

4 6 8 10 12 Years after Entering CHSS Institution

14

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A 100

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90 80

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70 Primary transplant 60 50 40 Surgical palliation

30 20 10 0 0

2

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Years after Entering CHSS Institution # at risk: Primary tx. 68 Surgical pall. 453

47 223

42 162

30 126

17 50

B FIGURE 3. Survival and instantaneous risk of death among patients with aortic atresia by treatment strategy. Wait-list deaths are included, as are deaths after any surgical palliation procedure. A, Instantaneous risk of death after surgical palliation compared with primary transplantation. Solid lines represent parametric estimates of instantaneous risk of death enclosed within dashed 68% confidence bands equivalent to  1 standard error. B, Survival. Solid lines represent parametric estimates of survival, enclosed within dashed 68% confidence bands equivalent to  1 standard error. Symbols are nonparametric Kaplan–Meier estimates with 68% confidence bars. CHSS, Congenital Heart Surgeons’ Society.

Thus, early mortality after the Norwood operation is substantially less than was observed in the mid-to-late 1990s, when patients entered our inception cohort.2 The National Heart, Lung, and Blood Institute–sponsored Single Ventricle Reconstruction trial enrolled 549 patients from 6

15 centers during the years 2005 to 2008, and 30-day and hospital mortality were 11.5% and 16.0%, respectively.13 The 10- and 20-year outcomes of the trial are being monitored. While we await these results, it is known already that risk out to 20 years after the Fontan operation is lower

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Congenital

100 90 80

Primary transplant

Survival (%)

70 60 50

Secondary transplant

40 30 20 10 0 0

1

# at risk: Primary tx. 59 Secondary tx. 19

52 15

2

6 3 4 5 Years after Transplant 44 14

43 9

7

39 6

8

9

33 5

than in earlier eras,3,4 brought about in part by innovations in improving energy transfer from the inferior vena cava to the pulmonary artery.14 However, the constant hazard of 1.3%/year reported by Dabal and colleagues3 remains approximately 20 times higher than the 0.072%/year for 20-year-old patients in the US general population. Primary Heart Transplantation Improved survival for initial surgical palliation is paralleled by improved survival of neonates and infants undergoing primary transplantation.5 Advantages of transplantation in infancy were suspected by Bailey and colleagues15 in the 1984 ‘‘Baby Fae’’ xenotransplant. Subsequently, several studies have identified superior survival among patients undergoing transplantation in early infancy,5,16 with 60% 25year survival among neonatal heart transplant recipients,16 substantially higher than that of infants undergoing transplantation between the ages 1 and 12 months. They documented even better outcomes in the recent era. Investigators have proposed an immunologic advantage for neonates undergoing transplantation, invoking relative tolerance that is likely multifactorial17: potential impairment in presentation of major histocompatibility complex antigens,18 potential induction of tolerance by exposure to certain foreign antigens such as isohemagglutinins determining blood groups,17 and diminished T-cell receptor diversity.19 However, primary transplantation for aortic atresia poses important issues related to the challenge of optimum use and allocation of a scarce resource: neonatal and infant

donor hearts.20 For most of these patients, there is another option—surgical palliation—that may not be available for some other types of critical congenital heart disease. Even if outcomes of primary transplantation are superior to surgical palliation, this is only true if wait-list plus posttransplant mortality is lower than mortality after surgical palliation. If more patients were listed for transplantation, wait-list mortality would increase unless more hearts became available.21,22 The 13% pretransplant wait-list mortality in this study could be the result of early introduction of neonatal transplantation at a few centers.16 However, there is no reason not to maximize primary neonatal transplantation. For example, ABO-incompatible transplantation is not uniformly performed across US centers, where the current allocation system prioritizes donor hearts to recipients of identical blood group. In Canada, allocation of donor hearts is based on clinical status, not blood group compatibility.23,24 Since changing their organ allocation practice, Canadian institutions have decreased their wait-list mortality from 58% to 7% in babies aged less than 6 months.23 Because the CHSS experience ended in 2000, discussion about when to recommend primary heart transplantation is confounded by improved survival after surgical palliation, particularly after the Norwood procedure.25 If we were to assume hypothetically that early and late results after a primary transplant strategy have remained constant since 2000, we could use the lower 70% confidence limit of the transplant strategy survival curve as a reference point. At 5 years, the lower 70% confidence limit is between 60%

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FIGURE 4. Survival after primary transplantation compared with transplantation after failed surgical palliation. Note that wait-list deaths are not included. Format is as in Figure 3.

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Physical

Emotional

Social

Psychosocial

School

Total

100

Score

75

50

25

Su

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Emotional

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r llia gic tio al n

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A

B FIGURE 5. Distribution of quality of life scores in each PedsQL domain for patients who received a transplant versus those who underwent surgical palliation. Dots represent mean values. Bars at the top, middle, and bottom of the boxes depict 15th, 50th, and 85th percentiles, respectively; top and bottom of the whiskers are maximum and minimum values. A, Raw transformed scores (see ‘‘Methods’’), where the general adolescent population has a mean value of 100. B, z-scores, where 0 represents the mean value for the general adolescent population, 1 represents 1 standard deviation below this, and so on.

and 65% (Figure 3, B). Many factors enter the decision to transplant other than just projected survival with an alternative therapy (in this case, first-stage palliation), but the 8

patient care team could justify a discussion about primary transplantation if the upper 70% confidence limit of predicted 5-year survival after first-stage palliation were less

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Physical Appearance

Compliance

Symptoms

Treatment Anxiety

Cognitive

Communication

100

Score

75

50

25

FIGURE 6. Distribution of quality of life scores in each PedsQL Cardiac Module domain for patients who received a transplant versus those who underwent surgical palliation. Format is as in Figure 5.

than approximately 60%.21,22 This might be particularly relevant for patients who have moderate or severe tricuspid regurgitation or moderate or severe right ventricular dysfunction prior to first-stage palliation, or have left ventricle to coronary artery fistulae. The reality remains that there is a paucity of donor hearts compared with demand. Thus, a recent Society of Thoracic Surgeons Congenital Heart Surgery Database report to participants revealed that from 2014 to 2017, 2016 patients with hypoplastic left heart syndrome underwent a Norwood procedure; during the same period, 113 underwent transplantation, with timing of transplantation at median age 1775 days (Q1-Q3, 274-3970), suggesting that few were primary transplants (Society of Thoracic Surgeons, personal communication, 2018). Transplantation After Surgical Palliation We observed a difference in post-transplant outcomes between patients who received primary transplantation and those who underwent transplantation after 1 or more palliative surgical procedures. However, Kirklin and colleagues26 report little difference in outcomes today between secondary transplantation and those for other forms of congenital heart disease. In contrast, 1-year mortality after listing for failed surgical palliation in the Single Ventricle Reconstruction trial was 47%, with 39% of listed patients dying on the wait-list.27 Although the difference may be explained by long-standing organ congestion and

dysfunction,26 age at transplant may also be a factor, as found in our study. In the Pediatric Heart Transplant Study, 1-year survival after listing for failed surgical palliation was 60%,28 and if the patient was younger than age 6 years at listing, the risk was greater than in older patients.29 A hybrid stage-1 palliation with ductal stenting and bilateral pulmonary artery banding has been proposed as a reasonable bridging strategy to transplantation.30 Health-Related Quality of Life Aortic valve atresia, whether treated with surgical palliation or primary transplantation, results in a challenging chronic condition with profound effects on health-related quality of life. What our questionnaires assessed was adolescents’ own opinions of how their health was affecting their daily life. These self-reports depend on patients’ expectations of how adolescents want to function. Manlhiot and colleagues31 demonstrated that having a healthy sibling was associated with lower self-reported functional health status, suggesting a possible disconnect among true physical, social, and mental limitations and self-perception of limitations. Adolescents in our study scored themselves lowest in school function, regardless of treatment strategy. Studies of patients with hypoplastic left heart physiology reveal a distinct pattern of neurodevelopmental and behavioral dysfunction characterized by mild cognitive impairment, impaired social interaction, and deficits in core

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communication skills, as well as inattention, impulsive behavior, and impaired executive function.32,33 Schoolage survivors are more likely to require remedial services, including tutoring, special education, and physical, occupational, and speech therapy. These findings are in accord with findings from other studies of patients with single-ventricle physiology after surgical palliation.34 The findings may be related in part to the burden of repeat interventions rather than to the underlying cardiac diagnosis. It is also likely related to the fact that many patients who undergo a Fontan procedure have reduced physical activity levels independent of exercise capacity and perceived worse general health, but not a reduction in other aspects of functional status.35 In transplant recipients, school performance is substantially lower than that of healthy children despite normal academic ability; a substantial number have behavioral problems (8% at age 6 months and >26% by age 2 to 5 years).36 However, DeMaso and colleagues37 found better outcomes; 78% of their study population showed good psychologic outcomes at a mean of 2.1 years after transplant, a finding maintained at 10 years. In our study, transplant recipients also reported fewer cardiac symptoms than adolescents who underwent surgical palliation. Sigfusson and colleagues38 found that children were active and generally returned to age-appropriate developmental, educational, social, and recreational activities after transplantation, with 89% to 100% capable of participating in normal activities for their age. Study Limitations The most important aspect of this study is continued follow-up through adolescence of a large inception cohort of neonates with a single diagnosis of aortic atresia across the North American continent; it is also its most important weakness, because subsequent advances in treatment have improved outcomes. Additionally, in the era during which these neonatal procedures were performed, only a few centers offered neonatal transplantation. Therefore, results of our study should be extrapolated to other single-ventricle diagnoses with caution, because we suspect the hazard of death after palliation may differ for each morphologic entity. Accurately characterizing patient status and healthrelated quality of life depends on the ability and permission to contact patients. Attempts to follow patients yearly were limited by wide geographic distribution and mobility, and requirements of many different institutional review boards with differing interpretations of the study design. Self-reports of health-related quality of life depend for accuracy on an ability to contact these adolescents, their willingness to respond to questionnaires, and their honesty in answering; illness perception itself affects self-reported quality of life.31 Nonwhite adolescents were less likely to 10

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return questionnaires than white adolescents. In addition, we presume that the most impaired adolescents could be underrepresented. We made no direct measurements of exercise capacity and did not conduct formal studies of neurodevelopmental and behavioral dysfunction. This study assesses health-related quality of life in patients with a rather homogeneous form of congenital heart disease. Because of this homogeneity, we are unable to conduct a risk-factor analysis for surgical palliation or primary transplantation. Other left ventricular outflow obstruction neonatal cohorts of the CHSS have addressed risk factors, as have other investigators.39 These data do not allow discussion of potential for more biventricular or 1-1/2 ventricle repairs in this patient cohort. CONCLUSIONS Compared with surgical palliation for aortic atresia in an era before year 2000, primary heart transplantation was associated with better survival that endured through adolescence, with no evidence of accelerating risk. We acknowledge that mortality of surgical palliation and both primary neonatal and secondary transplantation have improved substantially since year 2000. Self-reported health-related quality of life of adolescents managed by either strategy is lower than that of the general adolescent population, but similar to that of adolescents with other chronic diseases. Patients who underwent transplantation experienced fewer cardiac symptoms than those who completed surgical palliation, but no other differences in overall self-reported quality of life were observed between the groups. Although a strategy of primary heart transplantation could be considered a preferred strategy over surgical palliation for patients who have sufficient risk factors to predict a high probability of exceptionally poor midterm survival with a strategy of surgical palliation, it is likely more important to make every effort to maximize primary neonatal transplantation for newborns with an otherwise lethal congenital heart defect. It will be essential to continue following this cohort of patients into adulthood to monitor their clinical and physiologic status, transition of care, and self-reported health-related quality of life. Conflict of Interest Statement Authors have nothing to disclose with regard to commercial support. References 1. Donnellan A, Justice L. Preoperative stabilization of infants with hypoplastic left heart syndrome before stage I palliation. Crit Care Nurse. 2016;36:52-9. 2. Ohye RG, Schranz D, D’Udekem Y. Current therapy for hypoplastic left heart syndrome and related single ventricle lesions. Circulation. 2016;134:1265-79. 3. Dabal RJ, Kirklin JK, Kukreja M, Brown RN, Cleveland DC, Eddins MC, et al. The modern Fontan operation shows no increase in mortality out to 20 years: a new paradigm. J Thorac Cardiovasc Surg. 2014;148:2517-23.e1. 4. Poh CL, d’Udekem Y. Life after surviving Fontan surgery: a meta-analysis of the incidence and predictors of late death. Heart Lung Circ. 2018;27:552-9.

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5. John M, Bailey LL. Neonatal heart transplantation. Ann Cardiothorac Surg. 2018;7:118-25. 6. Jacobs ML, Blackstone EH, Bailey LL. Intermediate survival in neonates with aortic atresia: a multi-institutional study. The Congenital Heart Surgeons Society. J Thorac Cardiovasc Surg. 1998;116:417-31. 7. Ashburn DA, McCrindle BW, Tchervenkov CI, Jacobs ML, Lofland GK, Bove EL, et al. Outcomes after the Norwood operation in neonates with critical aortic stenosis or aortic valve atresia. J Thorac Cardiovasc Surg. 2003;125: 1070-82. 8. Varni JW. The PedsQLTM measurement model for the Pediatric Quality of Life InventoryTM. Available at: http://www.pedsql.org/. Accessed November 29, 2018. 9. Blackstone EH, Naftel DC, Turner ME Jr. The decomposition of time-varying hazard into phases, each incorporating a separate stream of concomitant information. J Am Stat Assoc. 1986;81:615-24. 10. Andersen PK, Borgan O, Gill RD, Keiding N. Statistical Models Based on Counting Processes. New York: Springer-Verlag; 1995:176-331. 11. Varni JW, Limbers CA, Burwinkle TM. Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL 4.0 Generic Core Scales. Health Qual Life Outcomes. 2007;5:43. 12. Ingerski LM, Modi AC, Hood KK, Pai AL, Zeller M, Piazza-Waggoner C, et al. Health-related quality of life across pediatric chronic conditions. J Pediatr. 2010; 156:639-44. 13. Tabbutt S, Ghanayem N, Ravishankar C, Sleeper LA, Cooper DS, Frank DU, et al. Risk factors for hospital morbidity and mortality after the Norwood procedure: a report from the Pediatric Heart Network Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg. 2012;144:882-95. 14. de Leval MR, Kilner P, Gewillig M, Bull C. Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex Fontan operations. Experimental studies and early clinical experience. J Thorac Cardiovasc Surg. 1988;96:682-95. 15. Bailey LL, Nehlsen-Cannarella SL, Doroshow RW, Jacobson JG, Martin RD, Allard MW, et al. Cardiac allotransplantation in newborns as therapy for hypoplastic left heart syndrome. N Engl J Med. 1986;315:949-51. 16. Chinnock RE, Bailey LL. Heart transplantation for congenital heart disease in the first year of life. Curr Cardiol Rev. 2011;7:72-84. 17. Platt JL, Cascalho M, West L. Lessons from cardiac transplantation in infancy. Pediatr Transplant. 2009;13:814-9. 18. White DJ, Gilks W. The ontogeny of immune responses. J Heart Lung Transplant. 1993;12:S301-8. 19. Ogle BM, West LJ, Driscoll DJ, Strome SE, Razonable RR, Paya CV, et al. Effacing of the T cell compartment by cardiac transplantation in infancy. J Immunol. 2006;176:1962-7. 20. Kon AA. Ethics of cardiac transplantation in hypoplastic left heart syndrome. Pediatr Cardiol. 2009;30:725-8. 21. Daly KP. Finding the correct role for heart transplant in the treatment of hypoplastic left heart syndrome. J Heart Lung Transplant. 2016;35:299-300. 22. Checchia PA, Larsen R, Sehra R, Daher N, Gundry SR, Razzouk AJ, et al. Effect of a selection and postoperative care protocol on survival of infants with hypoplastic left heart syndrome. Ann Thorac Surg. 2004;77:477-83; discussion 83. 23. West LJ, Karamlou T, Dipchand AI, Pollock-BarZiv SM, Coles JG, McCrindle BW. Impact on outcomes after listing and transplantation, of a strategy to accept ABO blood group-incompatible donor hearts for neonates and infants. J Thorac Cardiovasc Surg. 2006;131:455-61. 24. Urschel S, West LJ. ABO-incompatible heart transplantation. Curr Opin Pediatr. 2016;28:613-9.

25. Kane JM, Canar J, Kalinowski V, Johnson TJ, Hoehn KS. Management options and outcomes for neonatal hypoplastic left heart syndrome in the early twentyfirst century. Pediatr Cardiol. 2016;37:419-25. 26. Kirklin JK, Pearce FB, Dabal RJ, Carlo WF Jr, Mauchley DC. Challenges of cardiac transplantation following the Fontan procedure. World J Pediatr Congenit Heart Surg. 2017;8:480-6. 27. Kulkarni A, Neugebauer R, Lo Y, Gao Q, Lamour JM, Weinstein S, et al. Outcomes and risk factors for listing for heart transplantation after the Norwood procedure: an analysis of the Single Ventricle Reconstruction Trial. J Heart Lung Transplant. 2016;35:306-11. 28. Alsoufi B, Mahle WT, Manlhiot C, Deshpande S, Kogon B, McCrindle BW, et al. Outcomes of heart transplantation in children with hypoplastic left heart syndrome previously palliated with the Norwood procedure. J Thorac Cardiovasc Surg. 2016;151:167-74. 75.e1-2. 29. Carlo WF, West SC, McCulloch M, Naftel DC, Pruitt E, Kirklin JK, et al. Impact of initial Norwood shunt type on young hypoplastic left heart syndrome patients listed for heart transplant: a multi-institutional study. J Heart Lung Transplant. 2016;35:301-5. 30. Morray BH, Albers EL, Jones TK, Kemna MS, Permut LC, Law YM. Hybrid stage 1 palliation as a bridge to cardiac transplantation in patients with high-risk single ventricle physiology. Pediatr Transplant. 2018;22: e13307. 31. Manlhiot C, Knezevich S, Radojewski E, Cullen-Dean G, Williams WG, McCrindle BW. Functional health status of adolescents after the Fontan procedure–comparison with their siblings. Can J Cardiol. 2009;25: e294-300. 32. Goldberg CS, Schwartz EM, Brunberg JA, Mosca RS, Bove EL, Schork MA, et al. Neurodevelopmental outcome of patients after the Fontan operation: a comparison between children with hypoplastic left heart syndrome and other functional single ventricle lesions. J Pediatr. 2000;137:646-52. 33. Mahle WT, Clancy RR, Moss EM, Gerdes M, Jobes DR, Wernovsky G. Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome. Pediatrics. 2000;105:1082-9. 34. Idorn L, Jensen AS, Juul K, Overgaard D, Nielsen NP, Sorensen K, et al. Quality of life and cognitive function in Fontan patients, a population-based study. Int J Cardiol. 2013;168:3230-5. 35. McCrindle BW, Williams RV, Mital S, Clark BJ, Russell JL, Klein G, et al. Physical activity levels in children and adolescents are reduced after the Fontan procedure, independent of exercise capacity, and are associated with lower perceived general health. Arch Dis Child. 2007;92:509-14. 36. Wray J, Long T, Radley-Smith R, Yacoub M. Returning to school after heart or heart-lung transplantation: how well do children adjust? Transplantation. 2001; 72:100-6. 37. DeMaso DR, Douglas Kelley S, Bastardi H, O’Brien P, Blume ED. The longitudinal impact of psychological functioning, medical severity, and family functioning in pediatric heart transplantation. J Heart Lung Transplant. 2004;23: 473-80. 38. Sigfusson G, Fricker FJ, Bernstein D, Addonizio LJ, Baum D, Hsu DT, et al. Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years. J Pediatr. 1997; 130:862-71. 39. Meza JM, Hickey E, McCrindle B, Blackstone E, Anderson B, Overman D, et al. The optimal timing of stage-2-palliation after the Norwood operation. Ann Thorac Surg. 2018;105:193-9.

Key Words: aortic atresia, neonatal, Fontan, transplantation, surgical palliation, survival, quality of life

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APPENDIX E1. CONGENITAL HEART SURGEONS’ SOCIETY INSTITUTIONS THAT PARTICIPATED IN AORTIC ATRESIA STUDY Children’s Hospital of Philadelphia Children’s Hospital of Pittsburgh Children’s Hospital Los Angeles Cincinnati Children’s Hospital Medical Center Children’s Hospital of Michigan, Detroit Children’s Hospital of Buffalo Children’s Memorial Hospital, Chicago Children’s Mercy Hospital, Kansas City Children’s National Health System, Washington D.C. Cleveland Clinic Columbia Presbyterian Medical Center, New York Duke University Medical Center, Durham Loma Linda University Medical Center Mayo Clinic, Rochester Milton S. Hershey Medical Center, Hershey Montreal Children’s Hospital C.S. Mott Children’s Hospital, Ann Arbor St. Christopher’s Hospital for Children, Philadelphia Boston Children’s Hospital Children’s Hospital Colorado, Aurora The Hospital for Sick Children, Toronto University of Alabama at Birmingham University of Chicago University of Miami University of Nebraska Vanderbilt University Medical Center

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APPENDIX E2. HEALTH-RELATED QUALITY OF LIFE PedsQL Generic and Cardiac Modules The PedsQL generic form is a brief, practical, flexible, and developmentally appropriate questionnaire that uses a multidimensional modular approach to measure health-related quality of life in children and adolescents. It is age-specific and can include both a patient and parent version. It measures core dimensions of health as designated by the World Health Organization, as well as school functioning. The 4 multidimensional scales are physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items), and the summary scores include physical health summary, psychosocial health summary, and total score. The PedsQL Cardiac Module is similar, but includes questions specifically for adolescents with cardiac disease. Reported dimensions (or grouped categories of questions) include heart problems and treatment (7 items), treatment (3 items), perceived physical appearance (3 items), treatment anxiety (4 items), cognitive problems (5 items), and communication (3 items). Higher scores indicate fewer problems and better quality of life. Comparison of responders and nonresponders. A total of 80 patients, ranging from 12 to 19 years of age (mean 15  2.2), returned questionnaires. Clinical characteristics and cardiac morphology of patients who returned the questionnaires were generally similar to those of patients who did not (n ¼ 117; Table E1). However, there was slightly more tricuspid regurgitation at neonatal baseline in patients who returned the questionnaires, and they were more likely to be white. Despite the statistical significance, these differences between groups are likely not clinically important.

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Total Patients (n = 565)

Death (n = 195)

Bidirectional Glenn (n = 245)

Heart Transplant (n = 7)

Death (n = 24)

Fontan (n = 191)

Heart Transplant (n = 7)

Death (n = 18)

Heart Transplant (n = 5)

Fontan (n = 1)

BV Repair (n = 2)

BV Repair (n = 6)

Heart Transplant (n = 59)

Death (n = 9)

Retransplant (n = 1)

Death (n = 16)

No Treatment (n = 38)

Death (n = 38)

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Listed for Heart Transplant (n = 68)

Surgical Palliation (Norwood, n = 453)

Initial Management

FIGURE E1. CONSORT-style diagram of surgical treatment of patients with aortic atresia. BV, Biventricular.

100 90 80

# of patients

70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Institution Number Surgical Palliation

Primary Transplant

No Treatment

BV Repair

FIGURE E2. Institutional volume of neonates with aortic atresia managed by surgical palliation (blue), primary transplantation (red), biventricular repair (mauve), and no treatment (black).

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100

Alive without Fontan or transplant

90 Fontan

Percent in Each Category

80 70 60 50 40 Transplant

30 20

Death

10 0 0 # at risk: 245

1

2

3

208

43

5 6 7 4 8 Years after Bidirectional Glenn 12

9

10

11

12

5

5

1.00

0.75 Death (%/day)

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FIGURE E3. Competing risks after bidirectional Glenn/hemi-Fontan in patients with aortic atresia: alive without event (black dots and lines), Fontan (yellow triangles and lines), transplantation (red squares and lines), and death before any of these procedures (blue circles and lines). Solid lines represent parametric estimates of being in each category across time. These estimates are enclosed within dashed 68% confidence bands equivalent to  1 standard error. Symbols are nonparametric estimates with 68% confidence bars.

0.50

0.25

0.00 0

10

20

40 60 30 50 Days on Transplant Waitlist

70

80

90

FIGURE E4. Instantaneous risk of death on the heart transplant wait-list. Format is as in Figure 3, A.

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20

Death (%/year)

16

12

8

Secondary transplant

4 Primary transplant 0 0

1

2

3

4 6 5 Years after Transplant

7

8

9

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FIGURE E5. Hazard function for primary versus secondary heart transplantation, not including wait-list mortality, which was not documented for secondary transplant patients. Format is as in Figure 3, B.

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Physical

Emotional

Social

Psychosocial

School

Total

100

80

60

40

Score

100

80

60

40

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100

80

60

40 Healthy

Aortic Cardiac Diabetes Asthma Obesity Cerebral Atresia Palsy

Healthy

Aortic Cardiac Diabetes Asthma Obesity Cerebral Atresia Palsy

FIGURE E6. Distribution of quality of life scores in each PedsQL domain for patients with aortic atresia, in green, compared with healthy patients and those with other pediatric chronic diseases. Dots depict mean values, with error bars equivalent to  1 standard deviation.E1

E-Reference E1. Varni JW, Limbers CA, Burwinkle TM. Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL 4.0 Generic Core Scales. Health Qual Life Outcomes. 2007;5:43.

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TABLE E1. Characteristics of patients who returned questionnaires (responders) compared with those who did not (nonresponders)

Demographics Age at admission (y)y Female Race White Black Other

n* 117 117 76

Nonresponders (n ¼ 117) No. (%) or Mean ± SD 0/1/6 33 (28)

n* 80 80 49

48 (63) 5 (6.6) 23 (30)

Initial management group Surgical palliation Transplant Biventricular repair

117

101 87

62 78 53 73

99 (98) 38 (44) 32 (37) 17 (20) 58 (94) 40 (51) 0 (0)

99

66 58

74 (77) 16 (17) 4 (4.2) 2 (2.1) 8 (12)

80 71 59 59

53 56 51 60

64 64 64

.13

67 (94) 24 (41) 20 (34) 15 (25) 51 (96) 22 (39) 1 (2.0)

.5 .17 .3 .3

56 56 74 74

56 48

.01 29 (39) 24 (32) 15 (20) 6 (8.0) 1 (1.3) 0 (0) 42 (75) 5 (8.9) 54 (73) 16 (22) 4 (5.4) 0 (0) 7 (13)

.8 .3 .5

>.9 .9

16 (33) 22 (46) 10 (21) 47

1 (1.6) 10 (16) 52 (83) 4.0  1.2 1.8  0.81 5.7  1.8

.2 .7

50 (83) 7 (12) 2 (3.3) 1 (1.7) 0 (0) 0 (0)

19 (33) 25 (43) 14 (24) 63

>.9 .9 .008

64 (80) 12 (15) 4 (5.0)

75 44 (44) 43 (43) 10 (10) 0 (0) 2 (2.0) 0 (0) 60 (73) 3 (4.5)

P

43 (88) 2 (4.1) 4 (8.2)

68 (93) 4 (5.5) 1 (1.4) 0 (0) 0 (0) 0 (0)

82 66 96

0/1/7 22 (28)

80 86 (74) 29 (25) 2 (1.7)

Morphology and function ASD ASD size Small Medium Large ASD flow direction: left to right Multiple ASDs Abnormal pulmonary venous drainage Pulmonary regurgitation grade Normal Mild Mild-moderate Moderate Moderate-severe Severe Tricuspid regurgitation grade Normal Mild Mild-moderate Moderate Moderate-severe Severe Mitral atresia LV forms apex RV dysfunction Normal Mild Moderate Severe LV absent IVS pressure Bows to RV Flat Bows to LV Ascending aorta hypoplasia grade Mild Moderate Severe Right atrial area (cm2) Left atrial area (cm2) ASD jet width (mm)

Responders (n ¼ 80) No. (%) or Mean ± SD

56 56 54

.5 1 (2.1) 4 (8.5) 42 (89) 3.7  1.1 1.8  0.68 5.4  1.5

.18 .8 .3 (Continued)

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TABLE E1. Continued Characteristic

n*

Cardiac end-diastolic length (cm) End-systolic long-axis RV endocardial length (mm) End-diastolic long-axis RV epicardial length (mm) End-systolic short-axis RV endocardial length (mm) End-diastolic short-axis RV endocardial length (mm) Ascending aorta diameter (mm) PDA diameter (mm)

Nonresponders (n ¼ 117) No. (%) or Mean ± SD 2.9  0.40 2.8  0.34 3.3  0.33 3.3  0.90 5.2  1.0 2.5  0.92 4.7/6.4/7.6y

63 63 63 63 63 105 63

n* 53 53 51 48 49 75 54

Responders (n ¼ 80) No. (%) or Mean ± SD 2.8  0.30 2.8  0.30 3.3  0.32 3.4  1.3 5.2  1.6 2.5  0.99 5.1/6.2/7.8y

P .4 .3 .4 >.9 .8 .6 >.9

SD, Standard deviation; ASD, atrial septal defect; LV, left ventricle; RV, right ventricle; IVS, interventricular septum; PDA, patent ductus arteriosus. *Patients with data available. y15th/50th/85th percentiles.

CONG TABLE E2. Risk factors for death after heart transplantation Risk factor

Coefficient ± SE

Early phase Secondary transplantation Older age at transplantation

0.097  1.2 0.66  0.95

Late phase Secondary transplantation Older age at transplantation

0.83  0.61 0.39  0.082

P .9 .5 .17 <.0001

SE, Standard error.

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Surgical palliation or primary transplantation for aortic valve atresia Kathryn A. Stackhouse, MD, MS, Brian W. McCrindle, MD, Eugene H. Blackstone, MD, Jeevanantham Rajeswaran, PhD, James K. Kirklin, MD, Leonard L. Bailey, MD, Marshall L. Jacobs, MD, Christo I. Tchervenkov, MD, Jeffrey P. Jacobs, MD, and G€ osta B. Pettersson, MD, PhD, for the Congenital Heart Surgeons’ Society, Boston, Mass; Toronto, Ontario, and Montreal, Quebec, Canada; Cleveland, Ohio; Birmingham, Ala; Loma Linda, Calif; and Baltimore, Md Notwithstanding the limited availability of donor hearts, primary transplantation may be considered for aortic atresia with risk factors predictive of exceptionally poor survival after surgical palliation.

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000

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