As survival improves for adults with tetralogy of Fallot (TOF), long-term outcomes have taken on greater importance. We aimed to compare the long-term health, socioeconomic, and quality of life (QOL) outcomes between adult survivors and sibling controls. CHD PULSE is a cross-sectional survey from 2021 to 2023 across 11 Pediatric Cardiac Care Consortium centers; 3,133 adults with a history of CHD and 326 unaffected siblings completed surveys on health, socioeconomic, and QOL outcomes with the Patient-Reported Outcomes Measurement Information System (PROMIS). There were 337 TOF survivors, who were similar in age to controls (33.4 yrs vs 32.0 yrs, p = 0.076) but less likely to be female (56% vs 65%, p = 0.022). TOF survivors more frequently reported difficulty paying for medical care (31% vs 15%, p < 0.001), overnight hospitalizations (13% vs 7%, p = 0.015), and concern for future health (53% vs 38%, p < 0.001). They were less likely to have an associate’s degree or higher (53% vs 74%, p < 0.001) and more likely to have health-related work limitations (43% vs 8%, p < 0.001) or be unemployed within the preceding year (20% vs 7% p < 0.001). However, PROMIS scores were favorable for both TOF survivors and the sibling comparison group. In conclusion , adults with TOF face persistent medical, education, and socioeconomic challenges relative to unaffected siblings. However, PROMIS quality of life scores demonstrate resiliency in the TOF survivors, with similar self-perceived QOL to their siblings.
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD), with an incidence of approximately 42.1 per 100,000 live births. Advances in early surgical repair, perioperative management, and cardiology care have improved long-term survival, with contemporary data showing >90% survival at 25 years. , Studies of adolescents with TOF have identified increased risk of deficits in neurodevelopment ,, as well as psychiatric complications. This transition from pediatric to adult CHD care poses additional challenges, with many patients experiencing gaps in specialized follow-up. , Prior studies of adults with CHD have reported increased medical comorbidity, lower educational attainment, greater socioeconomic challenges, greater mental health burden, and impaired health-related quality of life (HRQoL) compared with the general population. However, TOF warrants specific attention because it is common, surgically complex, and associated with known risks for neurocognitive and educational difficulties. Importantly, prior work examining long-term outcomes in TOF has largely been limited to single-center studies. ,,, While HRQoL has been studied in CHD broadly, there is a need for examination using validated instruments within the TOF population. Additionally, few studies have controlled for familial and societal factors with the utilization of healthy sibling control group. , In this study, we aimed to evaluate medical, education, socioeconomic, and HRQoL outcomes among adults with TOF compared with sibling controls using data from a multicenter cross-sectional study of patients with CHD and siblings of individuals with CHD. We hypothesized that adults with TOF would demonstrate greater comorbidity burden, lower educational and socioeconomic attainment, and reduced HRQoL compared with siblings.
Methods
Study design
This cross-sectional study is a part of the CHD Project to Understand Lifelong Survivor Experience (CHD PULSE), the details and survey instruments of which have previously been described. Briefly, the goal of CHD PULSE was to assess long-term nonmortality outcomes among those with a history of CHD. Survey data collection took place from September 2021 to April 2023 across 11 US Centers in the Pediatric Care Consortium (PCCC), a network established in 1982 to assess and improve the quality of pediatric cardiac programs. All participants were over the age of 18 years old when contacted. Survey respondents included 3,133 patients with previous CHD intervention and 326 non-CHD siblings. Approval of this study was through central institutional review board (IRB) of the Western IRB as well as local IRB for participating centers as needed (STUDY00000303).
Study population
Individuals were included in this study if they had a documented diagnosis of TOF within the PCCC registry and had undergone at least one surgical or catheter-based intervention at a participating PCCC center. Diagnostic categorization was based on the initial cardiac diagnosis recorded in the registry at the time of first intervention, with confirmation by review of operative and procedural data. Surveys asked additional questions regarding the number and timing of interventions. Patients with TOF variants (e.g., TOF with pulmonary atresia or absent pulmonary valve) were included, whereas individuals whose diagnostic information could not be reliably distinguished from other conotruncal lesions were excluded. Living siblings who were closest in age to respondents were then recruited to serve as a control group; they completed surveys similar to those of the CHD population, but without CHD-specific questions.
Outcomes of interest
Medical
Medical and health access outcomes were drawn from the Health Insurance and Health Care sections of the CHD PULSE survey. Participants reported current insurance coverage and plan type, any loss of coverage in the prior 12 months, and whether cost prevented seeking needed care. Questions also assessed delayed or unpaid medical bills, and receipt of disability benefits. Respondents indicated whether they had ever been told by a clinician that they had specific comorbid conditions based on a predefined list with the option to input any other not covered. Health care utilization within the previous 12 months was assessed by reported emergency department visits, hospitalizations requiring overnight stay, and office visits to any provider. Concerns for future health and heart health were evaluated on a four-point Likert scale (not at all, not very, somewhat, very concerned). Female CHD respondents were additionally asked whether they had received counseling about pregnancy-related risks (special concerns about becoming pregnant, being advised to avoid pregnancy, or contraception options) and whether they had ever delayed or avoided pregnancy because of their heart condition.
Education
Respondents reported the highest degree or grade completed and if nonstandard education programs were used during elementary through high school, such as special education. Educational attainment was classified as graduate/professional, associate/bachelor’s, high-school/some college, or no high-school degree.
Psychosocial
Socioeconomic indicators included employment status in the past 12 months including part-time and full-time employment and whether health had limited opportunities for work or military service. Household income before taxes were reported categorically up to $75,000 or more. Respondents also rated their household’s financial situation (excellent, good, fair, poor). Marital status (ever vs never married) was also assessed.
Quality of life
Patient-reported quality of life outcomes were assessed via the CHD PULSE survey. This included instruments from the NIH-developed Patient-Reported Outcomes Measurement Information System (PROMIS). , The Patient-Reported PROMIS instruments are validated, standardized measures of physical, mental, and social health, allowing for comparison with population norms. The survey included the PROMIS Global Health (v1.0/1.1), Cognitive Function Short Form (v2.0 to 8a), Physical Function Short Form (v1.0 to 4a), Anxiety Short Form (v1.0 to 4a), Depression Short Form (v1.0 to 4a), and Ability to Participate in Social Roles and Activities Short Form (v2.0 to 4a). Higher scores reflected greater intensity of the measured domain, such that higher physical function scores indicated better functioning, while higher anxiety or depression scores indicated more symptoms. Each PROMIS domain measured a distinct construct. The global health survey produced separate physical and mental health summary scores. Physical health questions captured self-perception of overall health, physical capability, fatigue, and pain, while mental health questions evaluated mood, quality of life, social relationships, and emotional problems. The cognitive function survey assessed difficulty thinking, concentrating, and task-switching. The physical function short form provided more detailed assessment of day-to-day physical ability, including tasks such as chores and mobility. The anxiety and depression surveys quantified the frequency and severity of symptoms, though they are not diagnostic tools. Finally, the social roles and activities survey addressed the ability to engage in leisure and social activities with friends, family, or independently.
Statistical methods
Continuous and categorical variables were described using means with standard deviations (SD) and counts with percentages, respectively. Comparisons between TOF patients and siblings were conducted using Pearson’s Chi-squared test (Fisher’s exact when cell counts were <5) for categorical variables, while continuous variables used the Two Sample t -test. However, age followed a non-normal distribution, so medians and interquartile ranges (IQR) were provided, and group comparisons used the Wilcoxon rank sum test.
A subset analysis was performed using only TOF patients who had a participating non-TOF sibling (n = 66; 33 per group). This subset was analyzed using the same steps in the overall cohort but used the equivalent paired test—McNemar’s Chi-squared test (categorical variables) and Paired t -test (continuous variables). Age used the Wilcoxon signed rank sum test. For some variables, the McNemar’s Bowker test of symmetry (when variables have > 2 groups) could not be computed due to zero symmetric cell pairs, p-values were marked as N/A. To keep the analysis consistent with the overall cohort we did not collapse variables further, instead variables that could not be tested are interpreted descriptively, unless a binary or collapsed version is available.
PROMIS item responses were summed to generate raw scores for each domain and converted to standardized T-scores. Higher T-scores indicate more of the measured trait, with direction depending on the domain. Group mean T-scores with 95% confidence intervals (CI) were reported, and results were interpreted in relation to published PROMIS cut-points to provide clinical context.
Responses such as “unknown,” “not applicable,” or “don’t know” were coded as missing. Participants with missing data for a given measure were not included in percentage calculations and statistical tests. For selected outcomes (e.g., educational attainment, household income, concern about health), survey responses were dichotomized to improve interpretability and analytic power.
For all analyses, a p-value of < 0.05 was considered statistically significant. All data cleaning and statistical tests were performed in R Statistical Software (v4.2.1; R Core Team 2022).
Results
There were 337 respondents with primary diagnosis of TOF, including categorizations of TOF with absent pulmonary valve (n = 9) and TOF with pulmonary atresia (n = 53). Of 326 total sibling respondents, 33 were identified as siblings of individuals with TOF that were included in this study.
Analysis of overall cohort
Demographics
Compared to all siblings, TOF respondents were more likely to be male (44% vs 35%, p = 0.022) and more often identified as non-Hispanic Black (6% vs 1%). A larger proportion of TOF surveys were completed by proxy respondents (9% vs 1%, p < 0.001). Respondents and siblings were found to be of similar age (33.43 vs 32.00 p = 0.08) ( Table 1 ).
Table 1
Demographics of Tetralogy of Fallot Patients (TOF) vs All Sibling Controls
| Characteristic | TOF N = 337 | Sibling N = 326 | p-value |
|---|---|---|---|
| Sex | 0.022 | ||
| Female | 188 (56%) | 209 (65%) | |
| Male | 149 (44%) | 115 (35%) | |
| Unknown | 0 | 2 | |
| Age (years) | 33.43 (26.59, 39.33) | 32.00 (25.00, 39.00) | 0.076 |
| Unknown | 0 | 15 | |
| Age groups (years) | 0.688 | ||
| <25 | 64 (19%) | 69 (22%) | |
| 25 to 29 | 63 (19%) | 64 (21%) | |
| 30 to 34 | 69 (20%) | 53 (17%) | |
| 35 to 39 | 64 (19%) | 55 (18%) | |
| 40+ | 77 (23%) | 71 (23%) | |
| Unknown | 0 | 14 | |
| Race and ethnicity | <0.001 | ||
| Hispanic | 12 (4%) | 17 (5%) | |
| NH Black | 21 (6%) | 3 (1%) | |
| NH Other or Multiple Race | 24 (7%) | 15 (5%) | |
| NH White | 276 (83%) | 291 (89%) | |
| Unknown | 4 | 0 | |
| Survey respondent | <0.001 | ||
| By proxy | 30 (9%) | 2 (1%) | |
| Self | 300 (91%) | 324 (99%) | |
| Unknown | 7 | 0 |
Medical outcomes
Adults with TOF were significantly more likely to have received disability benefits (19% vs 5%, p < 0.001), to report difficulty paying for medical care (31% vs 15%, p < 0.001), and to endorse at least one comorbidity (82% vs 69%, p < 0.001). They also reported more overnight hospitalizations in the past year (13% vs 7%, p = 0.015). Concerns for their future health (53% vs 38%, p < 0.001) and heart health specifically (58% vs 23%, p < 0.001) was markedly higher among TOF survivors.
Insurance coverage was high in both groups (96% vs 97%, p = 0.25), and loss of coverage within the prior year was uncommon (5% vs 6%, p = 0.83). The proportion unable to seek needed care due to cost was similar (10% vs 9%, p = 0.61). Frequency of emergency department visits (21% vs 16%, p = 0.15) and self-reported anxiety (35% vs 38%, p = 0.47) or depression diagnoses (29% vs 29%, p = 0.99) did not differ significantly. Office visits with any provider were more common in those with history of operated TOF (90% vs 82%, p = 0.003) ( Table 2 ).
Table 2
Outcomes of Tetralogy of Fallot Patients (TOF) and All Siblings
| Variable | TOF N = 337 | Sibling N = 326 | p-value * | |
|---|---|---|---|---|
| Medical Outcomes | ||||
| Insurance Status | 0.251 | |||
| No | 15 (4%) | 9 (3%) | ||
| Yes | 319 (96%) | 312 (97%) | ||
| Unknown | 3 | 5 | ||
| Insurance plan | 0.004 | |||
| Government | 55 (20%) | 29 (10%) | ||
| More than one | 8 (3%) | 11 (4%) | ||
| Private or Military | 208 (77%) | 245 (86%) | ||
| Unknown | 66 | 41 | ||
| Lost insurance coverage in past 12 months | 0.836 | |||
| No | 296 (95%) | 292 (94%) | ||
| Yes | 16 (5%) | 17 (6%) | ||
| Unknown | 25 | 17 | ||
| Unable to seek needed care in past 12 months due to cost | 0.608 | |||
| No | 281 (90%) | 282 (91%) | ||
| Yes | 31 (10%) | 27 (9%) | ||
| Unknown | 25 | 17 | ||
| Ever received disability benefits | <0.001 | |||
| No | 247 (81%) | 291 (95%) | ||
| Yes | 58 (19%) | 16 (5%) | ||
| Unknown | 32 | 19 | ||
| Unable to pay or delayed payment for medical care, including medications, hospital stays, and doctors’ visits | <0.001 | |||
| No | 211 (69%) | 261 (85%) | ||
| Yes | 94 (31%) | 45 (15%) | ||
| Unknown | 32 | 20 | ||
| Any comorbidity | <0.001 | |||
| No | 62 (18%) | 100 (31%) | ||
| Yes | 275 (82%) | 226 (69%) | ||
| Number of comorbidities | <0.001 | |||
| 0 | 62 (18%) | 100 (31%) | ||
| 1 | 100 (30%) | 97 (30%) | ||
| 2 | 56 (17%) | 67 (21%) | ||
| 3 or more | 119 (35%) | 62 (19%) | ||
| History of Anxiety | 0.467 | |||
| No | 218 (65%) | 202 (62%) | ||
| Yes | 119 (35%) | 124 (38%) | ||
| History of Depression | 0.988 | |||
| No | 240 (71%) | 232 (71%) | ||
| Yes | 97 (29%) | 94 (29%) | ||
| Hospital ER visits in past 12 months | 0.147 | |||
| 0 | 262 (79%) | 269 (84%) | ||
| 1 or more | 68 (21%) | 52 (16%) | ||
| Unknown | 7 | 5 | ||
| Hospital visits in past 12 months and stayed overnight | 0.015 | |||
| 0 | 291 (87%) | 299 (93%) | ||
| 1 or more | 43 (13%) | 23 (7%) | ||
| Unknown | 3 | 4 | ||
| Office visits to any health provider in past 12 months | 0.003 | |||
| 0 | 33 (10%) | 59 (18%) | ||
| 1 or more | 297 (90%) | 266 (82%) | ||
| Unknown | 7 | 1 | ||
| Concern for future health | <0.001 | |||
| Not at all | 45 (14%) | 75 (23%) | ||
| Not very | 112 (34%) | 126 (39%) | ||
| Somewhat | 119 (36%) | 109 (34%) | ||
| Very | 55 (17%) | 14 (4%) | ||
| Unknown | 6 | 2 | ||
| Concern for future health, binary | <0.001 | |||
| Concerned | 174 (53%) | 123 (38%) | ||
| Not Concerned | 157 (47%) | 201 (62% | ||
| Concern for overall heart health | <0.001 | |||
| Not at all | 35 (11%) | 113 (35%) | ||
| Not very | 106 (32%) | 138 (43%) | ||
| Somewhat | 134 (40%) | 65 (20%) | ||
| Very | 57 (17%) | 8 (2%) | ||
| Unknown | 5 | 2 | ||
| Concern for heart health, binary | <0.001 | |||
| Concerned | 191 (58%) | 73 (23%) | ||
| Not Concerned | 141 (42%) | 251 (77% | ||
| Ever delayed pregnancy, CHD females only, n = 188 | N/A | |||
| No | 124 (66%) | |||
| Yes | 64 (34%) | |||
| Education Outcomes | ||||
| Education | <0.001 | |||
| Graduate or Professional degree | 131 (39%) | 160 (50%) | ||
| Associate or Bachelor degree | 45 (13%) | 79 (24%) | ||
| High School diploma/Some college | 146 (44%) | 72 (22%) | ||
| No High School degree | 13 (4%) | 12 (4%) | ||
| Unknown | 2 | 3 | ||
| Education, binary | <0.001 | |||
| Associates degree or higher | 176 (53%) | 239 (74%) | ||
| Some or no college | 159 (47%) | 84 (26%) | ||
| Special education | <0.001 | |||
| No | 249 (78%) | 296 (95%) | ||
| Yes | 72 (22%) | 17 (5%) | ||
| Unknown | 16 | 13 | ||
| Socioeconomic Outcomes | ||||
| Work for pay in past 12 months | <0.001 | |||
| Full-time | 209 (63%) | 238 (73%) | ||
| Part-time | 59 (18%) | 62 (19%) | ||
| No work | 66 (20%) | 24 (7%) | ||
| Unknown | 3 | 2 | ||
| Health affected military service or work | <0.001 | |||
| No | 175 (57%) | 282 (92%) | ||
| Yes | 130 (43%) | 24 (8%) | ||
| Unknown | 32 | 20 | ||
| Household income in past year ($) | <0.001 | |||
| 0 to 24,999 | 66 (24%) | 38 (14%) | ||
| 25,000 to 49,999 | 57 (21%) | 41 (15%) | ||
| 50,000 to 74,999 | 43 (16%) | 48 (17%) | ||
| 75,000 or more | 107 (39%) | 154 (55%) | ||
| Unknown | 64 | 45 | ||
| Household income in past year, binary ($) | <0.001 | |||
| 0 to 74,999 | 166 (61%) | 127 (45%) | ||
| 75,000 or more | 107 (39%) | 154 (55%) | ||
| Perception of finances | 0.026 | |||
| Excellent | 74 (22%) | 81 (25%) | ||
| Good | 178 (54%) | 179 (55%) | ||
| Only Fair | 59 (18%) | 58 (18%) | ||
| Poor | 20 (6%) | 5 (2%) | ||
| Unknown | 6 | 3 | ||
| Perception of finances, 3-levels | 0.363 | |||
| Excellent | 74 (22%) | 81 (25%) | ||
| Good | 178 (54%) | 179 (55%) | ||
| Poor or fair | 79 (24%) | 63 (20%) | ||
| Marital Status | 0.152 | |||
| Ever married | 154 (46%) | 168 (52%) | ||
| Never married | 180 (54%) | 157 (48%) | ||
| Unknown | 3 | 1 |
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