Antithrombotic therapy for patients with congenital heart disease. George Giannakoulas, MD, PhD AHEPA University Hospital Thessaloniki

Transcription

1 Antithrombotic therapy for patients with congenital heart disease George Giannakoulas, MD, PhD AHEPA University Hospital Thessaloniki

2 Disclosures Educational fees from Astra Zeneca, GSK Research fees from ΒΙΑΝΕΞ

3 22/162 pts (13.6%) had 29 cerebrovascular events Systemic hypertension, atrial fibrillation, microcytosis (MCV<82) and history of phlebotomy were independent risk factors Ammash et al. JACC 1996

4 Indications for antithrombotic therapy in congenital heart disease (CHD) Mechanical or bioprosthetic valves Atrial arrhythmias Issues specific to CHD Blalock-Taussig shunts Fontan circulation Cyanosis/Eisenmenger syndrome Conduits, stents and closure devices

5 Special issues when discussing antithrombotics in ACHD ACHD heterogeneity No large RCTs Low level of evidence in scientific guidelines Different pharmacokinetics of drugs in children, right heart failure or single ventricle physiology

6 Prosthetic and native valve disease

7 Refers to AVR and MVR Not a word for PVR (majority of patients seen in a congenital heart disease tertiary center)!

8 Atrial arrhythmias

9 N= % had atrial arrhythmia HR 2.50 for any adverse event HR 1.47 for mortality HR 1.55 for stroke

10 Issues specific for congenital heart disease

11 Blalock-Taussig shunts

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13 Fontan circulation

14 Thromboembolic events in Fontan Occur both early and late after the Fontan procedure Contribute to the failure of Fontan physiology Occur in the presence or absence of standard anticoagulation schemes Complex interaction of multiple factors

15 25-year old patient with atriopulmonary Fontan Slide from Dr Lilian Mantziari

16 Risk factors for thrombosis Type of operation Presence of thrombogenic material Dilated atria Arrhythmias Ventricular dysfunction Patent fenestration Liver congestion Protein-losing enteropathy

17 17% of adult Fontan patients had an intermediate or high probability for PE on VQ scan Pulmonary emboli were not present in any patients (30%) taking warfarin.

18 Cause and predictors of death in Fontan patients Khairy P et al. Circulation 2008

19 N=101 patients Thromboembolic events occurred in 15.3% Within the 1st postop year, 7/13 events occurred

20 Coumadin was the most effective prophylactic therapy in preventing thromboembolism Seipelt et al. Ann Thorac Surg 2002

21 Multicenter international randomized trial Primary endpoint (intention to treat) was thrombosis, (both thrombus that led to clinical events and the presence of asymptomatic or silent thromboemboli that were detected by TOE). The cumulative thrombosis rate was 23% while the clinical thrombosis event rate was 8% Monagle et al. JACC 2011

22 No significant difference between ASA and heparin/warfarin as primary thromboprophylaxis in the first 2 years after Fontan surgery Monagle et al. JACC 2011

23 Patients who often failed to meet target INR level were at higher risk of thromboembolism McCrindle et al. JACC 2013

24 Challenges of warfarin use Children require 25% less warfarin dose compared to children with other CHD 20% stopped the drug before the end of the study 41% of INR measurements were below the recommended therapeutic range Poor compliance with warfarin (<30% of INR measurements in therapeutic range) had greater risk of thrombosis

25 Recommendations American College of Chest Physicians (ACCP) guidelines recommend aspirin (1 5 mg/kg/d) or therapeutic unfractionated heparin followed by VKAs to achieve a target INR of 2.5 (range, )

26 Clinical practice In 1st year post-surgery risk is highest, therefore, later switch from anticoagulation to antiplatelet In old type atriopulmonary Fontan livelong anticoagulation with VKAs It is likely that the newer anticoagulants evaluated in adults with atrial fibrillation will be tested in Fontan patients

27 Eisenmenger syndrome

28 Eisenmenger syndrome OAC No OAC Fuster V et al. Circulation 1984

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30 In situ pulmonary thrombosis

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33 Our practice Oral anticoagulation with VKAs in patients with: in situ pulmonary thrombosis, history of thromboembolism atrial arrhythmias

34 ASD/PFO closure devices

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36 Thrombus after transcatheter closure of ASD with an Amplatzer septal occluder assessed by 3D echo Acar et al, Heart 2002

37 2% of ASD/PFO patients had thrombus formation on the device `

38 Predictors of thromboembolism Krumsdorf et al. J Am Coll Cardiol 2004

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40 ESC Guidelines Antiplatelet therapy is required for at least 6 months (aspirin 100 mg daily minimum).

41 Our practice after ASD perc closure Aspirin in young patients Dual antiplatelet therapy in atrial septal aneurysm, elderly with sinus rhythm, or in migraine. Combination should be used for at least 1 month and then only aspirin OAC in atrial fibrillation, clotting disorder, or in case of post-implant thrombus formation

42 16 year old boy with Ebstein s anomaly and a ischemic stroke Always individualize!

43 Take home messages Thrombotic events are frequent in CHD No data exist in deciding optimal antithrombotic therapy in different CHD subgroups Weight antithrombotic prophylaxis against high risk of bleeding Even in the same clinical entity (eg Fontan or post ASD device closure) individualization should be the guiding rule Poor INR control with warfarin has been associated with higher thromboembolic risk in Fontan population, therefore, studies are needed with new anticoagulants in CHD

44 Thank you for your attention

45 Important points Screening for hereditary thrombophilia before surgery Avoid creation of areas of stagnant flow such as pulmonary artery stumps or ascending aortas in aortic atresia Prothrombotic states such as increased factor VIII

46 Odegard et al. J Thorac Cardiovasc Surg 2003

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48 Should we routinely anticoagulate Eisenmenger patients? Broberg CS et al. JACC 2008

49 Management of anticoagulation during pregnancy

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