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Anticoagulation Management in Adult Patients with Congenital Heart Disease: a Narrative Review

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Anticoagulation Management in Adult Patients with Congenital Heart Disease: a Narrative Review 10 Review Article Anticoagulation management in adult patients with congenital heart disease: a narrative review Christoph Sinning1,2,3#^, Elvin Zengin1,3#, Stefan Blankenberg1,2, Carsten Rickers3, Yskert von Kodolitsch1, Gerhard Diller4*, Paulus Kirchhof1,2,5* 1Department of Cardiology, University Heart & Vascular Center Hamburg, Hamburg, Germany; 2German Center for Cardiovascular Science (DZHK) Hamburg/Lübeck/Kiel, Hamburg, Germany; 3Adult Congenital Heart Disease Section, University Heart Center Hamburg, Hamburg, Germany; 4Department of Cardiology III, University Hospital Münster, Münster, Germany; 5Institute of Cardiovascular Sciences and SWBH and UHB NHS Trusts, Birmingham, UK Contributions: (I) Conception and design: C Sinning, E Zengin, P Kirchhof, G Diller; (II) Administrative support: S Blankenberg, Y von Kodolitsch; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: C Sinning, E Zengin; (V) Data analysis and interpretation: C Sinning, E Zengin, P Kirchhof, G Diller; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors contributed equally as first author. *These authors contributed equally as senior authors. Correspondence to: Christoph Sinning, MD. Department of Cardiology, University Heart & Vascular Center Hamburg, Martinistr. 52, Germany. Email: [email protected]. Abstract: With improvements in treatment of congenital heart disease more paediatric patients are surviving with palliative or corrective interventions during childhood, thus becoming adults with congenital heart disease (ACHD). Overall, the ACHD population is at a higher risk of arrhythmias and stroke. The abnormal structure and function of their corrected hearts suggests that in addition to established stroke risk factors, such as prior stroke or older age, additional stroke risk factors need to be considered to determine the risk and establish the indication for oral anticoagulation (OAC) in ACHD patients. In structurally normal hearts non-vitamin-K oral anticoagulants (NOACs) offer at least equal stroke prevention with a better safety profile compared to vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) or pulmonary embolism. Current guidelines recommend NOACs in ACHD patients with simple lesions and indication for OAC, while there is less certainty about their safety in ACHD patients with moderate or complex congenital heart disease such as patients with transposition of the great arteries (TGA) after atrial switch operation (Senning or Mustard operation), Fontan circulation or congenital corrected transposition of the great arteries (ccTGA). This review summarises the available evidence characterising stroke risk in patients with ACHD and the use of anticoagulants and interventional therapies to reduce that risk. Keywords: Adults with congenital heart disease (ACHD); arrhythmias; non-vitamin-K oral anticoagulants; vitamin K antagonists; oral anticoagulation (OAC); CHA2DS2-VASc Score Submitted Jul 10, 2020. Accepted for publication Sep 29, 2020. doi: 10.21037/cdt-20-631 View this article at: http://dx.doi.org/10.21037/cdt-20-631 ^ ORCID: 0000-0002-7331-8840. © Cardiovascular Diagnosis and Therapy. All rights reserved. Cardiovasc Diagn Ther 2020 | http://dx.doi.org/10.21037/cdt-20-631 2 Sinning et al. Cardiac catheterization by real-time CMR Background Ease of use and wide-spread knowledge of the score underscore its usefulness, although the predictive ability The number of adults with congenital heart disease (ACHD) is modest. More recently, biomarkers have been proposed is steadily increasing as a consequence of new treatment (e.g., troponin, BNP, GDF-15, and others) to refine options and advances in medicine (1-3) as the number of stroke risk prediction (17,18). Thus, there is still a gap newborns with CHD remains constant (4). ACHD patients of studies addressing this issue in ACHD patients, who currently account for about two-thirds of the patient are much younger than patients with AF and are likely to population with CHD (5), Compared to about one-half³ at have a higher stroke risk. Unfortunately, risk of stroke and the beginning of the new millennium. Even severe CHD is embolism can only be roughly estimated based on results becoming more prevalent in adults, as shown by data from of single-centre studies or data with expert consensus level Quebec (5,6). In this context further morbidity in these from current guidelines for planning treatment. We present patients in regards of arrhythmias, stroke or pulmonary the following article in accordance with the Narrative embolism increases as well (Figure 1). Review reporting checklist (available at http://dx.doi. Arrhythmias, heart failure, pulmonary embolism and org/10.21037/cdt-20-631). stroke are the most common reasons for unplanned hospital admission in patients with congenital heart disease. Patients with ACHD also have a markedly increased risk of stroke Objectives compared to the general population (7-10). ACHD patients The objective of this review to summarize the different aged of 55 years or younger had a stroke rate 9 to 12 times indications for oral anticoagulation (OAC) in adult patients higher than in the general population, and 1 in 11 male with congenital heart disease. In addition the most recent and 1 in 15 female of the ACHD patients with ages from study results were included and how these may contribute 18 to 64 years had a reported stroke (11,12). According to to a better algorithm in patient selection for a certain previous studies, the ischemic stroke rate is 28.4 per 100,000 underlying congenital heart defect. Further a focus of the person years with ACHD in comparison to a control review is to give examples of special situations were OAC population with a stroke rate of 2.6 per 100,000 person might be indicated for example implantation of a prosthetic years (8). The same is true for reported haemorrhagic stroke heart valve or anticoagulation has to be carefully planned with 1.18 per 10,000 person years in ACHD patients (7). like during pregnancy. Most commonly treatment is complicated by comorbidities like heart failure, arrhythmias, arterial hypertension or impaired organ function of liver or kidneys (13). Although Methods prevention of stroke and pulmonary embolism has Literature search traditionally relied on vitamin K antagonists (VKA) such as warfarin, recent guidelines suggest the use of non-vitamin A literature search was performed in PubMed covering K oral anticoagulants (NOAC) in patients with ACHD publications up to April 2020. The following combinations of presenting with atrial fibrillation (AF), stroke or pulmonary keywords were used: anticoagulation and CHD, morbidity embolism (1,14). This is equally true for the highly and mortality in ACHD, guidelines anticoagulation and prevalent arrhythmias described in the ACHD cohort with ACHD, guidelines diagnostic and treatment of patients atrial flutter (AFl) and intraatrial tachycardias resulting with congenital heart disease. These search terms had to be from previous surgical procedures (1,14). In addition, identified anywhere in the text in the articles. The authors patients with certain complex congenital heart disease are at as well did choose literature depicting the current guidelines high risk of embolic complications even without diagnosed or multicenter trials, however most of the literature are arrhythmias. This includes patients with a univentricular of observational studies and guidelines for patients with heart in Fontan circulation, atrial switch operation for ACHD have the evidence level of expert opinion. transposition of the great arteries, or ACHD with advanced Both qualitative and quantitative studies were considered heart failure and associated complications (15,16). to elucidate the use of the different aspects regarding The CHA2DS2-VASc score, or an abbreviated version congenital heart disease, anticoagulation and combination without sex as an additional factor are recommended for of both. The search was restricted to original research, initial stroke risk estimation in patients with AF (1,14). humans, and papers published in English at any date. All © Cardiovascular Diagnosis and Therapy. All rights reserved. Cardiovasc Diagn Ther 2020 | http://dx.doi.org/10.21037/cdt-20-631 Cardiovascular Diagnosis and Therapy, 2020 3 Moderate complexity a. Anomalous pulmonary vein Complex lesions Simple complexity return (partial or total) a. All cyanotic heart diseases a. Isolated congenital mitral b. Atrioventricular septal defect (including Tetralogy of valve disease (partial or complete) Fallot) b. Isolated congenital aortic c. Coarctation of the aorta b. Fontan procedure valve disease (complex lesion) c. Mitral atresia c. Atrial septal defect d. Ebstein anomaly d. Tricuspid atresia d. Ventricular septal defect e. Moderate to severe e. Pulmonary atresia e. Patent ductus arteriosus pulmonary valve f. Single ventricle physiology f. Coarctation of the aorta stenosis/regurgitation g. Transposition of the great (simple lesion) f. Sinus venosus defect arteries g. Subaortic stenosis h. Heterotaxy syndromes h. Stradling mitral or tricuspid valve Increasing morbidity and mortality of the congenital heart defect Figure 1 Grading the complexity of congenital lesions with the prevalence and morbidity/mortality of ACHD patients. ACHD, adults with congenital heart disease. abstracts were reviewed to assess whether the article met ACHD patients the occurrence of stroke was associated with the inclusion criteria.
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