Innovations in Interventional Cardiology Kinepolis - Saturday 12-3-2011 CARDIO 2012
Innovations in Interventional Cardiology E.Benit MD Hasselt Heart Centre Belgium
Percutaneous left atrial appendage closure in atrial fibrillation
Atrial fibrillation Most common sustained cardiac arrhytmia (>6.000.000 patients in Europe) Higher prevalence in the elderly population : prevalence of AF rise from 1% among 55-59 years old patients to > 10% for those older than 80 (1). Silent AF is probably as frequent as diagnosed AF (1) Lloyd-Jones DM et al, Circulation 2004 ; 110: 1042-46
Atrial fibrillation Risk factor for stroke and thrombo-embolism Responsible for 10-15% of all ischemic strokes (1) In Europe, stroke is the third leading cause of death behind heart disease and cancer (2) The most common aetiological factors for AF are hypertension, heart failure, ischaemic heart disease and valvular disease (1) Hylek E M et al., Stroke 2006 ; 37(4) : 1075-80 (2) World Health Report 2004
The risk of stroke in non-anticoagulated patients increases with age from 1-5% / year in patients age 50-59 years to 23.5% / year in patients aged 80-89 years (1). Silent cerebral infarction may occur in patients with AF in up to 15% of cases (2). 35% of patients with AF will have a stroke in their lifetime (3). (1) Lin H i et al., Stroke 1996 ; 27(10) : 1760-1764 (2) D Holmes, Sem. In Neurology 2010 ; 30-5 : 528-534 (3) Wolf PA et al. Stroke 1991 ; 22: 983-8
In stroke-survivors at 3 months 15-30% are permanently disabled and an additional 20% require institutional care (1) The risk of stroke in patients with AF is increased irrespective of whether the arrhythmia is paroxysmal, persistent or permanent (accepted) (= whether AF is paroxysmal, persistent or permanent should not influence the choice of antithrombotic therapy) (2) (1) Smith WS et al., Stroke 2005 ; 36(7) : 1432-1438 (2) ESC guidelines atrial fibrillation 2010
What is Atrial Fibrillation? Sinus Rhythm Atrial Fibrillation AF involves the two upper chambers (atria) of the heart. Its name comes from the fibrillating (i.e., quivering) of the heart muscles of the atria, instead of a coordinated contraction
Natural time course of AF First detected AF Silent Paroxysmal Persistent Long-Standing Persistent Permanent Patients with paroxysmal AF should be regarded as having a stroke risk similar to those with persistent or permanent AF, in the presence of risk factors 2,3 time = Cardioversion 1 Adapted from Kirchhof, et al., Outcome parameters for trials in atrial fibrillation; Europace (2007) 9, 1006 1023 2 Hughes M, Lip GY. Stroke and thromboembolism in AF: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008;99:295 304. 3 Stroke in AF working group. Independent predictors of stroke in patients with AF: a systematic review. Neurology 2007;69:546 554
0 = low risk : no treatement or Aspirin (no treatment preferred) 1 = intermediate risk : Aspirin or OAC (OAC preferred) 2 = high risk : OAC
CHADS 2 score and stroke rate
Cha 2 ds 2 -vasc (stroke and thromboembolism risk) and Hasbled score (bleeding risk) in nonvalvular AF patients Cha 2 ds 2 -vasc score 0 = truly low risk patient : no antithrombotic treatment Cha 2 ds 2 -vasc score 1 = intermediate risk : OAC or Aspirin (preferred : AOC rather than Aspirin) Cha 2 ds 2 -vasc score 2-9 = high risk : OAC Exept for males who are < 65 years and have no risk factors, all AF patients should receive oral anticoagulation if absence of contraindications.
Adjusted stroke rate according to CHA 2 DS 2 -VASc score
IF HIGH CHA 2 DS 2 -VASC SCORE : MORE STROKES BUT ALSO MORE BLEEDING EVENTS! Optimum selection of patients with AF for anticoagulant therapy depends not only on assessment of their intrinsic risk of thromboembolism but also on identification of those at increased risk of bleeding complications.
Striking a fine balance Preventing Stroke - Avoiding Bleeds CHA 2 DS 2 -VASc - HAS-BLED
Oral OAC therapy (vitamine K antagonist like Warfarin) has been the cornerstone of treatment for stroke prevention in the setting of AF (1) : adjusted-dose warfarin reduce stroke by +/- 60% In AF patients Warfarin prevent more strokes than Aspirin but cause more (fatal) bleeding than Aspirin (2) (1) Hart RG et al. Ann intern Med 2007; 146(12) : 857-867 (2) Hart RG et al. Ann. Intern Med 1999 ; 131 ; 492-501
There are significant issues with Warfarin Narrow therapeutic range (INR target >2 and <3) Requires frequent monitoring and dose adjustments Interactions with some foods, medications (antiarrhythmic, antibiotics, ) and alcohol Genetic variations (Cyt P4502C9) (1) (1) Epstein RS et al. J.Am. Coll. Cardiol. 2010 ; 55(25) : 2804-2812
There are significant issues with Warfarin It is not always well tolerated (1) Even with frequent monitoring and dose adjustments, +/- 40% of the lab results are outside of the therapeutic range (Relative) contraindicated if uncontrolled hypertension, dementia, use of NSAID, recent internal bleeding (= +/-15% of AF patients) (2) Warfarin is not administered in many patients (+/- 50%) at risk for stroke, particulary in elderly patients (who are at the higher risk for stroke) (1) Waldo AL et al. J. Am. Coll. Cardiol. 2005 ; 46 : 1729 (2) Nieuwlaat R et al. European Heart Journal 2005 ; 26 : 2422-2434
Given the problems associated with Warfarin, there has been intense interest in developing alternative pharmacologic approaches Dual antiplatelet therapy (ASA + Clopidogrel) like in the Active W trial (1) or the Active A trial (2) Oral direct thrombine inhibitor : Dabitragan in the Rely trial (3) Oral direct Factor Xa Inhibitor : Rivaroxaban in the Rocket AF trial (4) or Apixaban in the Aristotle trial (5) And in developing new device strategies (1) Connolly s et al. Lancet 2006 ; 367 : 1903-12 (2) Connolly S et al. N. Eng.J.Med 2009 ; 360(20) : 2066-2078 (3) Connolly S et al. New Engl. J. Med 2009 ; 361 : 1139-51 (4) M. PATEL et al. N.Engl.J.Med 2011 ; 365 : 883-91 (5) C. GRANGER et al. N.Engl.J.Med 2011 ; 365 : 981-92
The device strategies are based upon the finding that the left atrial appendage is the source of thrombi in >90% of patients with nonvalvular AF (1). So left atrial appendage occluders have been developed : no need for further chronical anticoagulant therapy protection for the patient from thromboembolism (1) Blackshear JL et al. Ann. Thorac Surg 1999 ; 61(2) : 755-759
Although anticoagulation is the cornerstone therapy a lot of patients have a relative or absolute contraindication to anticoagulant treatment In this group of patients LAA occlusion has great potential given than in patients with non valvular atrial fibrillation, stroke is the result of thrombus from LAA and the fact that with successfull occlusion of LAA, 90% of the patients are protected
The anatomy of the LAA is very complex 1 or multiple lobes Big variations in size, diameter and length Multiple crevices and pockets (thrombus formation if stasis resulting from lack of contractility during AF
2 devices Watchman (Atritech) (protect AF trial) (1) (1) D. Holmes et al. Lancet 2009 ; 374 : 534-42
Amplatzer Cardiac plug (AGA)
Protect AF trial (D. Holmes et al.) Lancet 2009; 374 : 534-42 Adult patients with nonvalvular AF were eligible for inclusion in the trial if they had at least 1 of the following : previous CVA or TIA, congestive heart failure, diabetes, hypertension or >75 years old 707 eligible patients Randomisation 2:1 to percutaneous LAA closure (wathman = filter)device and subsequent discontinuation of Warfarin (intervention group n=463) or to Warfarin treatment with target INR >2 and <3 (control group; n=244)
Efficacy assessed by a primary composite endpoint of stroke, cardiovascular death and systemic embolism Results : at 1065 patient years of follow-up, the primary efficacy event rate was 3 per 100 patient years in the interventional group and 4.9 per 100 patient years in the control group => efficacy of percutaneous closure of the LAA was NON INFERIOR to that of Warfarin therapy. But there were more adverse safety events in the intervention group (periprocedural complications like airembolism, device embolisation and pericardial effusions)
1) Closure of the LAA might provide an alternative strategy to chronic Warfarin/OAC treatment for stroke prophylaxis in patients with nonvalvular AF 2) Indicated for patients with high cardioembolic risk and contraindications to Warfarin/OAC
Case : 69 years old History of hypertension, heart failure, renal failure, alcohol abusus 2009 : AF with tachycardiomyopathy electrical cardioversion (Chadsvasc 4/9, Hasbled 5/9) 05.2010 : CVA under Warfarin (INR 1) 11.2010 : Subdural hematoma + subarachnoidal bleeding under Warfarin (INR 3.6) (Chadsvasc 6/9, Hasbled 7/9) Indication+++ and contraindication+++ to OAC 02.2011 : Percutaneous LAA closure under general anesthesia and TOE ASA 6 months Clopidogrel 1 month Endocarditis profylaxis 6 months