Relationship of Patient and Medical Characteristics to Health Status i
http://www.100md.com
《循环学杂志》
the University of Toronto, Hospital for Sick Children, Toronto, Canada (B.W.M.)
University of Utah, Salt Lake City (R.V.W.)
New England Research Institutes, Watertown, Mass (P.D.M.)
Columbia University Medical Center, New York, NY (D.T.H.)
Children’s Hospital of Philadelphia, Philadelphia, Pa (S.M.P.)
Medical University of South Carolina, Charleston (A.M.A.)
Duke University Medical Center, Durham, NC (J.S.L.)
Children’s Hospital Boston, Boston, Mass (J.W.N.).
Abstract
Background— After the Fontan procedure, patients are at risk for suboptimal health status related to their complex healthcare experience, physiological limitations, medical complications, and guarded long-term prognosis.
Methods and Results— In the Pediatric Heart Network cross-sectional study of Fontan survivors 6 to 18 years of age, parents completed the Child Health Questionnaire, and scores were related in multivariable analysis to patient and medical characteristics obtained from medical record review. For 537 patients (mean age at study, 11.9 years; 60% male) with a median age at Fontan of 2.8 years (range, 0.7 to 14.6 years), parent-reported patient morbidities included deficits in vision in 33%, speech in 27%, and hearing in 7%, as well as problems with attention in 46%, learning in 43%, development in 24%, behavior in 23%, anxiety in 17%, and depression in 8%. Child Health Questionnaire summary scores were significantly lower than the US population sample for Physical Functioning (mean Z score, –0.47±1.19; P<0.001) and Psychosocial Functioning (–0.28±1.08; P<0.001). Parent-reported medical conditions and long-term and current medical problems explained the greatest amount of variation in the Physical Functioning scores. Parent-reported patient conditions, including behavior, learning, anxiety, and attention problems and depression, explained the greatest amount of variation in the Psychosocial Functioning scores. Lower family income had a negative impact on both Physical and Psychosocial Functioning.
Conclusions— There are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households.
Key Words: follow-up studies Fontan procedure heart defects, congenital health status quality of life
Introduction
As mortality related to congenital heart disease continues to decline, the focus of clinical care has turned to morbidity and quality of life. Health status has various domains, related primarily to physical functioning and psychosocial aspects.1 It may be affected by many factors, including medical history, current medical morbidity, perceptions, reactions and adaptations to health-related problems, available resources, and opportunities to deal with those problems, as well as the patient’s psychosocial milieu and support systems.2
Clinical Perspective p 1129
Patients with functional single ventricle who have undergone the Fontan procedure may be especially predisposed to poor health status. These patients are subjected to a complex and prolonged medical experience. They have diminished exercise tolerance imposed by their cardiovascular physiology.3,4 Moreover, Fontan patients may have important and debilitating morbidities5 and have a guarded long-term prognosis. We therefore sought to characterize health status and its sociodemographic and medical determinants in this high-risk population.
Methods
The Fontan Cross-Sectional Study was performed by the Pediatric Heart Network. The Pediatric Heart Network, which consists of 7 pediatric cardiac centers in the United States and Canada, a data coordinating center at the New England Research Institutes, and the Pediatric Heart Network chair, performs multicenter clinical studies with funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The primary aim of the Fontan Cross-Sectional Study was to assess the correlation between measures of health status, ventricular function, and exercise performance in children and adolescents who have survived a Fontan procedure. The present analysis and report focus only on the data collected from the medical record review and the parent report health status questionnaire. All 7 centers obtained local Institutional Review Board or Ethics Committee approval before initiating the study, and written informed consent was obtained for all subjects from either a parent or a legal guardian or from the subject if of legal age. Subject assent was also obtained per local guidelines.
Study Subjects
Eligible patients were identified by a preliminary medical record review of all children who had undergone a Fontan procedure and were currently followed up at 1 of the 7 centers. Study subjects were eligible if they were 6 to 18 years of age at the time of enrollment; had undergone a Fontan procedure at least 6 months before initial study testing; and agreed to have an echocardiogram, to complete a parent report health status questionnaire, and to have blood testing within 3 months of enrollment at one of the study centers. Exclusion criteria included the presence of a noncardiac medical or psychiatric disorder that would prevent successful completion of planned study testing or would invalidate the results of study testing. Additional criteria included ongoing or planned participation in another research protocol that would conflict with the present study, lack of reading fluency by the primary caregiver in English or Spanish, and pregnancy at the time of enrollment or pregnancy planned before the completion of study testing.
Medical Record Review
For enrolled study subjects, a detailed medical record review was performed through the use of standardized forms to abstract data on patient demographics, underlying cardiac anatomy, pre-Fontan characteristics (interim surgical and interventional catheterization procedures, complications, pre-Fontan clinical status), Fontan procedure characteristics (type of Fontan connection, fenestration, concomitant procedures, immediate complications, hospital course, and discharge status), and outcomes during follow-up after the Fontan procedure, including the most recent clinical assessment and testing.
Health Status Questionnaire
The study used the Child Health Questionnaire (CHQ) Parent Report Form (CHQ-PF50) as a generic measure of health status completed by the parent.6 The Parent Report CHQ, which measures the physical and psychosocial (eg, emotional, behavioral, and social) well-being of children 5 to 18 years of age, was to have been completed by a parent for all enrolled study subjects. The Parent Report CHQ measures components of physical and psychosocial functioning in 12 categories (subscales). Domains that contribute most heavily to the Physical Functioning summary score include physical functioning limitations, physical limitations on schoolwork or activities with friends, bodily pain, and general health perceptions. Domains that contribute most heavily to the Psychosocial Functioning summary score include mental health, limitations on schoolwork or activities from emotional or behavioral problems, general behavior, and self-esteem. Domains concerning the impact of the child’s health on the parents’ worries, concerns, and time; family activities; and family cohesion contribute to both summary scores. In addition, as part of the Parent Report CHQ that is not scored, parents are asked to indicate on a checklist if they had ever been told by a teacher, school official, doctor, nurse, or other health professional that their child had any of a list of noncardiac health conditions.
Data Analysis
Data are described as frequencies, medians with ranges, and means with standard deviations as appropriate. When data are missing, the number of available values is given. Parent Report CHQ scores were converted to Z scores on the basis of published normative data and tested for deviation from normal with single sample t tests.6,7 CHQ summary scores of Physical and Psychosocial Functioning were related to patient and medical history variables using t tests, ANOVA, and linear regression analysis. Variables that showed a significant bivariable relationship (P<0.05) then formed the variable set for multivariable analysis. For the purposes of multivariable analyses, missing values for predictor variables were informatively imputed and replaced with the mean of all nonmissing values. No variable was missing >5% of values. Patient and medical history variables were grouped and entered into separate multiple linear regression analysis for each of the CHQ summary scores of Physical Functioning and Psychosocial Functioning. The overall R2 for each regression was noted to determine the amount of variation in scores explained by each group of variables. Separate stepwise multivariable linear regression analyses were then performed for each of the CHQ summary scores of Physical and Psychosocial Functioning. Bootstrap bagging (repeated sampling and stepwise multivariable analysis of the main data set) and cluster analysis were used to guide and indicate reliability of variable selection for inclusion in the final multivariable models and to provide an assessment of reliability of variable selection. Given the large number of variables being tested, only those variables that were significant with a value of P<0.05 in the final models are reported to minimize the effects of multiple comparisons. In addition, the adjusted effects of the type of Fontan connection and study site were explored in each final model. All analyses were performed with SAS/STAT software, version 9.1 of the SAS System for Windows (SAS Institute Inc).
The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.
Results
Study Participation
The records of 1078 children who had undergone a Fontan procedure were screened. Of the 831 (77%) judged potentially eligible for the study, only 644 (60%) were found to be fully eligible after being contacted. The consent rate was 85%, and 546 children were enrolled with family consent. Different proportions of enrolled patients completed each of the study tests, and 9 parents did not complete the CHQ. The present study includes 537 enrolled patients who had medical record reviews and whose parents completed the Parent Report CHQ.
Patient and Clinical Characteristics
The table found in the online Data Supplement summarizes the frequencies and distributions of sociodemographic and medical history. Medical history before the Fontan procedure was complex; 2 cardiac surgeries were performed in 80% of subjects, and at least 1 interventional cardiac catheterization was done in 47%. Postoperative complications after the Fontan procedure were frequent; 40% of subjects had a postoperative length of hospital stay of 2 weeks, and 95% were discharged on at least 1 medication (mean number of medications, 3.7). During follow-up from the Fontan procedure to the study date, 23% of patients had at least 1 cardiac surgery, and 48% had at least 1 interventional cardiac catheterization, with 23% having at least 1 Fontan-related complication. At the time of enrollment in the present study, most patients (89%) were taking at least 1 daily medication, and the mean number of current medications was 2.4.
Health Status From the Parent Report CHQ
The Z scores of the domain and summary scores are presented in the Figure. Summary scores were significantly lower than the US population sample for both Physical Functioning (mean Z score, –0.47±1.19; P<0.0001) and Psychosocial Functioning (mean Z score, –0.28±1.08; P<0.0001). For all domains, scores of Fontan patients were significantly worse than those of the US population sample, except for the domains of Freedom From Bodily Pain, which was significantly better, and Behavior, which was not significantly different.
Domain scores from the Parent Report CHQ. Width of the bars represents the mean; error bars represent 1 SD (shown in only 1 direction for simplicity, although all statistical testing was 2 sided).
Frequencies of responses from the questions about noncardiac health conditions from the Parent Report CHQ, together with reported frequencies from a US population sample,6 are given in Table 1. The frequency of all conditions was higher in the Fontan patients than the US population sample, except for problems with allergies.
Variable Groups and Their Relation to CHQ Summary Scores
Individual multivariable regressions were performed for both the CHQ Physical and Psychosocial Functioning summary scores for groups of variables as defined in the table in the Data Supplement. In addition, the bivariable relationship between each variable and each summary score is also given in the Data Supplement table. The R2, or proportion of variance in the scores explained by each group of variables, is shown in Table 2. The greatest amount of variation in the Physical Functioning summary score was explained by parent-reported noncardiac conditions in the patient and long-term and current medical problems noted in the medical record. For Psychosocial Functioning summary scores, the parent-reported noncardiac conditions in the patient predominated. Nonmedical patient characteristics had a small influence on both Physical and Psychosocial Functioning summary scores, whereas pre-Fontan procedure status and Fontan procedure characteristics had a small influence on Physical Functioning summary scores only.
Independent Factors Associated With CHQ Summary Scores
Multivariable regression modeling was performed for the CHQ summary scores, with the reliability of variable selection assessed by bootstrap bagging. For Physical Functioning summary scores, 11 variables were independently significant, with an overall model R2 of 0.40, or 40% of the variation in scores explained. The medical variables associated with poorer Physical Functioning summary scores are shown in Table 3. These included a greater patient weight at Fontan procedure, fenestration not performed at Fontan procedure, other surgical procedures performed at Fontan procedure, arrhythmias occurring during follow-up, and a greater number of current medications at study enrollment. Additional noncardiac variables that were independently significant in the model included the noncardiac medical conditions of asthma, nonasthma respiratory problems, orthopedic problems, and learning problems. In addition, a parent not working because of the patient’s health and lower family income were significantly associated with lower scores. After these significant factors were controlled for, there was no significant relationship with type of Fontan connection (P=0.81) or study site (P=0.63).
A similar multivariable regression model determined independent factors significantly associated with poorer Psychosocial Functioning summary scores (Table 4). The overall R2 for this model was 0.34, and significant independent factors included the presence of behavior and learning problems, anxiety and attention problems, depression, and lower family income. After these significant factors were controlled for, there was no significant relationship with type of Fontan connection (trend toward higher scores with atriopulmonary and intracardiac lateral tunnel connections, P=0.06) or with study site (P=0.11).
Discussion
Summary
We noted that child and adolescent survivors of the Fontan procedure had important deficits in many domains of health status, primarily in Physical Functioning domains. The presence of noncardiac medical problems had the greatest impact on physical functioning health status scores, whereas few cardiac-specific factors were associated. For Psychosocial Functioning health status scores, problems with learning, behavior, attention, anxiety, and depression significantly lowered scores and were more prevalent in the Fontan patients than in a US population sample. Lower family income had a negative impact on both physical and psychosocial functioning.
Quality of Life
Quality of life is difficult to conceptualize, particularly in children, and has been defined as follows: "Rather than being a description of patients’ health status, quality of life is a reflection of the way that patients perceive and react to their health status and to other, nonmedical aspects of their lives."8 Strict adherence to this definition precludes quantitative assessment and application in larger population-based studies because assessment must necessarily include personal and qualitative evaluation. No criterion standard for the assessment of quality of life currently exists. In addition, controversy exists as to terminology, definition, conceptualization, and measurement. This makes any assessment of validity problematic; if one cannot agree on the concept being measured, then it cannot be certain that the designed assessment tool is truly measuring that concept. What we believe we have measured using the CHQ is the magnitude of perceived overall functioning as affected by health-related issues, which we have equated with the term health status.
Assessment of Health Status
The assessment of health status in children has only recently gained attention and importance, with increasing understanding of its conceptualization and measurement.1,9–13 Generic measures are useful for comparing patient groups with each other and with normal subjects, and the CHQ has been used extensively for this purpose.6 Disease-specific measures identify areas of specific concern and may be of greater use in assessing changes in health status over time and in response to interventions; these have only recently been considered for congenital heart disease.14 Furthermore, parents and their children may differ in assessments of the child’s health status.15–17 In this study of children 6 to 18 years of age, the Parent Report CHQ was used because the Child Report CHQ is not applicable to children <10 years of age.
Issues in Fontan Patients
The overall CHQ summary scores in our population were significantly below normal. They were also below those reported in other cardiac patients and pediatric chronic disease patients, except for children and adolescents with automatic implantable cardiodefibrillators (Table 5).18–24 The reasons why these patients scored so poorly are unclear, although the high prevalence of associated medical problems may have been a contributing factor. Neurodevelopmental outcomes are a common concern in Fontan patients, particularly for those with underlying hypoplastic left heart syndrome, and may contribute to poor health status.25,26 Wernovsky et al27 reported results of IQ and achievement testing in a cohort of Fontan patients ranging from 3 to 41 years of age. They noted normal cognitive outcome and academic function in the majority, but the average performance was below normal, particularly for those with underlying hypoplastic left heart syndrome and use of circulatory arrest for procedures before Fontan. In contrast, Goldberg et al25 noted lower cognitive scores for the those children who had the Fontan procedure and who had underlying hypoplastic left heart syndrome, but they also noted that overall scores were within the normal range. Difficulties in academic ability and achievement among children and adolescents with congenital heart disease have been associated with lower psychosocial functioning. In a cohort of 8-year-old children who had neonatal arterial switch operation for transposition of the great arteries, worse psychosocial functioning scores were associated with lower full-scale, verbal, and performance IQ scores, as well as worse academic achievement.19
Factors Affecting Health Status
Although as yet incompletely studied in children, the determinants of diminished health status have previously been studied in adults with congenital heart disease.28–31 As shown by van den Bosch et al,32 adult patients who had undergone a Fontan procedure scored significantly lower than normal in the domains of physical functioning, mental health, and general health perception. However, Saliba and colleagues33 showed that in adult patients with univentricular hearts, those <23 years of age scored better than older patients for health and dysfunction measures. Rose et al2 showed that the physical component of general health status was largely related to the level of cardiopulmonary functioning, whereas psychosocial aspects were more related to depressive symptomatology and adequacy of social support. A qualitative study by Claessens et al34 suggested that "feeling different" was a central theme related to psychosocial concerns and was a key factor in the perceived impact of the disease on the patient’s daily life.
Congenital heart disease can also adversely affect the quality of life of the parents. Lawoko et al35 reported lower quality of life, particularly among mothers, for parents of children with congenital heart disease related to feelings of distress and hopelessness and to financial concerns. Social support by the parents is important. MacPhee et al36 showed that quality-of-life scores for adolescents with inflammatory bowel disease depended more on their parent’s coping styles than their own. Similarly, DeMaso et al37 found that maternal perceptions were potent predictors of adjustment in school-age children with pediatric heart disease, suggesting that parental interactions are more significant predictors of emotional adjustment than medical severity.
Study Limitations
The results of this study must be viewed in light of some limitations. Because we cannot exclude an important subject selection bias, we therefore caution that the results are interpretable only for those subjects who met our defined entry criteria, most importantly those subjects followed up at major pediatric cardiac centers whose parents speak English and/or Spanish and have not had recent surgery. We would hypothesize that our entry criteria may have favored selection of subjects with better health status. The medical history data were collected from retrospective medical record review and must be viewed in light of the limitations of this data source. The use of parent or proxy report to assess health status with the CHQ has its limitations, given that parents tend to assess their children as functioning a lower level than the patients themselves. However, use of the Child Report CHQ was precluded, given the age range included, the fact that differences between parent and patient perceptions tend to quantitative rather than qualitative, and the fact that the study primarily sought to determine associations. Given the large number of variables tested, there is an issue of multiple comparisons. For that reason, only the results of multivariable associations, not bivariable analyses, are reported. In addition, the probability values for identified independent factors are, in general, highly significant, and thus might be expected to be robust. We also used bootstrapping to assess variable selection reliability, giving further evidence with regard to the robustness of the final models. We cannot confidently conclude that the Fontan patients are doing more poorly than normal because we did not simultaneously study a cohort of normal control children and because the use of the published normal data may not be relevant to our population. In addition, we do not know the clinical meaning of the magnitude of the observed deviations from normal. We would be reluctant to conclude that the patients are doing well, given that the scores observed in our study are lower than those observed in other patients with chronic conditions (Table 5).
Study Implications
We conclude that there are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households. Assessments of health status, particularly psychosocial issues, might be included in the study of these vulnerable patients for clinicians to better understand the complexities of these patients and to identify specific areas of unmet need. Clinicians need to be increasingly aware of these nonmedical morbidities and the impact they have on their patients. Opportunities and aspects of rehabilitation have, to date, received little attention in survivors of congenital heart disease; our study clearly points to a potential need.
Acknowledgments
This work was supported by U01 HL068270 (P.D. Mitchell), U01 HL068269 (Dr Li), U01 HL068292 (Dr Williams), U01 HL068290 (Dr Hsu), U01 HL068288 (Dr McCrindle), U01 HL068285 (Dr Newburger), U01 HL068281 (Dr Atz), and U01 HL068279 (Dr Paridon) from the National Heart, Lung, and Blood Institute, NIH/DHHS.
Disclosures
None.
References
Naughton MJ, Shumaker SA. The case for domains of function in quality of life assessment. Qual Life Res. 2003; 12 (suppl 1): 73–80.
Rose M, Kohler K, Kohler F, Sawitzky B, Fliege H, Klapp BF. Determinants of the quality of life of patients with congenital heart disease. Qual Life Res. 2005; 14: 35–43.
Zajac A, Tomkiewicz L, Podolec P, Tracz W, Malec E. Cardiorespiratory response to exercise in children after modified Fontan operation. Scand Cardiovasc J. 2002; 36: 80–85.
Miyairi T, Kawauchi M, Takamoto S, Morizuki O, Furuse A. Oxygen utilization and hemodynamic response during exercise in children after Fontan procedure. Jpn Heart J. 1998; 39: 659–669.
Freedom RM, Hamilton R, Yoo SJ, Mikailian H, Benson L, McCrindle B, Justino H, Williams WG. The Fontan procedure: analysis of cohorts and late complications. Cardiol Young. 2000; 10: 307–331.
Landgraf JM, Abetz L, Ware JE Jr. Child Health Questionnaire. Boston, Mass: The Health Institute, New England Medical Center; 1996.
Bellinger DC, Wypij D, duDuplessis AJ, Rappaport LA, Jonas RA, Wernovsky G, Newburger JW. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003; 126: 1385–1396.
Gill TM, Feinstein AR. A critical appraisal of the quality of quality-of-life measurements. JAMA. 1994; 272: 619–626.
Matza LS, Swensen AR, Flood EM, Secnik K, Leidy NK. Assessment of health-related quality of life in children: a review of conceptual, methodological, and regulatory issues. Value Health. 2004; 7: 79–92.
Erling A. Methodological considerations in the assessment of health-related quality of life in children. Acta Paediatr Suppl. 1999; 88: 106–107.
Spieth LE, Harris CV. Assessment of health-related quality of life in children and adolescents: an integrative review. J Pediatr Psychol. 1996; 21: 175–193.
Eiser C, Cotter I, Oades P, Seamark D, Smith R. Health-related quality-of-life measures for children. Int J Cancer Suppl. 1999; 12: 87–90.
Moons P, Van Deyk K, Budts W, De Geest S. Caliber of quality-of-life assessments in congenital heart disease: a plea for more conceptual and methodological rigor. Arch Pediatr Adolesc Med. 2004; 158: 1062–1069.
Kamphuis M, Zwinderman KH, Vogels T, Vliegen HW, Kamphuis RP, Ottenkamp J, Verloove-Vanhorick SP, Bruil J. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation. Qual Life Res. 2004; 13: 735–745.
Levi RB, Drotar D. Health-related quality of life in childhood cancer: discrepancy in parent-child reports. Int J Cancer Suppl. 1999; 12: 58–64.
Britto MT, Kotagal UR, Chenier T, Tsevat J, Atherton HD, Wilmott RW. Differences between adolescents’ and parents’ reports of health-related quality of life in cystic fibrosis. Pediatr Pulmonol. 2004; 37: 165–171.
Parsons SK, Barlow SE, Levy SL, Supran SE, Kaplan SH. Health-related quality of life in pediatric bone marrow transplant survivors: according to whom Int J Cancer Suppl. 1999; 12: 46–51.
Walker RE, Gauvreau K, Jenkins KJ. Health-related quality of life in children attending a cardiology clinic. Pediatr Cardiol. 2004; 25: 40–48.
Dunbar-Masterson C, Wypij D, Bellinger DC, Rappaport LA, Baker AL, Jonas RA, Newburger JW. General health status of children with D-transposition of the great arteries after the arterial switch operation. Circulation. 2001; 104 (suppl I): I-138–I-142.
Hirshfeld AB, Kahle AL, Clark BJ III, Bridges ND. Parent-reported health status after pediatric thoracic organ transplant. J Heart Lung Transplant. 2004; 23: 1111–1118.
DeMaso DR, Lauretti A, Spieth L, van der Feen JR, Jay KS, Gauvreau K, Walsh EP, Berul CI. Psychosocial factors and quality of life in children and adolescents with implantable cardioverter-defibrillators. Am J Cardiol. 2004; 93: 582–587.
Wake M, Hesketh K, Cameron F. The Child Health Questionnaire in children with diabetes: cross-sectional survey of parent and adolescent-reported functional health status. Diabet Med. 2000; 17: 700–707.
Friedlander SL, Larkin EK, Rosen CL, Palermo TM, Redline S. Decreased quality of life associated with obesity in school-aged children. Arch Pediatr Adolesc Med. 2003; 157: 1206–1211.
Klassen AF, Miller A, Fine S. Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit/hyperactivity disorder. Pediatrics. 2004; 114: e541–e547.
Goldberg CS, Schwartz EM, Brunberg JA, Mosca RS, Bove EL, Schork MA, Stetz SP, Cheatham JP, Kulik TJ. 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: 646–652.
Wernovsky G, Newburger J. Neurologic and developmental morbidity in children with complex congenital heart disease. J Pediatr. 2003; 142: 6–8.
Wernovsky G, Stiles KM, Gauvreau K, Gentles TL, duPlessis AJ, Bellinger DC, Walsh AZ, Burnett J, Jonas RA, Mayer JE, Newburger JW. Cognitive development after the Fontan operation. Circulation. 2000; 102: 883–889.
Lane DA, Lip GY, Millane TA. Quality of life in adults with congenital heart disease. Heart. 2002; 88: 71–75.
Simko LC, McGinnis KA. Quality of life experienced by adults with congenital heart disease. AACN Clin Issues. 2003; 14: 42–53.
Kamphuis M, Ottenkamp J, Vliegen HW, Vogels T, Zwinderman KH, Kamphuis RP, Verloove-Vanhorick SP. Health related quality of life and health status in adult survivors with previously operated complex congenital heart disease. Heart. 2002; 87: 356–362.
Tayebjee MH, Lip GY. Psychosocial functioning of adults with congenital heart disease: a neglected area. Eur Heart J. 2003; 24: 2159–2160.
van den Bosch AE, Roos-Hesselink JW, Van Domburg R, Bogers AJ, Simoons ML, Meijboom FJ. Long-term outcome and quality of life in adult patients after the Fontan operation. Am J Cardiol. 2004; 93: 1141–1145.
Saliba Z, Butera G, Bonnet D, Bonhoeffer P, Villain E, Kachaner J, Sidi D, Iserin L. Quality of life and perceived health status in surviving adults with univentricular heart. Heart. 2001; 86: 69–73.
Claessens P, Moons P, de Casterle BD, Cannaerts N, Budts W, Gewillig M. What does it mean to live with a congenital heart disease A qualitative study on the lived experiences of adult patients. Eur J Cardiovasc Nurs. 2005; 4: 3–10.
Lawoko S, Soares JJ. Quality of life among parents of children with congenital heart disease, parents of children with other diseases and parents of healthy children. Qual Life Res. 2003; 12: 655–666.
MacPhee M, Hoffenberg EJ, Feranchak A. Quality-of-life factors in adolescent inflammatory bowel disease. Inflamm Bowel Dis. 1998; 4: 6–11.
DeMaso DR, Campis LK, Wypij D, Bertram S, Lipshitz M, Freed M. The impact of maternal perceptions and medical severity on the adjustment of children with congenital heart disease. J Pediatr Psychol. 1991; 16: 137–149.(Brian W. McCrindle, MD, MPH; Richard V. )
University of Utah, Salt Lake City (R.V.W.)
New England Research Institutes, Watertown, Mass (P.D.M.)
Columbia University Medical Center, New York, NY (D.T.H.)
Children’s Hospital of Philadelphia, Philadelphia, Pa (S.M.P.)
Medical University of South Carolina, Charleston (A.M.A.)
Duke University Medical Center, Durham, NC (J.S.L.)
Children’s Hospital Boston, Boston, Mass (J.W.N.).
Abstract
Background— After the Fontan procedure, patients are at risk for suboptimal health status related to their complex healthcare experience, physiological limitations, medical complications, and guarded long-term prognosis.
Methods and Results— In the Pediatric Heart Network cross-sectional study of Fontan survivors 6 to 18 years of age, parents completed the Child Health Questionnaire, and scores were related in multivariable analysis to patient and medical characteristics obtained from medical record review. For 537 patients (mean age at study, 11.9 years; 60% male) with a median age at Fontan of 2.8 years (range, 0.7 to 14.6 years), parent-reported patient morbidities included deficits in vision in 33%, speech in 27%, and hearing in 7%, as well as problems with attention in 46%, learning in 43%, development in 24%, behavior in 23%, anxiety in 17%, and depression in 8%. Child Health Questionnaire summary scores were significantly lower than the US population sample for Physical Functioning (mean Z score, –0.47±1.19; P<0.001) and Psychosocial Functioning (–0.28±1.08; P<0.001). Parent-reported medical conditions and long-term and current medical problems explained the greatest amount of variation in the Physical Functioning scores. Parent-reported patient conditions, including behavior, learning, anxiety, and attention problems and depression, explained the greatest amount of variation in the Psychosocial Functioning scores. Lower family income had a negative impact on both Physical and Psychosocial Functioning.
Conclusions— There are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households.
Key Words: follow-up studies Fontan procedure heart defects, congenital health status quality of life
Introduction
As mortality related to congenital heart disease continues to decline, the focus of clinical care has turned to morbidity and quality of life. Health status has various domains, related primarily to physical functioning and psychosocial aspects.1 It may be affected by many factors, including medical history, current medical morbidity, perceptions, reactions and adaptations to health-related problems, available resources, and opportunities to deal with those problems, as well as the patient’s psychosocial milieu and support systems.2
Clinical Perspective p 1129
Patients with functional single ventricle who have undergone the Fontan procedure may be especially predisposed to poor health status. These patients are subjected to a complex and prolonged medical experience. They have diminished exercise tolerance imposed by their cardiovascular physiology.3,4 Moreover, Fontan patients may have important and debilitating morbidities5 and have a guarded long-term prognosis. We therefore sought to characterize health status and its sociodemographic and medical determinants in this high-risk population.
Methods
The Fontan Cross-Sectional Study was performed by the Pediatric Heart Network. The Pediatric Heart Network, which consists of 7 pediatric cardiac centers in the United States and Canada, a data coordinating center at the New England Research Institutes, and the Pediatric Heart Network chair, performs multicenter clinical studies with funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health. The primary aim of the Fontan Cross-Sectional Study was to assess the correlation between measures of health status, ventricular function, and exercise performance in children and adolescents who have survived a Fontan procedure. The present analysis and report focus only on the data collected from the medical record review and the parent report health status questionnaire. All 7 centers obtained local Institutional Review Board or Ethics Committee approval before initiating the study, and written informed consent was obtained for all subjects from either a parent or a legal guardian or from the subject if of legal age. Subject assent was also obtained per local guidelines.
Study Subjects
Eligible patients were identified by a preliminary medical record review of all children who had undergone a Fontan procedure and were currently followed up at 1 of the 7 centers. Study subjects were eligible if they were 6 to 18 years of age at the time of enrollment; had undergone a Fontan procedure at least 6 months before initial study testing; and agreed to have an echocardiogram, to complete a parent report health status questionnaire, and to have blood testing within 3 months of enrollment at one of the study centers. Exclusion criteria included the presence of a noncardiac medical or psychiatric disorder that would prevent successful completion of planned study testing or would invalidate the results of study testing. Additional criteria included ongoing or planned participation in another research protocol that would conflict with the present study, lack of reading fluency by the primary caregiver in English or Spanish, and pregnancy at the time of enrollment or pregnancy planned before the completion of study testing.
Medical Record Review
For enrolled study subjects, a detailed medical record review was performed through the use of standardized forms to abstract data on patient demographics, underlying cardiac anatomy, pre-Fontan characteristics (interim surgical and interventional catheterization procedures, complications, pre-Fontan clinical status), Fontan procedure characteristics (type of Fontan connection, fenestration, concomitant procedures, immediate complications, hospital course, and discharge status), and outcomes during follow-up after the Fontan procedure, including the most recent clinical assessment and testing.
Health Status Questionnaire
The study used the Child Health Questionnaire (CHQ) Parent Report Form (CHQ-PF50) as a generic measure of health status completed by the parent.6 The Parent Report CHQ, which measures the physical and psychosocial (eg, emotional, behavioral, and social) well-being of children 5 to 18 years of age, was to have been completed by a parent for all enrolled study subjects. The Parent Report CHQ measures components of physical and psychosocial functioning in 12 categories (subscales). Domains that contribute most heavily to the Physical Functioning summary score include physical functioning limitations, physical limitations on schoolwork or activities with friends, bodily pain, and general health perceptions. Domains that contribute most heavily to the Psychosocial Functioning summary score include mental health, limitations on schoolwork or activities from emotional or behavioral problems, general behavior, and self-esteem. Domains concerning the impact of the child’s health on the parents’ worries, concerns, and time; family activities; and family cohesion contribute to both summary scores. In addition, as part of the Parent Report CHQ that is not scored, parents are asked to indicate on a checklist if they had ever been told by a teacher, school official, doctor, nurse, or other health professional that their child had any of a list of noncardiac health conditions.
Data Analysis
Data are described as frequencies, medians with ranges, and means with standard deviations as appropriate. When data are missing, the number of available values is given. Parent Report CHQ scores were converted to Z scores on the basis of published normative data and tested for deviation from normal with single sample t tests.6,7 CHQ summary scores of Physical and Psychosocial Functioning were related to patient and medical history variables using t tests, ANOVA, and linear regression analysis. Variables that showed a significant bivariable relationship (P<0.05) then formed the variable set for multivariable analysis. For the purposes of multivariable analyses, missing values for predictor variables were informatively imputed and replaced with the mean of all nonmissing values. No variable was missing >5% of values. Patient and medical history variables were grouped and entered into separate multiple linear regression analysis for each of the CHQ summary scores of Physical Functioning and Psychosocial Functioning. The overall R2 for each regression was noted to determine the amount of variation in scores explained by each group of variables. Separate stepwise multivariable linear regression analyses were then performed for each of the CHQ summary scores of Physical and Psychosocial Functioning. Bootstrap bagging (repeated sampling and stepwise multivariable analysis of the main data set) and cluster analysis were used to guide and indicate reliability of variable selection for inclusion in the final multivariable models and to provide an assessment of reliability of variable selection. Given the large number of variables being tested, only those variables that were significant with a value of P<0.05 in the final models are reported to minimize the effects of multiple comparisons. In addition, the adjusted effects of the type of Fontan connection and study site were explored in each final model. All analyses were performed with SAS/STAT software, version 9.1 of the SAS System for Windows (SAS Institute Inc).
The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.
Results
Study Participation
The records of 1078 children who had undergone a Fontan procedure were screened. Of the 831 (77%) judged potentially eligible for the study, only 644 (60%) were found to be fully eligible after being contacted. The consent rate was 85%, and 546 children were enrolled with family consent. Different proportions of enrolled patients completed each of the study tests, and 9 parents did not complete the CHQ. The present study includes 537 enrolled patients who had medical record reviews and whose parents completed the Parent Report CHQ.
Patient and Clinical Characteristics
The table found in the online Data Supplement summarizes the frequencies and distributions of sociodemographic and medical history. Medical history before the Fontan procedure was complex; 2 cardiac surgeries were performed in 80% of subjects, and at least 1 interventional cardiac catheterization was done in 47%. Postoperative complications after the Fontan procedure were frequent; 40% of subjects had a postoperative length of hospital stay of 2 weeks, and 95% were discharged on at least 1 medication (mean number of medications, 3.7). During follow-up from the Fontan procedure to the study date, 23% of patients had at least 1 cardiac surgery, and 48% had at least 1 interventional cardiac catheterization, with 23% having at least 1 Fontan-related complication. At the time of enrollment in the present study, most patients (89%) were taking at least 1 daily medication, and the mean number of current medications was 2.4.
Health Status From the Parent Report CHQ
The Z scores of the domain and summary scores are presented in the Figure. Summary scores were significantly lower than the US population sample for both Physical Functioning (mean Z score, –0.47±1.19; P<0.0001) and Psychosocial Functioning (mean Z score, –0.28±1.08; P<0.0001). For all domains, scores of Fontan patients were significantly worse than those of the US population sample, except for the domains of Freedom From Bodily Pain, which was significantly better, and Behavior, which was not significantly different.
Domain scores from the Parent Report CHQ. Width of the bars represents the mean; error bars represent 1 SD (shown in only 1 direction for simplicity, although all statistical testing was 2 sided).
Frequencies of responses from the questions about noncardiac health conditions from the Parent Report CHQ, together with reported frequencies from a US population sample,6 are given in Table 1. The frequency of all conditions was higher in the Fontan patients than the US population sample, except for problems with allergies.
Variable Groups and Their Relation to CHQ Summary Scores
Individual multivariable regressions were performed for both the CHQ Physical and Psychosocial Functioning summary scores for groups of variables as defined in the table in the Data Supplement. In addition, the bivariable relationship between each variable and each summary score is also given in the Data Supplement table. The R2, or proportion of variance in the scores explained by each group of variables, is shown in Table 2. The greatest amount of variation in the Physical Functioning summary score was explained by parent-reported noncardiac conditions in the patient and long-term and current medical problems noted in the medical record. For Psychosocial Functioning summary scores, the parent-reported noncardiac conditions in the patient predominated. Nonmedical patient characteristics had a small influence on both Physical and Psychosocial Functioning summary scores, whereas pre-Fontan procedure status and Fontan procedure characteristics had a small influence on Physical Functioning summary scores only.
Independent Factors Associated With CHQ Summary Scores
Multivariable regression modeling was performed for the CHQ summary scores, with the reliability of variable selection assessed by bootstrap bagging. For Physical Functioning summary scores, 11 variables were independently significant, with an overall model R2 of 0.40, or 40% of the variation in scores explained. The medical variables associated with poorer Physical Functioning summary scores are shown in Table 3. These included a greater patient weight at Fontan procedure, fenestration not performed at Fontan procedure, other surgical procedures performed at Fontan procedure, arrhythmias occurring during follow-up, and a greater number of current medications at study enrollment. Additional noncardiac variables that were independently significant in the model included the noncardiac medical conditions of asthma, nonasthma respiratory problems, orthopedic problems, and learning problems. In addition, a parent not working because of the patient’s health and lower family income were significantly associated with lower scores. After these significant factors were controlled for, there was no significant relationship with type of Fontan connection (P=0.81) or study site (P=0.63).
A similar multivariable regression model determined independent factors significantly associated with poorer Psychosocial Functioning summary scores (Table 4). The overall R2 for this model was 0.34, and significant independent factors included the presence of behavior and learning problems, anxiety and attention problems, depression, and lower family income. After these significant factors were controlled for, there was no significant relationship with type of Fontan connection (trend toward higher scores with atriopulmonary and intracardiac lateral tunnel connections, P=0.06) or with study site (P=0.11).
Discussion
Summary
We noted that child and adolescent survivors of the Fontan procedure had important deficits in many domains of health status, primarily in Physical Functioning domains. The presence of noncardiac medical problems had the greatest impact on physical functioning health status scores, whereas few cardiac-specific factors were associated. For Psychosocial Functioning health status scores, problems with learning, behavior, attention, anxiety, and depression significantly lowered scores and were more prevalent in the Fontan patients than in a US population sample. Lower family income had a negative impact on both physical and psychosocial functioning.
Quality of Life
Quality of life is difficult to conceptualize, particularly in children, and has been defined as follows: "Rather than being a description of patients’ health status, quality of life is a reflection of the way that patients perceive and react to their health status and to other, nonmedical aspects of their lives."8 Strict adherence to this definition precludes quantitative assessment and application in larger population-based studies because assessment must necessarily include personal and qualitative evaluation. No criterion standard for the assessment of quality of life currently exists. In addition, controversy exists as to terminology, definition, conceptualization, and measurement. This makes any assessment of validity problematic; if one cannot agree on the concept being measured, then it cannot be certain that the designed assessment tool is truly measuring that concept. What we believe we have measured using the CHQ is the magnitude of perceived overall functioning as affected by health-related issues, which we have equated with the term health status.
Assessment of Health Status
The assessment of health status in children has only recently gained attention and importance, with increasing understanding of its conceptualization and measurement.1,9–13 Generic measures are useful for comparing patient groups with each other and with normal subjects, and the CHQ has been used extensively for this purpose.6 Disease-specific measures identify areas of specific concern and may be of greater use in assessing changes in health status over time and in response to interventions; these have only recently been considered for congenital heart disease.14 Furthermore, parents and their children may differ in assessments of the child’s health status.15–17 In this study of children 6 to 18 years of age, the Parent Report CHQ was used because the Child Report CHQ is not applicable to children <10 years of age.
Issues in Fontan Patients
The overall CHQ summary scores in our population were significantly below normal. They were also below those reported in other cardiac patients and pediatric chronic disease patients, except for children and adolescents with automatic implantable cardiodefibrillators (Table 5).18–24 The reasons why these patients scored so poorly are unclear, although the high prevalence of associated medical problems may have been a contributing factor. Neurodevelopmental outcomes are a common concern in Fontan patients, particularly for those with underlying hypoplastic left heart syndrome, and may contribute to poor health status.25,26 Wernovsky et al27 reported results of IQ and achievement testing in a cohort of Fontan patients ranging from 3 to 41 years of age. They noted normal cognitive outcome and academic function in the majority, but the average performance was below normal, particularly for those with underlying hypoplastic left heart syndrome and use of circulatory arrest for procedures before Fontan. In contrast, Goldberg et al25 noted lower cognitive scores for the those children who had the Fontan procedure and who had underlying hypoplastic left heart syndrome, but they also noted that overall scores were within the normal range. Difficulties in academic ability and achievement among children and adolescents with congenital heart disease have been associated with lower psychosocial functioning. In a cohort of 8-year-old children who had neonatal arterial switch operation for transposition of the great arteries, worse psychosocial functioning scores were associated with lower full-scale, verbal, and performance IQ scores, as well as worse academic achievement.19
Factors Affecting Health Status
Although as yet incompletely studied in children, the determinants of diminished health status have previously been studied in adults with congenital heart disease.28–31 As shown by van den Bosch et al,32 adult patients who had undergone a Fontan procedure scored significantly lower than normal in the domains of physical functioning, mental health, and general health perception. However, Saliba and colleagues33 showed that in adult patients with univentricular hearts, those <23 years of age scored better than older patients for health and dysfunction measures. Rose et al2 showed that the physical component of general health status was largely related to the level of cardiopulmonary functioning, whereas psychosocial aspects were more related to depressive symptomatology and adequacy of social support. A qualitative study by Claessens et al34 suggested that "feeling different" was a central theme related to psychosocial concerns and was a key factor in the perceived impact of the disease on the patient’s daily life.
Congenital heart disease can also adversely affect the quality of life of the parents. Lawoko et al35 reported lower quality of life, particularly among mothers, for parents of children with congenital heart disease related to feelings of distress and hopelessness and to financial concerns. Social support by the parents is important. MacPhee et al36 showed that quality-of-life scores for adolescents with inflammatory bowel disease depended more on their parent’s coping styles than their own. Similarly, DeMaso et al37 found that maternal perceptions were potent predictors of adjustment in school-age children with pediatric heart disease, suggesting that parental interactions are more significant predictors of emotional adjustment than medical severity.
Study Limitations
The results of this study must be viewed in light of some limitations. Because we cannot exclude an important subject selection bias, we therefore caution that the results are interpretable only for those subjects who met our defined entry criteria, most importantly those subjects followed up at major pediatric cardiac centers whose parents speak English and/or Spanish and have not had recent surgery. We would hypothesize that our entry criteria may have favored selection of subjects with better health status. The medical history data were collected from retrospective medical record review and must be viewed in light of the limitations of this data source. The use of parent or proxy report to assess health status with the CHQ has its limitations, given that parents tend to assess their children as functioning a lower level than the patients themselves. However, use of the Child Report CHQ was precluded, given the age range included, the fact that differences between parent and patient perceptions tend to quantitative rather than qualitative, and the fact that the study primarily sought to determine associations. Given the large number of variables tested, there is an issue of multiple comparisons. For that reason, only the results of multivariable associations, not bivariable analyses, are reported. In addition, the probability values for identified independent factors are, in general, highly significant, and thus might be expected to be robust. We also used bootstrapping to assess variable selection reliability, giving further evidence with regard to the robustness of the final models. We cannot confidently conclude that the Fontan patients are doing more poorly than normal because we did not simultaneously study a cohort of normal control children and because the use of the published normal data may not be relevant to our population. In addition, we do not know the clinical meaning of the magnitude of the observed deviations from normal. We would be reluctant to conclude that the patients are doing well, given that the scores observed in our study are lower than those observed in other patients with chronic conditions (Table 5).
Study Implications
We conclude that there are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households. Assessments of health status, particularly psychosocial issues, might be included in the study of these vulnerable patients for clinicians to better understand the complexities of these patients and to identify specific areas of unmet need. Clinicians need to be increasingly aware of these nonmedical morbidities and the impact they have on their patients. Opportunities and aspects of rehabilitation have, to date, received little attention in survivors of congenital heart disease; our study clearly points to a potential need.
Acknowledgments
This work was supported by U01 HL068270 (P.D. Mitchell), U01 HL068269 (Dr Li), U01 HL068292 (Dr Williams), U01 HL068290 (Dr Hsu), U01 HL068288 (Dr McCrindle), U01 HL068285 (Dr Newburger), U01 HL068281 (Dr Atz), and U01 HL068279 (Dr Paridon) from the National Heart, Lung, and Blood Institute, NIH/DHHS.
Disclosures
None.
References
Naughton MJ, Shumaker SA. The case for domains of function in quality of life assessment. Qual Life Res. 2003; 12 (suppl 1): 73–80.
Rose M, Kohler K, Kohler F, Sawitzky B, Fliege H, Klapp BF. Determinants of the quality of life of patients with congenital heart disease. Qual Life Res. 2005; 14: 35–43.
Zajac A, Tomkiewicz L, Podolec P, Tracz W, Malec E. Cardiorespiratory response to exercise in children after modified Fontan operation. Scand Cardiovasc J. 2002; 36: 80–85.
Miyairi T, Kawauchi M, Takamoto S, Morizuki O, Furuse A. Oxygen utilization and hemodynamic response during exercise in children after Fontan procedure. Jpn Heart J. 1998; 39: 659–669.
Freedom RM, Hamilton R, Yoo SJ, Mikailian H, Benson L, McCrindle B, Justino H, Williams WG. The Fontan procedure: analysis of cohorts and late complications. Cardiol Young. 2000; 10: 307–331.
Landgraf JM, Abetz L, Ware JE Jr. Child Health Questionnaire. Boston, Mass: The Health Institute, New England Medical Center; 1996.
Bellinger DC, Wypij D, duDuplessis AJ, Rappaport LA, Jonas RA, Wernovsky G, Newburger JW. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003; 126: 1385–1396.
Gill TM, Feinstein AR. A critical appraisal of the quality of quality-of-life measurements. JAMA. 1994; 272: 619–626.
Matza LS, Swensen AR, Flood EM, Secnik K, Leidy NK. Assessment of health-related quality of life in children: a review of conceptual, methodological, and regulatory issues. Value Health. 2004; 7: 79–92.
Erling A. Methodological considerations in the assessment of health-related quality of life in children. Acta Paediatr Suppl. 1999; 88: 106–107.
Spieth LE, Harris CV. Assessment of health-related quality of life in children and adolescents: an integrative review. J Pediatr Psychol. 1996; 21: 175–193.
Eiser C, Cotter I, Oades P, Seamark D, Smith R. Health-related quality-of-life measures for children. Int J Cancer Suppl. 1999; 12: 87–90.
Moons P, Van Deyk K, Budts W, De Geest S. Caliber of quality-of-life assessments in congenital heart disease: a plea for more conceptual and methodological rigor. Arch Pediatr Adolesc Med. 2004; 158: 1062–1069.
Kamphuis M, Zwinderman KH, Vogels T, Vliegen HW, Kamphuis RP, Ottenkamp J, Verloove-Vanhorick SP, Bruil J. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation. Qual Life Res. 2004; 13: 735–745.
Levi RB, Drotar D. Health-related quality of life in childhood cancer: discrepancy in parent-child reports. Int J Cancer Suppl. 1999; 12: 58–64.
Britto MT, Kotagal UR, Chenier T, Tsevat J, Atherton HD, Wilmott RW. Differences between adolescents’ and parents’ reports of health-related quality of life in cystic fibrosis. Pediatr Pulmonol. 2004; 37: 165–171.
Parsons SK, Barlow SE, Levy SL, Supran SE, Kaplan SH. Health-related quality of life in pediatric bone marrow transplant survivors: according to whom Int J Cancer Suppl. 1999; 12: 46–51.
Walker RE, Gauvreau K, Jenkins KJ. Health-related quality of life in children attending a cardiology clinic. Pediatr Cardiol. 2004; 25: 40–48.
Dunbar-Masterson C, Wypij D, Bellinger DC, Rappaport LA, Baker AL, Jonas RA, Newburger JW. General health status of children with D-transposition of the great arteries after the arterial switch operation. Circulation. 2001; 104 (suppl I): I-138–I-142.
Hirshfeld AB, Kahle AL, Clark BJ III, Bridges ND. Parent-reported health status after pediatric thoracic organ transplant. J Heart Lung Transplant. 2004; 23: 1111–1118.
DeMaso DR, Lauretti A, Spieth L, van der Feen JR, Jay KS, Gauvreau K, Walsh EP, Berul CI. Psychosocial factors and quality of life in children and adolescents with implantable cardioverter-defibrillators. Am J Cardiol. 2004; 93: 582–587.
Wake M, Hesketh K, Cameron F. The Child Health Questionnaire in children with diabetes: cross-sectional survey of parent and adolescent-reported functional health status. Diabet Med. 2000; 17: 700–707.
Friedlander SL, Larkin EK, Rosen CL, Palermo TM, Redline S. Decreased quality of life associated with obesity in school-aged children. Arch Pediatr Adolesc Med. 2003; 157: 1206–1211.
Klassen AF, Miller A, Fine S. Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit/hyperactivity disorder. Pediatrics. 2004; 114: e541–e547.
Goldberg CS, Schwartz EM, Brunberg JA, Mosca RS, Bove EL, Schork MA, Stetz SP, Cheatham JP, Kulik TJ. 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: 646–652.
Wernovsky G, Newburger J. Neurologic and developmental morbidity in children with complex congenital heart disease. J Pediatr. 2003; 142: 6–8.
Wernovsky G, Stiles KM, Gauvreau K, Gentles TL, duPlessis AJ, Bellinger DC, Walsh AZ, Burnett J, Jonas RA, Mayer JE, Newburger JW. Cognitive development after the Fontan operation. Circulation. 2000; 102: 883–889.
Lane DA, Lip GY, Millane TA. Quality of life in adults with congenital heart disease. Heart. 2002; 88: 71–75.
Simko LC, McGinnis KA. Quality of life experienced by adults with congenital heart disease. AACN Clin Issues. 2003; 14: 42–53.
Kamphuis M, Ottenkamp J, Vliegen HW, Vogels T, Zwinderman KH, Kamphuis RP, Verloove-Vanhorick SP. Health related quality of life and health status in adult survivors with previously operated complex congenital heart disease. Heart. 2002; 87: 356–362.
Tayebjee MH, Lip GY. Psychosocial functioning of adults with congenital heart disease: a neglected area. Eur Heart J. 2003; 24: 2159–2160.
van den Bosch AE, Roos-Hesselink JW, Van Domburg R, Bogers AJ, Simoons ML, Meijboom FJ. Long-term outcome and quality of life in adult patients after the Fontan operation. Am J Cardiol. 2004; 93: 1141–1145.
Saliba Z, Butera G, Bonnet D, Bonhoeffer P, Villain E, Kachaner J, Sidi D, Iserin L. Quality of life and perceived health status in surviving adults with univentricular heart. Heart. 2001; 86: 69–73.
Claessens P, Moons P, de Casterle BD, Cannaerts N, Budts W, Gewillig M. What does it mean to live with a congenital heart disease A qualitative study on the lived experiences of adult patients. Eur J Cardiovasc Nurs. 2005; 4: 3–10.
Lawoko S, Soares JJ. Quality of life among parents of children with congenital heart disease, parents of children with other diseases and parents of healthy children. Qual Life Res. 2003; 12: 655–666.
MacPhee M, Hoffenberg EJ, Feranchak A. Quality-of-life factors in adolescent inflammatory bowel disease. Inflamm Bowel Dis. 1998; 4: 6–11.
DeMaso DR, Campis LK, Wypij D, Bertram S, Lipshitz M, Freed M. The impact of maternal perceptions and medical severity on the adjustment of children with congenital heart disease. J Pediatr Psychol. 1991; 16: 137–149.(Brian W. McCrindle, MD, MPH; Richard V. )