Applicability of a supramaximal high-intensity interval training program for older adults previously not engaged in regular exercise; analyses of secondary outcomes from the Umeå HIT Study.

This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6-20), and affective state (Feeling Scale, FS -5-5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (-1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults.

Breastfeeding in primiparous women with congenital heart disease - a register study.

BACKGROUND: The number of pregnant women with congenital heart disease (CHD) is rising, and the disease poses increased risks of cardiovascular and obstetric complications during pregnancy, potentially impacting breastfeeding success. This study aimed to investigate breastfeeding in primiparous women with CHD compared to primiparous women without CHD, and to examine potential hindering factors for breastfeeding in women with CHD. METHODS: The data were gathered between 2014 and 2019 and obtained by merging the Swedish Congenital Heart Disease Register (SWEDCON) with the Swedish Pregnancy Register. Primiparous women ≥ 18 years of age with CHD (n = 578) were matched by age and municipality to 3049 women without CHD, giving birth after 22 gestational weeks. Multivariable logistic regression analysis was used to identify factors associated with non-breastfeeding in women with CHD. RESULTS: Fewer women with CHD breastfed than women without CHD two days (94% vs. 97%, p = 0.001) and four weeks after birth (84% vs. 89%, p = 0.006). When all women were analysed, having CHD was associated with non-breastfeeding at both two days and four weeks after birth. For women with CHD, body mass index (BMI) ≥ 30 (OR 3.1; 95% CI 1.4, 7.3), preterm birth (OR 6.4; 95% CI 2.1, 19.0), self-reported history of psychiatric illness (OR 2.4; 95% CI 1.2, 5.1), small for gestational age (OR 4.2; 95% CI 1.4, 12.2), and New York Heart Association Stages of Heart Failure class II - III (OR 6.0; 95% CI 1.4, 26.7) were associated with non-breastfeeding two days after birth. Four weeks after birth, factors associated with non-breastfeeding were BMI ≥ 30 (OR 4.3; 95% CI 2.1, 9.0), self-reported history of psychiatric illness (OR 2.2; 95% CI 1.2, 4.2), and preterm birth (OR 8.9; 95% CI 2.8, 27.9). CONCLUSIONS: The study shows that most women with CHD breastfeed, however, at a slightly lower proportion compared to women without CHD. In addition, factors related to the heart disease were not associated with non-breastfeeding four weeks after birth. Since preterm birth, BMI ≥ 30, and psychiatric illness are associated with non-breastfeeding, healthcare professionals should provide greater support to women with CHD having these conditions.

Frailty and Cognitive Function in Middle-Aged and Older Adults With Congenital Heart Disease.

BACKGROUND: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential. OBJECTIVES: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits. METHODS: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment. RESULTS: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income. CONCLUSIONS: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.

Time to childbirth and assisted reproductive treatment in women with congenital heart disease.

OBJECTIVE: To investigate the time to first childbirth and to compare the prevalence of assisted reproductive treatment (ART) in women with congenital heart disease (CHD) compared with women without CHD. METHODS: All women in the national register for CHD who had a registered first childbirth in the Swedish Pregnancy Register between 2014 and 2019 were identified. These individuals (cases) were matched by birth year and municipality to women without CHD (controls) in a 1:5 ratio. The time from the 18th birthday to the first childbirth and the prevalence of ART was compared between cases and controls. RESULTS: 830 first childbirths in cases were identified and compared with 4137 controls. Cases were slightly older at the time for first childbirth (28.9 vs 28.5 years, p=0.04) and ART was more common (6.1% vs 4.0%, p<0.01) compared with controls. There were no differences in ART when stratifying for the complexity of CHD. For all women, higher age was associated with ART treatment (OR 1.24, 95% CI 1.20 to 1.28). CONCLUSIONS: Women with and without CHD who gave birth to a first child did so at similar ages. ART was more common in women with CHD, but disease severity did not influence the need for ART. Age was an important risk factor for ART also in women with CHD and should be considered in consultations with these patients.

Symptoms during pregnancy in primiparous women with congenital heart disease.

Background: As more women with congenital heart disease (CHD) are reaching childbearing age, it becomes more common for their symptoms to be evaluated during pregnancy. However, pregnancy-related symptoms are similar to those caused by heart disease. This study investigated the prevalence of factors associated with symptoms during pregnancy in women with CHD. Methods: The national birth register was searched for primiparous women with CHD who were registered in the national quality register for patients with CHD. Results: Symptoms during the third trimester were reported in 104 of 465 evaluated women. The most common symptom was palpitations followed by dyspnea. Factors associated with symptoms were tested in a univariable model; higher NYHA classification (>1) (OR 11.3, 95%CI 5.5-23.2), low physical activity (≤3 h/week) (OR 2.1 95%CI 1.3-3.6) and educational level ≤ 12 years (OR 1.9 95%CI 1.2-3.0) were associated with having symptoms. In multivariable analysis, low physical activity level (OR 2.4 95%CI 1.2-5.0) and higher NYHA class (OR 11.3 95%CI 5.0-25.6) remained associated with symptoms during pregnancy. There were no cases with new onset of impaired systemic ventricular function during pregnancy. Conclusion: Symptoms during pregnancy are common in women with CHD but are often already present before pregnancy. Because ordinary symptoms during pregnancy often overlap with symptoms of heart disease, it is important to know if symptoms were present before pregnancy and if they became worse during pregnancy. These results should be included in pre-pregnancy counselling and considered in the monitoring during pregnancy.

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).

Intraoperative Radiation Therapy Delivered by Brachytherapy in Breast Cancer: An Interim Analysis of a Phase 2 Trial.

PURPOSE: Intraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method METHODS: Eligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan-Meier curve. RESULTS: Until February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient. CONCLUSION: Acknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

Self-rated health in primiparous women with congenital heart disease before, during and after pregnancy - A register study.

Background. Poor maternal self-rated health in healthy women is associated with adverse neonatal outcomes, but knowledge about self-rated health in pregnant women with congenital heart disease (CHD) is sparse. This study, therefore, investigated self-rated health before, during, and after pregnancy in women with CHD and factors associated with poor self-rated health. Methods. The Swedish national registers for CHD and pregnancy were merged and searched for primiparous women with data on self-rated health; 600 primiparous women with CHD and 3062 women in matched controls. Analysis was performed using descriptive statistics, chi-square test and logistic regression. Results. Women with CHD equally often rated their health as poor as the controls before (15.5% vs. 15.8%, p = .88), during (29.8% vs. 26.8% p = .13), and after pregnancy (18.8% vs. 17.6% p = .46). None of the factors related to heart disease were associated with poor self-rated health. Instead, factors associated with poor self-rated health during pregnancy in women with CHD were ≤12 years of education (OR 1.7, 95%CI 1.2-2.4) and self-reported history of psychiatric illness (OR 12.6, 95%CI 1.4-3.4). After pregnancy, solely self-reported history of psychiatric illness (OR 5.2, 95%CI 1.1-3.0) was associated with poor self-rated health. Conclusion. Women with CHD reported poor self-rated health comparable to controls before, during, and after pregnancy, and factors related to heart disease were not associated with poor self-rated health. Knowledge about self-rated health may guide professionals in reproductive counselling for women with CHD. Further research is required on how pregnancy affects self-rated health for the group in a long-term perspective.

Adipokines are possible risk markers for aortic stenosis requiring surgery.

OBJECTIVES: Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR). DESIGN: In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents. RESULTS: Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92-1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08-1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82-1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64-0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI). CONCLUSIONS: The adipokine leptin may promote the development of AS.

Pulmonary function in a cohort of heart-healthy individuals from Northern Sweden-a comparison with discordant reference values.

BACKGROUND: Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects. METHODS: The study population consisted of 285 healthy adults (148 males, 52%) between 20-90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model. RESULTS: No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models. CONCLUSIONS: Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study.

Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.

AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS: A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION: Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

Effects of Controlled Supramaximal High-Intensity Interval Training on Cardiorespiratory Fitness and Global Cognitive Function in Older Adults: The Umeå HIT Study-A Randomized Controlled Trial.

BACKGROUND: This study examined the effects of regulated and controlled supramaximal high-intensity interval training (HIT) adapted for older adults, compared to moderate-intensity training (MIT), on cardiorespiratory fitness; cognitive, cardiovascular, and muscular function; and quality of life. METHODS: Sixty-eight nonexercising older adults (66-79 years, 44% males) were randomized to 3 months of twice-weekly HIT (20-minute session including 10 × 6-second intervals) or MIT (40-minute session including 3 × 8-minute intervals) on stationary bicycles in an ordinary gym setting. Individualized target intensity was watt controlled with a standardized pedaling cadence and individual adjustment of the resistance load. Primary outcomes were cardiorespiratory fitness (V̇o2peak) and global cognitive function (unit-weighted composite). RESULTS: V̇o2peak increased significantly (mean 1.38 mL/kg/min, 95% CI [0.77, 1.98]), with no between-group difference (mean difference 0.05 [-1.17, 1.25]). Global cognition did not improve (0.02 [-0.05, 0.09]), nor differed between groups (0.11 [-0.03, 0.24]). Significant between-group differences in change were observed for working memory (0.32 [0.01, 0.64]), and maximal isometric knee extensor muscle strength (0.07 N·m/kg [0.003, 0.137]), both in favor of HIT. Irrespective of the group, there was a negative change in episodic memory (-0.15 [-0.28, -0.02]), a positive change in visuospatial ability (0.26 [0.08, 0.44]), and a decrease in systolic (-2.09 mmHg [-3.54, -0.64]) and diastolic (-1.27 mmHg [-2.31, -0.25]) blood pressure. CONCLUSIONS: In nonexercising older adults, 3 months of watt-controlled supramaximal HIT improved cardiorespiratory fitness and cardiovascular function to a similar extent as MIT, despite half the training time. In favor of HIT, there was an improvement in muscular function and a potential domain-specific effect on working memory. CLINICAL TRIAL REGISTRATION: NCT03765385.

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.

Sex differences and risk factors for bleeding in Alagille syndrome.

Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.

Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.

BACKGROUND AND AIMS: The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. METHODS: A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. RESULTS: The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. CONCLUSION: There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.

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.

Interventions in Adults With Repaired Coarctation of the Aorta.

Background Coarctation of the aorta coexists with other cardiac anomalies and has long-term complications, including recoarctation, which may require intervention after the primary coarctation repair. This study aims to clarify the prevalence of and risk factors for interventions related to the coarctation complex as well as late mortality in a large contemporary patient population. Methods and Results The Swedish National Register of Congenital Heart Disease was used, which comprised 683 adults with repaired coarctation of the aorta. Analysis was performed on freedom from intervention thereafter at the coarctation site, aortic valve, left ventricular outflow tract, or ascending aorta. One hundred ninety-six (29%) patients had at least 1 of these interventions. Estimated freedom from either of these interventions was 60% after 50 years. The risk of undergoing such an intervention was higher among men (hazard ratio, 1.6 [95% CI, 1.2-2.2]). Estimated freedom from another intervention at the coarctation site was 75% after 50 years. In women, there was an increase in interventions at the coarctation site after 45 years. Patients who underwent one of the previously mentioned interventions after the primary coarctation repair had poorer left ventricular function. Eighteen patients (3%) died during follow-up in the register. The standardized mortality ratio was 2.9 (95% CI, 1.7-4.3). Conclusions Interventions are common after coarctation repair. The risk for and time of interventions are affected by sex. Our results have implications for planning follow-up and giving appropriate medical advice to the growing population of adults with repaired coarctation of the aorta.

Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries.

Background Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short- (<10 years), mid- (10-20 years), and long-term (>20 years) follow-up after the operation. Methods and Results This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively. Conclusions Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.

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.