False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis

Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a significant delay in diagnosis when the awareness for presenting symptoms of cystic fibrosis declines. Neonatal cholestasis is one of the presenting symptoms of cystic fibrosis but can be easily missed when total parenteral nutrition has been given. Premature newborns are probably more at risk of a missed underlying diagnosis than term babies because their co-pathologies and management are often more complex. We present a case of a 10-week-old premature boy with a false negative newborn screening for cystic fibrosis, in whom cystic fibrosis presented with neonatal cholestasis. In this case, the immunoreactive trypsinogen/pancreatitis-associated protein/35 cystic fibrosis transmembrane regulator mutation analysis/sequencing method was used. Furthermore, an overview of the literature on missed diagnosis of cystic fibrosis due to a false negative newborn screen is provided. Cystic fibrosis (CF) should be considered in infants with neonatal cholestasis even when the newborn screening for CF is reported to be negativ

Weighing the risks: Thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease

Atrial arrhythmias are associated to thromboembolism and anticoagulant treatment is installed according to risk profile. This study aimed to assess the rate of thrombotic events and major bleedings in adults with congenital heart disease (CHD) and atrial arrhythmias, as well as to determine the predictive value of specific clinical features and two risk scores for thromboembolism and bleeding. In this retrospective study, a total of 229 adult CHD patients with atrial arrhythmias, were included. Incidence and risk factors of thromboembolism were assessed in patients without a mechanical valve (n = 191), whereas bleeding incidence and risk factors were studied in patients receiving vitamin K antagonists (n = 164). In 13 patients without a mechanical valve thrombotic events occurred, the first thrombotic event rate per year being 1.4%. A total of 29 patients on vitamin K antagonists suffered from major bleedings, at an annual first event rate of 4.4%. CHA2DS2-VASc score and HAS-BLED score predicted thromboembolic and bleeding risk best in a dichotomized form. At a cut-off of ≥ 2 for high risk the rate of thrombotic events was 3.0% per year compared to 0.7% for a score of <2 (HR 3.7; 95%-CI 1.2-11.5; p = 0.021). A major bleeding rate of 10.8% per year was found in patients on vitamin K antagonists for HAS-BLED ≥ 2 as opposed to 3.5% with a score of <2 (HR 2.6; 95%-CI: 1.1-6.6; 0.017). In adult CHD patients, thrombotic events and major bleedings are important complications of atrial arrhythmias and anticoagulant treatment. Assessment of thromboembolic and bleeding risk in this patients group can be performed with dichotomized CHA2DS2-VASc and HAS-BLED scores respectivel

Coagulation and Anticoagulation in Fontan Patients

Patients with a Fontan circulation for single-ventricle physiology are at increased risk of developing thromboembolic events. Thromboembolic events can lead to failure of the Fontan circulation, chronic sequelae in case of stroke, and early mortality. Controversies exist regarding the substrates, risk factors, and optimal detection methods for thromboembolic events. Despite the major clinical implications, there is currently no consensus regarding the optimal antithrombotic therapy to prevent or treat thromboembolic events after the Fontan procedure. In this review we aimed to untangle the available literature regarding antithrombotic prophylaxis and treatment for pediatric and adult Fontan patients. A decision-tree algorithm for thromboprophylaxis in Fontan patients is proposed. Additionally, the current state of knowledge is reviewed with respect to the epidemiology, pathophysiology, and detection of thromboembolic events in Fontan patients, and important evidence gaps are highlighted

Oral anticoagulant therapy in adults with congenital heart disease and atrial arrhythmias: Implementation of guidelines

Background: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. Methods: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. Results: In total, 225 adults (mean age 54 ± 15 years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54–80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc ≥ 1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n = 15) could not be demonstrated. Conclusions: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc ≥ 1 or Fontan circulation

Oral anticoagulant therapy in adults with congenital heart disease and atrial arrhythmias: Implementation of guidelines

Background: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. Methods: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. Results: In total, 225 adults (mean age 54 ± 15 years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54–80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc ≥ 1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n = 15) could not be demonstrated. Conclusions: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc ≥ 1 or Fontan circulation

Oral anticoagulant therapy in adults with congenital heart disease and atrial arrhythmias : Implementation of guidelines

Background: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. Methods: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. Results: In total, 225 adults (mean age 54 ± 15 years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54–80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc ≥ 1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n = 15) could not be demonstrated. Conclusions: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc ≥ 1 or Fontan circulation

Is Initiating NOACs for Atrial Arrhythmias Safe in Adults with Congenital Heart Disease?

Background: In recent years, non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have been increasingly prescribed to adults with congenital heart disease (CHD) and atrial arrhythmias without good evidence for either safety or efficacy. To address this gap, we initiated an ongoing prospective global registry (NOTE: non-vitamin K antagonist oral anticoagulants for thromboembolic prevention in patients with congenital heart disease). Using the NOTE registry data, the present study aimed to evaluate the occurrence of any adverse events during the initiation phase (first 30 days) of NOACs in adults with CHD and atrial arrhythmias. Methods and Results: For this prospective observational study, 99 adults with CHD and atrial arrhythmias (median age 49 years [IQR 38-61], 53% male) who initiated NOACs at or after the inclusion point were analysed. Thromboembolic events, major bleeding and other minor adverse events were assessed after the first 30 days since the initiation of NOACs. In 54 patients transitioning from VKA to NOACs, 8 minor adverse events (5 minor bleeding; 3 side-effects; 1 drop-out due to minor bleeding) occurred within 30 days after the transition. No adverse events were reported in 46 VKA-naive patients within 30 days after the initiation of NOACs. Conclusions: Initiation of NOACs and transition from VKA to NOACs seem to be safe during the first month, without major adverse events and with only limited minor side effects in adults with CHD and atrial arrhythmias. This global ongoing prospective registry enables precise collection of important clinical information in real-world adults with CHD, managed with NOACs