Secundum atrial septal defect is associated with reduced survival in adult men.

AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients. METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43). CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.

Sex differences in hospital mortality in adults with congenital heart disease: the impact of reproductive health.

OBJECTIVES: The study objectives were to analyze sex differences in hospital mortality of adult patients with congenital heart disease (CHD) and to determine the impact of health services associated with pregnancy on outcomes in women. BACKGROUND: The determinants of sex differences in the demographic distribution of CHD are poorly understood. METHODS: The Quebec CHD database and the Dutch CONCOR (CONgenital CORvitia) registry were used to identify patients with CHD aged 18 to 65 years who were hospitalized between 1996 and 2005. Regression analyses were used to compare 30-day in-hospital mortality in men versus women and in women aged 18 to 45 years with versus without a pregnancy history, after adjustment for age, CHD severity, comorbidities, and admission diagnosis. RESULTS: Of 39,776 patients followed for 259,741 patient years, 19,099 patients (48%) had 54,195 admissions (62% among women). In those aged 18 to 45 years, 30-day in-hospital mortality was higher in men compared with women with nonpregnancy admissions (adjusted rate ratio: 1.36; 95% confidence interval: 1.02 to 1.81). The adjusted rate ratio for 30-day in-hospital mortality in women with a pregnancy history compared with those without was 0.49 (95% confidence interval: 0.24 to 0.99). A history of pregnancy was not associated with an overall increase in medical encounters. CONCLUSIONS: We demonstrated a protective effect of sex on in-hospital mortality in women with CHD of reproductive age that did not correlate with increased medical surveillance. Future studies need to explore other mechanisms to account for our observations. Understanding the determinants of the sex distribution of adults with CHD is important for our ability to predict demographic changes in the population with CHD.

Social burden and lifestyle in adults with congenital heart disease.

We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group.

Circumstances of death in adult congenital heart disease.

BACKGROUND: Circumstances of death have been described for various cardiovascular diseases, but this study is the first for adults with congenital heart disease (CHD). METHODS: Review of medical records and additional information from treating cardiologists and general practitioners, for circumstances of all deaths in a national registry of over 8000 adults with CHD. RESULTS: Of 8595 patients, 231 (2.7%) patients died over 26,500 patient years. Main causes of death were progressive heart failure (26%) and sudden cardiac death (22%). Mortality was highest in the northern, most rural region of the country (p ≤ 0.05). Overall, death occurred out-of-hospital in approximately 35%, but more frequently in rural than in urban areas (55% versus 32%, p ≤ 0.05). Mortality was almost equally distributed throughout the seasons, although fall showed a slightly higher mortality rate. Cardiovascular death occurred suddenly in nearly 40%. Sudden cardiovascular death occurred in 8% during exercise, and most often out-of-hospital (62%). Of non-sudden cardiovascular deaths 18% had occurred out-of-hospital. CONCLUSION: In adult patients with congenital heart disease, mortality shows substantial regional and subtle seasonal variation. Death usually occurs at rest; approximately 1 of 10 sudden cardiovascular deaths occur during exercise.

Triggering mechanisms of stent thrombosis.

AIMS: The aim of this study was to determine the role of potential triggers of stent thrombosis. METHODS AND RESULTS: Patients (n = 437) with "definite" ST were recruited consecutively in the setting of a large multicentre observational cohort study. Patients were interviewed with validated questionnaires to identify one of the following triggers: i) timing of onset of ST, ii) performance of vigorous ( ≥ 6 MET) physical activity in the two hours preceding ST, iii) presence of emotional stress (experiencing a serious life event in the 14 days preceding the ST or feelings of anger in the 12 hours of ST) and iv) presence of a documented active infection at the time of ST. A total of 363 patients (83.1%) were able to supply adequate information. A significant trigger was identified in 83 patients (22.9%). Analysis of the different categories according to timing of ST revealed a higher prevalence of triggers with an increasing time-interval between index PCI and ST. Analysis of circadian variation showed a steep peak incidence from 7 am-12 pm. CONCLUSIONS: Triggering mechanisms such as time of the day, physical exertion, emotional stress and infection may play an important role in a considerable number of patients presenting with ST, in particular in patients with (very) late ST.

Mortality in adult congenital heart disease: are national registries reliable for cause of death?

BACKGROUND: Statistics on cause-specific mortality are important for prognostic research. The aim of this study was to assess the utility of the national mortality registry in research on causes of death in adult patients with congenital heart disease (CHD). METHODS: The CONCOR registry of over 10,000 adults with CHD was used to verify the causes of death provided by the WHO guidelines based national mortality registry, by linkage. RESULTS: Of 7277 patients linked to the national mortality registry, 196 (2.4%) were recorded deceased, versus 228 deceased patients (3.1%) recorded in the CONCOR registry, during a follow-up of 25,900 patient years. Median age at death was 48.9 years. Of all deaths in the CONCOR registry, 77% had a cardiovascular origin; nearly 50% were due to progressive heart failure and arrhythmias. The national mortality registry recorded death due to progressive heart failure and arrhythmias in only 8.5%. Moreover, this registry recorded death with an 'unspecified' cause in approximately 30%, primarily containing patients who died due to progressive heart failure and arrhythmias according to their medical records. CONCLUSION: WHO guidelines based national mortality registries lack the specificity and completeness needed for accurate research on causes of death in adult patients with CHD.

The changing epidemiology of congenital heart disease.

Congenital heart disease is the most common congenital disorder in newborns. Advances in cardiovascular medicine and surgery have enabled most patients to reach adulthood. Unfortunately, prolonged survival has been achieved at a cost, as many patients suffer late complications, of which heart failure and arrhythmias are the most prominent. Accordingly, these patients need frequent follow-up by physicians with specific knowledge in the field of congenital heart disease. However, planning of care for this population is difficult, because the number of patients currently living with congenital heart disease is difficult to measure. Birth prevalence estimates vary widely according to different studies, and survival rates have not been well recorded. Consequently, the prevalence of congenital heart disease is unclear, with estimates exceeding the number of patients currently seen in cardiology clinics. New developments continue to influence the size of the population of patients with congenital heart disease. Prenatal screening has led to increased rates of termination of pregnancy. Improved management of complications has changed the time and mode of death caused by congenital heart disease. Several genetic and environmental factors have been shown to be involved in the etiology of congenital heart disease, although this knowledge has not yet led to the implementation of preventative measures. In this Review, we give an overview of the etiology, birth prevalence, current prevalence, mortality, and complications of congenital heart disease.

The influence of clinical characteristics, laboratory and inflammatory markers on 'high on-treatment platelet reactivity' as measured with different platelet function tests.

High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are independently associated with an increased risk of atherothrombotic events. However, despite this positive correlation, the definitions of both HCPR and HAPR vary largely throughout studies and between different platelet function assays. The aim of the present study was to explore clinical and laboratory parameters that are associated with HCPR and HAPR as measured with different platelet function tests. 530 clopidogrel and aspirin pre-treated patients undergoing elective PCI (percutaneous coronary intervention) were enrolled. Platelet function measurements were performed with: optical aggregometry, the VerifyNow device and PFA-100 cartridges (including the novel INNOVANCE P2Y assay). HCPR as measured with Adenosin-Di-Phospate-induced (ADP) aggregation based tests was associated with clinical factors such as older age, female gender and Diabetes mellitus (DM). The VerifyNow P2Y12 assay was significantly influenced by haemoglobin and haematocrit levels. HAPR as measured with aggregation based tests was significantly influenced by the presence of malignancy, BMI (Body-Mass Index), older age and increased levels of hsCRP (high sensitivity c-reactive proteine). The PFA-100 COL/EPI (collagen-epinephrine) and COL/ADP (collagen-ADP) cartridges were significantly influenced by monocyte count, hs-CRP, MPV (mean platelet volume), vWF-antigen (von Willebrand factor) and vWF-activity. HCPR as measured with the novel INNOVANCE P2Y cartridge was associated with clinical determinants such as BMI, female gender, impaired LVEF (left ventricular ejection fraction), renal failure and dosing of clopidogrel. Laboratory markers that were associated with HCPR as measured with INNOVANCE P2Y were platelet count, white blood cells (WBC), hsCRP and fibrinogen. Both HCPR and HAPR are highly dependent on the type of platelet function assay. Each platelet function assay, in turn, is significantly influenced by distinct clinical and laboratory variables.

Time does not heal every wound: coronary stent thrombosis of a bare-metal stent more than one decade after its implantation.

In the present report, we describe a unique case of very late stent thrombosis with a bare-metal stent that occurred more than a decade after stent implantation. Potential explanations for the late stent thrombosis are non-compliance to aspirin, late acquired malapposition of the stent, progression of atherosclerosis or in-stent restenosis. In our patient, none of these explanations seems to have played a role. Although the occurrence of (very) late stent thrombosis is not uncommon with drug-eluting stent (DES), it is rather unusual with bare-metal stent (BMS). Nevertheless, cardiologists should be aware of the potential complication of late stent thrombosis, even with bare-metal stents.

Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry.

OBJECTIVES: This study sought to comprehensively identify predictors of stent thrombosis (ST). BACKGROUND: Given the devastating consequences of ST, efforts should be directed toward risk stratification to identify patients at highest risk for ST. METHODS: Consecutive patients with angiographic ST were enrolled. Patients who did not suffer from a ST were randomly selected in a 2:1 ratio and were matched for: 1) percutaneous coronary intervention (PCI) indication; 2) same date of index PCI; and 3) same interventional center. RESULTS: Of 21,009 patients treated with either a bare-metal or drug-eluting stent, 437 patients (2.1%) presented with a definite ST. A total of 140 STs were acute, 180 were subacute, 58 were late, and 59 were very late. Undersizing of the coronary stent, Thrombolysis In Myocardial Infarction flow grade <3, present malignancy, presence of intermediate coronary artery disease proximal and distal to the culprit lesion, dissection, lack of aspirin, bifurcation lesions, ejection fraction <30%, and younger age were associated with ST. The lack of clopidogrel therapy at the time of ST in the first 30 days after the index PCI (hazard ratio [HR]: 36.5, 95% confidence interval [CI]: 8.0 to 167.8), between 30 days and 6 months after the index PCI (HR: 4.6, 95% CI: 1.4 to 15.3), and beyond 6 months (HR: 5.9, 95% CI: 1.7 to 19.8) after the index PCI was strongly associated with ST. CONCLUSIONS: Important correlates of ST were identified. Discontinuation of clopidogrel, undersizing of the coronary stent, present malignancy, and intermediate (>or=50% to <70% stenosis) coronary artery disease proximal to the culprit lesion were the strongest predictors of ST.