Heart failure in patients with congenital heart disease after a cancer diagnosis.

AIMS: Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. METHODS: CHD patients (n = 69 799) and randomly selected non-CHD controls (n = 650 406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n = 1309) were propensity score-matched with non-CHD patients who developed cancer (n = 9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non-CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score-matched with CHD patients without cancer (n = 68 490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. RESULTS: Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow-up time of 8.5 ± 8.7. Comparatively, in the propensity-matched control population, 29 (1.1%) non-CHD cancer patients (mean follow-up time of 7.3 ± 7.5) and 101 (4.5%) CHD patients without cancer (mean follow-up time of 9.9 ± 9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post-cancer diagnosis compared with the non-CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83-6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13-2.07). CONCLUSIONS: CHD patients face a more than four-fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non-CHD cancer patients, may be more attributable to CHD itself than to cancer treatment-related side effects.

Outcomes after cancer diagnosis in children and adult patients with congenital heart disease in Sweden: a registry-based cohort study.

OBJECTIVE: Patients with congenital heart disease (CHD) have an increased cancer risk. The aim of this study was to determine cancer-related mortality in CHD patients compared with non-CHD controls, compare ages at cancer diagnosis and death, and explore the most fatal cancer diagnoses. DESIGN: Registry-based cohort study. SETTING AND PARTICIPANTS: CHD patients born between 1970 and 2017 were identified using Swedish Health Registers. Each was matched by birth year and sex with 10 non-CHD controls. Included were those born in Sweden with a cancer diagnosis. RESULTS: Cancer developed in 758 out of 67814 CHD patients (1.1%), with 139 deaths (18.3%)-of which 41 deaths occurred in patients with genetic syndromes. Cancer was the cause of death in 71.9% of cases. Across all CHD patients, cancer accounted for 1.8% of deaths. Excluding patients with genetic syndromes and transplant recipients, mortality risk between CHD patients with cancer and controls showed no significant difference (adjusted HR 1.17; 95% CI 0.93 to 1.49). CHD patients had a lower median age at cancer diagnosis-13.0 years (IQR 2.9-30.0) in CHD versus 24.6 years (IQR 8.6-35.1) in controls. Median age at death was 15.1 years (IQR 3.6-30.7) in CHD patients versus 18.5 years (IQR 6.1-32.7) in controls. The top three fatal cancer diagnoses were ill-defined, secondary and unspecified, eye and central nervous system tumours and haematological malignancies. CONCLUSIONS: Cancer-related deaths constituted 1.8% of all mortalities across all CHD patients. Among CHD patients with cancer, 18.3% died, with cancer being the cause in 71.9% of cases. Although CHD patients have an increased cancer risk, their mortality risk post-diagnosis does not significantly differ from non-CHD patients after adjustements and exclusion of patients with genetic syndromes and transplant recipients. However, CHD patients with genetic syndromes and concurrent cancer appear to be a vulnerable group.

Corrigendum to "Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017)" [The Lancet Regional Health-Europe 18 (2022) 100407].

[This corrects the article DOI: 10.1016/j.lanepe.2022.100407.].

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Mortality in Patients With Ebstein Anomaly.

BACKGROUND: Low birth prevalence and referral bias constitute significant obstacles to elucidating the natural history of Ebstein anomaly (EA). OBJECTIVES: An extensive 2-country register-based collaboration was performed to investigate the mortality in patients with EA. METHODS: Patients born from 1970 to 2017 and diagnosed with EA were identified in Danish and Swedish nationwide medical registries. Each patient was matched by birth year and sex with 10 control subjects from the general population. Cumulative mortality and HR of mortality were computed using Kaplan-Meier failure function and Cox proportional regression model. RESULTS: The study included 530 patients with EA and 5,300 matched control subjects with a median follow-up of 11 years. In the EA cohort, 43% (228) underwent cardiac surgery. Cumulative mortality was lower for patients diagnosed in the modern era (the year 2000 and later) than for those diagnosed in the prior era (P < 0.001). Patients with isolated lesion displayed lower cumulative mortality than patients with complex lesions did (P < 0.001). Patients with a presumed mild EA anatomy displayed a 35-year cumulative mortality of 11% (vs 4% for the matched control subjects; P < 0.001), yielding an HR for mortality of 6.0 (95% CI: 2.7-13.6), whereas patients with presumed severe EA demonstrated an HR of 36.2 (95% CI: 15.5-84.4) compared with control subjects and a cumulative mortality of 18% 35 years following diagnosis. CONCLUSIONS: Mortality in patients with EA is high irrespective of presence of concomitant congenital cardiac malformations and time of diagnosis compared with the general population, but overall mortality has improved in the contemporary era.

Survival Trends in Children With Tetralogy of Fallot in Sweden From 1970 to 2017.

Importance: Mortality in patients with tetralogy of Fallot (TOF) has decreased substantially since the start of surgical correction of this abnormality in the 1950s. However, nationwide data in Sweden comparing survival trends among pediatric patients with TOF with the general population are still limited. Objective: To study survival trends in pediatric patients with TOF and compare them with matched controls. Design, Setting, and Participants: A Swedish registry-based, nationwide, matched cohort study was conducted; data were collected from national health registers from January 1, 1970, to December 31, 2017. Patients with a registered diagnosis of TOF as well as controls without TOF matched by birth year and sex were included in the study. Follow-up data were collected from birth to age 18 years, death, or the end of follow-up (December 31, 2017), whichever occurred first. Data analysis was performed from September 10 to December 20, 2022. Survival trends among patients with TOF were compared with matched controls using Cox proportional hazards regression and Kaplan-Meier survival analyses. Main Outcomes and Measures: All-cause mortality during childhood in patients with TOF and matched controls. Results: The population included 1848 patients (1064 [57.6%] males; mean [SD] age, 12.4 [6.7] years) with TOF and 16 354 matched controls. The number of patients who underwent congenital cardiac surgery (henceforth, surgery group) was 1527 (897 [58.7%] males). In the whole TOF population from birth until age 18 years, 286 patients (15.5%) died during a mean (SD) follow-up time of 12.4 (6.7) years. In the surgery group, 154 of 1527 patients (10.1%) died during a follow-up time of 13.6 (5.7) years with a mortality risk of 21.9 (95% CI, 16.2-29.7) compared with matched controls. When stratified by birth period, a substantial decrease in the mortality risk was noted in the surgery group, from 40.6 (95% CI, 21.9-75.4) in those born in the 1970s to 11.1 (95% CI, 3.4-36.4) in those born in the 2010s. Survival increased from 68.5% to 96.0%. The risk of mortality for surgery decreased from 0.52 in the 1979s to 0.19 in the 2010s. Conclusions and Relevance: The findings of this study suggest there has been substantial improvement in survival in children with TOF who underwent surgery from 1970 to 2017. However, the mortality rate is still significantly higher in this group compared with matched controls. Predictors of good and poor outcomes in this group need to be further explored, with the modifiable ones evaluated for further outcome improvements.

Transcatheter Intervention for Coarctation of the Aorta: A Nordic Population-Based Registry With Long-Term Follow-Up.

BACKGROUND: Coarctation of the aorta (CoA), a congenital narrowing of the proximal descending thoracic aorta, is a relatively common form of congenital heart disease. Untreated significant CoA has a major impact on morbidity and mortality. In the past 3 decades, transcatheter intervention (TCI) for CoA has evolved as an alternative to surgery. OBJECTIVES: The authors report on all TCIs for CoA performed from 2000 to 2016 in 4 countries covering 25 million inhabitants, with a mean follow-up duration of 6.9 years. METHODS: During the study period, 683 interventions were performed on 542 patients. RESULTS: The procedural success rate was 88%, with 9% considered partly successful. Complications at the intervention site occurred in 3.5% of interventions and at the access site in 3.5%. There was no in-hospital mortality. During follow-up, TCI for CoA reduced the presence of hypertension significantly from 73% to 34%, but despite this, many patients remained hypertensive and in need of continuous antihypertensive treatment. Moreover, 8% to 9% of patients needed aortic and/or aortic valve surgery during follow-up. CONCLUSIONS: TCI for CoA can be performed with a low risk for complications. Lifetime follow-up after TCI for CoA seems warranted.

Patient selection for long-term secondary prevention with ticagrelor: insights from PEGASUS-TIMI 54.

AIM: In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor. METHODS AND RESULTS: PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups. CONCLUSION: In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk. CLINICAL TRIAL REGISTRATION: NCT01225562 ClinicalTrials.gov.

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

BACKGROUND: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. OBJECTIVES: The authors aimed to determine factors associated with survival in a large cohort of such individuals. METHODS: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017).

Background: Increasing survival of patients with congenital heart disease (CHD) will result in an increased risk of age-dependent acquired diseases later in life. We aimed to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation and cardiac surgery. Methods: Patients with CHD born between 1930 and 2017 were identified using Swedish Health Registers. Each patient with CHD (n = 89,542) was matched by sex and birth year with ten controls without CHD (n = 890,472) from the Swedish Total Population Register. Findings: 4012 patients with CHD (4·5%) and 35,218 controls (4·0%) developed cancer. The median follow-up time was 58·8 (IQR 42·4-69·0) years. The overall cancer risk was 1·23 times higher (95% confidence interval (CI) 1·19-1·27) in patients with CHD compared with matched controls, and remained significant when patients with syndromes and organ transplant recipients were excluded. The risk of cancer was higher in all CHD age groups, and in patients that underwent cardiac surgery during the first year after birth (Hazard Ratio 1·83; 95% CI 1·32-2·54). The highest risk was found in children (0-17 years), HR 3·21 (95% CI 2·90-3·56). Interpretation: The cancer risk in patients with CHD was 23% higher than in matched controls without CHD. The highest risk was found in children and in the latest birth cohort (1990-2017). Funding: Funding by the Swedish state (Grant Number: 236611), the Swedish Research Council (Grant Number: 2019-00193), the Swedish Childhood Cancer Fund (Grant Number: SP2017-0012) and the Swedish Heart-Lung Foundation (Grant Number: 20190724).

Outcome and survival after open heart surgery for adults with congenital heart disease - a single center experience.

Introduction. Congenital heart disease (CHD) is the most common type of birth defect today. The adult congenital heart disease (ACHD) population is constantly growing and becoming older and more patients require cardiac surgery. The objective of this study was to review the surgical outcome of the open heart procedures performed on ACHD patients in the last 10 years at Sahlgrenska University Hospital (SUH) through a retrospective descriptive cohort study. Methods. A retrospective data collection was performed for 421 patients who underwent a total of 439 surgical procedures between 2009 and 2018 at the Cardiothoracic department in SUH. The primary outcomes were early (<30 days) and late survival. Secondary outcomes were postoperative complications and independent risk factors for postoperative complications. Results. 30-day mortality was 1.9%. Long-term survival after 3, 5 and 10 years were 96% ± 1, 94.3% ± 1.3 and 92.4% ± 1.8. 82 major complications occurred after 46 procedures (11.6%). The most common major complication was re-exploration due to hemorrhage. Risk factors for major complications were acute surgery and prolonged extracorporeal circulation time. 173 minor complications occurred after 90 procedures (22.5%). The most common minor complication was prolonged intensive care unit stay (>48 h). Conclusion. This study presents satisfactory early and midterm survival. The survival and frequency of major postoperative complications are well in line with what other studies have presented. Patients undergoing resternotomies had no increased risk for mortality or postoperative complications.

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.

Mortality burden in patients born with Ebstein's anomaly: a 40-year nationwide cohort study.

AIMS: Survival rates for unoperated patients with Ebstein's anomaly (EA) are unknown. We estimated overall long-term mortality in operated and unoperated EA patients, compared with the general population in Sweden. METHODS AND RESULTS: Using national medical registries, Swedish individuals born 1970-93 and diagnosed with EA between 1970 and 2011 were included. The hazard ratio for overall mortality for EA patients (n = 216) vs. the matched comparison cohort (n = 2160) was 43.7 [95% confidence interval (CI): 24.8-82.5]. Mortality risk for EA patients (vs. controls) decreased as birth period progressed, with hazard ratios declining from 63.6 (95% CI: 26.3-191.8) for those born in the 1970s to 34.4 (95% CI: 15.8-83.1) for those born in the 1980s and 20.2 (95% CI: 1.6-632.5) for those born at the beginning of 1990s. The overall mortality hazard ratios for unoperated and operated patients with EA (vs. controls) were 30.2 (95% CI: 13.8-73.3) and 63.7 (95% CI: 28.1-172.5), respectively. The risk of mortality among unoperated EA patients (vs. controls) declined with progressing birth period, with hazard ratios declining from 58.4 (95% CI: 15.1-415.2) in the 1970s to 22.9 (95% CI: 8.0-75.3) in the 1980s and 10.2 (95% CI: 0.3-395.9) in the 1990s. CONCLUSION: Overall all-cause mortality for patients with EA declined dramatically from 64 times to 20 times that of controls without EA, from the 1970s to the early 1990s. Unoperated patients with EA had better survival than did operated patients, possibly reflecting the higher severity of disease or more severe associated cardiac defects in patients undergoing surgery.

Secular trends in cardiovascular risk factors among women aged 45-54 years in Gothenburg, Sweden, from 1980 to 2014.

BACKGROUND: A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34 years. METHODS: Six population-based, cross-sectional samples of women (n = 2294) mean age: 49.8 years (range: 45-54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. RESULTS: Body mass index (BMI) increased over time, with a mean BMI of 24.7 kg/m2 in 1980 to 25.7 kg/m2 in 2013-2014, corresponding to a weight gain of 4.5 kg, together with an increase in the proportion of obese individuals (BMI ≥ 30 kg/m2) from 10.4 to 16.6% (p = 0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p = 0.0006) and from 37.7 to 24.5% (p < 0.0001) respectively. Mean total serum cholesterol levels decreased from 6.23 (SD 1.09) mmol/L in 1980 to 5.43 (SD 0.98) mmol/L in 2013-2014 (p < 0.0001). Self-reported leisure time regular exercise increased from 7.8% in 1980 to 35.6% in 2013-2014 (p < 0.0001). For women born in 1963, the prevalence ratio of not having any of five major cardiovascular risk factors was 1.82 (95% confidence interval (CI) 1.38-2.41), compared with women born in 1925-1934. CONCLUSION: The trend towards increasing obesity, more leisure-time physical activity and less smoking remains, while the decrease in serum cholesterol appears to have abated.

Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial.

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P=0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.

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.

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.

Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls.

Importance: Adult patients with congenital heart disease (CHD) have an increased incidence of cancer, presumably owing to repeated radiation exposure, genetic predisposition, or repeated stress factors during heart interventions. However, there are limited data on the risk of cancer in children and young adults with CHD compared with the general population. Objective: To determine the risk of developing cancer from birth to age 41 years among patients with CHD compared with healthy matched controls. Design, Setting, and Participants: This registry-based, matched, prospective cohort study in Sweden used data from the Patient and Cause of Death Registers. Successive cohorts of patients with CHD born from 1970 to 1979, 1980 to 1989, and 1990 to 1993 were identified. Each patient (n = 21 982) was matched for birth year, sex, and county with 10 controls without CHD from the general population (n = 219 816). Follow-up and comorbidity data were collected from 1970 until 2011. Data analysis began in September 2018 and concluded in February 2019. Main Outcomes and Measures: Risk of cancer among children and young adults with CHD and among healthy controls. Results: Among 21 982 individuals with CHD and 219 816 healthy matched controls, 428 patients with CHD (2.0%) and 2072 controls (0.9%) developed cancer. Among patients with CHD, the mean (SD) age at follow-up was 26.6 (8.4) years, and 11 332 participants (51.6%) were men. Among healthy controls, the mean (SD) age at follow-up was 28.5 (9.1) years, and 113 319 participants (51.6%) were men. By the age of 41 years, 1 of 50 patients with CHD developed cancer. The overall hazard ratio (HR) for cancer was 2.24 (95% CI, 2.01-2.48) in children and young adults with CHD compared with controls. Risk increased by each successive birth cohort to an HR of 3.37 (95% CI, 2.60-4.35) among those born from 1990 to 1993. The risk of cancer was similar in men and women with CHD (men: HR, 2.41; 95% CI, 2.08-2.79; women: HR, 2.08; 95% CI, 1.80-2.41). The HR for cancer among patients with CHD who underwent surgery was 1.95 (95% CI, 1.58-2.33) compared with controls; for patients with CHD who had not undergone surgery, the HR was 2.43 (95% CI, 2.12-2.76). According to a hierarchical classification, a significantly increased risk of cancer was found among patients with complex heart lesions, such as conotruncal defects (HR, 2.29; 95% CI, 1.62-3.25), compared with healthy controls. Conclusions and Relevance: Children and young adult patients with CHD had an increased risk of developing cancer compared with healthy matched controls, and the risk was significantly higher among patients with CHD from the most recent birth cohort. An increased risk of cancer in all CHD lesion groups was found, and a systematic screening for cancer could be considered for this at-risk group of patients.

Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.

AIMS: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment. METHODS AND RESULTS: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58). CONCLUSION: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT01225562.

Cardiovascular risk factors in adults with coarctation of the aorta.

BACKGROUND: The aging patient with adult congenital heart disease (ACHD) faces the risk of developing atherosclerotic disease. Patients with coarctation of the aorta (CoA) are especially vulnerable because of an inherent high risk of developing hypertension. However, data on the prevalence of other cardiovascular risk factors are scarce. Therefore, this study aimed to describe the prevalence of traditional cardiovascular risk factors (diabetes, hypertension, hyperlipidemia, smoking, obesity, and sedentary lifestyle) in adult patients with CoA. METHODS: Patients with CoA who were registered at the ACHD clinic in Gothenburg were asked to participate in a comprehensive cardiovascular risk assessment. This assessment included a glucose tolerance test, cholesterol profile, ambulatory blood pressure measurements, and a lifestyle questionnaire. RESULTS: A total of 72 patients participated. The median age was 43.5 years and 58.3% were men. Sixty-six (91.7%) patients had ≥one cardiovascular risk factor and 40.3% had ≥three risk factors. Three (4.2%) patients were newly diagnosed with diabetes or impaired glucose tolerance. More than half of the patients had hyperlipidemia (n = 42, 58.3%) and 35 patients (48.6%) were overweight or obese. Only three (4.2%) patients smoked regularly. Of the 60 patients who underwent 24-hour ambulatory blood pressure measurement, 33 (55.0%) were hypertensive. Of the 30 patients with known hypertension only 9 (30.0%) had well-controlled blood pressure on ambulatory blood pressure measurement. CONCLUSIONS: Cardiovascular risk factors among patients with CoA are prevalent. This may indicate a need for more aggressive screening strategies of traditional risk factors to minimize the risk of these patients also developing atherosclerotic disease.