NCVH Birmingham 2013 August 24, Michael S. Bailey, MD Birmingham Heart Clinic

Transcription

1 NCVH Birmingham 2013 August 24, 2013 Michael S. Bailey, MD Birmingham Heart Clinic

2 NCVH Birmingham 2015 August 29, 2015 Michael S. Bailey, MD Birmingham Heart Clinic

3 Left Atrial Anatomy Part of a larger structure called the Heart

4 Function: Left Atrium To allow uninterrupted venous return to the heart Continuous flow, even in atrial systole To provide a decompression chamber for ventricular systole LV contraction and MV closure provides a compression wave that would interrupt continuous venous inflow into the atrium otherwise To detect low filling states and signal hypothalamus to release vasopressin, among others

5 Anatomy

6 Left Atrium In normal sinus rhythm with normal cardiac function, flow into and out of the left atrial appendage is brisk. LAA is very contractile in NSR, not so much in severe cardiac disease Diastolic dysfunction High LA pressure Systolic dysfunction High LA pressure, dilated atria Atrial fibrillation, Flutter, maybe others

7 From: The Left Atrial Appendage: Anatomy, Function, and Noninvasive Evaluation J Am Coll Cardiol Img. 2014;7(12): doi: /j.jcmg Figure Legend: Change in Size of the LAA During the Cardiac Cycle in a Patient in SR In this patient in SR, the LAA (arrowhead) can be seen in varying sizes during the different phases (A to F) of the cardiac cycle (yellow arrow pointing to time frame of cycle). SR = sinus rhythm; other abbreviation as in Figure 1. Date of download: 8/29/2015 Copyright The American College of Cardiology. All rights reserved.

8 Atrial fibrillation Short term LA Appendage Major reduction in contraction and flow Encourages accumulation of thrombus in the appendage Reduction in cardiac output Long term Continued reduction in cardiac output Remodeling of atrium and appendage, loss of muscle and dilatation of the LA and appendage Increasing risk for thrombus with worsening structure and function of atrium and appendage

9 From: The Left Atrial Appendage: Anatomy, Function, and Noninvasive Evaluation J Am Coll Cardiol Img. 2014;7(12): doi: /j.jcmg Figure Legend: Diameter and Area Changes of the LAA Orifice During the Cardiac Cycle (Top) A patient in normal SR who had LAA contractility. Systole (A) and diastole (B). (Bottom) A patient with long-lasting AF. Systole (C) and diastole (D). Note the difference in area between systole and diastole in the patients in SR opposed to the minimal change in the area in the patient in AF where there is considerably reduced contractility. In this patient in AF, the LAA orifice is markedly enlarged; note that a 32-mm Carpentier ring in the mitral position (bottom right in C and D, red arrow) is visually smaller in diameter than the LAA orifice (yellow arrow). AF is associated with structural remodeling of the LAA, which includes dilation of the chamber and reduction in pectinate muscles (not shown). AF = atrial fibrillation; SR = sinus rhythm; other abbreviation as in Figure 1. Date of download: 8/29/2015 Copyright The American College of Cardiology. All rights reserved.

10 LA with Atrial Fibrillation Why do we care about the LA and the LAA? Stroke Up to 30% of strokes are from thrombus formation in the atrium, mostly the left atrial appendage (90%). Major factor in morbidity and mortality as we age Increasing costs of caring for the population, especially since embolic stroke should be preventable!

11 LAA Thrombus

12 From: The Left Atrial Appendage: Anatomy, Function, and Noninvasive Evaluation J Am Coll Cardiol Img. 2014;7(12): doi: /j.jcmg Figure Legend: TEE Imaging of the LAA TEE images in (A, B) 2D X-plane view demonstrating a finding suspicious of a thrombus (arrow). (C) With the use of contrast, a thrombus is now clearly demonstrated, as well as in the 3D view (D) (Online Videos 1, 2, and 3). Abbreviations as in Figure 1. Date of download: 8/29/2015 Copyright The American College of Cardiology. All rights reserved.

13 LA thrombus leads to Embolic Shower of Thrombi Clot ejected from atrial appendage, usually after change in contraction status Af to nsr Does not matter if by shock, meds, spontaneous cv Can occur weeks later.

14 Anicoagulation can lead to this. Bleeding Subdural Hematoma GI Intracranial Subdural Muscular Ocular Surface manifestatins Ecchymoses, hematoma, petechia And so on

15 Current State of the Art Oral anticoagulation If risk of stroke high enough with AF, you should have: warfarin dabigatran rivaroxaban Apixaban edoxaban Pros: Works, prevents strokes Can be inexpensive Requires just taking a pill Lots of experience from medical community dealing with anticoagulation

16 So much effort Warfarin Rat poison D-Con Other agents are great as long as no bleeding events occur and that pt can remember to take them There has to be a better way

17 Left Atrium as a Target for Therapy Maybe we could eliminate the LAA Surgery Not new Often with MV repair or replacement Sounds like this is the way to go. LAA

18 Surgical LAA Ligation Literature is not robust Retrospective review 205 pts Significantly less embolic events in those with ligated LAA Prospective data lacking, but underway (LAAOS III) Current literature shows no clear advantage in what literature exists Incomplete ligation in 30-55%, with residual thrombus later on in up to 50% Left atrial appendage as a target for reducing strokes: Justifiable rationale? Safe and effective approaches? Faisal F. Syed, Samuel J. Asirvatham Heart Rhythm - February 2011 (Vol. 8, Issue 2, Pages , DOI: /j.hrthm )

19 Percutaneous LAA Occlusion Watchman Boston Scientific Clinical trials complete Protect AF Prevail FDA approved Catheter based Percutaneous Minimally invasive Amplatzer St Jude Clinical trials underway Catheter based Minimally invasive

20 Old Paradigm: Previously dominated by a single medical therapy (warfarin) Warfarin - (d-con, Rodex) Chemical Profile 1/85 CHEMICAL name: 3(a-acetonylbenzyl)-4-hydroxycoumarin (56) TRADE name(s): d-con, RAX (69); Cov-R-Tox, Kypfarin, Rodex, Tox- Hid (56). FORMULATION(S): It is formulated in ready-to-use baits and as concentrates in cornstarch for mixing at a 1:19 ratio with cornmeal or other materials (56). Dust (10 g a.i./kg) for use in holes and runs; dust (1 and 5 g/kg) for admixture with suitable protein-rich bait (62). TYPE: Rodenticide (anticoagulant)

21 New Paradigm Pharmacologic Still using D-Con (warfarin) Dabigatran, Rivaroxaban, Apixaban, Edoxaban Mechanical LAA ligation (Exclusion) Surgical treatment, usually with concomitant valve surgery (LAAOS III) LARIAT Percutaneous method that is poorly researched and prone to complication Not indicated for stroke prevention LAA occlusion Watchman only approved device for stroke prevention in NVAF Plaato no longer being studied Amplatzer plug no longer being studied

22 Watchman

23 Watchman

24 Watchman Approved March 13, 2015 Indication: NVAF with at least one risk factor for stroke, able to take anticoagulation, and has a compelling reason to not take anticoagulation

25 Clinical Trial Overview Prospective clinical trials 2 Continued access programs 2

26 Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial FibrillationClinical Perspective by Vivek Y. Reddy, Shephal K. Doshi, Horst Sievert, Maurice Buchbinder, Petr Neuzil, Kenneth Huber, Jonathan L. Halperin, and David Holmes PROTECT AF Circulation Volume 127(6): February 12, 2013

27 Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial FibrillationClinical Perspective Randomized trial comparing Watchman to warfarin Non-inferiority trial 2:1 randomiztion NVAF with 1 risk factor for stroke and could take warfarin Intended for 5 yr follow up Primary efficacy end point stroke, systemic embolism, cardiovascular death Primary safety endpoint Device embolization requiring retrieval Pericardial effusion requiring drainage Serious bleeding requiring transfusion Critical site bleeding

28 Trial patient profile. Reddy V et al. Circulation 2013;127:

29 Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial FibrillationClinical Perspective Efficacy endpoint 3.0 events in device group vs. 4.9 events in control group (per 100 pt yrs) Met pre-specified NI endpoint 2.3 vs 3.2 strokes per 100 pt yrs 1 vs 6 hemorrhagic strokes in Watchman vs control (NI) Safety endpoint 7.4 vs 4.4 events per 100 pt yrs Implant complications, primarily effusion Dropped to 5.5 vs 3.6 per 100 pt yrs at 2.3 yrs follow up, indicating the presence of a learning curve

30 Kaplan-Meier curves of landmark analyses of the primary efficacy end point. Reddy V et al. Circulation 2013;127:

31 Prevail PREVAIL: Prospective Randomized EVAluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation Versus Long Term Warfarin Therapy Prospective, randomized, multicenter study to provide additional information on the safety and efficacy of the WATCHMAN LAA Closure Technology Confirmatory study conducted to provide additional information on the implant procedure and complication rates associated with the device

32 Study Goals and Design Similar design to PROTECT AF: prospective randomized 2:1 (device: control) trial 407 randomized patients from 41 US centers Confirm the results of PROTECT AF and demonstrate improved safety profile Inclusion of new centers and new operators to document that enhancements to the training program are effective Roll-in phase allowed new centers to implant 2 patients prior to randomization phase

33 Primary Endpoints Acute: Death, systemic embolism, ischemic stroke, major device related complications requiring intervention Timepoint = 7 days post randomization Comparison of composite of stroke, systemic embolism, and cardiovascular/unexplained death Timepoint = 18 months Comparison of ischemic stroke or systemic embolism occurring >7 days post randomization Timepoint = 18 months

34 First Primary Endpoint N Subjects % (n/n) 95% CI¹ % (6/269) 2.618% ¹CI is one-sided 6 events in device group Success based on upper 95% CI bound for percentage of subjects with event Pre-specified criterion met for first primary endpoint (95% Upper confidence bound < 2.67%)

35 Second Primary Endpoint Device and control event rate = Similar 18-month event rates in both groups Upper 95% CI bound slightly higher than allowed to meet success criterion (<1.75%)

36 Third Primary Endpoint Device 18-Month Rate Control 18-Month Rate 18-Month Rate Difference (95% CI) ( , ) Pre-specified non-inferiority criterion met for third primary endpoint (95% CI Upper Bound < %) Endpoint success in the presence of an over performing control group

37 Conclusions Despite implantation in higher risk patients the Watchman device can be safely implanted by new operators 2 of 3 primary endpoints were met even in the presence of an over performing control group The Watchman device is an alternative to oral anticoagulation therapy for thromboembolic prevention in patients with non valvular atrial fibrillation

38 LAA Occlusion Conclusions 2015 Surgical data poor but will be building Watchman device approved for use, very limited access to the procedure at this time. Much more to learn, more clinical trials to come.

39 LAA Occlusion Questions? Answers?