Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated. METHODS AND RESULTS: A cross-sectional descriptive study examining 98 stable adult patients with CCHD with a medical questionnaire, blood samples, MRI of the cerebrum (n=72), multidetector CT imaging (MDCT) of the thorax (n=76) and pulmonary scintigraphy (ventilation/perfusion/single-photon emission computerised tomography/CT) (n=66). The prevalence of cerebral infarction and pulmonary thrombosis according to imaging were 47% and 31%, respectively. Comparing the findings with previous medical history revealed a large under-reporting of thrombosis with only 22% of the patients having a clinical history of stroke and 25% of pulmonary thrombosis. There was no association between the degree of erythrocytosis or haemostatic abnormalities and the prevalence of thrombosis. CONCLUSIONS: Patients with CCHD have a prevalence of both cerebral and pulmonary thrombosis of around 30%-40%, which is much higher than that reported previously. Furthermore, there is a large discrepancy between clinical history and imaging findings, suggesting a high prevalence of silent thrombotic events. Neither erythrocytosis nor haemostatic abnormalities were associated with the prevalence of thrombosis in patients with CCHD. TRIAL REGISTRATION NUMBER: http://www.cvk.sum.dk/CVK/Home/English.aspx (H-KF-2006-4068).

Anticoagulation in adults with congenital heart disease: The who, the when and the how?

Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts. Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable recommendations for which patients are likely to benefit from which anticoagulation treatments, when they should be considered and how these would be carried out.

Socioeconomic status and cutaneous malignant melanoma in Northern Europe.

Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM) in Northern Europe, despite equal access to health care. SES per se is not responsible for this association, which must be ascribed to important risk factors for CMM such as intermittent ultraviolet radiation (UVR) exposure, and screening for CMM possibly owing to a greater knowledge and understanding of CMM. Our review of the literature showed that high SES is associated with increased risk of CMM, thinner tumours, increased survival and decreased mortality from CMM - the latter shown among women, and in recent studies also among men. There is evidence that high SES is associated with sun holidays, whereas low SES is associated with the use of sunbeds. Findings suggest that high SES is associated with the use of physicians and dermatologists for marks and moles, possibly owing to more knowledge and better understanding of CMM. We conclude that there has been a true increase in CMM incidence among high SES individuals in Northern Europe probably due to past intense intermittent UVR exposure, especially in connection with sun holidays. However, the increased risk of CMM and a better outcome of CMM in high SES individuals may also be conditioned by frequent recourse to physicians, which may be ascribed to more knowledge and better understanding of CMM, although more studies on this subject are warranted. Thicker CMM tumours and increased CMM mortality among low SES individuals in recent decades may reflect exposure to intermittent UVR, such as the use of sunbeds, as well as delayed diagnosis.

The actual management of common arrhythmias and other ECG abnormalities in children.

Primary cardiac arrhythmias are much less common in infants and children than adults and the symptoms presented may be vague and nonspecific. Though true emergencies due to unstable arrhythmias in children are rare it is critical to identify and appropriately manage these arrhythmias, since when left untreated, arrhythmias may lead to cardiopulmonary compromise and arrest. Most children with a primary arrhythmia present to a pediatrician, cardiologists, or emergency physicians before being referred to a pediatric cardiologist for assessment and management. Thus, the pediatricians, cardiologists, and emergency physicians have to be able to recognize the arrhythmia and in some cases to provide the acute treatment. This article is intended to provide diagnostic and management guidelines of the most common types of arrhythmias seen in children with structurally normal hearts.

Arrhythmia and exercise intolerance in Fontan patients: current status and future burden.

BACKGROUND: Long-term survival after the Fontan procedure shows excellent results but is associated with a persistent risk of arrhythmias and exercise intolerance. We aimed to analyze the current burden of clinically relevant arrhythmia and severe exercise intolerance in Danish Fontan patients and furthermore, to estimate the future burden from analysis of mortality and the current burden related to age. METHODS: All Danish citizens with Fontan completion from 1981 to 2009 were identified (n=235). Surviving patients performed exercise test, Holter monitoring, echocardiography, pulmonary function test, and blood sampling and medical history was retrieved from medical records. RESULTS: Twenty-six (11%) patients died or had heart transplantation (HTx) after a mean (± SD) post-Fontan follow-up of 8.3 ± 5.7 years. Excluding perioperative deaths (n=8), a linear probability of HTx-free survival was observed and estimated to 99.1% per year. Prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age and was found in 32% and 85% of patients ≥ 20 years, respectively. Thus, from survival data and logistic regression models the future prevalence of patients, clinically relevant arrhythmia and severe exercise intolerance were estimated, revealing a considerable augmentation. Furthermore, resting and maximum cardiac index, resting stroke volume index and pulmonary diffusing capacity decreased significantly with age while diastolic and systolic ventricular function was unchanged. CONCLUSIONS: The prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age in Danish Fontan patients. The future Fontan burden was estimated showing an increase in the prevalence of older patients, clinically relevant arrhythmia, and severe exercise intolerance.

The haematocrit--an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease(CCHD) have haemostatic abnormalities, which result in an increased risk of bleeding. The cause is unknown, but recent studies have indicated that an elevated haematocrit, which is present in cyanotic patients, could be an important factor. The aim of this study was to characterize the haemostatic profile, examine how changes in haematocrit affect the haemostatic profile, and whether a haematocrit reduction could terminate bleeding in CCHD patients. METHODS: This was a prospective, multicenter study. The haemostatic profile consisting of haematocrit, platelet count and thrombelastography(TEG) was characterized in ninety-eight CCHD patients. To evaluate the influence of haematocrit on the haemostatic profile, 21 of the patients underwent phlebotomy and 16 patients received treatment with an iron supplement. Furthermore ten patients with haemoptysis underwent phlebotomy. The haemostatic profile was reevaluated after interventions. RESULTS: TEG revealed that patients with CCHD and elevated haematocrit were hypocoagulable due to reduced clot formation and strength. Furthermore a positive correlation between elevated haematocrit and hypocoagulability was present. Interventions such as phlebotomy and treatment with supplemental iron causing significant haematocrit changes confirmed the correlation between haematocrit and the haemostatic profile. Finally a haematocrit reduction by phlebotomy successfully terminated haemoptysis in ten CCHD patients. CONCLUSION: Patients with CCHD and elevated haematocrit are hypocoagulable. The hypocoagulable haemostatic profile is positively correlated to increasing haematocrit. An intervention, which increases or decreases haematocrit, changes the haemostatic profile. A haematocrit reduction seems to improve the haemostatic profile, and may thereby terminate bleeding. However, these results warrant further studies.

Univentricular hearts in Denmark 1977 to 2009: incidence and survival.

BACKGROUND: The incidence of children born with functional univentricular heart (UVH) and their prognosis presumably changed substantially in recent years. This is due to introduction of fetal echocardiography and potential termination of pregnancy (TOP) when UVH is diagnosed (UVH TOP), and to improvements in treatment. We aimed to explore changes in incidence, to estimate changes in survival, and to describe predictors of mortality in UVH patients. METHODS: Using a population-based design we identified all UVH cases in Denmark from 1977 to 2009. RESULTS: 703 UVH live births and 106 UVH TOP were identified. A dramatic decrease in birth incidence of UVH patients and a corresponding increase in UVH TOP was observed in recent years. Mean incidence rate of UVH (live births and UVH TOP) was 0.39 per 1000 births. In adjusted analysis survival improved significantly from birth era 1977-1989 to 1990-1999 (HR 2.65, 95% confidence interval (CI), 2.06-3.42) but not significantly from 1990-1999 to 2000-2009 (HR 0.77, 95% CI, 0.57-1.05). In the birth era 2000-2009, the lowest five-year survival was seen with hypoplastic left heart syndrome (HLHS) (18.8%), whereas the best survival was seen with tricuspid atresia (79.8%). Adjusted risk of death was 7.3 times higher in the HLHS group compared to the tricuspid atresia group (95% CI, 3.94-13.47). CONCLUSIONS: This study demonstrates a dramatic decrease in birth incidence of UVH patients most probably due to a corresponding increase in UVH TOP. Despite survival improved after introduction of Fontan surgery, survival has not improved significantly during the last 20years.

Thromboembolic complications in Fontan patients: population-based prevalence and exploration of the etiology.

After the Fontan procedure, patients face an increased risk for thromboembolic events (TE). The etiology for this increased thrombogenecity is incompletely understood. This study aimed to determine the prevalence of TE in Danish Fontan patients and to bring new insights into the etiology of TE. Using a population-based design, we retrospectively identified all TEs in 210 Fontan patients. Whole blood assays (thromboelastography, thromboelastography functional fibrinogen and Multiplate) reflecting global hemostasis, clot strength and platelet aggregation were analyzed prospectively in 112 patients and plasma was analyzed in 76 patients for biomarkers reflecting endothelial-, glycocalyx-, platelet-, and fibrinolysis function (histone-complexed DNA fragments, Protein C, soluble CD40 ligand, soluble thrombomodulin, syndecan-1, tissue-type plasminogen activator). The results were compared in groups stratified according to age, antithrombotic therapy, TE, and glycocalyx degradation (syndecan-1 < or ≥ median). Correlation between biomarkers and demographic-, anatomical-, clinical- and biochemical parameters was investigated. The prevalence of TE was 8.1 % after a mean follow-up of 8.4 years. None of the stratified groups demonstrated evidence of hypercoagulability in the whole blood assays and no unexpected significant differences were found between the groups. All biomarkers, except protein C, correlated with one another and after stratification of glycocalyx degradation only syndecan-1 levels ≥ median correlated with other biomarkers. The prevalence of TEs was 8.1 % after mean follow-up of 8.4 years. Overall, the hemostatic profile appeared normal, however, in a subset of patients, evidence of some endothelial activation/damage including glycocalyx degradation and fibrinolysis was found, identifying a potentially more thrombogenic group.

Fibrinogen function is impaired in whole blood from patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have haemostatic abnormities associated with bleeding and thrombo-embolic events. The haemostatic abnormalities are not fully understood, but recent studies indicate that elevated haematocrit and fibrinogen function may be of importance. The aim of this study was to characterise the haemostatic profile and examine the potential role of haematocrit on clot formation and strength in CCHD patients. Furthermore to examine whether CCHD patients with history of haemoptysis have diminished fibrinogen function compared to those without haemoptysis. METHODS: In a prospective study 75 adult CCHD patients had haematocrit, platelet count, and plasma fibrinogen concentration examined. Furthermore thrombelastography(TEG) as well as TEG Functional Fibrinogen(TEG FF) assay evaluating fibrinogen function(FLEV) was performed. Data were compared with historical data regarding previous haemoptysis in CCHD patients. RESULTS: Haematocrit was 57 ± 8% and platelet counts in the lower normal range. TEG revealed a hypocoagulable condition with impaired clot formation. TEG values were correlated to haematocrit, indicating that elevated haematocrit causes impaired clot formation and strength. Despite high levels of plasma fibrinogen, TEG FF demonstrated that FLEV was diminished and negatively correlated to haematocrit. Furthermore CCHD patients with previous history of haemoptysis had significantly lower FLEV compared to CCHD patients without haemoptysis. CONCLUSION: Patients with CCHD are hypocoagulable mainly due to impaired fibrinogen function. Despite a low platelet count, platelet function does not seem to be severely affected in CCHD patients. Haemostasis, and especially fibrinogen function, is negatively affected by elevated haematocrit, and fibrinogen function is diminished in CCHD patients with haemoptysis.

Sun behaviour after cutaneous malignant melanoma: a study based on ultraviolet radiation measurements and sun diary data.

BACKGROUND: It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. OBJECTIVES: In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun behaviour. METHODS: The study population consisted of 24 patients recently diagnosed with CMM during the 7 months preceding the start of the study; 51 controls who matched these recently diagnosed patients in age, sex, occupation and constitutive skin type; and 29 patients diagnosed with CMM between 12 months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. RESULTS: The UVR dose of recently diagnosed patients on days with body exposure was one-third lower, and the number of days using sunscreen was double that of matched controls. However, in patients diagnosed more than 12 months earlier, the UVR dose on days with body exposure was one-third higher and the number of days using sunscreen was half that of recently diagnosed patients. CONCLUSIONS: Patients with CMM limited their UVR dose on days with body exposure, and by using sunscreen further reduced UVR reaching the skin, although only immediately after diagnosis.

Sun exposure before and after a diagnosis of cutaneous malignant melanoma: estimated by developments in serum vitamin D, skin pigmentation and interviews.

BACKGROUND: Previous studies on ultraviolet radiation (UVR) exposure before and after a diagnosis of cutaneous malignant melanoma (CMM) have been based primarily on questionnaires. Objective measures are needed. OBJECTIVES: To assess changes in UVR exposure in patients with CMM using objective surrogate parameters in a descriptive study. METHODS: Ten patients recently diagnosed with CMM during the 5 months (autumn and winter) preceding study start in February 2009; 21 patients diagnosed from 12 months to 6 years before study start; and 15 controls, who matched the recently diagnosed patients on age, sex, residential area, constitutive skin type and occupation completed the investigations. UVR exposure before and after diagnosis of CMM was assessed using measures of serum 25-hydro vitamin D [25(OH)D], skin pigmentation and by interviews. Winter 25(OH)D was used as a surrogate parameter of UVR exposure the previous summer - the summer before CMM diagnosis in recently diagnosed patients. RESULTS: Winter 25(OH)D was significantly higher among recently diagnosed patients compared with controls (P = 0·02, R² = 0·60) and patients diagnosed up to 6 years earlier (P = 0·01). The increase in 25(OH)D during the summer after diagnosis was significantly lower for recently diagnosed patients than for controls (P = 0·005, R² = 0·51) and patients diagnosed up to 6 years earlier (P = 0·008). No difference was found in summer 25(OH)D between the groups. CONCLUSIONS: Our findings suggest that patients with CMM had a higher UVR exposure the summer before diagnosis than did controls and patients diagnosed up to 6 years earlier, and that after diagnosis UVR exposure fell to the level of controls in patients with CMM.