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ORIGINAL ARTICLES: PEDIATRIC CARDIAC

PEDIATRIC CARDIAC SURGERY:The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org.To take the CME activity related to this article, you must have either an STS member or anindividual non-member subscription to the journal.

Functional Health Status of Adults With Tetralogyof Fallot: Matched Comparison With HealthySiblingsRachel Knowles, MBChB, PhD, Gruschen Veldtman, MD, Edward J. Hickey, MD,Timothy Bradley, MD, Aungkana Gengsakul, MD, Gary D. Webb, MD,William G. Williams, MD, and Brian W. McCrindle, MDDivision of Cardiology, Department of Pediatrics, and Division of Cardiovascular Surgery, Department of Surgery, University of

Toronto, The Hospital for Sick Children, Toronto; and the Division of Cardiology, Department of Medicine, University of Toronto,Toronto General Hospital, Toronto, Ontario, Canada

Background. Survival prospects for adults with re-paired tetralogy of Fallot (TOF) are now excellent. Atten-tion should therefore shift to assessing and improvingfunctional health status and quality of life. We aimed toassess late functional health status of adults survivingTOF repair by matched comparison to their healthysiblings.

Methods. All 1,693 TOF repairs performed at our insti-tution between 1946 and 1990 were reviewed. A matchedcomparison was undertaken whereby presumed survi-vors and their healthy sibling were contacted and askedto complete the Ontario Health Survey 1990 and the36-Item Short Form Health Survey (SF-36) questionnaire.

Results. Both questionnaires were completed by 224adult survivors and their sibling closest in age. Adultswith repaired TOF had lower scores for self-perceivedgeneral health status (p < 0.001), were less likely to rate

their health as good or excellent (p < 0.001), and had

dren, 555 University Ave, Toronto, ON M5G 1X8, Canada; e-mail:brian.mccrindle@sickkids.ca.

© 2012 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

lower SF-36 scores for physical functioning and generalhealth (p � 0.001) than their siblings. However, patientsreported similar satisfaction with their lives, similarlevels of social participation and support, and were aslikely to be in long-term partnerships. Worse physicaland mental health scores were associated with older ageat surgery and at time of questionnaire completion andrecent requirement for noncardiac medication.

Conclusions. Although reporting lower functionalhealth status then their siblings, quality of life and lifesatisfaction for adults who underwent surgery for TOFduring childhood is comparable to that of their siblingswithout heart defects. Follow-up of younger adults isrequired to understand current health outcomes attribut-able to improvements in the management of TOF.

(Ann Thorac Surg 2012;94:124–32)

© 2012 by The Society of Thoracic Surgeons

Congenital heart defects are diagnosed in 8 to 10 per10,000 live births each year in North America and

are the leading cause of death due to congenital anoma-lies [1, 2]. Tetralogy of Fallot (TOF) affects 44 per 100,000total births in Canada [3] and is associated with othergenetic syndromes, such as chromosome 22q11 deletionand Down syndrome. Advances in diagnosis and treat-ment have led to continuing reduction of mortality, andthe outlook for children operated on today is vastlydifferent than it was 30 years ago [4-7]. Whereas in the1960s, early mortality for TOF exceeded 25%, nearly 90%of children born with the lesion today are likely to liveinto their fifth decade [8]. Consequently, assessing and

Accepted for publication Sept 14, 2011.

Address correspondence to Dr McCrindle, The Hospital for Sick Chil-

optimizing functional health status and quality of life forthese survivors is now of central importance [9].

Initial follow-up studies of adult survivors with TOFhave suggested that they lead relatively normal lives withgood late functional status [6, 10�12] and, in general,perceive their quality of life to be good [13�15]. Bycontrast, others have suggested that, in comparison withhealthy adults, patients with repaired TOF have lowerlevels of educational achievement and are less likely tobe in employment, particularly if there is associateddevelopmental delay [11, 14�16]. In a large series of 840adult survivors with TOF, we recently demonstrated theirphysical performance to be significantly reduced com-pared with healthy North American counterparts [17].

Many of these reports are observational studies involv-ing small case series or otherwise rarely employed direct

control groups for comparison [13�15]. Instruments for

0003-4975/$36.00http://dx.doi.org/10.1016/j.athoracsur.2011.09.056

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assessing functional health status, for example, the 36-Item Short Form Health Survey (SF-36), may have re-ported means and standard deviations for large popula-tions of “healthy” subjects, but such norms are crudereferences to assessing an individual patient with acomplex heart defect.

We initiated the Global Outcomes Tracking in Congeni-tal Heart Adults (GOTCHA) project with the goal of char-acterizing late functional health status of adult survivorswith TOF from a well-characterized inception cohort. Theapproach was all inclusive, in an attempt to capture theentire spectrum of patients with TOF. Specifically, weaimed to quantify physical, functional, social, and mentalhealth well-being for these patients by a direct matchedcomparison with their healthy sibling closest in age.

Material and Methods

The study received full a priori approval from the Re-search Ethics Boards of The Hospital for Sick Children,Toronto, and Toronto General Hospital (and thereforeconformed to the ethical considerations of the 1975 Dec-laration of Helsinki). All 1,693 patients who underwentsurgical repair of TOF at our institution and were bornbetween 1927 (when records began) and 1984 were iden-tified. All survivors would, therefore, have been aged 18years or older at the time of this project’s inception in2003. The study involved undertaking qualitative func-tional health assessment of adult survivors with TOF andmaking a paired comparison with their healthy siblingclosest in age. Enrollment for this investigation, there-fore, involved two phases: (1) locating and recruitingpotential survivors, and (2) identification and recruitmentof patients with a sibling for participation.

Patient LocatingThe GOTCHA project involved locating potential survivorsfrom this total 1,693, irrespective of their TOF subtype,coexisting morphology, subsequent clinical and operativehistory, or current location of clinical follow-up (or lack of).The design was all inclusive, in an attempt to represent theentire spectrum of adult survivors with TOF from a definedinstitutional inception cohort, thus specifying a defineddenominator. Patients were located through their lastknown contact details, or otherwise through their lastknown physician (primary care or specialist). Follow-uptook place over a 3-year period and continued until everypotential avenue for locating patients had been exhausted.All patients successfully located were contacted directly bytelephone or mail, or both.

Request for ParticipationAfter enrollment, informed consent was obtained from thepatient to complete subjective assessment of functionalhealth status using the Ontario Health Survey 1990 (OHS)and the SF-36. Patients willing to participate were asked torecruit their sibling closest in age if available. A require-ment for sibling participation was that the sibling be freefrom major congenital or other health problems

(“healthy”). Patients who had no healthy sibling or whose

sibling refused to participate were not included in thepresent analysis. Enrolled patients and their siblings wereboth mailed the OHS 1990 and SF-36 to complete andreturn to the investigators.

Study CohortOf the 1,693-patient denominator, 514 (33%) were known tohave died by the time of the project’s inception in 2003.Therefore, 1,179 patients were targeted during the patient-locating phase of the GOTCHA project; 437 (26%) wereuntraceable, and 742 were successfully located and con-tacted. A total of 224 patients (36%) had a healthy siblingwho agreed to participate, and these 224 pairs are thesubject of this study (Fig 1). All 224 participating patients(100%) completed the surveys, and 222 siblings (99%) com-pleted the surveys.

Functional Health SurveysThe postal questionnaire included two standardized instru-ments: the OHS 1990 self-completed health questionnaire[18] and the SF-36 general health status instrument [19]. TheOHS 1990 has been used to measure self-reported health inthe Ontario population in 1990 and 1996/1997 and includesseven sections: health, medicine and drugs, smoking, alco-hol, family, life in general, and physical activities. Re-sponses to certain questions are used to derive norm-referenced scores (Table 1), including the well-being score[18, 19], physical activity frequency score and physicalactivity index [20], social support index [18], family func-tioning score [18], and the Shortened Michigan AlcoholScreening Test (SMAST) [20, 21].

The SF-36 [19] is a generic health survey designed toassess functional health status and health-related quality oflife and comprises eight multiple-item components or do-mains. Scores for each domain are derived from differentquestions; a single question measures reported change inhealth over the past year. The SF-36 has been routinelyused in populations with TOF and heart failure, and refer-ence values are available for the Canadian population [22].

Data AnalysisQuestionnaires were scored using published methodology[18, 19]. Scores were compared between matched pairs ofpatients and siblings using paired t tests, the Wilcoxonsigned-rank test, and McNemar’s test as appropriate, andZ-scores were calculated for comparisons with populationreference data. Linear regression analysis was performed toidentify patient’s demographic, medical, and surgical char-acteristics potentially affecting SF-36 scores. Variables wereevaluated only if they were clinically likely to be predictiveof quality of life, and excluded if the number affected wasless than 10% of the total sample or if data were missing formore than 10%. Factors found to be significantly associatedwith SF-36 scores in univariate analysis were evaluatedfurther through multivariable regression analyses for eachSF-36 score using a backward elimination selection. Statis-tical analyses were undertaken in Stata version 8 (Stata-Corp, College Station, TX). Significance was considered for

p values less than 0.05.

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Results

RespondentsThe median age of patients participating in the siblingcomparison was 33 years (range, 18 to 60 years) and 50%(112 of 224) were female. The median age of siblings was34 years (range, 14 to 70 years). The median difference inage between patients and their sibling was 3 years(interquartile range, 2 to 5 years). Of the siblings, 60%(134 of 224) were female, and 126 pairs (56%) wereconcordant regarding sex. No significant differences inpatient demography were identified between contactedpatients who participated in the study and those who didnot.

General StatusPatient-specific clinical and surgical details, currenthealth status, and health care utilization is shown inTable 2. The median age of corrective surgery was 7years. Fifteen patients (7%) in the patient-sibling studysample were noted to have a congenital syndrome (Down

Fig 1. Flow diagram illustrating the origin ofthe study population (n � 224 patients) fromthe total denominator (n � 1,693) of all pa-tients diagnosed with tetralogy of Fallot (TOF)at our institution and who were born before1984.

syndrome � 8; chromosomal deletion 22q11 � 5; dele-

tion; unspecified other � 2), often associated with devel-opmental delay.

Few surviving patients had undergone major compli-cations since surgery, but only half of the patient samplewas currently free of any cardiac symptoms. Femaleswere significantly more likely than males to experiencepalpitations (p � 0.05), have ankle edema (p � 0.03), or tocomplain of unusual fatigue (p � 0.04). Overall, olderpatients tended to report more cardiac symptoms.

Ontario Health SurveyPERCEIVED HEALTH AND WELL-BEING. A lower proportion ofpatients perceived their general health to be excellent orvery good compared with their siblings (54% versus 66%,p � 0.001). Subjective general health scores for siblingswere comparable to those of Ontario residents in popu-lation health surveys [23].

No differences in well-being scores for patients andsiblings were observed (p � 0.96): a “high” state ofwell-being was achieved by 47% of patients and 53%

of siblings, a “medium” state of well-being by 27% of

mot

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patients and 21% of siblings, and a “low” state of well-being was described by 26% of both patients and siblings.Patients and siblings were similar with regard to theirdegree of satisfaction with life and the proportion whodescribed experiencing feelings of severe stress (7%) orlimiting pain and discomfort (2% to 3%).HEALTH SERVICE UTILIZATION. Health care use by patientsand siblings is detailed in Table 3. Ninety-three percentof patients (208 of 224) considered their current medicalneeds to be adequately met. The proportion of patients(97%) attending a family physician is higher than for theOntario population overall, of whom only 80% will attendtheir family physicians during a 12-month period [23].Women were significantly more likely than men to beattending a cardiologist (p � 0.01) and taking noncardiacmedications (p � 0.02). Overall, 47% were currentlytaking noncardiac medications, and this was significantlymore likely for older patients (p � 0.001).

Patients were significantly more likely to have had arecent health assessment. Whereas 92% of patients hadtheir blood pressure checked within the past 2 years(more than half in the last 6 months), only 84% of siblingshad a blood pressure measurement within this time (p �0.001). Patients were also significantly more likely thansiblings to have taken prescription medication in the lastmonth (55% versus 41%, p � 0.001). The most commonlyused medications were pain relievers, which were takenby 70% of patients and siblings (no difference) and by

Table 1. Domain Descriptions of the Ontario Health Survey a

Ontario Health Survey 1990 scores [18]Well-being score Respondents agree o

seven indicators: enperceived stress, pe

Frequency score The physical activitywhich the respondthan 15 minutes in

Physical activity score Respondents report pduration/frequencyreflect the daily enduring the precedi

Social support index An index valid for rederived from the namount of leisure tand the availability

Family functioning The family functionin[29]. A score aboveindicates better fam

SMAST The Shortened Michieffects of alcohol on

Short Form-36 domains [19]Physical functioning The extent to which hRole–physical The extent to which hBodily pain The intensity and effeGeneral health Self-perception of cuVitality Feeling of energy, ratSocial functioning The extent to which hMental health General mental healtRole–emotional The extent to which e

65% of Ontario residents for longer than a 4-week period.

Patients were significantly more likely to be taking med-icine for the heart or for blood pressure (15% versus 7%,p � 0.002). Patients were also significantly more likely tohave used antibiotics in the preceding month (18% ver-sus 8%, p � 0.004), but not other types of noncardiacmedication. Only 8% of patients and 3% of siblingsreported taking more than three types of prescriptiondrugs in the preceding month.PHYSICAL ACTIVITY. There were no significant differences inthe level of activity undertaken by patients and siblingsin their daily life or employment, which in most casesinvolved standing or walking but not carrying or lifting.Fewer than 10% of all respondents considered theircurrent levels of daily activity to be putting their health atrisk; there were no significant differences between pa-tients and their siblings.

Frequency scores (Table 1) were not significantly dif-ferent between patients and siblings (p � 0.14), norbetween the proportions of patients and siblings whowere regular, occasional, or infrequent participants inphysical activities (p � 0.44). The proportions falling intoeach physical activity category were similar to those forOntario residents overall (Table 3). However, a statisti-cally significant difference in the physical activity index ofpatient and sibling groups was identified (mean differ-ence 0.45 kcal/kg per hour, p � 0.02). In comparison withOntario residents, both patients and siblings had lower

hort Form-36 Assessment

gree with one positive and one negative statement for each of, control of emotions, state of morale, interest in life,ed state of health, and satisfaction with relationships.ency score is calculated from the number of occasions in

articipated in any leisure-time physical activity lasting moreast 4 weeks.

cal activities undertaken in leisure time, and theuch activities. A physical activity index is then calculated toexpenditure (kcal/kg per hour) per respondent for all activitiesweeks.dents between 16 and 59 years of age (n � 206). The index iser of relatives and friends who a respondent felt close to, thespent alone or with others, satisfaction with their social life,confident.re is derived from the McMaster Family Assessment Devicesuggests dysfunctional family relationships; a lower scoreunctioning.

lcohol Screening Test [20] surveys alcohol consumption andlth, social, and work activities to identify problem drinking.

limits general physical activities such as walking.limits performing specific physical tasks.

pain on normal activities.overall health.han fatigue.

interferes with social activities.ll-being.ional problems interfere with daily activities

nd S

r disaergyrceiv

frequent pthe physiof s

ergyng 4sponumbimeof ag sco2.17ily f

gan Ahea

ealthealthct of

rrenther tealth

h we

physical activity indices.

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FAMILY FUNCTIONING AND SOCIAL SUPPORT. There was no sig-nificant difference between the social support indexscores of patients and their siblings (p � 0.22). Bothpatients and siblings visited family and friends morethan once per week and more than 80% expressedsatisfaction with their social life. Similar proportions ofpatients and siblings were married or living with apartner (53% versus 58%, p � 0.30), but patients of bothsexes were less likely to have children of their own (39%versus 51%, p � 0.006).

Patients were significantly more likely to have familyfunctioning scores [18] reflecting better family function-ing than their siblings (p � 0.001). A family functioningscore indicating a dysfunctional family life was found in

Table 2. Cohort Characteristics for the 224 Adult SurvivorsWith Tetralogy of Fallot Who Were Matched With HealthySiblings and Undertook Functional Health Assessment

VariableNo. orMean

Percentor SD

Baseline morphologyPulmonary stenosis 212 95%Pulmonary atresia 11 5%Absent pulmonary valve 1 �1%Noncardiac congenital

syndrome15 7%

Initial corrective managementCorrective surgery 213 95%No patch used during repair 56 25%Transannular patch 71 32%Patch elsewhere to RVOT 69 31%Conduit 6 3%Other 22 10%Mean age at corrective

surgery, years7.4 �4.3

Postoperative outcomesDevelopmental delay 16 7%Postoperative stroke 4 2%Permanent pacemaker 16 7%Ventricular tachyarrhythmia 14 6%Pulmonary valve replacement 36 16%

Telephone interview (n � 224)Family physician follow-up 219 97%Cardiologist follow-up 188 83%Toronto Adult Congenital

Clinic follow-up163 73%

Currently taking medication 106 47%Cardiac symptoms 117 52%Chest pain at rest 27 12%Chest pain on exertion 33 15%Palpitations 74 33%Dyspnea 44 20%Syncope 4 2%Fatigue 38 17%

Data are expressed as percentages of nonmissing values.

RVOT � right ventricular outflow tract; SD � standard deviation.

23% of siblings but in only 10% of patients (p � 0.001).

Approximately 13% of patients (29 of 220) and 15% ofsiblings (33 of 222) reported having thoughts of commit-ting suicide during their lives (p � 0.58), and 5% reportedsuicidal thoughts in the past 12 months. Fewer patients(3%) than siblings (5%) had attempted suicide. Theserates for suicidal ideation are similar to those recordedelsewhere [24, 25] and do not suggest a higher rate forpatients with general medical problems as recordedpreviously in a North American population [26].BEHAVIOR. Significantly fewer patients were current ciga-rette smokers compared with their siblings (16% versus23%, p � 0.009). Patients who were current smokers hadsimilar daily cigarette consumption (12 to 14 cigarettes)as their siblings but started smoking on average 2 yearslater than their siblings at 17 years old (p � 0.05). Fewpatients or siblings had attempted to quit smoking in the

Table 3. Use of Medication and Reported Physical Activityfor Patients and Siblings

Reported Medicationsand Activity Patients Siblings

OntarioResidentsa

Medication typePrescription medicine 55%b 41%b

Pain relievers 73% 70% 65%Cardiac or

hypertensive15%b 7%b

Gastrointestinal andlaxatives

19% 14%

Tranquillizers 8% 6% 4%Antibiotics 18%b 8%b

Cough or coldremedies

15% 9% 20%

Allergy medications 11% 16%Opiates (codeine,

meperidine, ormorphine)

7% 8%

Antidepressants 6% 5% 3%Diet pills or

stimulants1% 4%

Vitamin supplements 46% 43%Frequency of physical

activityRegular, �12 times a

month49% 52% 49%

Occasional, 4 to 11times a month

24% 27% 20%

Infrequent, 0 to 3times a month

28% 21% 24%

Intensity of physicalactivity

Inactive, 1.5 kcal/kgdaily

73% 63% 56%

Moderately active, 1.5to 2.9 kcal/kgdaily

15% 21% 23%

Active, �3 kcal/kgdaily

12% 16% 21%

Data are expressed as percentage of the total nonmissing values. aFrom

the Public Health Research, Education, and Development Program, 2000[23]. bStatistically significant difference between patients and siblings.

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last year, although both groups equally recognized thatthey were at risk of future health problems due to theircigarette smoking.

There were no significant differences in the propor-tions of patients and siblings who fell into each alcoholconsumption category (Table 4) [18]. There was no dif-ference in the age at which patients and siblings starteddrinking alcohol (17 to 20 years old; p � 0.25) or betweenthe weekly alcohol consumption of patients and siblingswho are current drinkers (p � 0.08). There were nooverall differences between patient and sibling scores(p � 0.79) on the SMAST for drinking problems.

Respondents were also asked about use of illicit drugs.One third of patients and siblings had used marijuana at

Table 4. Patient- and Sibling-Reported Use of Alcohol andIllicit Drugs

Alcohol and Illicit Drug Use Patients SiblingsOntario

Residentsa

Alcohol consumptionFormer drinkerb 6% 2% —Former at-risk drinkerc 2% 1% —Other current drinkerd 67% 71% 52%Current occasional drinkere 17% 17% 21%Never 9% 9% —

Drug useMarijuana 32% 33% —Cocaine or crack 3% 5% —LSD 5% 7% —Amphetamines 4% 6% —Heroin �1% �1% —Glue, solvents, or gasoline �1% �1% —

Data are expressed as percentage of the total nonmissing values. Differ-ences were not significant between patients and siblings, or betweenstudy subjects and published data for Ontario residents. aFrom PublicHealth Research, Education, and Development Program, 2000 [23].bDrank alcohol in the past but not for the past 12 months. cDrank morethan 12 drinks alcohol every week in the past but not for the past 12months. dDrinks alcohol at least once per month. eDrinks alcohol lessthan once per month.

LSD � lysergic acid diethylamide.

Table 5. Patient Versus Sibling Short Form-36 Domain Score

Short Form-36 Domain

Patients

n Mean Score

Physical functioning 224 82.4a

Role–physical 222 81.1Bodily pain 223 80.3a

General health 224 64.2a

Vitality/energy 222 60.6a

Social functioning 223 86.3Role–emotional 221 84.8Mental health 221 75.6

In addition, comparisons were made with published Canadian normativefrom Canadian norm (z-score) [22] at p less than 0.05.

NS � nonsignificant; SD � standard deviation.

least five times in their lifetime; 17% of patients and 14%of siblings had used it in the last year (Table 4). Fewerthan 4% of patients and fewer than 2% of siblings hadused illicit drugs other than marijuana in the past 12months.

SF-36 QuestionnaireShort-Form 36 scores were significantly lower for pa-tients than for siblings in the domains of physical func-tioning, physical role, and general health (all p � 0.001). Atrend toward patients also having lower vitality scoresthan their siblings was also noted (Table 5). These differ-ences indicate that patients were more limited in theirdaily physical activity, had greater difficulty fulfillingroles at work due to physical limitations, had poorerself-perceived general health, and experienced morefatigue than their siblings. However, when comparedwith their siblings, patients experienced no more emo-tional problems, limitation in social activities, or bodilypain than their siblings.

Sibling SF-36 z-scores were not worse than Canadiannorms [22] except for their perceived general healthstatus, which was worse than normal (p � 0.001). PatientSF-36 z-scores were worse than Canadian norms forphysical functioning, general health, and vitality (p �0.007, p � 0.001, and p � 0.001 respectively).

There was no difference in patient and sibling ratingsof changes in their health over the past 12 months (p �0.40): 60% considered that their health had not changedover the past 12 months, 25% considered that their healthhad improved, and approximately 15% indicated theyhad worse health now than 1 year ago.

For siblings, as for patients, older age at the time ofquestionnaire completion was associated with assigninglower scores for physical role, emotional role, and mentalhealth. Risk hazard analysis suggests that older age atoperation and the current use of noncardiac medicationwere strongly associated with lower SF-36 scores forpatients in physical (p � 0.03), general health (p � 0.01),and vitality domains (p � 0.02). Some additional riskfactors, such as having a stroke (p � 0.01) or congenitalsyndrome (p � 0.01) were associated with lower physical

Matched Comparison (Paired t Test)

Siblings

p ValueCanadian Norm

Mean (SD)Mean Score

90.5a �0.0001 85.8 (20.0)89.7a �0.0001 82.1 (33.2)82.1a NS 75.6 (23.0)73.1a �0.0001 77.0 (17.7)63.6 NS 65.8 (18.0)87.8 NS 86.2 (19.8)83.6 NS 84.0 (31.7)76.0 NS 77.5 (15.3)

as a z-score deviation from the mean. aMean score significantly different

s in

n

222222224224222224224222

data

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functioning in univariate analysis, but affected only asmall proportion of patients and were excluded fromfurther analysis. After taking into account other factors,older current age was associated with lower mentalhealth scores (p � 0.02) and reoperation with loweremotional role (p � 0.03) and social functioning scores(p � 0.01). Corrective surgery, as opposed to palliativesurgery only, was associated with improved social func-tioning (p � 0.01) and general health scores (p � 0.01),whereas older age at operation, reoperation, and use ofnoncardiac medication were all associated with lowergeneral health scores (p � 0.02, p � 0.01, and p � 0.01,respectively). Preoperative and intraoperative variableswere not found to be associated with SF-36 outcomes.

Comment

Our study confirms that adult survivors with repairedTOF have significant decrements in physical functionalstatus and perceptions of general health compared withboth large aggregates of control populations and theirmatched healthy siblings. However, despite this, pa-tients’ overall quality of life, social functioning, andemotional and mental health well-being are not different.Therefore, patients appear to adjust well for their phys-ical compromises, or develop coping strategies. In addi-tion, patients may have a greater appreciation of theirhealth and social needs, as evidenced by significantlylower rates of harmful behavior (smoking, for example)and significantly better functioning family units.

Various studies have now suggested that adults withrepaired TOF are able to lead fairly normal lives [6,10-15]. Our investigation also demonstrates that adultswith TOF can expect a good quality of life and a highlevel of social participation, comparable with that of thehealthy adult population. In addition, the marital rate iscomparable between patients and their siblings, imply-ing normal development of relationships. However, thesignificantly lower prevalence of children among marriedTOF patients is interesting. It is unclear whether that hassocial or emotional causes, or otherwise is attributable todifferences in fertility rates for adult patients.

In comparison with sibling and population controls,adults affected by TOF achieved significantly lowerscores on the physical functioning, physical role, andgeneral health scales of the SF-36 and tend towardhaving lower vitality, indicating that they experiencedifficulties in meeting the physical demands of normaldaily activities and employment. Previous studies com-paring patients with TOF with published general popu-lation norms have found less significant decreases inphysical functioning scores [13, 27], but that may reflectdifferences in the demographic and socioeconomic char-acteristics of the patient group and published norms. Ourobservation of differences in the general health domainbetween siblings and published normative data empha-sizes the limitations of using large population aggregatesfor control comparison. Instead, matching patients tosiblings likely controls for many influential factors in

physical and social development.

Although previous authors have reported that adultswith TOF participate in normal leisure sports [12, 15],there are no data available with regard to exercise work-load and a healthy control group. In our study, using avalidated questionnaire, patients reported exercisingwith similar frequency as their siblings, but the level ofwork represented by regular sporting and leisure activi-ties was significantly less for patients than for theirsiblings. More than 70% of patients fell into the categoryof inactive, despite more than 50% participating in phys-ical activities more than four times per week. Thesefindings suggest that adults with repaired TOF cannotcope with the extra demands of physical exercise to thesame extent as the general population. It is uncertainwhether these physical limitations are true restrictionsimposed by the condition or self-imposed by adults as aresult of medical advice or perceived ill-health. However,an awareness of their physical limitations might conceiv-ably also contribute to the lower rate of child-bearingobserved in the patient group.

Adults affected by TOF achieved significantly lowerscores for self-perceived general health status on theSF-36 and were less likely to rate their health as good orexcellent than their siblings. Unsurprisingly, because oftheir cardiac condition, patients also had a significantlyhigher frequency of contact with health care services anduse of cardiac and antibiotic medication than the healthypopulation. Importantly, one quarter of patients were notreceiving any cardiology follow-up despite the likelihoodof increasing complications over time [7].

In view of the physical limitations and lower generalhealth status experienced by adults with TOF, it isperhaps surprising to find no differences between pa-tients and healthy controls with regard to self-perceivedquality of life; however, this was also the finding ofsmaller studies utilizing normal controls [14, 15]. Inaddition, patients in this study described lower rates ofsuicidal ideation and attempted suicide compared withsiblings, in contrast to previous reports suggesting thatsuicide is an important contributor to late death in adultswith TOF [7]. In certain aspects of their lives, such asfamily functioning, patients were better adjusted thantheir siblings. Previous authors have suggested that pa-tients develop specific coping strategies, and may denytheir limitations or may lower their expectations [13, 14].Qualitative inquiry has further suggested that adultswith TOF undertake a continual process of normaliza-tion, thus acknowledging their physical limitations andactively managing their lives to minimize the effects ofthe heart defect on their physical and social roles [28].That may also explain the willingness of adults with TOFto participate in risk behaviors, such as smoking, alcohol,and illicit drug use, to the same level as their siblings.

Study LimitationsWe recognize several limitations in our study. First, theretrospective all-inclusive study design introduces limi-tations: the difficulties in locating and recruiting patientswho may now be remote from our institution’s clinical

program, the high proportion of patients lost to follow-

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up, the morphologic and clinical heterogeneity within thecohort, and the 6 decades of surgical repair techniquesspanned by the study. Many patients may not be repre-sentative of children undergoing TOF repair in the con-temporary era. Nevertheless, all these limitations alsorepresent benefits of using an all-inclusive inceptioncohort as the patient denominator. No patient has beenintentionally excluded because of morphologic subtypeor clinical complications. Therefore, the cohort trulyrepresents the adult population with repaired TOF forwhom we care in clinical practice today. Second, animportant source of bias may be introduced into thisstudy if nonresponders differed from subjects who par-ticipated. However, adult patients in the sibling studyappeared representative of subjects included in thelarger GOTCHA study in terms of age, sex, or operativeexperience. Finally, we note that difficulties in locatingpatients also serve to emphasize the deficiencies in cardio-vascular health care surveillance that some TOF survivorsare experiencing. For example, we estimate that as many as25% of this patient cohort were under no formal cardiologyfollow-up at the time of recruitment. We would insteadsuggest that all adults with repaired TOF ought to benefitfrom the continued care of a specialist cardiologist.

In summary, functional health status and quality of lifeis good for adults who underwent surgery for TOF duringchildhood, and most lead normal lives, with good socialparticipation. However, patients report significant decre-ments in physical functioning and perceived generalhealth. These compromises in physical and general healthappear well-tolerated by these patients. Nevertheless, ef-forts to more closely assess and improve late physicalfunctional health are likely to translate into improved latefunctional health status and quality of life for adults livingwith repaired TOF. In addition, more widespread availabil-ity of cardiac rehabilitation programs for children andadults with congenital heart disease may further negate theimpact of impaired physical functional health; as many as20% to 25% of our cohort were under no formal congenitalcardiology surveillance at the time of follow-up.

The GOTCHA program, including this study, has been sup-ported by generous grants from the Heart and Stroke Founda-tion of Ontario (NA 4109, NA 4876), and the CIBC WorldMarkets Children’s Miracle Foundation. The authors of thismanuscript have certified that they comply with the Principles ofEthical Publishing in the International Journal of Cardiology[30].

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INVITED COMMENTARY

This article [1] describes a very important and wellthought out study in an understudied aspect of adultcongenital heart disease (CHD). Quality of life studies inadults are not done nearly as well or as often as they arein younger patients with CHD.

One important finding of this study is that thesepatients have a similar degree of satisfaction with lifecompared with their siblings despite having more phys-ical limitations and a lower perception of their generalhealth.

It was somewhat surprising to see that only 5 of the 224patients had deletion of 22q11. It is typically seen in up to12% to 15% of patients with tetralogy of Fallot; this mayhave been caused by a selection bias because of whoagreed to participate in the study. We also wonder if asignificant proportion of the older adults in the studymay never have been tested for 22q11 syndrome by ourcurrent techniques. This is important because 22q11 isinherited as an autosomal dominant trait, with a 50% riskof passing the gene defect to the next generation, andthere appears to be an increased risk later in life ofautoimmune disorders.

Probably the most important statistic from this articleis that up to 25% of patients do not have or have not hada recent follow-up evaluation by a cardiologist, or betteryet an adult CHD specialist. This is despite the recentadult CHD management guidelines that suggest at least

We look forward to seeing a similar study 20 yearsfrom now to see if the patients are in a better state ofhealth when a study again uses a cross section of “allcomers.” This will be especially interesting with theinclusion of patients who have had complete repair asneonates.

Raymond T. Fedderly, MD

Department of Pediatric CardiologyChildren’s Hospital of WisconsinMedical College of Wisconsin9000 W Wisconsin AveMilwaukee, WI 53226e-mail: fedderly@mcw.edu

Michael G. Earing, MD

Divisions of Adult Cardiovascular Medicineand Pediatric Cardiology

Medical College of Wisconsin9000 W Wisconsin AveMilwaukee, WI 53226

Reference

1. Knowles R, Veldtman G, Hickey EJ, et al. Functional healthstatus of adults with tetralogy of Fallot: matched comparison

with healthy siblings. Ann Thorac Surg 2012;94:124–32.

0003-4975/$36.00http://dx.doi.org/10.1016/j.athoracsur.2011.09.071