Anxiety and Depression in Adults With Congenital Heart Disease.

BACKGROUND: A comprehensive understanding of adult congenital heart disease outcomes must include psychological functioning. Our multisite study offered the opportunity to explore depression and anxiety symptoms within a global sample. OBJECTIVES: In this substudy of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults With Congenital Heart Disease-International Study), the authors we investigated the prevalence of elevated depression and anxiety symptoms, explored associated sociodemographic and medical factors, and examined how quality of life (QOL) and health status (HS) differ according to the degree of psychological symptoms. METHODS: Participants completed the Hospital Anxiety and Depression Scale, which includes subscales for symptoms of anxiety (HADS-A) and depression (HADS-D). Subscale scores of 8 or higher indicate clinically elevated symptoms and can be further categorized as mild, moderate, or severe. Participants also completed analogue scales on a scale of 0 to 100 for QOL and HS. Analysis of variance was performed to investigate whether QOL and HS differed by symptom category. RESULTS: Of 3,815 participants from 15 countries (age 34.8 ± 12.9 years; 52.7% female), 1,148 (30.1%) had elevated symptoms in one or both subscales: elevated HADS-A only (18.3%), elevated HADS-D only (2.9%), or elevations on both subscales (8.9%). Percentages varied among countries. Both QOL and HS decreased in accordance with increasing HADS-A and HADS-D symptom categories (P < 0.001). CONCLUSIONS: In this global sample of adults with congenital heart disease, almost one-third reported elevated symptoms of depression and/or anxiety, which in turn were associated with lower QOL and HS. We strongly advocate for the implementation of strategies to recognize and manage psychological distress in clinical settings. (Patient-Reported Outcomes in Adults With Congenital Heart Disease [APPROACH-IS]; NCT02150603).

Clinical and Sociodemographic Factors Associated With Health-Related Quality of Life in Patients With Adult Congenital Heart Disease　- A Nationwide Cross-Sectional Multicenter Study.

BACKGROUND: Little is known about clinical or sociodemographic factors that influence health-related quality of life (HRQoL) in patients with adult congenital heart disease (ACHD).Methods and Results: We conducted a nationwide prospective cross-sectional multicenter study at 4 large ACHD centers in Japan. From November 2016 to June 2018, we enrolled 1,223 ACHD patients; 1,025 patients had an HRQoL score. Patients completed a questionnaire survey, including sociodemographic characteristics, and the 36-Item Short-Form Health Survey (SF-36). To determine factors associated with HRQoL, correlations between 2 SF-36 summary scores (i.e., physical component score [PCS] and mental component score [MCS]) and other clinical or sociodemographic variables were examined using linear regression analysis. In multivariable analysis, poorer PCS was significantly associated with 11 variables, including older age, higher New York Heart Association class, previous cerebral infarction, being unemployed, and limited participation in physical education classes and sports clubs. Poorer MCS was associated with congenital heart disease of great complexity, being part of a non-sports club, current smoking, and social drinking. Student status and a higher number of family members were positively correlated with MCS. CONCLUSIONS: This study demonstrates that HRQoL in ACHD patients is associated with various clinical and sociodemographic factors. Further studies are needed to clarify whether some of these factors could be targets for future intervention programs to improve HRQoL outcomes.

Patient-reported outcomes in the aging population of adults with congenital heart disease: results from APPROACH-IS.

The congenital heart disease (CHD) population now comprises an increasing number of older persons in their 6th decade of life and beyond. We cross-sectionally evaluated patient-reported outcomes (PROs) in persons with CHD aged 60 years or older, and contrasted these with PROs of younger patients aged 40-59 years and 18-39 years. Adjusted for demographic and medical characteristics, patients ≥60 years had a lower Physical Component Summary, higher Mental Component Summary, and lower anxiety (Hospital Anxiety and Depression Scale-Anxiety) scores than patients in the two younger categories. For satisfaction with life, older persons had a higher score than patients aged 40-59 years. Registration: ClinicalTrials.gov NCT02150603.

Rationale, design and methodology of APPROACH-IS II: International study of patient-reported outcomes and frailty phenotyping in adults with congenital heart disease.

BACKGROUND: In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II. METHODS/DESIGN: APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments. DISCUSSION: APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD.

Heart Failure and Patient-Reported Outcomes in Adults With Congenital Heart Disease from 15 Countries.

Background Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease. Methods and Results As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms. Conclusions HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02150603.

Objective and Personalized Assessment of Disease-Related Knowledge Among Patients With Congenital Heart Disease　- Development and Validation of the Japanese Version of the Leuven Knowledge Questionnaire for Congenital Heart Disease.

Background: Disease understanding in patients with congenital heart disease is important in transitional and lifelong care. This study aimed to develop the Japanese version of the Leuven Knowledge Questionnaire for Congenital Heart Disease (LKQCHD) and identify factors associated with disease-related knowledge. Methods and Results: After confirming the content and face validity of the scale, a questionnaire including the LKQCHD was distributed to 59 eligible patients aged >16 years attending a university hospital. For the 58 participants who responded (30 males, 28 females; median age 22 years), the mean (±SD) LKQCHD total score was 53.7±15.4, with mean (±SD) scores for each domain as follows: Disease and Treatment, 68.3±19.7; Preventing Complications, 45.8±19.0; Physical Activity, 74.1±34.1; Sex and Heredity, 37.9±35.4; and Contraception and Pregnancy, 40.2±29.1. Regarding known-groups validity, we found a positive correlation between the LKQCHD score and age (ρ=0.268, P=0.042), and a significantly low LKQCHD score in the moderate/severe disease group (η2=0.131, P=0.021). Regarding convergent validity, the LKQCHD score was positively correlated with the total and subscale scores of the Resilience Assessment Tool (r=0.213 [P=0.109] and r=0.405 [P=0.002], respectively). Conclusions: We confirmed the validity of the Japanese version of the LKQCHD, concluding that patient education regarding long-term complications, prevention methods, heredity, pregnancy, and childbirth is needed.

Phenotypes of adults with congenital heart disease around the globe: a cluster analysis.

OBJECTIVE: To derive cluster analysis-based groupings for adults with congenital heart disease (ACHD) when it comes to perceived health, psychological functioning, health behaviours and quality of life (QoL). METHODS: This study was part of a larger worldwide multicentre study called APPROACH-IS; a cross sectional study which recruited 4028 patients (2013-2015) from 15 participating countries. A hierarchical cluster analysis was performed using Ward's method in order to group patients with similar psychological characteristics, which were defined by taking into consideration the scores of the following tests: Sense Of Coherence, Health Behavior Scale (physical exercise score), Hospital Anxiety Depression Scale, Illness Perception Questionnaire, Satisfaction with Life Scale and the Visual Analogue Scale scores of the EQ-5D perceived health scale and a linear analogue scale (0-100) measuring QoL. RESULTS: 3768 patients with complete data were divided into 3 clusters. The first and second clusters represented 89.6% of patients in the analysis who reported a good health perception, QoL, psychological functioning and the greatest amount of exercise. Patients in the third cluster reported substantially lower scores in all PROs. This cluster was characterised by a significantly higher proportion of females, a higher average age the lowest education level, more complex forms of congenital heart disease and more medical comorbidities. CONCLUSIONS: This study suggests that certain demographic and clinical characteristics may be linked to less favourable health perception, quality of life, psychological functioning, and health behaviours in ACHD. This information may be used to improve psychosocial screening and the timely provision of psychosocial care.

Patient-Reported Outcomes in Adults With Congenital Heart Disease Following Hospitalization (from APPROACH-IS).

In this international study, we (1) compared patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) who had versus had not been hospitalized during the previous 12 month, (2) contrasted PROs in patients who had been hospitalized for cardiac surgery versus nonsurgical reasons, (3) assessed the magnitude of differences between the groups (i.e., effect sizes), and (4) explored differential effect sizes between countries. APPROACH-IS was a cross-sectional, observational study that enrolled 4,028 patients from 15 countries (median age 32 years; 53% females). Self-report questionnaires were administered to measure PROs: health status; anxiety and depression; and quality of life. Overall, 668 patients (17%) had been hospitalized in the previous 12 months. These patients reported poorer outcomes on all PROs, with the exception of anxiety. Patients who underwent cardiac surgery demonstrated a better quality of life compared with those who were hospitalized for nonsurgical reasons. For significant differences, the effect sizes were small, whereas they were negligible in nonsignificant comparisons. Substantial intercountry differences were observed. For various PROs, moderate to large effect sizes were found comparing different countries. In conclusion, adults with CHD who had undergone hospitalization in the previous year had poorer PROs than those who were medically stable. Researchers ought to account for the timing of recruitment when conducting PRO research as hospitalization can impact results.

Sense of coherence in adults with congenital heart disease in 15 countries: Patient characteristics, cultural dimensions and quality of life.

BACKGROUND: Previous studies have found that sense of coherence (SOC) is positively related to quality of life (QoL) in persons with chronic conditions. In congenital heart disease (CHD), the evidence is scant. AIMS: We investigated (i) intercountry variation in SOC in a large international sample of adults with CHD; (ii) the relationship between demographic and clinical characteristics and SOC; (iii) the relationship between cultural dimensions of countries and SOC; and (iv) variation in relative importance of SOC in explaining QoL across the countries. METHODS: APPROACH-IS was a cross-sectional, observational study, with 4028 patients from 15 countries enrolled. SOC was measured using the 13-item SOC scale (range 13-91) and QoL was assessed by a linear analog scale (range 0-100). RESULTS: The mean SOC score was 65.5±13.2. Large intercountry variation was observed with the strongest SOC in Switzerland (68.8±11.1) and the lowest SOC in Japan (59.9±14.5). A lower SOC was associated with a younger age; lower educational level; with job seeking, being unemployed or disabled; unmarried, divorced or widowed; from a worse functional class; and simple CHD. Power distance index and individualism vs collectivism were cultural dimensions significantly related to SOC. SOC was positively associated with QoL in all participating countries and in the total sample, with an explained variance ranging from 5.8% in Argentina to 30.4% in Japan. CONCLUSION: In adults with CHD, SOC is positively associated with QoL. The implementation of SOC-enhancing interventions might improve QoL, but strategies would likely differ across countries given the substantial variation in explained variance.

Atrial arrhythmias and patient-reported outcomes in adults with congenital heart disease: An international study.

BACKGROUND: Atrial arrhythmias (ie, intra-atrial reentrant tachycardia and atrial fibrillation) are a leading cause of morbidity and hospitalization in adults with congenital heart disease (CHD). Little is known about their effect on quality of life and other patient-reported outcomes (PROs) in adults with CHD. OBJECTIVE: The purpose of this study was to assess the impact of atrial arrhythmias on PROs in adults with CHD and explore geographic variations. METHODS: Associations between atrial arrhythmias and PROs were assessed in a cross-sectional study of adults with CHD from 15 countries spanning 5 continents. A propensity-based matching weight analysis was performed to compare quality of life, perceived health status, psychological distress, sense of coherence, and illness perception in patients with and those without atrial arrhythmias. RESULTS: A total of 4028 adults with CHD were enrolled, 707 (17.6%) of whom had atrial arrhythmias. After applying matching weights, patients with and those without atrial arrhythmias were comparable with regard to age (mean 40.1 vs 40.2 years), demographic variables (52.5% vs 52.2% women), and complexity of CHD (15.9% simple, 44.8% moderate, and 39.2% complex in both groups). Patients with atrial arrhythmias had significantly worse PRO scores with respect to quality of life, perceived health status, psychological distress (ie, depression), and illness perception. A summary score that combines all PRO measures was significantly lower in patients with atrial arrhythmias (-3.3%; P = .0006). Differences in PROs were consistent across geographic regions. CONCLUSION: Atrial arrhythmias in adults with CHD are associated with an adverse impact on a broad range of PROs consistently across various geographic regions.

Development of a 3D Cell Culture System Using Amphiphilic Polydepsipeptides and Its Application to Hepatic Differentiation.

Various three-dimensional (3D) culture systems are available to provide more accurate in vivo mimicry than two-dimensional (2D) cultures. Synthetic and/or xeno-free biomaterials are desired, as they would provide lower batch-to-batch variability and high repeatability. Here, we introduce a 3D culture system using nanofibers composed of an amphiphilic polydepsipeptide-based polymer named HYDROX, which turns into 3D nanofibers after hydration. Our system produces a large amount of cell aggregates and requires only the seeding of a cell mixture. In addition, cells cultured with HYDROX can be collected with only a centrifugation procedure, and analytical assays can then be performed. Here, we applied HYDROX to hepatic differentiation from induced pluripotent stem cells. The cells cultured with HYDROX formed aggregates and HYDROX strongly promoted hepatic differentiation and maturation in terms of functions such as the positive ratio of alpha-1 antitrypsin, the production of albumin, the cytochrome P450 (CYP) 3A4 activity, and the low-density-lipoprotein uptake ability. In addition, primary human hepatocytes cultured with HYDROX showed significantly improved CYP3A4 gene expression and activity. The viscoelasticity and stiffness of HYDROX can be modulated by varying the concentration of the synthetic polymer, thereby providing a suitable microenvironment for the differentiation of cells with various characteristics toward a target cell type. Our findings demonstrated that HYDROX is a promising biomaterial for 3D cultures in research fields ranging from basic cell research to drug discovery.

Physical Functioning, Mental Health, and Quality of Life in Different Congenital Heart Defects: Comparative Analysis in 3538 Patients From 15 Countries.

BACKGROUND: We compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects. METHODS: In the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect. RESULTS: Patients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%). CONCLUSIONS: Some types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes.

Healthcare system inputs and patient-reported outcomes: a study in adults with congenital heart defect from 15 countries.

BACKGROUND: The relationship between healthcare system inputs (e.g., human resources and infrastructure) and mortality has been extensively studied. However, the association between healthcare system inputs and patient-reported outcomes remains unclear. Hence, we explored the predictive value of human resources and infrastructures of the countries' healthcare system on patient-reported outcomes in adults with congenital heart disease. METHODS: This cross-sectional study included 3588 patients with congenital heart disease (median age = 31y; IQR = 16.0; 52% women; 26% simple, 49% moderate, and 25% complex defects) from 15 countries. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviors, and quality of life. The assessed inputs of the healthcare system were: (i) human resources (i.e., density of physicians and nurses, both per 1000 people) and (ii) infrastructure (i.e., density of hospital beds per 10,000 people). Univariable, multivariable, and sensitivity analyses using general linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences. RESULTS: Sensitivity analyses showed that higher density of physicians was significantly associated with better self-reported physical and mental health, less psychological distress, and better quality of life. A greater number of nurses was significantly associated with better self-reported physical health, less psychological distress, and less risky health behavior. No associations between a higher density of hospital beds and patient-reported outcomes were observed. CONCLUSIONS: This explorative study suggests that density of human resources for health, measured on country level, are associated with patient-reported outcomes in adults with congenital heart disease. More research needs to be conducted before firm conclusions about the relationships observed can be drawn. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150603. Registered 30 May 2014.

Employment status and contributing factors among adults with congenital heart disease in Japan.

BACKGROUND: Working is an important concern in transitional care for adults with congenital heart disease (ACHD) because work connects people with society. Employment status is correlated with gender, but studies on patient employment by gender have rarely been conducted. This study therefore aimed to examine the employment status of ACHD by gender and to explore the factors influencing this status. METHODS: In this study, 193 Japanese ACHD (mean age: men-33.62 years, women-32.69 years; 89 men, no students included) completed a questionnaire including questions about employment status, an evaluation of hindrances to employment, the Linear Analog Scale to assess quality of life (QOL), and the Satisfaction with Life Scale (SWLS). RESULTS: In the study sample, 13 of 89 (14.6%) men and 13 of 104 (12.5%) women did not have a job. These rates were higher than the national standard rates in Japan (men: 5.0%, women: 2.9%). Of these patients, only one man and one woman listed their illness as a reason for their unemployment. The factors thought to explain unemployment were age for men and disease severity for women (P < 0.05 for both). Unemployed patients had significantly lower QOL and SWLS scores. CONCLUSIONS: Most ACHD can join the workforce but a higher percentage of ACHD do not work and find it challenging to have a career compared with the general population. Moreover, because unemployed patients have low QOL and SWLS scores, obtaining work is crucial to enable these people to have mentally and emotionally stable and fulfilling lives.

Health behaviours reported by adults with congenital heart disease across 15 countries.

BACKGROUND: Health behaviours are essential to maintain optimal health and reduce the risk of cardiovascular complications in adults with congenital heart disease. This study aimed to describe health behaviours in adults with congenital heart disease in 15 countries and to identify patient characteristics associated with optimal health behaviours in the international sample. DESIGN: This was a cross-sectional observational study. METHODS: Adults with congenital heart disease (n = 4028, median age = 32 years, interquartile range 25-42 years) completed self-report measures as part of the Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS). Participants reported on seven health behaviours using the Health Behaviors Scale-Congenital Heart Disease. Demographic and medical characteristics were assessed via medical chart review and self-report. Multivariate path analyses with inverse sampling weights were used to investigate study aims. RESULTS: Health behaviour rates for the full sample were 10% binge drinking, 12% cigarette smoking, 6% recreational drug use, 72% annual dental visit, 69% twice daily tooth brushing, 27% daily dental flossing and 43% sport participation. Pairwise comparisons indicated that rates differed between countries. Rates of substance use behaviours were higher in younger, male participants. Optimal dental health behaviours were more common among older, female participants with higher educational attainment while sports participation was more frequent among participants who were younger, male, married, employed/students, with higher educational attainment, less complex anatomical defects and better functional status. CONCLUSIONS: Health behaviour rates vary by country. Predictors of health behaviours may reflect larger geographic trends. Our findings have implications for the development and implementation of programmes for the assessment and promotion of optimal health behaviours in adults with congenital heart disease.

Implantable cardioverter-defibrillators and patient-reported outcomes in adults with congenital heart disease: An international study.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are increasingly being used to prevent sudden death in the growing population of adults with congenital heart disease (CHD). However, little is known about their impact on patient-reported outcomes (PROs). OBJECTIVE: The purpose of this study was to assess and compare PROs in adults with CHD with and without ICDs. METHODS: A propensity-based matching weight analysis was conducted to evaluate PROs in an international cross-sectional study of adults with CHD from 15 countries across 5 continents. RESULTS: A total of 3188 patients were included: 107 with ICDs and 3081 weight-matched controls without ICDs. ICD recipients were an average age of 40.1 ± 12.4 years, and >95% had moderate or complex CHD. Defibrillators were implanted for primary and secondary prevention in 38.3% and 61.7%, respectively. Perceived health status, psychological distress, sense of coherence, and health behaviors did not differ significantly among patients with and without ICDs. However, ICD recipients had a more threatening view of their illness (relative % difference 8.56; P = .011). Those with secondary compared to primary prevention indications had a significantly lower quality-of-life score (Linear Analogue Scale 72.0 ± 23.1 vs 79.2 ± 13.0; P = .047). Marked geographic variations were observed. Overall sense of well-being, assessed by a summary score that combines various PROs, was significantly lower in ICD recipients (vs controls) from Switzerland, Argentina, Taiwan, and the United States. CONCLUSION: In an international cohort of adults with CHD, ICDs were associated with a more threatening illness perception, with a lower quality of life in those with secondary compared to primary prevention indications. However, marked geographic variability in PROs was observed.

Prevalence and Effects of Cigarette Smoking, Cannabis Consumption, and Co-use in Adults From 15 Countries With Congenital Heart Disease.

BACKGROUND: The prevalence and effects of cigarette smoking and cannabis use in persons with congenital heart disease (CHD) are poorly understood. We (1) described the prevalence of cigarette smoking, cannabis consumption, and co-use in adults with CHD; (2) investigated intercountry differences; (3) tested the relative effects on physical functioning, mental health, and quality of life (QOL); and (4) quantified the differential effect of cigarette smoking, cannabis use, or co-use on those outcomes. METHODS: APPROACH-IS was a cross-sectional study, including 4028 adults with CHD from 15 countries. Patients completed questionnaires to measure physical functioning, mental health, and QOL. Smoking status and cannabis use were assessed by means of the Health Behaviour Scale-Congenital Heart Disease. Linear models with doubly robust estimations were computed after groups were balanced with the use of propensity weighting. RESULTS: Overall, 14% of men and 11% of women smoked cigarettes only; 8% of men and 4% of women consumed cannabis only; and 4% of men and 1% of women used both substances. Large intercountry variations were observed, with Switzerland having the highest prevalence for smoking cigarettes (24% of men, 19% of women) and Canada the highest for cannabis use (19% of men, 4% of women). Cigarette smoking had a small negative effect on patient-reported outcomes, and the effect of cannabis was negligible. The effect of co-use was more prominent, with a moderate negative effect on mental health. CONCLUSIONS: We found significant intercountry variability in cigarette and cannabis use in adults with CHD. Co-use has the most detrimental effects on patient-reported outcomes.

Differential impact of physical activity type on depression in adults with congenital heart disease: A multi-center international study.

OBJECTIVE: This study aimed to examine the association between physical activity (PA) and depression in a large international cohort of adults with congenital heart disease (ACHD) as data about the differential impact of PA type on depression in this population are lacking. METHODS: In 2018, we conducted a cross-sectional assessment of 3908 ACHD recruited from 24 ACHD-specialized centers in 15 countries between April 2013 to March 2015. The Hospital Anxiety and Depression Scale was used to assess self-reported depressive symptoms and the Health-Behavior Scale-Congenital Heart Disease was used to collect PA information. Cochran-Armitage tests were performed to assess trends between depressive symptom levels and PA participation. Chi-Square and Wilcoxon Rank Sum tests were utilized to examine relations between depressive symptom levels and patient characteristics. Stepwise multivariable models were then constructed to understand the independent impact of PA on depressive symptoms. RESULTS: The overall prevalence of elevated depressive symptoms in this sample was 12% with significant differences in rates between countries (p < .001). Physically active individuals were less likely to be depressed than those who were sedentary. Of the 2 PA domains examined, sport participation rather than active commute was significantly associated with reduced symptoms of depression. After adjustment in multivariable analysis, sport participation was still significantly associated with 38% decreased probability of depressive symptoms (p < .001). CONCLUSIONS: Sport participation is independently associated with reduced depressive symptoms. The development and promotion of sport-related exercise prescriptions uniquely designed for ACHD may improve depression status in this unique population.

Tailored cell sheet engineering using microstereolithography and electrochemical cell transfer.

Postoperative adhesion and occlusion remain a serious issue associated with various surgeries, including endoscopic surgery, in which proliferated fibrous tissues stick to adjacent tissues and often cause severe complications. Cell sheet engineering has emerged as an effective approach not only for cell transplantation but also for the treatment of postoperative adhesion and occlusion. However, as the tissues in the body, such as middle ear and small intestine, and typical operative sites are non-flat and spatially complicated, tailored cell sheets with three-dimensional (3D) configurations may lead to widespread use of this approach. In the present study, we used microstereolithography, biocompatible gold plating, and electrochemical cell detachment to achieve this purpose. Various objects with dimensions ranging from millimeter- to micrometer-scale were fabricated with photocurable resin using lab-made equipment for microstereolithography. To coat the fabricated objects with a thin gold layer, conventional cyanide-based gold plating was unusable because it severely damaged almost all cells. Electroless non-cyanide gold plating we prepared was cytocompatible and suitable for electrochemical cell detachment. Cell sheets on the gold-plated substrate could be directly transplanted into a mouse intraperitoneally using electrochemical cell detachment. We further demonstrated that cell sheets grown on gold-coated 3D objects were rapidly detached along with the desorption of electroactive-oligopeptide monolayer and transferred to a surrounding hydrogel. This approach may provide a promising strategy to prepare and directly transplant tailor-made cell sheets with suitable configurations.

Perceived Health Mediates Effects of Physical Activity on Quality of Life in Patients With a Fontan Circulation.

Patients with a Fontan circulation are at risk of a sedentary lifestyle. Given the direct relationship between physical activity and health, promotion of physical activity has the potential to improve outcomes, including quality of life (QOL). This study aimed to describe self-reported physical activity levels in adult Fontan patients and examine associations between physical activity, perceived health status and QOL. The sample consisted of 177 Fontan patients (Mage = 27.5 ± 7.6 years, 52% male) who reported their physical activity, perceived health status, and QOL as part of the cross-sectional Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study. Descriptive statistics and univariate analyses of variance with planned contrasts were computed to describe physical activity characteristics. Mediation analyses tested whether perceived health status variables mediated the association between physical activity and QOL. Forty-six percent of patients were sedentary while only 40% met international physical activity guidelines. Higher physical activity was associated with younger age, lower NYHA class, higher perceived general health, and greater QOL. Patients who commuted by walking and engaged in sports reported better perceived health and QOL. Mediation analyses revealed that perceived general health but not NYHA functional class mediated the association between physical activity and QOL (αß = 0.22, 95% confidence interval = 0.04 to 0.49). In conclusion, Fontan patients likely benefit from regular physical activity, having both higher perceived general health and functional capacity; greater perceived health status may contribute to enhanced QOL. In conclusion, these data support the pivotal role of regular physical activity for Fontan patients.