MSAC and PASC - Department of Health | Welcome to the ...



Application 1374Final protocol to guide the assessment of subcutaneous implantable cardioverter defibrillator therapyMay 2014Table of Contents TOC \o "1-3" \h \z \u MSAC and PASC PAGEREF _Toc387411682 \h 3Purpose of this document PAGEREF _Toc387411683 \h 3Background PAGEREF _Toc387411684 \h 4Purpose of application PAGEREF _Toc387411685 \h 4Current arrangements for public reimbursement PAGEREF _Toc387411686 \h 5Regulatory status PAGEREF _Toc387411687 \h 7Intervention PAGEREF _Toc387411688 \h 8Description PAGEREF _Toc387411689 \h 8Delivery of the intervention PAGEREF _Toc387411690 \h 8Prerequisites PAGEREF _Toc387411691 \h 8Co-administered and associated interventions PAGEREF _Toc387411692 \h 9Patient Selection for subcutaneous ICD PAGEREF _Toc387411693 \h 9Medical condition and population eligible for the proposed intervention PAGEREF _Toc387411694 \h 10Proposed MBS listing PAGEREF _Toc387411695 \h 12Clinical place for proposed intervention PAGEREF _Toc387411696 \h 13Comparator PAGEREF _Toc387411697 \h 14Clinical claim PAGEREF _Toc387411698 \h 15Outcomes and health care resources affected by introduction of proposed intervention PAGEREF _Toc387411699 \h 16Outcomes PAGEREF _Toc387411700 \h 16Health care resources PAGEREF _Toc387411701 \h 16Proposed structure of economic evaluation PAGEREF _Toc387411702 \h 19References PAGEREF _Toc387411703 \h 23MSAC and PASCThe Medical Services Advisory Committee (MSAC) is an independent expert committee appointed by the Australian Government Health Minister to strengthen the role of evidence in health financing decisions in Australia. MSAC advises the Commonwealth Minister for Health on the evidence relating to the safety, effectiveness, and cost-effectiveness of new and existing medical technologies and procedures and under what circumstances public funding should be supported.The Protocol Advisory Sub-Committee (PASC) is a standing sub-committee of MSAC. Its primary objective is the determination of protocols to guide clinical and economic assessments of medical interventions proposed for public funding.Purpose of this documentThis document is intended to provide a protocol that will be used to guide the assessment of an intervention for a particular population of patients. The draft protocol will be finalised after inviting relevant stakeholders to provide input to the protocol. The final protocol will provide the basis for the assessment of the intervention.The protocol guiding the assessment of the health intervention has been developed using the widely accepted “PICO” approach. The PICO approach involves a clear articulation of the following aspects of the research question that the assessment is intended to answer:Patients – specification of the characteristics of the patients in whom the intervention is to be considered for use;Intervention – specification of the proposed interventionComparator – specification of the therapy most likely to be replaced by the proposed interventionOutcomes – specification of the health outcomes and the healthcare resources likely to be affected by the introduction of the proposed interventionBackgroundA proposal for an application requesting Medicare Benefits Schedule (MBS) listing for the insertion of a subcutaneous implantable cardioverter defibrillator (ICD) electrode was received from Boston Scientific by the Department of Health and Ageing in September 2013. Conventional (transvenous) ICD therapy consists of a generator, which is usually implanted in a pocket in the pectoral region below the left clavicle, and a transvenous right ventricular lead that contains the shock coils and pacing electrode (single-chamber ICD). Additional leads may also be connected to the right atrium (dual-chamber ICD) or left ventricle (cardiac resynchronisation therapy) for the purposes of pacing, sensing and defibrillation. Currently, transvenous ICD devices are able to provide cardiac pacing to treat dangerously low heart rates (bradycardia), if present. However, the majority of patients implanted with an ICD do not have a bradycardia pacing indication. Insertion of the subcutaneous ICD is clinically similar to the insertion of a transvenous ICD, yet the subcutaneous ICD leads do not need to be inserted into the vasculature of the heart. Rather, they are placed under the skin of the patients’ chest.ICDs represent a highly effective therapy for primary and secondary prevention of sudden cardiac death (SCD), treatment of life threatening ventricular arrhythmias. The cost-effectiveness of ICDs in primary and secondary prevention is widely accepted ADDIN EN.CITE <EndNote><Cite><Author>Charles</Author><Year>2007</Year><RecNum>40</RecNum><DisplayText>(Charles &amp; Gammage, 2007)</DisplayText><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383281430">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Charles, R.D.</author><author>Gammage, M.D.</author></authors></contributors><titles><title>Heart Rhythm Management Devices: Guidance for Commissioners</title><secondary-title>National Heart Rhythm Management Device Taskforce</secondary-title></titles><periodical><full-title>National Heart Rhythm Management Device Taskforce</full-title></periodical><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>(Charles & Gammage, 2007), and in Australia, their use is reimbursed through Medicare. However, implantation of endocardial leads using a transvenous approach can be associated with significant procedural and long term complications ADDIN EN.CITE <EndNote><Cite><Author>DiMarco</Author><Year>2003</Year><RecNum>7</RecNum><DisplayText>(DiMarco, 2003)</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383086706">7</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>DiMarco, J. P.</author></authors></contributors><auth-address>Electrophysiology Laboratory, Cardiovascular Division, Department of Medicine, University of Virginia Health System, Charlottesville 22908-0158, USA. jdimarco@virginia.edu</auth-address><titles><title>Implantable cardioverter-defibrillators</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></periodical><alt-periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></alt-periodical><pages>1836-47</pages><volume>349</volume><number>19</number><edition>2003/11/07</edition><keywords><keyword>Anti-Arrhythmia Agents/therapeutic use</keyword><keyword>Arrhythmias, Cardiac/therapy</keyword><keyword>Clinical Trials as Topic</keyword><keyword>*Defibrillators, Implantable/adverse effects/contraindications/standards/trends</keyword><keyword>Equipment Failure</keyword><keyword>Humans</keyword><keyword>Postoperative Complications</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov 6</date></pub-dates></dates><isbn>0028-4793</isbn><accession-num>14602883</accession-num><urls></urls><electronic-resource-num>10.1056/NEJMra035432</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(DiMarco, 2003). The subcutaneous ICD system provides the same clinical benefits as transvenous ICDs while minimising the risk of some long-term complications associated with transvenous ICD lead failure. The subcutaneous ICD system is intended to provide defibrillation therapy for the treatment of life threatening ventricular arrhythmias in patients who do not have symptomatic bradycardia, incessant ventricular tachycardia (VT), or spontaneous, frequently occurring VT that is reliably terminated with anti-tachycardia pacing. There is an unmet clinical need and new line of therapy for those patients (particularly children and younger adults) with life threatening ventricular arrhythmias who may have difficult anatomy for transvenous lead insertion, and for whom a pacing lead is not needed.Purpose of applicationThe following protocol will outline the proposed approach to evaluate comparative effectiveness, safety and costs associated with insertion of a subcutaneous ICD lead compared to a transvenous ICD lead for patients indicated for subcutaneous ICD therapy. Specifically, subcutaneous ICD is only indicated for the treatment of life-threatening ventricular arrhythmias in patients who do not have symptomatic bradycardia, incessant VT, or spontaneous, frequently recurring VT that is reliably terminated with anti-tachycardia pacing. This patient group represents a subgroup of all patients currently receiving transvenous ICD systems.Current arrangements for public reimbursementThe application is seeking MBS listing for subcutaneous ICD therapy. The cost of the generator associated with subcutaneous ICD leads will separately require consideration for reimbursement through the Prostheses List. There are existing MBS items for insertion of transvenous ICD leads in primary prevention (item 38384; Table 1) and secondary prevention (item 38390; Table 2). The associated MBS items for the insertion or replacement of an automatic defibrillator generator are items 38387 and 38393.Subcutaneous ICDSubcutaneous ICD systems are not currently being used in Australia. This is the first MSAC application related to the use of the subcutaneous ICD devices. The S-ICD?, developed by Cameron Health, received a CE mark in 2009 ADDIN EN.CITE <EndNote><Cite><Author>Lobodzinski</Author><Year>2011</Year><RecNum>22</RecNum><DisplayText>(Lobodzinski, 2011)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383118993">22</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lobodzinski, S. S.</author></authors></contributors><auth-address>Department of Electrical and Biomedical Engineering, California State University Long Beach, CA, USA. slobo@csulb.edu</auth-address><titles><title>Subcutaneous implantable cardioverter-defibrillator (S-ICD)</title><secondary-title>Cardiol J</secondary-title><alt-title>Cardiology journal</alt-title></titles><periodical><full-title>Cardiol J</full-title><abbr-1>Cardiology journal</abbr-1></periodical><alt-periodical><full-title>Cardiol J</full-title><abbr-1>Cardiology journal</abbr-1></alt-periodical><pages>326-31</pages><volume>18</volume><number>3</number><edition>2011/06/11</edition><keywords><keyword>Death, Sudden, Cardiac/epidemiology/prevention &amp; control</keyword><keyword>Defibrillators, Implantable/adverse effects/statistics &amp; numerical data/*trends</keyword><keyword>Device Approval</keyword><keyword>Electrodes, Implanted/adverse effects/statistics &amp; numerical data/*trends</keyword><keyword>Europe</keyword><keyword>Humans</keyword><keyword>*Prosthesis Design</keyword><keyword>Prosthesis Implantation/*methods/trends</keyword><keyword>Risk Factors</keyword><keyword>Tachycardia, Ventricular/*therapy</keyword></keywords><dates><year>2011</year></dates><isbn>1898-018x</isbn><accession-num>21660928</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Lobodzinski, 2011) and US Food and Drug Administration (FDA) approval in 2012 ADDIN EN.CITE <EndNote><Cite><Author>FDA</Author><Year>2012</Year><RecNum>23</RecNum><DisplayText>(FDA, 2012)</DisplayText><record><rec-number>23</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383119789">23</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>FDA</author></authors></contributors><titles><title>Device Approvals and Clearances: Subcutaneous Implantable Defibrillator (S-ICD) - P110042</title></titles><dates><year>2012</year></dates><urls><related-urls><url>;(FDA, 2012). S-ICD? is currently available in the US, New Zealand, UK and several other European countries, including the Netherlands, Denmark, Germany, France and Italy. Over 2,000 procedures have been conducted worldwide.Transvenous ICD The 2006 MSAC assessment report of ICDs for prevention of SCD ADDIN EN.CITE <EndNote><Cite><Author>MSAC</Author><Year>2006</Year><RecNum>35</RecNum><DisplayText>(MSAC, 2006)</DisplayText><record><rec-number>35</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383260284">35</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>MSAC</author></authors></contributors><titles><title>“Implantable cardiac defibrillators for prevention of sudden cardiac death, Reference 32”</title></titles><dates><year>2006</year></dates><urls><related-urls><url>[Internet] Available from: $File/MSAC%20Ref%2032%20-%20ICDs.pdf [accessed 15 October 2013]</url></related-urls></urls></record></Cite></EndNote>(MSAC Ref 32) recommended the listing of ICD implantation on the MBS for primary prevention for patients with a left ventricular ejection fraction (LVEF) of ≤ 30 per cent at least one month after a myocardial infarct (MI) when the patient has received optimal medical therapy (OMT); and patients with chronic heart failure (CHF) associated with mild to moderate symptoms (New York Heart Association (NYHA) II and III) and a LVEF ≤ 35 per cent when the patient has received OMT.Evidence based US and European practice guidelines recommend traditional ICD therapy for primary and secondary prevention of SCD PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FcHN0ZWluPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjEwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihFcHN0ZWluIGV0IGFsLiwgMjAwODsgWmlw

ZXMgZXQgYWwuLCAyMDA2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xMDwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5

ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMDk0MTkwIj4xMDwva2V5Pjwv

Zm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlw

ZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RXBzdGVpbiwgQS4gRS48L2F1dGhvcj48

YXV0aG9yPkRpbWFyY28sIEouIFAuPC9hdXRob3I+PGF1dGhvcj5FbGxlbmJvZ2VuLCBLLiBBLjwv

YXV0aG9yPjxhdXRob3I+RXN0ZXMsIE4uIEEuLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkZyZWVkbWFu

LCBSLiBBLjwvYXV0aG9yPjxhdXRob3I+R2V0dGVzLCBMLiBTLjwvYXV0aG9yPjxhdXRob3I+R2ls

bGlub3YsIEEuIE0uPC9hdXRob3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0aG9yPjxhdXRo

b3I+SGFtbWlsbCwgUy4gQy48L2F1dGhvcj48YXV0aG9yPkhheWVzLCBELiBMLjwvYXV0aG9yPjxh

dXRob3I+SGxhdGt5LCBNLiBBLjwvYXV0aG9yPjxhdXRob3I+TmV3YnksIEwuIEsuPC9hdXRob3I+

PGF1dGhvcj5QYWdlLCBSLiBMLjwvYXV0aG9yPjxhdXRob3I+U2Nob2VuZmVsZCwgTS4gSC48L2F1

dGhvcj48YXV0aG9yPlNpbGthLCBNLiBKLjwvYXV0aG9yPjxhdXRob3I+U3RldmVuc29uLCBMLiBX

LjwvYXV0aG9yPjxhdXRob3I+U3dlZW5leSwgTS4gTy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250

cmlidXRvcnM+PHRpdGxlcz48dGl0bGU+QUNDL0FIQS9IUlMgMjAwOCBndWlkZWxpbmVzIGZvciBE

ZXZpY2UtQmFzZWQgVGhlcmFweSBvZiBDYXJkaWFjIFJoeXRobSBBYm5vcm1hbGl0aWVzOiBleGVj

dXRpdmUgc3VtbWFyeTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5IZWFydCBSaHl0aG08L3NlY29u

ZGFyeS10aXRsZT48YWx0LXRpdGxlPkhlYXJ0IHJoeXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFs

IG9mIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2Rp

Y2FsPjxmdWxsLXRpdGxlPkhlYXJ0IFJoeXRobTwvZnVsbC10aXRsZT48YWJici0xPkhlYXJ0IHJo

eXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFsIG9mIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eTwv

YWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5

dGhtPC9mdWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJu

YWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48

cGFnZXM+OTM0LTU1PC9wYWdlcz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjY8L251bWJlcj48

ZWRpdGlvbj4yMDA4LzA2LzA3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbWVyaWNhbiBI

ZWFydCBBc3NvY2lhdGlvbjwva2V5d29yZD48a2V5d29yZD5BcnJoeXRobWlhcywgQ2FyZGlhYy9w

aHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+QXRyaW92ZW50cmljdWxh

ciBCbG9jay90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgUGFjaW5nLCBBcnRpZmlj

aWFsPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGhpZXMvdGhlcmFweTwva2V5d29yZD48

a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPipF

bGVjdHJpYyBDb3VudGVyc2hvY2s8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPlNpbm9hdHJpYWwgTm9kZS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+

U29jaWV0aWVzLCBNZWRpY2FsPC9rZXl3b3JkPjxrZXl3b3JkPlRob3JhY2ljIFN1cmdlcnk8L2tl

eXdvcmQ+PGtleXdvcmQ+VW5pdGVkIFN0YXRlczwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48

eWVhcj4yMDA4PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+SnVuPC9kYXRlPjwvcHViLWRhdGVzPjwv

ZGF0ZXM+PGlzYm4+MTU0Ny01MjcxPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE4NTM0Mzc3PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9q

LmhydGhtLjIwMDguMDQuMDE1PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFi

YXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8

L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlppcGVzPC9BdXRob3I+PFll

YXI+MjAwNjwvWWVhcj48UmVjTnVtPjIxPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yMTwv

cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0

dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTE1MjA5Ij4yMTwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WmlwZXMsIEQuIFAuPC9hdXRob3I+

PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+Qm9yZ2dyZWZlLCBNLjwvYXV0aG9y

PjxhdXRob3I+QnV4dG9uLCBBLiBFLjwvYXV0aG9yPjxhdXRob3I+Q2hhaXRtYW4sIEIuPC9hdXRo

b3I+PGF1dGhvcj5Gcm9tZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0

aG9yPjxhdXRob3I+S2xlaW4sIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3NzLCBBLiBKLjwvYXV0aG9y

PjxhdXRob3I+TXllcmJ1cmcsIFIuIEouPC9hdXRob3I+PGF1dGhvcj5QcmlvcmksIFMuIEcuPC9h

dXRob3I+PGF1dGhvcj5RdWlub25lcywgTS4gQS48L2F1dGhvcj48YXV0aG9yPlJvZGVuLCBELiBN

LjwvYXV0aG9yPjxhdXRob3I+U2lsa2EsIE0uIEouPC9hdXRob3I+PGF1dGhvcj5UcmFjeSwgQy48

L2F1dGhvcj48YXV0aG9yPlNtaXRoLCBTLiBDLiwgSnIuPC9hdXRob3I+PGF1dGhvcj5KYWNvYnMs

IEEuIEsuPC9hdXRob3I+PGF1dGhvcj5BZGFtcywgQy4gRC48L2F1dGhvcj48YXV0aG9yPkFudG1h

biwgRS4gTS48L2F1dGhvcj48YXV0aG9yPkFuZGVyc29uLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+

SHVudCwgUy4gQS48L2F1dGhvcj48YXV0aG9yPkhhbHBlcmluLCBKLiBMLjwvYXV0aG9yPjxhdXRo

b3I+TmlzaGltdXJhLCBSLjwvYXV0aG9yPjxhdXRob3I+T3JuYXRvLCBKLiBQLjwvYXV0aG9yPjxh

dXRob3I+UGFnZSwgUi4gTC48L2F1dGhvcj48YXV0aG9yPlJpZWdlbCwgQi48L2F1dGhvcj48YXV0

aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48YXV0aG9yPkJsYW5jLCBKLiBKLjwvYXV0aG9yPjxh

dXRob3I+QnVkYWosIEEuPC9hdXRob3I+PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRo

b3I+RGVhbiwgVi48L2F1dGhvcj48YXV0aG9yPkRlY2tlcnMsIEouIFcuPC9hdXRob3I+PGF1dGhv

cj5EZXNwcmVzLCBDLjwvYXV0aG9yPjxhdXRob3I+RGlja3N0ZWluLCBLLjwvYXV0aG9yPjxhdXRo

b3I+TGVrYWtpcywgSi48L2F1dGhvcj48YXV0aG9yPk1jR3JlZ29yLCBLLjwvYXV0aG9yPjxhdXRo

b3I+TWV0cmEsIE0uPC9hdXRob3I+PGF1dGhvcj5Nb3JhaXMsIEouPC9hdXRob3I+PGF1dGhvcj5P

c3RlcnNwZXksIEEuPC9hdXRob3I+PGF1dGhvcj5UYW1hcmdvLCBKLiBMLjwvYXV0aG9yPjxhdXRo

b3I+WmFtb3Jhbm8sIEouIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRs

ZXM+PHRpdGxlPkFDQy9BSEEvRVNDIDIwMDYgZ3VpZGVsaW5lcyBmb3IgbWFuYWdlbWVudCBvZiBw

YXRpZW50cyB3aXRoIHZlbnRyaWN1bGFyIGFycmh5dGhtaWFzIGFuZCB0aGUgcHJldmVudGlvbiBv

ZiBzdWRkZW4gY2FyZGlhYyBkZWF0aDogYSByZXBvcnQgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ug

b2YgQ2FyZGlvbG9neS9BbWVyaWNhbiBIZWFydCBBc3NvY2lhdGlvbiBUYXNrIEZvcmNlIGFuZCB0

aGUgRXVyb3BlYW4gU29jaWV0eSBvZiBDYXJkaW9sb2d5IENvbW1pdHRlZSBmb3IgUHJhY3RpY2Ug

R3VpZGVsaW5lcyAoV3JpdGluZyBDb21taXR0ZWUgdG8gRGV2ZWxvcCBHdWlkZWxpbmVzIGZvciBN

YW5hZ2VtZW50IG9mIFBhdGllbnRzIFdpdGggVmVudHJpY3VsYXIgQXJyaHl0aG1pYXMgYW5kIHRo

ZSBQcmV2ZW50aW9uIG9mIFN1ZGRlbiBDYXJkaWFjIERlYXRoKTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5KIEFtIENvbGwgQ2FyZGlvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5h

bCBvZiB0aGUgQW1lcmljYW4gQ29sbGVnZSBvZiBDYXJkaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRs

ZXM+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIENv

bGxlZ2Ugb2YgQ2FyZGlvbG9neTwvZnVsbC10aXRsZT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz5l

MjQ3LTM0NjwvcGFnZXM+PHZvbHVtZT40ODwvdm9sdW1lPjxudW1iZXI+NTwvbnVtYmVyPjxlZGl0

aW9uPjIwMDYvMDkvMDU8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFudGktQXJyaHl0aG1p

YSBBZ2VudHMvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgT3V0cHV0

LCBMb3c8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9r

ZXl3b3JkPjxrZXl3b3JkPkNhdGhldGVyIEFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRo

LCBTdWRkZW4sIENhcmRpYWMvKmV0aW9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tl

eXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3

b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgQXJyZXN0L2V0

aW9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgRnVuY3Rpb24gVGVzdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50

cmljdWxhci8qY29tcGxpY2F0aW9ucy8qZHJ1ZyB0aGVyYXB5L3BoeXNpb3BhdGhvbG9neTwva2V5

d29yZD48a2V5d29yZD5WZW50cmljdWxhciBGaWJyaWxsYXRpb24vKmNvbXBsaWNhdGlvbnMvKmRy

dWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHll

YXI+MjAwNjwveWVhcj48cHViLWRhdGVzPjxkYXRlPlNlcCA1PC9kYXRlPjwvcHViLWRhdGVzPjwv

ZGF0ZXM+PGlzYm4+MDczNS0xMDk3PC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE2OTQ5NDc4PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9q

LmphY2MuMjAwNi4wNy4wMTA8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJh

c2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwv

bGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FcHN0ZWluPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjEwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihFcHN0ZWluIGV0IGFsLiwgMjAwODsgWmlw

ZXMgZXQgYWwuLCAyMDA2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xMDwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5

ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMDk0MTkwIj4xMDwva2V5Pjwv

Zm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlw

ZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RXBzdGVpbiwgQS4gRS48L2F1dGhvcj48

YXV0aG9yPkRpbWFyY28sIEouIFAuPC9hdXRob3I+PGF1dGhvcj5FbGxlbmJvZ2VuLCBLLiBBLjwv

YXV0aG9yPjxhdXRob3I+RXN0ZXMsIE4uIEEuLCAzcmQ8L2F1dGhvcj48YXV0aG9yPkZyZWVkbWFu

LCBSLiBBLjwvYXV0aG9yPjxhdXRob3I+R2V0dGVzLCBMLiBTLjwvYXV0aG9yPjxhdXRob3I+R2ls

bGlub3YsIEEuIE0uPC9hdXRob3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0aG9yPjxhdXRo

b3I+SGFtbWlsbCwgUy4gQy48L2F1dGhvcj48YXV0aG9yPkhheWVzLCBELiBMLjwvYXV0aG9yPjxh

dXRob3I+SGxhdGt5LCBNLiBBLjwvYXV0aG9yPjxhdXRob3I+TmV3YnksIEwuIEsuPC9hdXRob3I+

PGF1dGhvcj5QYWdlLCBSLiBMLjwvYXV0aG9yPjxhdXRob3I+U2Nob2VuZmVsZCwgTS4gSC48L2F1

dGhvcj48YXV0aG9yPlNpbGthLCBNLiBKLjwvYXV0aG9yPjxhdXRob3I+U3RldmVuc29uLCBMLiBX

LjwvYXV0aG9yPjxhdXRob3I+U3dlZW5leSwgTS4gTy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250

cmlidXRvcnM+PHRpdGxlcz48dGl0bGU+QUNDL0FIQS9IUlMgMjAwOCBndWlkZWxpbmVzIGZvciBE

ZXZpY2UtQmFzZWQgVGhlcmFweSBvZiBDYXJkaWFjIFJoeXRobSBBYm5vcm1hbGl0aWVzOiBleGVj

dXRpdmUgc3VtbWFyeTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5IZWFydCBSaHl0aG08L3NlY29u

ZGFyeS10aXRsZT48YWx0LXRpdGxlPkhlYXJ0IHJoeXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFs

IG9mIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2Rp

Y2FsPjxmdWxsLXRpdGxlPkhlYXJ0IFJoeXRobTwvZnVsbC10aXRsZT48YWJici0xPkhlYXJ0IHJo

eXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFsIG9mIHRoZSBIZWFydCBSaHl0aG0gU29jaWV0eTwv

YWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5

dGhtPC9mdWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJu

YWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48

cGFnZXM+OTM0LTU1PC9wYWdlcz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjY8L251bWJlcj48

ZWRpdGlvbj4yMDA4LzA2LzA3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbWVyaWNhbiBI

ZWFydCBBc3NvY2lhdGlvbjwva2V5d29yZD48a2V5d29yZD5BcnJoeXRobWlhcywgQ2FyZGlhYy9w

aHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+QXRyaW92ZW50cmljdWxh

ciBCbG9jay90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgUGFjaW5nLCBBcnRpZmlj

aWFsPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGhpZXMvdGhlcmFweTwva2V5d29yZD48

a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPipF

bGVjdHJpYyBDb3VudGVyc2hvY2s8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPlNpbm9hdHJpYWwgTm9kZS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+

U29jaWV0aWVzLCBNZWRpY2FsPC9rZXl3b3JkPjxrZXl3b3JkPlRob3JhY2ljIFN1cmdlcnk8L2tl

eXdvcmQ+PGtleXdvcmQ+VW5pdGVkIFN0YXRlczwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48

eWVhcj4yMDA4PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+SnVuPC9kYXRlPjwvcHViLWRhdGVzPjwv

ZGF0ZXM+PGlzYm4+MTU0Ny01MjcxPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE4NTM0Mzc3PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9q

LmhydGhtLjIwMDguMDQuMDE1PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFi

YXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8

L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlppcGVzPC9BdXRob3I+PFll

YXI+MjAwNjwvWWVhcj48UmVjTnVtPjIxPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yMTwv

cmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0

dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTE1MjA5Ij4yMTwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WmlwZXMsIEQuIFAuPC9hdXRob3I+

PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+Qm9yZ2dyZWZlLCBNLjwvYXV0aG9y

PjxhdXRob3I+QnV4dG9uLCBBLiBFLjwvYXV0aG9yPjxhdXRob3I+Q2hhaXRtYW4sIEIuPC9hdXRo

b3I+PGF1dGhvcj5Gcm9tZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0

aG9yPjxhdXRob3I+S2xlaW4sIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3NzLCBBLiBKLjwvYXV0aG9y

PjxhdXRob3I+TXllcmJ1cmcsIFIuIEouPC9hdXRob3I+PGF1dGhvcj5QcmlvcmksIFMuIEcuPC9h

dXRob3I+PGF1dGhvcj5RdWlub25lcywgTS4gQS48L2F1dGhvcj48YXV0aG9yPlJvZGVuLCBELiBN

LjwvYXV0aG9yPjxhdXRob3I+U2lsa2EsIE0uIEouPC9hdXRob3I+PGF1dGhvcj5UcmFjeSwgQy48

L2F1dGhvcj48YXV0aG9yPlNtaXRoLCBTLiBDLiwgSnIuPC9hdXRob3I+PGF1dGhvcj5KYWNvYnMs

IEEuIEsuPC9hdXRob3I+PGF1dGhvcj5BZGFtcywgQy4gRC48L2F1dGhvcj48YXV0aG9yPkFudG1h

biwgRS4gTS48L2F1dGhvcj48YXV0aG9yPkFuZGVyc29uLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+

SHVudCwgUy4gQS48L2F1dGhvcj48YXV0aG9yPkhhbHBlcmluLCBKLiBMLjwvYXV0aG9yPjxhdXRo

b3I+TmlzaGltdXJhLCBSLjwvYXV0aG9yPjxhdXRob3I+T3JuYXRvLCBKLiBQLjwvYXV0aG9yPjxh

dXRob3I+UGFnZSwgUi4gTC48L2F1dGhvcj48YXV0aG9yPlJpZWdlbCwgQi48L2F1dGhvcj48YXV0

aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48YXV0aG9yPkJsYW5jLCBKLiBKLjwvYXV0aG9yPjxh

dXRob3I+QnVkYWosIEEuPC9hdXRob3I+PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRo

b3I+RGVhbiwgVi48L2F1dGhvcj48YXV0aG9yPkRlY2tlcnMsIEouIFcuPC9hdXRob3I+PGF1dGhv

cj5EZXNwcmVzLCBDLjwvYXV0aG9yPjxhdXRob3I+RGlja3N0ZWluLCBLLjwvYXV0aG9yPjxhdXRo

b3I+TGVrYWtpcywgSi48L2F1dGhvcj48YXV0aG9yPk1jR3JlZ29yLCBLLjwvYXV0aG9yPjxhdXRo

b3I+TWV0cmEsIE0uPC9hdXRob3I+PGF1dGhvcj5Nb3JhaXMsIEouPC9hdXRob3I+PGF1dGhvcj5P

c3RlcnNwZXksIEEuPC9hdXRob3I+PGF1dGhvcj5UYW1hcmdvLCBKLiBMLjwvYXV0aG9yPjxhdXRo

b3I+WmFtb3Jhbm8sIEouIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRs

ZXM+PHRpdGxlPkFDQy9BSEEvRVNDIDIwMDYgZ3VpZGVsaW5lcyBmb3IgbWFuYWdlbWVudCBvZiBw

YXRpZW50cyB3aXRoIHZlbnRyaWN1bGFyIGFycmh5dGhtaWFzIGFuZCB0aGUgcHJldmVudGlvbiBv

ZiBzdWRkZW4gY2FyZGlhYyBkZWF0aDogYSByZXBvcnQgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ug

b2YgQ2FyZGlvbG9neS9BbWVyaWNhbiBIZWFydCBBc3NvY2lhdGlvbiBUYXNrIEZvcmNlIGFuZCB0

aGUgRXVyb3BlYW4gU29jaWV0eSBvZiBDYXJkaW9sb2d5IENvbW1pdHRlZSBmb3IgUHJhY3RpY2Ug

R3VpZGVsaW5lcyAoV3JpdGluZyBDb21taXR0ZWUgdG8gRGV2ZWxvcCBHdWlkZWxpbmVzIGZvciBN

YW5hZ2VtZW50IG9mIFBhdGllbnRzIFdpdGggVmVudHJpY3VsYXIgQXJyaHl0aG1pYXMgYW5kIHRo

ZSBQcmV2ZW50aW9uIG9mIFN1ZGRlbiBDYXJkaWFjIERlYXRoKTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5KIEFtIENvbGwgQ2FyZGlvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5h

bCBvZiB0aGUgQW1lcmljYW4gQ29sbGVnZSBvZiBDYXJkaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRs

ZXM+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIENv

bGxlZ2Ugb2YgQ2FyZGlvbG9neTwvZnVsbC10aXRsZT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz5l

MjQ3LTM0NjwvcGFnZXM+PHZvbHVtZT40ODwvdm9sdW1lPjxudW1iZXI+NTwvbnVtYmVyPjxlZGl0

aW9uPjIwMDYvMDkvMDU8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFudGktQXJyaHl0aG1p

YSBBZ2VudHMvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgT3V0cHV0

LCBMb3c8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9r

ZXl3b3JkPjxrZXl3b3JkPkNhdGhldGVyIEFibGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRo

LCBTdWRkZW4sIENhcmRpYWMvKmV0aW9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tl

eXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3

b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgQXJyZXN0L2V0

aW9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgRnVuY3Rpb24gVGVzdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50

cmljdWxhci8qY29tcGxpY2F0aW9ucy8qZHJ1ZyB0aGVyYXB5L3BoeXNpb3BhdGhvbG9neTwva2V5

d29yZD48a2V5d29yZD5WZW50cmljdWxhciBGaWJyaWxsYXRpb24vKmNvbXBsaWNhdGlvbnMvKmRy

dWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHll

YXI+MjAwNjwveWVhcj48cHViLWRhdGVzPjxkYXRlPlNlcCA1PC9kYXRlPjwvcHViLWRhdGVzPjwv

ZGF0ZXM+PGlzYm4+MDczNS0xMDk3PC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE2OTQ5NDc4PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9q

LmphY2MuMjAwNi4wNy4wMTA8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJh

c2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwv

bGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE.DATA (Epstein et al., 2008; Zipes et al., 2006), and Medicare funding through the MBS is available for primary and secondary prevention of SCD.Table SEQ Table \* ARABIC 1 Current MBS item descriptor for insertion of transvenous ICD lead (primary prevention)Category 3 – Therapeutic ProceduresMBS: 38384AUTOMATIC DEFIBRILLATOR, insertion of patches for, or insertion of transvenous endocardial defibrillation electrodes for, primary prevention of sudden cardiac death in: - patients with a left ventricular ejection fraction of less than or equal to 30% at least one month after a myocardial infarct when the patient has received optimised medical therapy; or - patients with chronic heart failure associated with mild to moderate symptoms (NYHA II and III) and a left ventricular ejection fraction less than or equal to 35% when the patient has received optimised medical therapy. Not being a service associated with a service to which item 38213 applies Multiple Services Rule (Anaes.) (Assist.) Fee: $1,052.65Explanatory note:T8.67 Implantable Cardioverter Defibrillator (Items 38384 and 38387)Items 38384 and 38387 apply only to patients who meet the criteria listed in the item descriptor, and to patients who do not meet the criteria listed in the descriptor but have previously had an ICD device inserted and who prior to its insertion met the criteria and now need the device replaced.Table SEQ Table \* ARABIC 2 Current MBS item descriptor for insertion of transvenous ICD lead (secondary prevention)Category 3 – Therapeutic ProceduresMBS: 38390AUTOMATIC DEFIBRILLATOR, insertion of patches for, or insertion of transvenous endocardial defibrillation electrodes for - not for patients with heart failure or as primary prevention for tachycardia arrhythmias. Not being a service associated with a service to which item 38213 applies Multiple Services Rule (Anaes.) (Assist.) Fee: $1,052.65(No explanatory notes)A comparison between the processes for inserting a transvenous ICD and subcutaneous ICD is provided in REF _Ref371073914 \h \* MERGEFORMAT Table 3. The implications of these differences for the economic evaluation will be considered in more detail in the submission based assessment and will be used to determine an appropriate fee for the service.Table SEQ Table \* ARABIC 3 Implant procedure comparison between subcutaneous ICD lead and transvenous ICD leadSteps in the delivery of interventionProposed Service – Insertion of a subcutaneous ICD leadCurrent Service (MBS items 38384, 38390)Sedation TypeConscious or general sedationConscious or general sedationImaging TechniqueX-ray may be used post-implant to validate optimal pulse generator to lead placementFluoroscopyProcedural StepsPrep timeDevice pocket formationSubcutaneous lead placement (additional incisions and suturing required)Electrode terminal pin connection to deviceDevice programming & testing performedPocket closurePrep time Device pocket formationTransvenous lead placement under fluoroscopy Electrode terminal pin connection to deviceDevice programming & testing performedPocket closureProcedure TimeApprox. 1 hourApprox. 1 hour REF _Ref387241111 \h Table 4 presents historical and current utilisation and expenditure data for the MBS services 38384 and 38390 between July 2008 and June 2013. These data indicate a slight trend towards growth for primary prevention of SCD since 2008, while services (and MBS expenditure) for secondary prevention have remained relatively stable over the same period. It is important to note that the proposed subcutaneous ICD system will only be used in a proportion of the patient population described in REF _Ref387241111 \h Table 4. Table SEQ Table \* ARABIC 4 Count and expenditure of MBS services for transvenous ICD lead insertion from July 2008- June 2013MBS item numberPeriodServicesMBS expenditure a38384(Primary prevention)Jul 2008 – Jun 2009775$305,140Jul 2009 – Jun 2010852$322,988Jul 2010 – Jun 2011961$381,122Jul 2011 – Jun 20121,085$453,463Jul 2012 – Jun 20131,014$450,798Total4,687$1,913,51238390(Secondary prevention)Jul 2008 – Jun 2009934$424,541Jul 2009 – Jun 2010767$345,990Jul 2010 – Jun 2011821$374,031Jul 2011 – Jun 2012841$395,822Jul 2012 – Jun 2013864$426,467Total4,227$1,966,851a MBS items listed in Group T8 are subject to Multiple Operations Rule (see note T8.2 of MBS)Regulatory statusBoston Scientific’s Q-TRAK? S-ICD? lead and SQ-RX? Pulse Generator are currently listed in the Australian Register of Therapeutic Goods (ARTG).Table SEQ Table \* ARABIC 5 ARTG listings for subcutaneous ICD componentsARTG numberStart dateProduct nameIntended purpose21949923/01/2014SQ-RX Pulse GeneratorAn active implantable component of the S-ICD System. The S-ICD System is intended to provide defibrillation therapy for the treatment of life-threatening ventricular tachyarrhythmias in patients who do not have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently recurring ventricular tachycardia that is reliably terminated with anti-tachycardia. pacing.21950023/01/2014Q-TRAK Subcutaneous Lead,A component of the S-ICD System, which is prescribed for patients when cardiac arrhythmia management is warranted. The S-ICD System detects cardiac activity and provides defibrillation therapy.InterventionDescriptionThe subcutaneous ICD system provides defibrillation therapy in the event of a life threatening ventricular arrhythmia. Insertion of the subcutaneous ICD is clinically similar to the insertion of a transvenous ICD, however the subcutaneous ICD lead does not need to be inserted into the vasculature of the heart. Rather, it is placed under the skin of the patients’ chest. Shock therapy is delivered from an electrode to the ICD generator, which are both implanted subcutaneously. An overview of Boston Scientific’s Q-TRAK? S-ICD? lead and SQ-RX? Pulse Generator is provided as an appendix to this protocol.Medicare funding for subcutaneous ICD therapy would allow clinicians and patients another treatment option for ventricular arrhythmia. The application is not intended to be limited to Boston Scientific’s technology or a specific trademark. ICD technology is not indicated for other conditions; therefore there is a low risk of use outside this patient population. Delivery of the interventionBoston Scientific’s S-ICD? is comprised of the SQ-RX? model pulse generator and connected Q-TRAK? model subcutaneous lead (3mm, bipolar parasternal lead, polycarbonate urethane 55D). The Q-GUIDE? lead tunneling tool and Q-TECH? programming device are used during implantation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb2JvZHppbnNraTwvQXV0aG9yPjxZZWFyPjIwMTE8L1ll

YXI+PFJlY051bT4yMjwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQXlkaW4gZXQgYWwuLCAyMDEyOyBE

YWJpcmkgQWJrZW5hcmkgZXQgYWwuLCAyMDExOyBMb2JvZHppbnNraSwgMjAxMSk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MjI8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5

IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRp

bWVzdGFtcD0iMTM4MzExODk5MyI+MjI8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48

YXV0aG9yPkxvYm9kemluc2tpLCBTLiBTLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9y

cz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgRWxlY3RyaWNhbCBhbmQgQmlvbWVkaWNhbCBF

bmdpbmVlcmluZywgQ2FsaWZvcm5pYSBTdGF0ZSBVbml2ZXJzaXR5IExvbmcgQmVhY2gsIENBLCBV

U0EuIHNsb2JvQGNzdWxiLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlN1YmN1dGFu

ZW91cyBpbXBsYW50YWJsZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxsYXRvciAoUy1JQ0QpPC90aXRs

ZT48c2Vjb25kYXJ5LXRpdGxlPkNhcmRpb2wgSjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+

Q2FyZGlvbG9neSBqb3VybmFsPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwt

dGl0bGU+Q2FyZGlvbCBKPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FyZGlvbG9neSBqb3VybmFsPC9h

YmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYXJkaW9sIEo8

L2Z1bGwtdGl0bGU+PGFiYnItMT5DYXJkaW9sb2d5IGpvdXJuYWw8L2FiYnItMT48L2FsdC1wZXJp

b2RpY2FsPjxwYWdlcz4zMjYtMzE8L3BhZ2VzPjx2b2x1bWU+MTg8L3ZvbHVtZT48bnVtYmVyPjM8

L251bWJlcj48ZWRpdGlvbj4yMDExLzA2LzExPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5E

ZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2VwaWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNvbnRy

b2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlL2FkdmVyc2Ug

ZWZmZWN0cy9zdGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhLyp0cmVuZHM8L2tleXdvcmQ+

PGtleXdvcmQ+RGV2aWNlIEFwcHJvdmFsPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9kZXMsIElt

cGxhbnRlZC9hZHZlcnNlIGVmZmVjdHMvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YS8q

dHJlbmRzPC9rZXl3b3JkPjxrZXl3b3JkPkV1cm9wZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8

L2tleXdvcmQ+PGtleXdvcmQ+KlByb3N0aGVzaXMgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPlBy

b3N0aGVzaXMgSW1wbGFudGF0aW9uLyptZXRob2RzL3RyZW5kczwva2V5d29yZD48a2V5d29yZD5S

aXNrIEZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+VGFjaHljYXJkaWEsIFZlbnRyaWN1bGFyLyp0

aGVyYXB5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRl

cz48aXNibj4xODk4LTAxOHg8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjE2NjA5Mjg8L2FjY2Vzc2lv

bi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUt

ZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRl

PjxDaXRlPjxBdXRob3I+RGFiaXJpIEFia2VuYXJpPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48

UmVjTnVtPjI0PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yNDwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAy

MnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTMzMjQ3Ij4yNDwva2V5PjwvZm9yZWlnbi1rZXlz

PjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9yPjxhdXRob3I+

VGhldW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+VmFsaywgUy4gRC48L2F1dGhvcj48YXV0aG9y

PlZhbiBCZWxsZSwgWS48L2F1dGhvcj48YXV0aG9yPmRlIEdyb290LCBOLiBNLjwvYXV0aG9yPjxh

dXRob3I+SGFpdHNtYSwgRC48L2F1dGhvcj48YXV0aG9yPk11c2tlbnMtSGVlbXNrZXJrLCBBLjwv

YXV0aG9yPjxhdXRob3I+U3ppbGktVG9yb2ssIFQuPC9hdXRob3I+PGF1dGhvcj5Kb3JkYWVucywg

TC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRt

ZW50IG9mIENhcmRpb2xvZ3ksIEVyYXNtdXMgTUMsIFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRz

LjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNsaW5pY2FsIGV4cGVyaWVuY2Ugd2l0aCBh

IG5vdmVsIHN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBkZWZpYnJpbGxhdG9yIHN5c3RlbSBpbiBh

IHNpbmdsZSBjZW50ZXI8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2xpbiBSZXMgQ2FyZGlvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9n

eSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FsdC10

aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DbGluIFJlcyBDYXJkaW9sPC9m

dWxsLXRpdGxlPjxhYmJyLTE+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9neSA6IG9mZmlj

aWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FiYnItMT48L3Blcmlv

ZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRpb2w8L2Z1bGwt

dGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDogb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwvYWx0LXBlcmlv

ZGljYWw+PHBhZ2VzPjczNy00NDwvcGFnZXM+PHZvbHVtZT4xMDA8L3ZvbHVtZT48bnVtYmVyPjk8

L251bWJlcj48ZWRpdGlvbj4yMDExLzAzLzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5B

ZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFz

LCBDYXJkaWFjL3BoeXNpb3BhdGhvbG9neS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPipEZWZp

YnJpbGxhdG9ycywgSW1wbGFudGFibGUvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3JkPjxrZXl3b3Jk

PkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5d29yZD48a2V5

d29yZD5IZWFydCBEaXNlYXNlcy9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtl

eXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWlk

ZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+UmVjdXJyZW5jZS9wcmV2ZW50aW9uICZhbXA7IGNv

bnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxrZXl3b3JkPlZl

bnRyaWN1bGFyIEZpYnJpbGxhdGlvbi9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPlNlcDwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE4NjEtMDY4NDwvaXNibj48YWNjZXNzaW9u

LW51bT4yMTQxNjE5MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3RvbTI+UG1jMzE2

NzA0MDwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAwNy9zMDAzOTItMDEx

LTAzMDMtNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRl

cj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48

L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5BeWRpbjwvQXV0aG9yPjxZZWFyPjIwMTI8L1ll

YXI+PFJlY051bT4yNTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MjU8L3JlYy1udW1iZXI+

PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1

eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzEzMzMxOCI+MjU8L2tleT48L2ZvcmVpZ24t

a2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRy

aWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkF5ZGluLCBBLjwvYXV0aG9yPjxhdXRob3I+SGFydGVs

LCBGLjwvYXV0aG9yPjxhdXRob3I+U2NobHV0ZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5CdXR0ZXIs

IEMuPC9hdXRob3I+PGF1dGhvcj5Lb2JlLCBKLjwvYXV0aG9yPjxhdXRob3I+U2VpZmVydCwgTS48

L2F1dGhvcj48YXV0aG9yPkdvc2F1LCBOLjwvYXV0aG9yPjxhdXRob3I+SG9mZm1hbm4sIEIuPC9h

dXRob3I+PGF1dGhvcj5Ib2ZmbWFubiwgTS48L2F1dGhvcj48YXV0aG9yPlZldHRvcmF6emksIEUu

PC9hdXRob3I+PGF1dGhvcj5XaWxrZSwgSS48L2F1dGhvcj48YXV0aG9yPldlZ3NjaGVpZGVyLCBL

LjwvYXV0aG9yPjxhdXRob3I+UmVpY2hlbnNwdXJuZXIsIEguPC9hdXRob3I+PGF1dGhvcj5FY2th

cmR0LCBMLjwvYXV0aG9yPjxhdXRob3I+U3RldmVuLCBELjwvYXV0aG9yPjxhdXRob3I+V2lsbGVt

cywgUy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBh

cnRtZW50IG9mIEVsZWN0cm9waHlzaW9sb2d5LCBVbml2ZXJzaXR5IEhlYXJ0IENlbnRlciwgSGFt

YnVyZywgR2VybWFueS4gYXlkaW5AdWtlLmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+

U2hvY2sgZWZmaWNhY3kgb2Ygc3ViY3V0YW5lb3VzIGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1k

ZWZpYnJpbGxhdG9yIGZvciBwcmV2ZW50aW9uIG9mIHN1ZGRlbiBjYXJkaWFjIGRlYXRoOiBpbml0

aWFsIG11bHRpY2VudGVyIGV4cGVyaWVuY2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2lyYyBB

cnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2lyY3Vs

YXRpb24uIEFycmh5dGhtaWEgYW5kIGVsZWN0cm9waHlzaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwv

ZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5

c2lvbG9neTwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+

Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0

aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5c2lvbG9neTwvYWJici0xPjwvYWx0LXBlcmlv

ZGljYWw+PHBhZ2VzPjkxMy05PC9wYWdlcz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjU8L251

bWJlcj48ZWRpdGlvbj4yMDEyLzA4LzI4PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVs

dDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4s

IENhcmRpYWMvKnByZXZlbnRpb24gJmFtcDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD4qRGVm

aWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVjaG9jYXJkaW9ncmFw

aHk8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBT

dHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkdlcm1hbnk8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5z

PC9rZXl3b3JkPjxrZXl3b3JkPkxvZ2lzdGljIE1vZGVsczwva2V5d29yZD48a2V5d29yZD5NYWdu

ZXRpYyBSZXNvbmFuY2UgSW1hZ2luZzwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxr

ZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPlBhdGllbnQgU2VsZWN0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlByaW1hcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TZWNv

bmRhcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3Jk

PjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci9waHlzaW9wYXRob2xvZ3kvKnRoZXJh

cHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJlYXRtZW50IE91dGNvbWU8L2tleXdvcmQ+PC9rZXl3b3Jk

cz48ZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48cHViLWRhdGVzPjxkYXRlPk9jdDwvZGF0ZT48L3B1

Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE5NDEtMzA4NDwvaXNibj48YWNjZXNzaW9uLW51bT4yMjky

MzI3NDwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PjEwLjExNjEvY2lyY2VwLjExMi45NzMzMzk8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1

YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb2JvZHppbnNraTwvQXV0aG9yPjxZZWFyPjIwMTE8L1ll

YXI+PFJlY051bT4yMjwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQXlkaW4gZXQgYWwuLCAyMDEyOyBE

YWJpcmkgQWJrZW5hcmkgZXQgYWwuLCAyMDExOyBMb2JvZHppbnNraSwgMjAxMSk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MjI8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5

IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRp

bWVzdGFtcD0iMTM4MzExODk5MyI+MjI8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48

YXV0aG9yPkxvYm9kemluc2tpLCBTLiBTLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9y

cz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgRWxlY3RyaWNhbCBhbmQgQmlvbWVkaWNhbCBF

bmdpbmVlcmluZywgQ2FsaWZvcm5pYSBTdGF0ZSBVbml2ZXJzaXR5IExvbmcgQmVhY2gsIENBLCBV

U0EuIHNsb2JvQGNzdWxiLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlN1YmN1dGFu

ZW91cyBpbXBsYW50YWJsZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxsYXRvciAoUy1JQ0QpPC90aXRs

ZT48c2Vjb25kYXJ5LXRpdGxlPkNhcmRpb2wgSjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+

Q2FyZGlvbG9neSBqb3VybmFsPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwt

dGl0bGU+Q2FyZGlvbCBKPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FyZGlvbG9neSBqb3VybmFsPC9h

YmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYXJkaW9sIEo8

L2Z1bGwtdGl0bGU+PGFiYnItMT5DYXJkaW9sb2d5IGpvdXJuYWw8L2FiYnItMT48L2FsdC1wZXJp

b2RpY2FsPjxwYWdlcz4zMjYtMzE8L3BhZ2VzPjx2b2x1bWU+MTg8L3ZvbHVtZT48bnVtYmVyPjM8

L251bWJlcj48ZWRpdGlvbj4yMDExLzA2LzExPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5E

ZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2VwaWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNvbnRy

b2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlL2FkdmVyc2Ug

ZWZmZWN0cy9zdGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhLyp0cmVuZHM8L2tleXdvcmQ+

PGtleXdvcmQ+RGV2aWNlIEFwcHJvdmFsPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9kZXMsIElt

cGxhbnRlZC9hZHZlcnNlIGVmZmVjdHMvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YS8q

dHJlbmRzPC9rZXl3b3JkPjxrZXl3b3JkPkV1cm9wZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8

L2tleXdvcmQ+PGtleXdvcmQ+KlByb3N0aGVzaXMgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPlBy

b3N0aGVzaXMgSW1wbGFudGF0aW9uLyptZXRob2RzL3RyZW5kczwva2V5d29yZD48a2V5d29yZD5S

aXNrIEZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+VGFjaHljYXJkaWEsIFZlbnRyaWN1bGFyLyp0

aGVyYXB5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRl

cz48aXNibj4xODk4LTAxOHg8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjE2NjA5Mjg8L2FjY2Vzc2lv

bi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUt

ZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRl

PjxDaXRlPjxBdXRob3I+RGFiaXJpIEFia2VuYXJpPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48

UmVjTnVtPjI0PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yNDwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAy

MnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTMzMjQ3Ij4yNDwva2V5PjwvZm9yZWlnbi1rZXlz

PjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9yPjxhdXRob3I+

VGhldW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+VmFsaywgUy4gRC48L2F1dGhvcj48YXV0aG9y

PlZhbiBCZWxsZSwgWS48L2F1dGhvcj48YXV0aG9yPmRlIEdyb290LCBOLiBNLjwvYXV0aG9yPjxh

dXRob3I+SGFpdHNtYSwgRC48L2F1dGhvcj48YXV0aG9yPk11c2tlbnMtSGVlbXNrZXJrLCBBLjwv

YXV0aG9yPjxhdXRob3I+U3ppbGktVG9yb2ssIFQuPC9hdXRob3I+PGF1dGhvcj5Kb3JkYWVucywg

TC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRt

ZW50IG9mIENhcmRpb2xvZ3ksIEVyYXNtdXMgTUMsIFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRz

LjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNsaW5pY2FsIGV4cGVyaWVuY2Ugd2l0aCBh

IG5vdmVsIHN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBkZWZpYnJpbGxhdG9yIHN5c3RlbSBpbiBh

IHNpbmdsZSBjZW50ZXI8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2xpbiBSZXMgQ2FyZGlvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9n

eSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FsdC10

aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DbGluIFJlcyBDYXJkaW9sPC9m

dWxsLXRpdGxlPjxhYmJyLTE+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9neSA6IG9mZmlj

aWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FiYnItMT48L3Blcmlv

ZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRpb2w8L2Z1bGwt

dGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDogb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwvYWx0LXBlcmlv

ZGljYWw+PHBhZ2VzPjczNy00NDwvcGFnZXM+PHZvbHVtZT4xMDA8L3ZvbHVtZT48bnVtYmVyPjk8

L251bWJlcj48ZWRpdGlvbj4yMDExLzAzLzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5B

ZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFz

LCBDYXJkaWFjL3BoeXNpb3BhdGhvbG9neS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPipEZWZp

YnJpbGxhdG9ycywgSW1wbGFudGFibGUvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3JkPjxrZXl3b3Jk

PkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5d29yZD48a2V5

d29yZD5IZWFydCBEaXNlYXNlcy9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtl

eXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWlk

ZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+UmVjdXJyZW5jZS9wcmV2ZW50aW9uICZhbXA7IGNv

bnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxrZXl3b3JkPlZl

bnRyaWN1bGFyIEZpYnJpbGxhdGlvbi9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPlNlcDwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE4NjEtMDY4NDwvaXNibj48YWNjZXNzaW9u

LW51bT4yMTQxNjE5MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3RvbTI+UG1jMzE2

NzA0MDwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAwNy9zMDAzOTItMDEx

LTAzMDMtNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRl

cj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48

L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5BeWRpbjwvQXV0aG9yPjxZZWFyPjIwMTI8L1ll

YXI+PFJlY051bT4yNTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MjU8L3JlYy1udW1iZXI+

PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1

eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzEzMzMxOCI+MjU8L2tleT48L2ZvcmVpZ24t

a2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRy

aWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkF5ZGluLCBBLjwvYXV0aG9yPjxhdXRob3I+SGFydGVs

LCBGLjwvYXV0aG9yPjxhdXRob3I+U2NobHV0ZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5CdXR0ZXIs

IEMuPC9hdXRob3I+PGF1dGhvcj5Lb2JlLCBKLjwvYXV0aG9yPjxhdXRob3I+U2VpZmVydCwgTS48

L2F1dGhvcj48YXV0aG9yPkdvc2F1LCBOLjwvYXV0aG9yPjxhdXRob3I+SG9mZm1hbm4sIEIuPC9h

dXRob3I+PGF1dGhvcj5Ib2ZmbWFubiwgTS48L2F1dGhvcj48YXV0aG9yPlZldHRvcmF6emksIEUu

PC9hdXRob3I+PGF1dGhvcj5XaWxrZSwgSS48L2F1dGhvcj48YXV0aG9yPldlZ3NjaGVpZGVyLCBL

LjwvYXV0aG9yPjxhdXRob3I+UmVpY2hlbnNwdXJuZXIsIEguPC9hdXRob3I+PGF1dGhvcj5FY2th

cmR0LCBMLjwvYXV0aG9yPjxhdXRob3I+U3RldmVuLCBELjwvYXV0aG9yPjxhdXRob3I+V2lsbGVt

cywgUy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBh

cnRtZW50IG9mIEVsZWN0cm9waHlzaW9sb2d5LCBVbml2ZXJzaXR5IEhlYXJ0IENlbnRlciwgSGFt

YnVyZywgR2VybWFueS4gYXlkaW5AdWtlLmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+

U2hvY2sgZWZmaWNhY3kgb2Ygc3ViY3V0YW5lb3VzIGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1k

ZWZpYnJpbGxhdG9yIGZvciBwcmV2ZW50aW9uIG9mIHN1ZGRlbiBjYXJkaWFjIGRlYXRoOiBpbml0

aWFsIG11bHRpY2VudGVyIGV4cGVyaWVuY2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2lyYyBB

cnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2lyY3Vs

YXRpb24uIEFycmh5dGhtaWEgYW5kIGVsZWN0cm9waHlzaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwv

ZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5

c2lvbG9neTwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+

Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0

aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5c2lvbG9neTwvYWJici0xPjwvYWx0LXBlcmlv

ZGljYWw+PHBhZ2VzPjkxMy05PC9wYWdlcz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjU8L251

bWJlcj48ZWRpdGlvbj4yMDEyLzA4LzI4PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVs

dDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4s

IENhcmRpYWMvKnByZXZlbnRpb24gJmFtcDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD4qRGVm

aWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVjaG9jYXJkaW9ncmFw

aHk8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBT

dHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkdlcm1hbnk8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5z

PC9rZXl3b3JkPjxrZXl3b3JkPkxvZ2lzdGljIE1vZGVsczwva2V5d29yZD48a2V5d29yZD5NYWdu

ZXRpYyBSZXNvbmFuY2UgSW1hZ2luZzwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxr

ZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPlBhdGllbnQgU2VsZWN0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlByaW1hcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TZWNv

bmRhcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3Jk

PjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci9waHlzaW9wYXRob2xvZ3kvKnRoZXJh

cHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJlYXRtZW50IE91dGNvbWU8L2tleXdvcmQ+PC9rZXl3b3Jk

cz48ZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48cHViLWRhdGVzPjxkYXRlPk9jdDwvZGF0ZT48L3B1

Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE5NDEtMzA4NDwvaXNibj48YWNjZXNzaW9uLW51bT4yMjky

MzI3NDwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PjEwLjExNjEvY2lyY2VwLjExMi45NzMzMzk8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1

YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Aydin et al., 2012; Dabiri Abkenari et al., 2011; Lobodzinski, 2011).Lead placement is via anatomical incisions made at the mid-axillary line, xiphoid mid-line and superior parasternal area. The lead is then inserted subcutaneously via a tunnelling tool and sutured in place. An incision and pocket is created in the vicinity of the left 5th and 6th intercostal spaces at the mid-axillary line where the ICD generator is implanted. Once connected to the lead, it is placed in the pocket and sutured closed.A comparison of transvenous ICD and subcutaneous ICD insertion will be presented in the submission based assessment. PrerequisitesImplantation of a subcutaneous ICD device is clinically similar to the insertion of a transvenous ICD in terms of staffing, procedure time and required infrastructure. As such, the necessary capabilities to perform subcutaneous ICD implantation are already established at the relevant clinics and institutions. Unlike transvenous ICD, subcutaneous ICD does not require fluoroscopy or other medical imaging systems found in an electrophysiology laboratory. Therefore, it is expected that this procedure will decrease the burden on current imaging infrastructure and associated costs to the MBS. As is the case for transvenous ICD lead insertion, all subcutaneous ICD lead insertions will take place in a hospital setting.Furthermore, as those specialists involved in the insertion of a subcutaneous ICD lead would be the same with the expanded listing as currently required, the proposed listing is not expected to lead to any incremental resource requirements. Manufacturers of subcutaneous ICD technology provide training to hospital staff.Co-administered and associated interventionsThe diagnostic tests required to establish whether a patient is indicated for subcutaneous ICD therapy are the same as for transvenous ICD. Optimal medical and pharmaceutical therapy for chronic heart failure would be provided in accordance with Australian clinical practice guidelines ADDIN EN.CITE <EndNote><Cite><Author>Krum</Author><Year>2011</Year><RecNum>26</RecNum><DisplayText>(Krum, Jelinek, Stewart, Sindone, &amp; Atherton, 2011)</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183520">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Krum, H.</author><author>Jelinek, M. V.</author><author>Stewart, S.</author><author>Sindone, A.</author><author>Atherton, J. J.</author></authors></contributors><auth-address>Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. henry.krum@monash.edu</auth-address><titles><title>2011 update to National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines for the prevention, detection and management of chronic heart failure in Australia, 2006</title><secondary-title>Med J Aust</secondary-title><alt-title>The Medical journal of Australia</alt-title></titles><periodical><full-title>Med J Aust</full-title><abbr-1>The Medical journal of Australia</abbr-1></periodical><alt-periodical><full-title>Med J Aust</full-title><abbr-1>The Medical journal of Australia</abbr-1></alt-periodical><pages>405-9</pages><volume>194</volume><number>8</number><edition>2011/04/19</edition><keywords><keyword>Australia</keyword><keyword>Cardiac Surgical Procedures</keyword><keyword>Cardiovascular Agents/therapeutic use</keyword><keyword>Heart Failure/complications/*diagnosis/*therapy</keyword><keyword>Humans</keyword><keyword>New Zealand</keyword><keyword>Practice Guidelines as Topic</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 18</date></pub-dates></dates><isbn>0025-729x</isbn><accession-num>21495941</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Krum, Jelinek, Stewart, Sindone, & Atherton, 2011). In the majority of patients receiving ICD therapy, medications would remain unchanged after device implantation.Subcutaneous ICD system implantation is commonly provided under conscious or general sedation, as is transvenous ICD. An anaesthetist may be required to provide the appropriate level of sedation. There is no need for fluoroscopy or other medical imaging systems found in an electrophysiology laboratory.Diagnosis and medication use for patients receiving a subcutaneous ICD is expected to be similar to transvenous ICD patients. Subcutaneous ICD may be associated with less imaging. Replacement proceduresThe insertion of a subcutaneous ICD lead and associated generator is a once-off procedure and the therapy is for the lifetime of the patient. If the patient requires a new generator (in the event that the battery expires) then the new generator can be connected to the existing subcutaneous ICD lead i.e. there is no additional cost for technology or physician fee for replacement of a subcutaneous ICD lead. This is no different to insertion and replacement of a transvenous ICD generator.The insertion of a subcutaneous ICD lead is a once-off procedure. This is same as for a transvenous ICD lead. Any differences in lead and generator longevity will be evaluated in the submission based assessment. Patient Selection for subcutaneous ICDIt is important to assess the clinical need of each individual ICD patient, in order to avoid exposure to potentially harmful surgery if it is unnecessary. Such a selection process is currently performed in clinical practice by the treating cardiologist or cardiac specialist when determining the appropriate transvenous ICD system (single-chamber, dual-chamber or CRT-D), and the necessary functions of that system (defibrillation, pacing, resynchronisation etc.). This process will continue should the subcutaneous ICD system be included on the MBS, as the treating clinician will determine which of their patients are clinically appropriate for subcutaneous ICD therapy. The subcutaneous ICD system provides a reliable alternative for a large population of ICD patients, but may be more preferable for certain patient groups such as: Younger patients that will require decades of ICD therapy – expected to be patients with a life expectancy greater than 15 years In patients who are at high risk for infection – patients with diabetes, renal impairment, paediatric and small patients In patients with difficult venous anatomy – patients with left persistent superior vena cava (LPSVC), capped ICD leads, occluded veins and diseased or mechanical tricuspid valvesThe identification of these preferential patient sub-groups for subcutaneous ICD therapy is yet to be quantified in clinical trials. Therefore, the proposed submission does not intend to demonstrate differences in clinical outcomes for patients who may be preferable for subcutaneous ICD therapy. Rather, it will focus on all patients in need of defibrillation therapy for the treatment of life-threatening ventricular arrhythmias, in whom pacing is not required.Medical condition and population eligible for the proposed interventionChronic heart failureHeart failure is a complex syndrome resulting from any structural or functional cardiac abnormality that reduces the ability of the heart to function as a pump ADDIN EN.CITE <EndNote><Cite><Author>Cowie</Author><Year>2002</Year><RecNum>27</RecNum><DisplayText>(Cowie &amp; Zaphiriou, 2002)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183689">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cowie, M. R.</author><author>Zaphiriou, A.</author></authors></contributors><auth-address>Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London SW3 6LY. m.cowie@ic.ac.uk</auth-address><titles><title>Management of chronic heart failure</title><secondary-title>Bmj</secondary-title><alt-title>BMJ (Clinical research ed.)</alt-title></titles><periodical><full-title>Bmj</full-title><abbr-1>BMJ (Clinical research ed.)</abbr-1></periodical><alt-periodical><full-title>Bmj</full-title><abbr-1>BMJ (Clinical research ed.)</abbr-1></alt-periodical><pages>422-5</pages><volume>325</volume><number>7361</number><edition>2002/08/24</edition><keywords><keyword>Clinical Trials as Topic</keyword><keyword>Communication</keyword><keyword>Heart Failure/diagnosis/*therapy</keyword><keyword>Humans</keyword><keyword>Life Style</keyword><keyword>Patient Education as Topic</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 24</date></pub-dates></dates><isbn>0959-535x</isbn><accession-num>12193359</accession-num><urls></urls><custom2>Pmc1123941</custom2><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Cowie & Zaphiriou, 2002), and is a major cause of morbidity and mortality in Western societies. The condition is characterised by dyspnoea, fatigue, and fluid retention ADDIN EN.CITE <EndNote><Cite><Author>Cowie</Author><Year>2002</Year><RecNum>27</RecNum><DisplayText>(Cowie &amp; Zaphiriou, 2002)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183689">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cowie, M. R.</author><author>Zaphiriou, A.</author></authors></contributors><auth-address>Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London SW3 6LY. m.cowie@ic.ac.uk</auth-address><titles><title>Management of chronic heart failure</title><secondary-title>Bmj</secondary-title><alt-title>BMJ (Clinical research ed.)</alt-title></titles><periodical><full-title>Bmj</full-title><abbr-1>BMJ (Clinical research ed.)</abbr-1></periodical><alt-periodical><full-title>Bmj</full-title><abbr-1>BMJ (Clinical research ed.)</abbr-1></alt-periodical><pages>422-5</pages><volume>325</volume><number>7361</number><edition>2002/08/24</edition><keywords><keyword>Clinical Trials as Topic</keyword><keyword>Communication</keyword><keyword>Heart Failure/diagnosis/*therapy</keyword><keyword>Humans</keyword><keyword>Life Style</keyword><keyword>Patient Education as Topic</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 24</date></pub-dates></dates><isbn>0959-535x</isbn><accession-num>12193359</accession-num><urls></urls><custom2>Pmc1123941</custom2><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Cowie & Zaphiriou, 2002). Patients with heart failure have limited exercise capacity, frequent need for hospitalisation, high rates of mortality and an impaired quality of life ADDIN EN.CITE <EndNote><Cite><Author>Hare</Author><Year>2002</Year><RecNum>28</RecNum><DisplayText>(Hare, 2002)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183799">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hare, J. M.</author></authors></contributors><titles><title>Cardiac-resynchronization therapy for heart failure</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></periodical><alt-periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></alt-periodical><pages>1902-5</pages><volume>346</volume><number>24</number><edition>2002/06/14</edition><keywords><keyword>Cardiac Pacing, Artificial/*methods</keyword><keyword>Exercise Tolerance</keyword><keyword>Heart Failure/physiopathology/*therapy</keyword><keyword>Humans</keyword><keyword>Pacemaker, Artificial</keyword></keywords><dates><year>2002</year><pub-dates><date>Jun 13</date></pub-dates></dates><isbn>0028-4793</isbn><accession-num>12063376</accession-num><urls></urls><electronic-resource-num>10.1056/NEJMed020028</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Hare, 2002). The effectiveness of cardiac muscle contraction is represented by the measurement of LVEF. This is calculated as the percentage of blood present in the heart that is ejected with each contraction. The fraction is normally greater than 50%. The effect to which the symptoms of heart failure affect functional capacity can be assessed using the NYHA classification PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BaG1lZDwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl

Y051bT4zNjwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQWhtZWQsIDIwMDM7IEtydW0gZXQgYWwuLCAy

MDExKTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4zNjwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAy

MnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMjYyMTY0Ij4zNjwva2V5PjwvZm9yZWlnbi1rZXlz

PjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+QWhtZWQsIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJp

YnV0b3JzPjxhdXRoLWFkZHJlc3M+RGl2aXNpb24gb2YgR2Vyb250b2xvZ3kgYW5kIEdlcmlhdHJp

YyBNZWRpY2luZSwgU2Nob29sIG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIEFsYWJhbWEgYXQg

QmlybWluZ2hhbSBhbmQgSGVhcnQgRmFpbHVyZSBDbGluaWMgYW5kIFNlY3Rpb24gb2YgR2Vyb250

b2xvZ3ksIFZBIE1lZGljYWwgQ2VudGVyLCBCaXJtaW5naGFtLCBBbGFiYW1hIDM1Mjk0LTIwNDEs

IFVTQS4gYWFobWVkQHVhYi5lZHU8L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BbWVyaWNh

biBDb2xsZWdlIG9mIENhcmRpb2xvZ3kvQW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb24gQ2hyb25p

YyBIZWFydCBGYWlsdXJlIEV2YWx1YXRpb24gYW5kIE1hbmFnZW1lbnQgZ3VpZGVsaW5lczogcmVs

ZXZhbmNlIHRvIHRoZSBnZXJpYXRyaWMgcHJhY3RpY2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

SiBBbSBHZXJpYXRyIFNvYzwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0

aGUgQW1lcmljYW4gR2VyaWF0cmljcyBTb2NpZXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlv

ZGljYWw+PGZ1bGwtdGl0bGU+SiBBbSBHZXJpYXRyIFNvYzwvZnVsbC10aXRsZT48YWJici0xPkpv

dXJuYWwgb2YgdGhlIEFtZXJpY2FuIEdlcmlhdHJpY3MgU29jaWV0eTwvYWJici0xPjwvcGVyaW9k

aWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SiBBbSBHZXJpYXRyIFNvYzwvZnVsbC10

aXRsZT48YWJici0xPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIEdlcmlhdHJpY3MgU29jaWV0eTwv

YWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEyMy02PC9wYWdlcz48dm9sdW1lPjUxPC92

b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGVkaXRpb24+MjAwMy8wMS8yMjwvZWRpdGlvbj48a2V5

d29yZHM+PGtleXdvcmQ+QWRyZW5lcmdpYyBiZXRhLUFudGFnb25pc3RzL3RoZXJhcGV1dGljIHVz

ZTwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFuZ2lvdGVuc2luLUNv

bnZlcnRpbmcgRW56eW1lIEluaGliaXRvcnMvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3

b3JkPkNocm9uaWMgRGlzZWFzZTwva2V5d29yZD48a2V5d29yZD5FY2hvY2FyZGlvZ3JhcGh5PC9r

ZXl3b3JkPjxrZXl3b3JkPkdlcmlhdHJpY3M8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgRmFpbHVy

ZS9kaWFnbm9zaXMvKmRydWcgdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+SHlkcmFsYXppbmUvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3Jk

PlByYWN0aWNlIEd1aWRlbGluZXMgYXMgVG9waWM8L2tleXdvcmQ+PGtleXdvcmQ+VmFzb2RpbGF0

b3IgQWdlbnRzL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29yZD5WZW50cmljdWxhciBE

eXNmdW5jdGlvbiwgTGVmdC9kaWFnbm9zaXMvZHJ1ZyB0aGVyYXB5PC9rZXl3b3JkPjwva2V5d29y

ZHM+PGRhdGVzPjx5ZWFyPjIwMDM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KYW48L2RhdGU+PC9w

dWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDAyLTg2MTQgKFByaW50KSYjeEQ7MDAwMi04NjE0PC9p

c2JuPjxhY2Nlc3Npb24tbnVtPjEyNTM0ODU2PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48

cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxs

YW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPktydW08

L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNOdW0+MjY8L1JlY051bT48cmVjb3JkPjxyZWMt

bnVtYmVyPjI2PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0i

ZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxODM1

MjAiPjI2PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNs

ZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5LcnVtLCBILjwv

YXV0aG9yPjxhdXRob3I+SmVsaW5laywgTS4gVi48L2F1dGhvcj48YXV0aG9yPlN0ZXdhcnQsIFMu

PC9hdXRob3I+PGF1dGhvcj5TaW5kb25lLCBBLjwvYXV0aG9yPjxhdXRob3I+QXRoZXJ0b24sIEou

IEouPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+Q2VudHJl

IG9mIENhcmRpb3Zhc2N1bGFyIFJlc2VhcmNoIGFuZCBFZHVjYXRpb24gaW4gVGhlcmFwZXV0aWNz

LCBEZXBhcnRtZW50IG9mIEVwaWRlbWlvbG9neSBhbmQgUHJldmVudGl2ZSBNZWRpY2luZSwgTW9u

YXNoIFVuaXZlcnNpdHksIE1lbGJvdXJuZSwgVklDLiBoZW5yeS5rcnVtQG1vbmFzaC5lZHU8L2F1

dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT4yMDExIHVwZGF0ZSB0byBOYXRpb25hbCBIZWFydCBG

b3VuZGF0aW9uIG9mIEF1c3RyYWxpYSBhbmQgQ2FyZGlhYyBTb2NpZXR5IG9mIEF1c3RyYWxpYSBh

bmQgTmV3IFplYWxhbmQgR3VpZGVsaW5lcyBmb3IgdGhlIHByZXZlbnRpb24sIGRldGVjdGlvbiBh

bmQgbWFuYWdlbWVudCBvZiBjaHJvbmljIGhlYXJ0IGZhaWx1cmUgaW4gQXVzdHJhbGlhLCAyMDA2

PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk1lZCBKIEF1c3Q8L3NlY29uZGFyeS10aXRsZT48YWx0

LXRpdGxlPlRoZSBNZWRpY2FsIGpvdXJuYWwgb2YgQXVzdHJhbGlhPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TWVkIEogQXVzdDwvZnVsbC10aXRsZT48YWJici0x

PlRoZSBNZWRpY2FsIGpvdXJuYWwgb2YgQXVzdHJhbGlhPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxh

bHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5NZWQgSiBBdXN0PC9mdWxsLXRpdGxlPjxhYmJyLTE+

VGhlIE1lZGljYWwgam91cm5hbCBvZiBBdXN0cmFsaWE8L2FiYnItMT48L2FsdC1wZXJpb2RpY2Fs

PjxwYWdlcz40MDUtOTwvcGFnZXM+PHZvbHVtZT4xOTQ8L3ZvbHVtZT48bnVtYmVyPjg8L251bWJl

cj48ZWRpdGlvbj4yMDExLzA0LzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BdXN0cmFs

aWE8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlhYyBTdXJnaWNhbCBQcm9jZWR1cmVzPC9rZXl3b3Jk

PjxrZXl3b3JkPkNhcmRpb3Zhc2N1bGFyIEFnZW50cy90aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+

PGtleXdvcmQ+SGVhcnQgRmFpbHVyZS9jb21wbGljYXRpb25zLypkaWFnbm9zaXMvKnRoZXJhcHk8

L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk5ldyBaZWFsYW5kPC9r

ZXl3b3JkPjxrZXl3b3JkPlByYWN0aWNlIEd1aWRlbGluZXMgYXMgVG9waWM8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkFwciAxODwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjUtNzI5eDwvaXNibj48YWNjZXNzaW9u

LW51bT4yMTQ5NTk0MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PHJlbW90ZS1kYXRhYmFz

ZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9s

YW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BaG1lZDwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl

Y051bT4zNjwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQWhtZWQsIDIwMDM7IEtydW0gZXQgYWwuLCAy

MDExKTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4zNjwvcmVjLW51bWJlcj48Zm9y

ZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAy

MnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMjYyMTY0Ij4zNjwva2V5PjwvZm9yZWlnbi1rZXlz

PjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+QWhtZWQsIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJp

YnV0b3JzPjxhdXRoLWFkZHJlc3M+RGl2aXNpb24gb2YgR2Vyb250b2xvZ3kgYW5kIEdlcmlhdHJp

YyBNZWRpY2luZSwgU2Nob29sIG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIEFsYWJhbWEgYXQg

QmlybWluZ2hhbSBhbmQgSGVhcnQgRmFpbHVyZSBDbGluaWMgYW5kIFNlY3Rpb24gb2YgR2Vyb250

b2xvZ3ksIFZBIE1lZGljYWwgQ2VudGVyLCBCaXJtaW5naGFtLCBBbGFiYW1hIDM1Mjk0LTIwNDEs

IFVTQS4gYWFobWVkQHVhYi5lZHU8L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BbWVyaWNh

biBDb2xsZWdlIG9mIENhcmRpb2xvZ3kvQW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb24gQ2hyb25p

YyBIZWFydCBGYWlsdXJlIEV2YWx1YXRpb24gYW5kIE1hbmFnZW1lbnQgZ3VpZGVsaW5lczogcmVs

ZXZhbmNlIHRvIHRoZSBnZXJpYXRyaWMgcHJhY3RpY2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

SiBBbSBHZXJpYXRyIFNvYzwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0

aGUgQW1lcmljYW4gR2VyaWF0cmljcyBTb2NpZXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlv

ZGljYWw+PGZ1bGwtdGl0bGU+SiBBbSBHZXJpYXRyIFNvYzwvZnVsbC10aXRsZT48YWJici0xPkpv

dXJuYWwgb2YgdGhlIEFtZXJpY2FuIEdlcmlhdHJpY3MgU29jaWV0eTwvYWJici0xPjwvcGVyaW9k

aWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SiBBbSBHZXJpYXRyIFNvYzwvZnVsbC10

aXRsZT48YWJici0xPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIEdlcmlhdHJpY3MgU29jaWV0eTwv

YWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEyMy02PC9wYWdlcz48dm9sdW1lPjUxPC92

b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGVkaXRpb24+MjAwMy8wMS8yMjwvZWRpdGlvbj48a2V5

d29yZHM+PGtleXdvcmQ+QWRyZW5lcmdpYyBiZXRhLUFudGFnb25pc3RzL3RoZXJhcGV1dGljIHVz

ZTwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFuZ2lvdGVuc2luLUNv

bnZlcnRpbmcgRW56eW1lIEluaGliaXRvcnMvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3

b3JkPkNocm9uaWMgRGlzZWFzZTwva2V5d29yZD48a2V5d29yZD5FY2hvY2FyZGlvZ3JhcGh5PC9r

ZXl3b3JkPjxrZXl3b3JkPkdlcmlhdHJpY3M8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgRmFpbHVy

ZS9kaWFnbm9zaXMvKmRydWcgdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+SHlkcmFsYXppbmUvdGhlcmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3Jk

PlByYWN0aWNlIEd1aWRlbGluZXMgYXMgVG9waWM8L2tleXdvcmQ+PGtleXdvcmQ+VmFzb2RpbGF0

b3IgQWdlbnRzL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29yZD5WZW50cmljdWxhciBE

eXNmdW5jdGlvbiwgTGVmdC9kaWFnbm9zaXMvZHJ1ZyB0aGVyYXB5PC9rZXl3b3JkPjwva2V5d29y

ZHM+PGRhdGVzPjx5ZWFyPjIwMDM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KYW48L2RhdGU+PC9w

dWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDAyLTg2MTQgKFByaW50KSYjeEQ7MDAwMi04NjE0PC9p

c2JuPjxhY2Nlc3Npb24tbnVtPjEyNTM0ODU2PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48

cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxs

YW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPktydW08

L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNOdW0+MjY8L1JlY051bT48cmVjb3JkPjxyZWMt

bnVtYmVyPjI2PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0i

ZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxODM1

MjAiPjI2PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNs

ZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5LcnVtLCBILjwv

YXV0aG9yPjxhdXRob3I+SmVsaW5laywgTS4gVi48L2F1dGhvcj48YXV0aG9yPlN0ZXdhcnQsIFMu

PC9hdXRob3I+PGF1dGhvcj5TaW5kb25lLCBBLjwvYXV0aG9yPjxhdXRob3I+QXRoZXJ0b24sIEou

IEouPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+Q2VudHJl

IG9mIENhcmRpb3Zhc2N1bGFyIFJlc2VhcmNoIGFuZCBFZHVjYXRpb24gaW4gVGhlcmFwZXV0aWNz

LCBEZXBhcnRtZW50IG9mIEVwaWRlbWlvbG9neSBhbmQgUHJldmVudGl2ZSBNZWRpY2luZSwgTW9u

YXNoIFVuaXZlcnNpdHksIE1lbGJvdXJuZSwgVklDLiBoZW5yeS5rcnVtQG1vbmFzaC5lZHU8L2F1

dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT4yMDExIHVwZGF0ZSB0byBOYXRpb25hbCBIZWFydCBG

b3VuZGF0aW9uIG9mIEF1c3RyYWxpYSBhbmQgQ2FyZGlhYyBTb2NpZXR5IG9mIEF1c3RyYWxpYSBh

bmQgTmV3IFplYWxhbmQgR3VpZGVsaW5lcyBmb3IgdGhlIHByZXZlbnRpb24sIGRldGVjdGlvbiBh

bmQgbWFuYWdlbWVudCBvZiBjaHJvbmljIGhlYXJ0IGZhaWx1cmUgaW4gQXVzdHJhbGlhLCAyMDA2

PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk1lZCBKIEF1c3Q8L3NlY29uZGFyeS10aXRsZT48YWx0

LXRpdGxlPlRoZSBNZWRpY2FsIGpvdXJuYWwgb2YgQXVzdHJhbGlhPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TWVkIEogQXVzdDwvZnVsbC10aXRsZT48YWJici0x

PlRoZSBNZWRpY2FsIGpvdXJuYWwgb2YgQXVzdHJhbGlhPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxh

bHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5NZWQgSiBBdXN0PC9mdWxsLXRpdGxlPjxhYmJyLTE+

VGhlIE1lZGljYWwgam91cm5hbCBvZiBBdXN0cmFsaWE8L2FiYnItMT48L2FsdC1wZXJpb2RpY2Fs

PjxwYWdlcz40MDUtOTwvcGFnZXM+PHZvbHVtZT4xOTQ8L3ZvbHVtZT48bnVtYmVyPjg8L251bWJl

cj48ZWRpdGlvbj4yMDExLzA0LzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BdXN0cmFs

aWE8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlhYyBTdXJnaWNhbCBQcm9jZWR1cmVzPC9rZXl3b3Jk

PjxrZXl3b3JkPkNhcmRpb3Zhc2N1bGFyIEFnZW50cy90aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+

PGtleXdvcmQ+SGVhcnQgRmFpbHVyZS9jb21wbGljYXRpb25zLypkaWFnbm9zaXMvKnRoZXJhcHk8

L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk5ldyBaZWFsYW5kPC9r

ZXl3b3JkPjxrZXl3b3JkPlByYWN0aWNlIEd1aWRlbGluZXMgYXMgVG9waWM8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkFwciAxODwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjUtNzI5eDwvaXNibj48YWNjZXNzaW9u

LW51bT4yMTQ5NTk0MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PHJlbW90ZS1kYXRhYmFz

ZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9s

YW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE.DATA (Ahmed, 2003; Krum et al., 2011) ( REF _Ref371070921 \h \* MERGEFORMAT Table 6 ). Under this system, subjective symptoms are used to rank patients according to their functional capacity into four classes.Table SEQ Table \* ARABIC 6 NYHA classification of functional class for heart failure (NHF/CSANZ, 2011)Class INo limitations. Ordinary physical activity does not cause undue fatigue, dyspnoea or palpitations (asymptomatic left ventricular dysfunction).Class IISlight limitation of physical activity. Ordinary physical activity results in fatigue, palpitation, dyspnoea or angina pectoris (mild chronic heart failure).Class IIIMarked limitation of physical activity. Less than ordinary physical activity leads to symptoms (moderate chronic heart failure).Class IVUnable to carry on any physical activity without discomfort. Symptoms of CHF present at rest (severe chronic heart failure).Sudden cardiac arrest and sudden cardiac deathSCD is an abrupt loss of consciousness and unexpected death due to cardiac causes. It is a terminal event in approximately 35-50 per cent of patients with chronic heart failure ADDIN EN.CITE <EndNote><Cite><Author>Packer</Author><Year>1992</Year><RecNum>29</RecNum><DisplayText>(Packer, 1992)</DisplayText><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183887">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Packer, M.</author></authors></contributors><auth-address>Department of Medicine, Mount Sinai School of Medicine, City University of New York, N.Y. 10029.</auth-address><titles><title>Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>I50-6</pages><volume>85</volume><number>1 Suppl</number><edition>1992/01/01</edition><keywords><keyword>Arrhythmias, Cardiac/*complications/epidemiology/etiology</keyword><keyword>Cardiac Output, Low/*complications</keyword><keyword>Chronic Disease</keyword><keyword>Death, Sudden, Cardiac/*etiology</keyword><keyword>Heart Ventricles</keyword><keyword>Humans</keyword><keyword>Prevalence</keyword></keywords><dates><year>1992</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0009-7322 (Print)&#xD;0009-7322</isbn><accession-num>1728505</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Packer, 1992). Most SCDs are caused by acute, fatal ventricular arrhythmia; mostly VT and ventricular fibrillation (VF). Epidemiologic data indicate that structural coronary artery disease and their consequences are the cause of 80% of arrhythmias causing these SCD events PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdWlrdXJpPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48

UmVjTnVtPjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihIdWlrdXJpLCBDYXN0ZWxsYW5vcywgJmFt

cDsgTXllcmJ1cmcsIDIwMDE7IE15ZXJidXJnLCBJbnRlcmlhbiwgTWl0cmFuaSwgS2Vzc2xlciwg

JmFtcDsgQ2FzdGVsbGFub3MsIDE5OTcpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVy

PjMwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVw

dDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxODQwNDQiPjMw

PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8

L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5IdWlrdXJpLCBILiBWLjwv

YXV0aG9yPjxhdXRob3I+Q2FzdGVsbGFub3MsIEEuPC9hdXRob3I+PGF1dGhvcj5NeWVyYnVyZywg

Ui4gSi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBh

cnRtZW50IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE91bHUsIEZpbmxhbmQuIGhlaWtraS5o

dWlrdXJpQG91bHUuZmk8L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5TdWRkZW4gZGVhdGgg

ZHVlIHRvIGNhcmRpYWMgYXJyaHl0aG1pYXM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TiBFbmds

IEogTWVkPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5UaGUgTmV3IEVuZ2xhbmQgam91cm5h

bCBvZiBtZWRpY2luZTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxl

Pk4gRW5nbCBKIE1lZDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFs

IG9mIG1lZGljaW5lPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10

aXRsZT5OIEVuZ2wgSiBNZWQ8L2Z1bGwtdGl0bGU+PGFiYnItMT5UaGUgTmV3IEVuZ2xhbmQgam91

cm5hbCBvZiBtZWRpY2luZTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE0NzMtODI8

L3BhZ2VzPjx2b2x1bWU+MzQ1PC92b2x1bWU+PG51bWJlcj4yMDwvbnVtYmVyPjxlZGl0aW9uPjIw

MDIvMDEvMTc8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkcmVuZXJnaWMgYmV0YS1BbnRh

Z29uaXN0cy90aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdvcmQ+QW1pb2Rhcm9uZS90aGVy

YXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdvcmQ+QW50aS1BcnJoeXRobWlhIEFnZW50cy8qdGhl

cmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJkaWFjLypjb21w

bGljYXRpb25zL2RydWcgdGhlcmFweS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkJhcm9yZWZs

ZXg8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9rZXl3

b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvZXBpZGVtaW9sb2d5LypldGlvbG9n

eS8qcHJldmVudGlvbiAmYW1wOyBjb250cm9sPC9rZXl3b3JkPjxrZXl3b3JkPkRlZmlicmlsbGF0

b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD5FbGVjdHJvY2FyZGlvZ3JhcGh5PC9r

ZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IFJhdGU8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPlByaW1hcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5Qcm9nbm9z

aXM8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBGYWN0b3JzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRh

dGVzPjx5ZWFyPjIwMDE8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3YgMTU8L2RhdGU+PC9wdWIt

ZGF0ZXM+PC9kYXRlcz48aXNibj4wMDI4LTQ3OTMgKFByaW50KSYjeEQ7MDAyOC00NzkzPC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjExNzk0MTk3PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxl

Y3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTA1Ni9ORUpNcmEwMDA2NTA8L2VsZWN0cm9uaWMtcmVz

b3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2Ut

cHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxB

dXRob3I+TXllcmJ1cmc8L0F1dGhvcj48WWVhcj4xOTk3PC9ZZWFyPjxSZWNOdW0+MzE8L1JlY051

bT48cmVjb3JkPjxyZWMtbnVtYmVyPjMxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBh

cHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1l

c3RhbXA9IjEzODMxODQzODEiPjMxPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9

IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1

dGhvcj5NeWVyYnVyZywgUi4gSi48L2F1dGhvcj48YXV0aG9yPkludGVyaWFuLCBBLiwgSnIuPC9h

dXRob3I+PGF1dGhvcj5NaXRyYW5pLCBSLiBNLjwvYXV0aG9yPjxhdXRob3I+S2Vzc2xlciwgSy4g

TS48L2F1dGhvcj48YXV0aG9yPkNhc3RlbGxhbm9zLCBBLjwvYXV0aG9yPjwvYXV0aG9ycz48L2Nv

bnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRpdmlzaW9uIG9mIENhcmRpb2xvZ3ksIFVuaXZlcnNp

dHkgb2YgTWlhbWkgU2Nob29sIG9mIE1lZGljaW5lLCBKYWNrc29uIE1lbW9yaWFsIEhvc3BpdGFs

LCBhbmQgVkEgTWVkaWNhbCBDZW50ZXIsIEZsb3JpZGEgMzMxMDEsIFVTQS48L2F1dGgtYWRkcmVz

cz48dGl0bGVzPjx0aXRsZT5GcmVxdWVuY3kgb2Ygc3VkZGVuIGNhcmRpYWMgZGVhdGggYW5kIHBy

b2ZpbGVzIG9mIHJpc2s8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+QW0gSiBDYXJkaW9sPC9zZWNv

bmRhcnktdGl0bGU+PGFsdC10aXRsZT5UaGUgQW1lcmljYW4gam91cm5hbCBvZiBjYXJkaW9sb2d5

PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBDYXJkaW9s

PC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIEFtZXJpY2FuIGpvdXJuYWwgb2YgY2FyZGlvbG9neTwv

YWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBDYXJk

aW9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIEFtZXJpY2FuIGpvdXJuYWwgb2YgY2FyZGlvbG9n

eTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEwZi0xOWY8L3BhZ2VzPjx2b2x1bWU+

ODA8L3ZvbHVtZT48bnVtYmVyPjViPC9udW1iZXI+PGVkaXRpb24+MTk5Ny8wOS8xODwvZWRpdGlv

bj48a2V5d29yZHM+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QW50aS1BcnJoeXRo

bWlhIEFnZW50cy9hZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+Q29yb25hcnkgRGlz

ZWFzZS9lcGlkZW1pb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RGVhdGgsIFN1ZGRlbiwgQ2FyZGlh

Yy8qZXBpZGVtaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkRpc2Vhc2UgU3VzY2VwdGliaWxpdHk8

L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVk

aWVzPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5JbmNpZGVuY2U8

L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5

d29yZD48a2V5d29yZD5Qb3B1bGF0aW9uIER5bmFtaWNzPC9rZXl3b3JkPjxrZXl3b3JkPlByZXZh

bGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBBc3Nlc3NtZW50PC9rZXl3b3JkPjxrZXl3b3Jk

PlJpc2sgRmFjdG9yczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJpY3VsYXIv

KmVwaWRlbWlvbG9neS9ldGlvbG9neTwva2V5d29yZD48a2V5d29yZD5Ub3JzYWRlcyBkZSBQb2lu

dGVzL2NoZW1pY2FsbHkgaW5kdWNlZDwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4x

OTk3PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+U2VwIDExPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0

ZXM+PGlzYm4+MDAwMi05MTQ5IChQcmludCkmI3hEOzAwMDItOTE0OTwvaXNibj48YWNjZXNzaW9u

LW51bT45MjkxNDQ1PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNl

LXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xh

bmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdWlrdXJpPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48

UmVjTnVtPjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihIdWlrdXJpLCBDYXN0ZWxsYW5vcywgJmFt

cDsgTXllcmJ1cmcsIDIwMDE7IE15ZXJidXJnLCBJbnRlcmlhbiwgTWl0cmFuaSwgS2Vzc2xlciwg

JmFtcDsgQ2FzdGVsbGFub3MsIDE5OTcpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVy

PjMwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVw

dDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxODQwNDQiPjMw

PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8

L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5IdWlrdXJpLCBILiBWLjwv

YXV0aG9yPjxhdXRob3I+Q2FzdGVsbGFub3MsIEEuPC9hdXRob3I+PGF1dGhvcj5NeWVyYnVyZywg

Ui4gSi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBh

cnRtZW50IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE91bHUsIEZpbmxhbmQuIGhlaWtraS5o

dWlrdXJpQG91bHUuZmk8L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5TdWRkZW4gZGVhdGgg

ZHVlIHRvIGNhcmRpYWMgYXJyaHl0aG1pYXM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TiBFbmds

IEogTWVkPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5UaGUgTmV3IEVuZ2xhbmQgam91cm5h

bCBvZiBtZWRpY2luZTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxl

Pk4gRW5nbCBKIE1lZDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFs

IG9mIG1lZGljaW5lPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10

aXRsZT5OIEVuZ2wgSiBNZWQ8L2Z1bGwtdGl0bGU+PGFiYnItMT5UaGUgTmV3IEVuZ2xhbmQgam91

cm5hbCBvZiBtZWRpY2luZTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE0NzMtODI8

L3BhZ2VzPjx2b2x1bWU+MzQ1PC92b2x1bWU+PG51bWJlcj4yMDwvbnVtYmVyPjxlZGl0aW9uPjIw

MDIvMDEvMTc8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkcmVuZXJnaWMgYmV0YS1BbnRh

Z29uaXN0cy90aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdvcmQ+QW1pb2Rhcm9uZS90aGVy

YXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdvcmQ+QW50aS1BcnJoeXRobWlhIEFnZW50cy8qdGhl

cmFwZXV0aWMgdXNlPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJkaWFjLypjb21w

bGljYXRpb25zL2RydWcgdGhlcmFweS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkJhcm9yZWZs

ZXg8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9rZXl3

b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvZXBpZGVtaW9sb2d5LypldGlvbG9n

eS8qcHJldmVudGlvbiAmYW1wOyBjb250cm9sPC9rZXl3b3JkPjxrZXl3b3JkPkRlZmlicmlsbGF0

b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD5FbGVjdHJvY2FyZGlvZ3JhcGh5PC9r

ZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IFJhdGU8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPlByaW1hcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5Qcm9nbm9z

aXM8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBGYWN0b3JzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRh

dGVzPjx5ZWFyPjIwMDE8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3YgMTU8L2RhdGU+PC9wdWIt

ZGF0ZXM+PC9kYXRlcz48aXNibj4wMDI4LTQ3OTMgKFByaW50KSYjeEQ7MDAyOC00NzkzPC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjExNzk0MTk3PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxl

Y3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTA1Ni9ORUpNcmEwMDA2NTA8L2VsZWN0cm9uaWMtcmVz

b3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2Ut

cHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxB

dXRob3I+TXllcmJ1cmc8L0F1dGhvcj48WWVhcj4xOTk3PC9ZZWFyPjxSZWNOdW0+MzE8L1JlY051

bT48cmVjb3JkPjxyZWMtbnVtYmVyPjMxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBh

cHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1l

c3RhbXA9IjEzODMxODQzODEiPjMxPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9

IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1

dGhvcj5NeWVyYnVyZywgUi4gSi48L2F1dGhvcj48YXV0aG9yPkludGVyaWFuLCBBLiwgSnIuPC9h

dXRob3I+PGF1dGhvcj5NaXRyYW5pLCBSLiBNLjwvYXV0aG9yPjxhdXRob3I+S2Vzc2xlciwgSy4g

TS48L2F1dGhvcj48YXV0aG9yPkNhc3RlbGxhbm9zLCBBLjwvYXV0aG9yPjwvYXV0aG9ycz48L2Nv

bnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRpdmlzaW9uIG9mIENhcmRpb2xvZ3ksIFVuaXZlcnNp

dHkgb2YgTWlhbWkgU2Nob29sIG9mIE1lZGljaW5lLCBKYWNrc29uIE1lbW9yaWFsIEhvc3BpdGFs

LCBhbmQgVkEgTWVkaWNhbCBDZW50ZXIsIEZsb3JpZGEgMzMxMDEsIFVTQS48L2F1dGgtYWRkcmVz

cz48dGl0bGVzPjx0aXRsZT5GcmVxdWVuY3kgb2Ygc3VkZGVuIGNhcmRpYWMgZGVhdGggYW5kIHBy

b2ZpbGVzIG9mIHJpc2s8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+QW0gSiBDYXJkaW9sPC9zZWNv

bmRhcnktdGl0bGU+PGFsdC10aXRsZT5UaGUgQW1lcmljYW4gam91cm5hbCBvZiBjYXJkaW9sb2d5

PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBDYXJkaW9s

PC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIEFtZXJpY2FuIGpvdXJuYWwgb2YgY2FyZGlvbG9neTwv

YWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBDYXJk

aW9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIEFtZXJpY2FuIGpvdXJuYWwgb2YgY2FyZGlvbG9n

eTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEwZi0xOWY8L3BhZ2VzPjx2b2x1bWU+

ODA8L3ZvbHVtZT48bnVtYmVyPjViPC9udW1iZXI+PGVkaXRpb24+MTk5Ny8wOS8xODwvZWRpdGlv

bj48a2V5d29yZHM+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QW50aS1BcnJoeXRo

bWlhIEFnZW50cy9hZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+Q29yb25hcnkgRGlz

ZWFzZS9lcGlkZW1pb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RGVhdGgsIFN1ZGRlbiwgQ2FyZGlh

Yy8qZXBpZGVtaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkRpc2Vhc2UgU3VzY2VwdGliaWxpdHk8

L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVk

aWVzPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5JbmNpZGVuY2U8

L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5

d29yZD48a2V5d29yZD5Qb3B1bGF0aW9uIER5bmFtaWNzPC9rZXl3b3JkPjxrZXl3b3JkPlByZXZh

bGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBBc3Nlc3NtZW50PC9rZXl3b3JkPjxrZXl3b3Jk

PlJpc2sgRmFjdG9yczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJpY3VsYXIv

KmVwaWRlbWlvbG9neS9ldGlvbG9neTwva2V5d29yZD48a2V5d29yZD5Ub3JzYWRlcyBkZSBQb2lu

dGVzL2NoZW1pY2FsbHkgaW5kdWNlZDwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4x

OTk3PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+U2VwIDExPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0

ZXM+PGlzYm4+MDAwMi05MTQ5IChQcmludCkmI3hEOzAwMDItOTE0OTwvaXNibj48YWNjZXNzaW9u

LW51bT45MjkxNDQ1PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNl

LXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xh

bmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE.DATA (Huikuri, Castellanos, & Myerburg, 2001; Myerburg, Interian, Mitrani, Kessler, & Castellanos, 1997). Dilated and hypertrophic cardiomyopathies account for the second largest number of sudden deaths from cardiac causes ADDIN EN.CITE <EndNote><Cite><Author>Zipes</Author><Year>1998</Year><RecNum>32</RecNum><DisplayText>(Zipes &amp; Wellens, 1998)</DisplayText><record><rec-number>32</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383185613">32</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zipes, D. P.</author><author>Wellens, H. J.</author></authors></contributors><auth-address>Krannert Institute of Cardiology, Indiana University School of Medicine and the Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202-4800, USA.ts]</auth-address><titles><title>Sudden cardiac death</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>2334-51</pages><volume>98</volume><number>21</number><edition>1998/11/24</edition><keywords><keyword>Death, Sudden, Cardiac/*etiology/*prevention &amp; control</keyword><keyword>Humans</keyword><keyword>Risk Factors</keyword></keywords><dates><year>1998</year><pub-dates><date>Nov 24</date></pub-dates></dates><isbn>0009-7322 (Print)&#xD;0009-7322</isbn><accession-num>9826323</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Zipes & Wellens, 1998). Other cardiac disorders, such as valvular or congenital heart diseases, acquired infiltrative disorders, and primary electrophysiological disorders account for only a small proportion of the sudden deaths that may occur in the general population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdWlrdXJpPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48

UmVjTnVtPjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihIdWlrdXJpIGV0IGFsLiwgMjAwMSk8L0Rp

c3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MzA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5

cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVw

NWEiIHRpbWVzdGFtcD0iMTM4MzE4NDA0NCI+MzA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0

aG9ycz48YXV0aG9yPkh1aWt1cmksIEguIFYuPC9hdXRob3I+PGF1dGhvcj5DYXN0ZWxsYW5vcywg

QS48L2F1dGhvcj48YXV0aG9yPk15ZXJidXJnLCBSLiBKLjwvYXV0aG9yPjwvYXV0aG9ycz48L2Nv

bnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgTWVkaWNpbmUsIFVuaXZlcnNp

dHkgb2YgT3VsdSwgRmlubGFuZC4gaGVpa2tpLmh1aWt1cmlAb3VsdS5maTwvYXV0aC1hZGRyZXNz

Pjx0aXRsZXM+PHRpdGxlPlN1ZGRlbiBkZWF0aCBkdWUgdG8gY2FyZGlhYyBhcnJoeXRobWlhczwv

dGl0bGU+PHNlY29uZGFyeS10aXRsZT5OIEVuZ2wgSiBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0

LXRpdGxlPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFsIG9mIG1lZGljaW5lPC9hbHQtdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TiBFbmdsIEogTWVkPC9mdWxsLXRpdGxlPjxh

YmJyLTE+VGhlIE5ldyBFbmdsYW5kIGpvdXJuYWwgb2YgbWVkaWNpbmU8L2FiYnItMT48L3Blcmlv

ZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk4gRW5nbCBKIE1lZDwvZnVsbC10aXRs

ZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFsIG9mIG1lZGljaW5lPC9hYmJyLTE+PC9h

bHQtcGVyaW9kaWNhbD48cGFnZXM+MTQ3My04MjwvcGFnZXM+PHZvbHVtZT4zNDU8L3ZvbHVtZT48

bnVtYmVyPjIwPC9udW1iZXI+PGVkaXRpb24+MjAwMi8wMS8xNzwvZWRpdGlvbj48a2V5d29yZHM+

PGtleXdvcmQ+QWRyZW5lcmdpYyBiZXRhLUFudGFnb25pc3RzL3RoZXJhcGV1dGljIHVzZTwva2V5

d29yZD48a2V5d29yZD5BbWlvZGFyb25lL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29y

ZD5BbnRpLUFycmh5dGhtaWEgQWdlbnRzLyp0aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdv

cmQ+QXJyaHl0aG1pYXMsIENhcmRpYWMvKmNvbXBsaWNhdGlvbnMvZHJ1ZyB0aGVyYXB5L3RoZXJh

cHk8L2tleXdvcmQ+PGtleXdvcmQ+QmFyb3JlZmxleDwva2V5d29yZD48a2V5d29yZD5DYXJkaW9t

eW9wYXRoaWVzL2NvbXBsaWNhdGlvbnM8L2tleXdvcmQ+PGtleXdvcmQ+RGVhdGgsIFN1ZGRlbiwg

Q2FyZGlhYy9lcGlkZW1pb2xvZ3kvKmV0aW9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8

L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxr

ZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgUmF0ZTwv

a2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+UHJpbWFyeSBQcmV2ZW50

aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb2dub3Npczwva2V5d29yZD48a2V5d29yZD5SaXNrIEZh

Y3RvcnM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwMTwveWVhcj48cHViLWRh

dGVzPjxkYXRlPk5vdiAxNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjgtNDc5

MyAoUHJpbnQpJiN4RDswMDI4LTQ3OTM8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTE3OTQxOTc8L2Fj

Y2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDU2

L05FSk1yYTAwMDY1MDwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5n

dWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdWlrdXJpPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48

UmVjTnVtPjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihIdWlrdXJpIGV0IGFsLiwgMjAwMSk8L0Rp

c3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MzA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5

cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVw

NWEiIHRpbWVzdGFtcD0iMTM4MzE4NDA0NCI+MzA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0

aG9ycz48YXV0aG9yPkh1aWt1cmksIEguIFYuPC9hdXRob3I+PGF1dGhvcj5DYXN0ZWxsYW5vcywg

QS48L2F1dGhvcj48YXV0aG9yPk15ZXJidXJnLCBSLiBKLjwvYXV0aG9yPjwvYXV0aG9ycz48L2Nv

bnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgTWVkaWNpbmUsIFVuaXZlcnNp

dHkgb2YgT3VsdSwgRmlubGFuZC4gaGVpa2tpLmh1aWt1cmlAb3VsdS5maTwvYXV0aC1hZGRyZXNz

Pjx0aXRsZXM+PHRpdGxlPlN1ZGRlbiBkZWF0aCBkdWUgdG8gY2FyZGlhYyBhcnJoeXRobWlhczwv

dGl0bGU+PHNlY29uZGFyeS10aXRsZT5OIEVuZ2wgSiBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0

LXRpdGxlPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFsIG9mIG1lZGljaW5lPC9hbHQtdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TiBFbmdsIEogTWVkPC9mdWxsLXRpdGxlPjxh

YmJyLTE+VGhlIE5ldyBFbmdsYW5kIGpvdXJuYWwgb2YgbWVkaWNpbmU8L2FiYnItMT48L3Blcmlv

ZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk4gRW5nbCBKIE1lZDwvZnVsbC10aXRs

ZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBqb3VybmFsIG9mIG1lZGljaW5lPC9hYmJyLTE+PC9h

bHQtcGVyaW9kaWNhbD48cGFnZXM+MTQ3My04MjwvcGFnZXM+PHZvbHVtZT4zNDU8L3ZvbHVtZT48

bnVtYmVyPjIwPC9udW1iZXI+PGVkaXRpb24+MjAwMi8wMS8xNzwvZWRpdGlvbj48a2V5d29yZHM+

PGtleXdvcmQ+QWRyZW5lcmdpYyBiZXRhLUFudGFnb25pc3RzL3RoZXJhcGV1dGljIHVzZTwva2V5

d29yZD48a2V5d29yZD5BbWlvZGFyb25lL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29y

ZD5BbnRpLUFycmh5dGhtaWEgQWdlbnRzLyp0aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdv

cmQ+QXJyaHl0aG1pYXMsIENhcmRpYWMvKmNvbXBsaWNhdGlvbnMvZHJ1ZyB0aGVyYXB5L3RoZXJh

cHk8L2tleXdvcmQ+PGtleXdvcmQ+QmFyb3JlZmxleDwva2V5d29yZD48a2V5d29yZD5DYXJkaW9t

eW9wYXRoaWVzL2NvbXBsaWNhdGlvbnM8L2tleXdvcmQ+PGtleXdvcmQ+RGVhdGgsIFN1ZGRlbiwg

Q2FyZGlhYy9lcGlkZW1pb2xvZ3kvKmV0aW9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8

L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxr

ZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+SGVhcnQgUmF0ZTwv

a2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+UHJpbWFyeSBQcmV2ZW50

aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb2dub3Npczwva2V5d29yZD48a2V5d29yZD5SaXNrIEZh

Y3RvcnM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwMTwveWVhcj48cHViLWRh

dGVzPjxkYXRlPk5vdiAxNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjgtNDc5

MyAoUHJpbnQpJiN4RDswMDI4LTQ3OTM8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTE3OTQxOTc8L2Fj

Y2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDU2

L05FSk1yYTAwMDY1MDwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5n

dWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA (Huikuri et al., 2001).Ventricular arrhythmias can occur in individuals with or without a cardiac disorder. There is a great deal of overlap between clinical presentations and the severity and type of heart disease. For example, stable and well-tolerated VT can occur in the individual with previous MI and impaired ventricular function. The prognosis and management are individualised according to symptom burden and severity of underlying heart disease, in addition to the clinical presentation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaXBlczwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl

Y051bT4yMTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oWmlwZXMgZXQgYWwuLCAyMDA2KTwvRGlzcGxh

eVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4yMTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxr

ZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIg

dGltZXN0YW1wPSIxMzgzMTE1MjA5Ij4yMTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3Jz

PjxhdXRob3I+WmlwZXMsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9y

PjxhdXRob3I+Qm9yZ2dyZWZlLCBNLjwvYXV0aG9yPjxhdXRob3I+QnV4dG9uLCBBLiBFLjwvYXV0

aG9yPjxhdXRob3I+Q2hhaXRtYW4sIEIuPC9hdXRob3I+PGF1dGhvcj5Gcm9tZXIsIE0uPC9hdXRo

b3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0aG9yPjxhdXRob3I+S2xlaW4sIEcuPC9hdXRo

b3I+PGF1dGhvcj5Nb3NzLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+TXllcmJ1cmcsIFIuIEouPC9h

dXRob3I+PGF1dGhvcj5QcmlvcmksIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5RdWlub25lcywgTS4g

QS48L2F1dGhvcj48YXV0aG9yPlJvZGVuLCBELiBNLjwvYXV0aG9yPjxhdXRob3I+U2lsa2EsIE0u

IEouPC9hdXRob3I+PGF1dGhvcj5UcmFjeSwgQy48L2F1dGhvcj48YXV0aG9yPlNtaXRoLCBTLiBD

LiwgSnIuPC9hdXRob3I+PGF1dGhvcj5KYWNvYnMsIEEuIEsuPC9hdXRob3I+PGF1dGhvcj5BZGFt

cywgQy4gRC48L2F1dGhvcj48YXV0aG9yPkFudG1hbiwgRS4gTS48L2F1dGhvcj48YXV0aG9yPkFu

ZGVyc29uLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+SHVudCwgUy4gQS48L2F1dGhvcj48YXV0aG9y

PkhhbHBlcmluLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+TmlzaGltdXJhLCBSLjwvYXV0aG9yPjxh

dXRob3I+T3JuYXRvLCBKLiBQLjwvYXV0aG9yPjxhdXRob3I+UGFnZSwgUi4gTC48L2F1dGhvcj48

YXV0aG9yPlJpZWdlbCwgQi48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48

YXV0aG9yPkJsYW5jLCBKLiBKLjwvYXV0aG9yPjxhdXRob3I+QnVkYWosIEEuPC9hdXRob3I+PGF1

dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+RGVhbiwgVi48L2F1dGhvcj48YXV0aG9y

PkRlY2tlcnMsIEouIFcuPC9hdXRob3I+PGF1dGhvcj5EZXNwcmVzLCBDLjwvYXV0aG9yPjxhdXRo

b3I+RGlja3N0ZWluLCBLLjwvYXV0aG9yPjxhdXRob3I+TGVrYWtpcywgSi48L2F1dGhvcj48YXV0

aG9yPk1jR3JlZ29yLCBLLjwvYXV0aG9yPjxhdXRob3I+TWV0cmEsIE0uPC9hdXRob3I+PGF1dGhv

cj5Nb3JhaXMsIEouPC9hdXRob3I+PGF1dGhvcj5Pc3RlcnNwZXksIEEuPC9hdXRob3I+PGF1dGhv

cj5UYW1hcmdvLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+WmFtb3Jhbm8sIEouIEwuPC9hdXRob3I+

PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRpdGxlPkFDQy9BSEEvRVNDIDIwMDYg

Z3VpZGVsaW5lcyBmb3IgbWFuYWdlbWVudCBvZiBwYXRpZW50cyB3aXRoIHZlbnRyaWN1bGFyIGFy

cmh5dGhtaWFzIGFuZCB0aGUgcHJldmVudGlvbiBvZiBzdWRkZW4gY2FyZGlhYyBkZWF0aDogYSBy

ZXBvcnQgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neS9BbWVyaWNhbiBIZWFy

dCBBc3NvY2lhdGlvbiBUYXNrIEZvcmNlIGFuZCB0aGUgRXVyb3BlYW4gU29jaWV0eSBvZiBDYXJk

aW9sb2d5IENvbW1pdHRlZSBmb3IgUHJhY3RpY2UgR3VpZGVsaW5lcyAoV3JpdGluZyBDb21taXR0

ZWUgdG8gRGV2ZWxvcCBHdWlkZWxpbmVzIGZvciBNYW5hZ2VtZW50IG9mIFBhdGllbnRzIFdpdGgg

VmVudHJpY3VsYXIgQXJyaHl0aG1pYXMgYW5kIHRoZSBQcmV2ZW50aW9uIG9mIFN1ZGRlbiBDYXJk

aWFjIERlYXRoKTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEFtIENvbGwgQ2FyZGlvbDwvc2Vj

b25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gQ29sbGVnZSBv

ZiBDYXJkaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRp

dGxlPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvZnVsbC10

aXRsZT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz5lMjQ3LTM0NjwvcGFnZXM+PHZvbHVtZT40ODwv

dm9sdW1lPjxudW1iZXI+NTwvbnVtYmVyPjxlZGl0aW9uPjIwMDYvMDkvMDU8L2VkaXRpb24+PGtl

eXdvcmRzPjxrZXl3b3JkPkFudGktQXJyaHl0aG1pYSBBZ2VudHMvdGhlcmFwZXV0aWMgdXNlPC9r

ZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgT3V0cHV0LCBMb3c8L2tleXdvcmQ+PGtleXdvcmQ+Q2Fy

ZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9rZXl3b3JkPjxrZXl3b3JkPkNhdGhldGVyIEFi

bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvKmV0aW9sb2d5

LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRv

cnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tl

eXdvcmQ+PGtleXdvcmQ+SGVhcnQgQXJyZXN0L2V0aW9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtl

eXdvcmQ+SGVhcnQgRnVuY3Rpb24gVGVzdHM8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci8qY29tcGxpY2F0aW9ucy8qZHJ1

ZyB0aGVyYXB5L3BoeXNpb3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5WZW50cmljdWxhciBG

aWJyaWxsYXRpb24vKmNvbXBsaWNhdGlvbnMvKmRydWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8

L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwNjwveWVhcj48cHViLWRhdGVzPjxk

YXRlPlNlcCA1PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDczNS0xMDk3PC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjE2OTQ5NDc4PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxl

Y3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9qLmphY2MuMjAwNi4wNy4wMTA8L2VsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaXBlczwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl

Y051bT4yMTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oWmlwZXMgZXQgYWwuLCAyMDA2KTwvRGlzcGxh

eVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4yMTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxr

ZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIg

dGltZXN0YW1wPSIxMzgzMTE1MjA5Ij4yMTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3Jz

PjxhdXRob3I+WmlwZXMsIEQuIFAuPC9hdXRob3I+PGF1dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9y

PjxhdXRob3I+Qm9yZ2dyZWZlLCBNLjwvYXV0aG9yPjxhdXRob3I+QnV4dG9uLCBBLiBFLjwvYXV0

aG9yPjxhdXRob3I+Q2hhaXRtYW4sIEIuPC9hdXRob3I+PGF1dGhvcj5Gcm9tZXIsIE0uPC9hdXRo

b3I+PGF1dGhvcj5HcmVnb3JhdG9zLCBHLjwvYXV0aG9yPjxhdXRob3I+S2xlaW4sIEcuPC9hdXRo

b3I+PGF1dGhvcj5Nb3NzLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+TXllcmJ1cmcsIFIuIEouPC9h

dXRob3I+PGF1dGhvcj5QcmlvcmksIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5RdWlub25lcywgTS4g

QS48L2F1dGhvcj48YXV0aG9yPlJvZGVuLCBELiBNLjwvYXV0aG9yPjxhdXRob3I+U2lsa2EsIE0u

IEouPC9hdXRob3I+PGF1dGhvcj5UcmFjeSwgQy48L2F1dGhvcj48YXV0aG9yPlNtaXRoLCBTLiBD

LiwgSnIuPC9hdXRob3I+PGF1dGhvcj5KYWNvYnMsIEEuIEsuPC9hdXRob3I+PGF1dGhvcj5BZGFt

cywgQy4gRC48L2F1dGhvcj48YXV0aG9yPkFudG1hbiwgRS4gTS48L2F1dGhvcj48YXV0aG9yPkFu

ZGVyc29uLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+SHVudCwgUy4gQS48L2F1dGhvcj48YXV0aG9y

PkhhbHBlcmluLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+TmlzaGltdXJhLCBSLjwvYXV0aG9yPjxh

dXRob3I+T3JuYXRvLCBKLiBQLjwvYXV0aG9yPjxhdXRob3I+UGFnZSwgUi4gTC48L2F1dGhvcj48

YXV0aG9yPlJpZWdlbCwgQi48L2F1dGhvcj48YXV0aG9yPlByaW9yaSwgUy4gRy48L2F1dGhvcj48

YXV0aG9yPkJsYW5jLCBKLiBKLjwvYXV0aG9yPjxhdXRob3I+QnVkYWosIEEuPC9hdXRob3I+PGF1

dGhvcj5DYW1tLCBBLiBKLjwvYXV0aG9yPjxhdXRob3I+RGVhbiwgVi48L2F1dGhvcj48YXV0aG9y

PkRlY2tlcnMsIEouIFcuPC9hdXRob3I+PGF1dGhvcj5EZXNwcmVzLCBDLjwvYXV0aG9yPjxhdXRo

b3I+RGlja3N0ZWluLCBLLjwvYXV0aG9yPjxhdXRob3I+TGVrYWtpcywgSi48L2F1dGhvcj48YXV0

aG9yPk1jR3JlZ29yLCBLLjwvYXV0aG9yPjxhdXRob3I+TWV0cmEsIE0uPC9hdXRob3I+PGF1dGhv

cj5Nb3JhaXMsIEouPC9hdXRob3I+PGF1dGhvcj5Pc3RlcnNwZXksIEEuPC9hdXRob3I+PGF1dGhv

cj5UYW1hcmdvLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+WmFtb3Jhbm8sIEouIEwuPC9hdXRob3I+

PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRpdGxlPkFDQy9BSEEvRVNDIDIwMDYg

Z3VpZGVsaW5lcyBmb3IgbWFuYWdlbWVudCBvZiBwYXRpZW50cyB3aXRoIHZlbnRyaWN1bGFyIGFy

cmh5dGhtaWFzIGFuZCB0aGUgcHJldmVudGlvbiBvZiBzdWRkZW4gY2FyZGlhYyBkZWF0aDogYSBy

ZXBvcnQgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neS9BbWVyaWNhbiBIZWFy

dCBBc3NvY2lhdGlvbiBUYXNrIEZvcmNlIGFuZCB0aGUgRXVyb3BlYW4gU29jaWV0eSBvZiBDYXJk

aW9sb2d5IENvbW1pdHRlZSBmb3IgUHJhY3RpY2UgR3VpZGVsaW5lcyAoV3JpdGluZyBDb21taXR0

ZWUgdG8gRGV2ZWxvcCBHdWlkZWxpbmVzIGZvciBNYW5hZ2VtZW50IG9mIFBhdGllbnRzIFdpdGgg

VmVudHJpY3VsYXIgQXJyaHl0aG1pYXMgYW5kIHRoZSBQcmV2ZW50aW9uIG9mIFN1ZGRlbiBDYXJk

aWFjIERlYXRoKTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEFtIENvbGwgQ2FyZGlvbDwvc2Vj

b25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiB0aGUgQW1lcmljYW4gQ29sbGVnZSBv

ZiBDYXJkaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRp

dGxlPkpvdXJuYWwgb2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvZnVsbC10

aXRsZT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz5lMjQ3LTM0NjwvcGFnZXM+PHZvbHVtZT40ODwv

dm9sdW1lPjxudW1iZXI+NTwvbnVtYmVyPjxlZGl0aW9uPjIwMDYvMDkvMDU8L2VkaXRpb24+PGtl

eXdvcmRzPjxrZXl3b3JkPkFudGktQXJyaHl0aG1pYSBBZ2VudHMvdGhlcmFwZXV0aWMgdXNlPC9r

ZXl3b3JkPjxrZXl3b3JkPkNhcmRpYWMgT3V0cHV0LCBMb3c8L2tleXdvcmQ+PGtleXdvcmQ+Q2Fy

ZGlvbXlvcGF0aGllcy9jb21wbGljYXRpb25zPC9rZXl3b3JkPjxrZXl3b3JkPkNhdGhldGVyIEFi

bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvKmV0aW9sb2d5

LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVmaWJyaWxsYXRv

cnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHk8L2tl

eXdvcmQ+PGtleXdvcmQ+SGVhcnQgQXJyZXN0L2V0aW9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtl

eXdvcmQ+SGVhcnQgRnVuY3Rpb24gVGVzdHM8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci8qY29tcGxpY2F0aW9ucy8qZHJ1

ZyB0aGVyYXB5L3BoeXNpb3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5WZW50cmljdWxhciBG

aWJyaWxsYXRpb24vKmNvbXBsaWNhdGlvbnMvKmRydWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8

L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwNjwveWVhcj48cHViLWRhdGVzPjxk

YXRlPlNlcCA1PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDczNS0xMDk3PC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjE2OTQ5NDc4PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxl

Y3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9qLmphY2MuMjAwNi4wNy4wMTA8L2VsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE.DATA (Zipes et al., 2006). Evidence based best practice guidelines recommend ICD therapy for primary and secondary prevention of SCD PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaXBlczwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl

Y051bT4yMTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oRXBzdGVpbiBldCBhbC4sIDIwMDg7IFppcGVz

IGV0IGFsLiwgMjAwNik8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MjE8L3JlYy1u

dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6

ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzExNTIwOSI+MjE8L2tleT48L2Zv

cmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+

PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlppcGVzLCBELiBQLjwvYXV0aG9yPjxhdXRo

b3I+Q2FtbSwgQS4gSi48L2F1dGhvcj48YXV0aG9yPkJvcmdncmVmZSwgTS48L2F1dGhvcj48YXV0

aG9yPkJ1eHRvbiwgQS4gRS48L2F1dGhvcj48YXV0aG9yPkNoYWl0bWFuLCBCLjwvYXV0aG9yPjxh

dXRob3I+RnJvbWVyLCBNLjwvYXV0aG9yPjxhdXRob3I+R3JlZ29yYXRvcywgRy48L2F1dGhvcj48

YXV0aG9yPktsZWluLCBHLjwvYXV0aG9yPjxhdXRob3I+TW9zcywgQS4gSi48L2F1dGhvcj48YXV0

aG9yPk15ZXJidXJnLCBSLiBKLjwvYXV0aG9yPjxhdXRob3I+UHJpb3JpLCBTLiBHLjwvYXV0aG9y

PjxhdXRob3I+UXVpbm9uZXMsIE0uIEEuPC9hdXRob3I+PGF1dGhvcj5Sb2RlbiwgRC4gTS48L2F1

dGhvcj48YXV0aG9yPlNpbGthLCBNLiBKLjwvYXV0aG9yPjxhdXRob3I+VHJhY3ksIEMuPC9hdXRo

b3I+PGF1dGhvcj5TbWl0aCwgUy4gQy4sIEpyLjwvYXV0aG9yPjxhdXRob3I+SmFjb2JzLCBBLiBL

LjwvYXV0aG9yPjxhdXRob3I+QWRhbXMsIEMuIEQuPC9hdXRob3I+PGF1dGhvcj5BbnRtYW4sIEUu

IE0uPC9hdXRob3I+PGF1dGhvcj5BbmRlcnNvbiwgSi4gTC48L2F1dGhvcj48YXV0aG9yPkh1bnQs

IFMuIEEuPC9hdXRob3I+PGF1dGhvcj5IYWxwZXJpbiwgSi4gTC48L2F1dGhvcj48YXV0aG9yPk5p

c2hpbXVyYSwgUi48L2F1dGhvcj48YXV0aG9yPk9ybmF0bywgSi4gUC48L2F1dGhvcj48YXV0aG9y

PlBhZ2UsIFIuIEwuPC9hdXRob3I+PGF1dGhvcj5SaWVnZWwsIEIuPC9hdXRob3I+PGF1dGhvcj5Q

cmlvcmksIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5CbGFuYywgSi4gSi48L2F1dGhvcj48YXV0aG9y

PkJ1ZGFqLCBBLjwvYXV0aG9yPjxhdXRob3I+Q2FtbSwgQS4gSi48L2F1dGhvcj48YXV0aG9yPkRl

YW4sIFYuPC9hdXRob3I+PGF1dGhvcj5EZWNrZXJzLCBKLiBXLjwvYXV0aG9yPjxhdXRob3I+RGVz

cHJlcywgQy48L2F1dGhvcj48YXV0aG9yPkRpY2tzdGVpbiwgSy48L2F1dGhvcj48YXV0aG9yPkxl

a2FraXMsIEouPC9hdXRob3I+PGF1dGhvcj5NY0dyZWdvciwgSy48L2F1dGhvcj48YXV0aG9yPk1l

dHJhLCBNLjwvYXV0aG9yPjxhdXRob3I+TW9yYWlzLCBKLjwvYXV0aG9yPjxhdXRob3I+T3N0ZXJz

cGV5LCBBLjwvYXV0aG9yPjxhdXRob3I+VGFtYXJnbywgSi4gTC48L2F1dGhvcj48YXV0aG9yPlph

bW9yYW5vLCBKLiBMLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0

aXRsZT5BQ0MvQUhBL0VTQyAyMDA2IGd1aWRlbGluZXMgZm9yIG1hbmFnZW1lbnQgb2YgcGF0aWVu

dHMgd2l0aCB2ZW50cmljdWxhciBhcnJoeXRobWlhcyBhbmQgdGhlIHByZXZlbnRpb24gb2Ygc3Vk

ZGVuIGNhcmRpYWMgZGVhdGg6IGEgcmVwb3J0IG9mIHRoZSBBbWVyaWNhbiBDb2xsZWdlIG9mIENh

cmRpb2xvZ3kvQW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb24gVGFzayBGb3JjZSBhbmQgdGhlIEV1

cm9wZWFuIFNvY2lldHkgb2YgQ2FyZGlvbG9neSBDb21taXR0ZWUgZm9yIFByYWN0aWNlIEd1aWRl

bGluZXMgKFdyaXRpbmcgQ29tbWl0dGVlIHRvIERldmVsb3AgR3VpZGVsaW5lcyBmb3IgTWFuYWdl

bWVudCBvZiBQYXRpZW50cyBXaXRoIFZlbnRyaWN1bGFyIEFycmh5dGhtaWFzIGFuZCB0aGUgUHJl

dmVudGlvbiBvZiBTdWRkZW4gQ2FyZGlhYyBEZWF0aCk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

SiBBbSBDb2xsIENhcmRpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkpvdXJuYWwgb2Yg

dGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxh

bHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNhbiBDb2xsZWdl

IG9mIENhcmRpb2xvZ3k8L2Z1bGwtdGl0bGU+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+ZTI0Ny0z

NDY8L3BhZ2VzPjx2b2x1bWU+NDg8L3ZvbHVtZT48bnVtYmVyPjU8L251bWJlcj48ZWRpdGlvbj4y

MDA2LzA5LzA1PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbnRpLUFycmh5dGhtaWEgQWdl

bnRzL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29yZD5DYXJkaWFjIE91dHB1dCwgTG93

PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGhpZXMvY29tcGxpY2F0aW9uczwva2V5d29y

ZD48a2V5d29yZD5DYXRoZXRlciBBYmxhdGlvbjwva2V5d29yZD48a2V5d29yZD5EZWF0aCwgU3Vk

ZGVuLCBDYXJkaWFjLypldGlvbG9neS8qcHJldmVudGlvbiAmYW1wOyBjb250cm9sPC9rZXl3b3Jk

PjxrZXl3b3JkPkRlZmlicmlsbGF0b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD5F

bGVjdHJvY2FyZGlvZ3JhcGh5PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IEFycmVzdC9ldGlvbG9n

eS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IEZ1bmN0aW9uIFRlc3RzPC9rZXl3b3Jk

PjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJpY3Vs

YXIvKmNvbXBsaWNhdGlvbnMvKmRydWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+

PGtleXdvcmQ+VmVudHJpY3VsYXIgRmlicmlsbGF0aW9uLypjb21wbGljYXRpb25zLypkcnVnIHRo

ZXJhcHkvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIw

MDY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5TZXAgNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVz

Pjxpc2JuPjA3MzUtMTA5NzwvaXNibj48YWNjZXNzaW9uLW51bT4xNjk0OTQ3ODwvYWNjZXNzaW9u

LW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMTYvai5qYWNj

LjIwMDYuMDcuMDEwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXBy

b3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1

YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkVwc3RlaW48L0F1dGhvcj48WWVhcj4y

MDA4PC9ZZWFyPjxSZWNOdW0+MTA8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjEwPC9yZWMt

bnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDll

emR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMwOTQxOTAiPjEwPC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5FcHN0ZWluLCBBLiBFLjwvYXV0aG9yPjxh

dXRob3I+RGltYXJjbywgSi4gUC48L2F1dGhvcj48YXV0aG9yPkVsbGVuYm9nZW4sIEsuIEEuPC9h

dXRob3I+PGF1dGhvcj5Fc3RlcywgTi4gQS4sIDNyZDwvYXV0aG9yPjxhdXRob3I+RnJlZWRtYW4s

IFIuIEEuPC9hdXRob3I+PGF1dGhvcj5HZXR0ZXMsIEwuIFMuPC9hdXRob3I+PGF1dGhvcj5HaWxs

aW5vdiwgQS4gTS48L2F1dGhvcj48YXV0aG9yPkdyZWdvcmF0b3MsIEcuPC9hdXRob3I+PGF1dGhv

cj5IYW1taWxsLCBTLiBDLjwvYXV0aG9yPjxhdXRob3I+SGF5ZXMsIEQuIEwuPC9hdXRob3I+PGF1

dGhvcj5IbGF0a3ksIE0uIEEuPC9hdXRob3I+PGF1dGhvcj5OZXdieSwgTC4gSy48L2F1dGhvcj48

YXV0aG9yPlBhZ2UsIFIuIEwuPC9hdXRob3I+PGF1dGhvcj5TY2hvZW5mZWxkLCBNLiBILjwvYXV0

aG9yPjxhdXRob3I+U2lsa2EsIE0uIEouPC9hdXRob3I+PGF1dGhvcj5TdGV2ZW5zb24sIEwuIFcu

PC9hdXRob3I+PGF1dGhvcj5Td2VlbmV5LCBNLiBPLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRy

aWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5BQ0MvQUhBL0hSUyAyMDA4IGd1aWRlbGluZXMgZm9yIERl

dmljZS1CYXNlZCBUaGVyYXB5IG9mIENhcmRpYWMgUmh5dGhtIEFibm9ybWFsaXRpZXM6IGV4ZWN1

dGl2ZSBzdW1tYXJ5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkhlYXJ0IFJoeXRobTwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwg

b2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGlj

YWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5

dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9h

YmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5IZWFydCBSaHl0

aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5h

bCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxw

YWdlcz45MzQtNTU8L3BhZ2VzPjx2b2x1bWU+NTwvdm9sdW1lPjxudW1iZXI+NjwvbnVtYmVyPjxl

ZGl0aW9uPjIwMDgvMDYvMDc8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFtZXJpY2FuIEhl

YXJ0IEFzc29jaWF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJkaWFjL3Bo

eXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5BdHJpb3ZlbnRyaWN1bGFy

IEJsb2NrL3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlhYyBQYWNpbmcsIEFydGlmaWNp

YWw8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy90aGVyYXB5PC9rZXl3b3JkPjxr

ZXl3b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+KkVs

ZWN0cmljIENvdW50ZXJzaG9jazwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtl

eXdvcmQ+U2lub2F0cmlhbCBOb2RlL3BoeXNpb3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5T

b2NpZXRpZXMsIE1lZGljYWw8L2tleXdvcmQ+PGtleXdvcmQ+VGhvcmFjaWMgU3VyZ2VyeTwva2V5

d29yZD48a2V5d29yZD5Vbml0ZWQgU3RhdGVzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5

ZWFyPjIwMDg8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PC9k

YXRlcz48aXNibj4xNTQ3LTUyNzE8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTg1MzQzNzc8L2FjY2Vz

c2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ou

aHJ0aG0uMjAwOC4wNC4wMTU8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJh

c2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwv

bGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaXBlczwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl

Y051bT4yMTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oRXBzdGVpbiBldCBhbC4sIDIwMDg7IFppcGVz

IGV0IGFsLiwgMjAwNik8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MjE8L3JlYy1u

dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6

ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzExNTIwOSI+MjE8L2tleT48L2Zv

cmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+

PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlppcGVzLCBELiBQLjwvYXV0aG9yPjxhdXRo

b3I+Q2FtbSwgQS4gSi48L2F1dGhvcj48YXV0aG9yPkJvcmdncmVmZSwgTS48L2F1dGhvcj48YXV0

aG9yPkJ1eHRvbiwgQS4gRS48L2F1dGhvcj48YXV0aG9yPkNoYWl0bWFuLCBCLjwvYXV0aG9yPjxh

dXRob3I+RnJvbWVyLCBNLjwvYXV0aG9yPjxhdXRob3I+R3JlZ29yYXRvcywgRy48L2F1dGhvcj48

YXV0aG9yPktsZWluLCBHLjwvYXV0aG9yPjxhdXRob3I+TW9zcywgQS4gSi48L2F1dGhvcj48YXV0

aG9yPk15ZXJidXJnLCBSLiBKLjwvYXV0aG9yPjxhdXRob3I+UHJpb3JpLCBTLiBHLjwvYXV0aG9y

PjxhdXRob3I+UXVpbm9uZXMsIE0uIEEuPC9hdXRob3I+PGF1dGhvcj5Sb2RlbiwgRC4gTS48L2F1

dGhvcj48YXV0aG9yPlNpbGthLCBNLiBKLjwvYXV0aG9yPjxhdXRob3I+VHJhY3ksIEMuPC9hdXRo

b3I+PGF1dGhvcj5TbWl0aCwgUy4gQy4sIEpyLjwvYXV0aG9yPjxhdXRob3I+SmFjb2JzLCBBLiBL

LjwvYXV0aG9yPjxhdXRob3I+QWRhbXMsIEMuIEQuPC9hdXRob3I+PGF1dGhvcj5BbnRtYW4sIEUu

IE0uPC9hdXRob3I+PGF1dGhvcj5BbmRlcnNvbiwgSi4gTC48L2F1dGhvcj48YXV0aG9yPkh1bnQs

IFMuIEEuPC9hdXRob3I+PGF1dGhvcj5IYWxwZXJpbiwgSi4gTC48L2F1dGhvcj48YXV0aG9yPk5p

c2hpbXVyYSwgUi48L2F1dGhvcj48YXV0aG9yPk9ybmF0bywgSi4gUC48L2F1dGhvcj48YXV0aG9y

PlBhZ2UsIFIuIEwuPC9hdXRob3I+PGF1dGhvcj5SaWVnZWwsIEIuPC9hdXRob3I+PGF1dGhvcj5Q

cmlvcmksIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5CbGFuYywgSi4gSi48L2F1dGhvcj48YXV0aG9y

PkJ1ZGFqLCBBLjwvYXV0aG9yPjxhdXRob3I+Q2FtbSwgQS4gSi48L2F1dGhvcj48YXV0aG9yPkRl

YW4sIFYuPC9hdXRob3I+PGF1dGhvcj5EZWNrZXJzLCBKLiBXLjwvYXV0aG9yPjxhdXRob3I+RGVz

cHJlcywgQy48L2F1dGhvcj48YXV0aG9yPkRpY2tzdGVpbiwgSy48L2F1dGhvcj48YXV0aG9yPkxl

a2FraXMsIEouPC9hdXRob3I+PGF1dGhvcj5NY0dyZWdvciwgSy48L2F1dGhvcj48YXV0aG9yPk1l

dHJhLCBNLjwvYXV0aG9yPjxhdXRob3I+TW9yYWlzLCBKLjwvYXV0aG9yPjxhdXRob3I+T3N0ZXJz

cGV5LCBBLjwvYXV0aG9yPjxhdXRob3I+VGFtYXJnbywgSi4gTC48L2F1dGhvcj48YXV0aG9yPlph

bW9yYW5vLCBKLiBMLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0

aXRsZT5BQ0MvQUhBL0VTQyAyMDA2IGd1aWRlbGluZXMgZm9yIG1hbmFnZW1lbnQgb2YgcGF0aWVu

dHMgd2l0aCB2ZW50cmljdWxhciBhcnJoeXRobWlhcyBhbmQgdGhlIHByZXZlbnRpb24gb2Ygc3Vk

ZGVuIGNhcmRpYWMgZGVhdGg6IGEgcmVwb3J0IG9mIHRoZSBBbWVyaWNhbiBDb2xsZWdlIG9mIENh

cmRpb2xvZ3kvQW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb24gVGFzayBGb3JjZSBhbmQgdGhlIEV1

cm9wZWFuIFNvY2lldHkgb2YgQ2FyZGlvbG9neSBDb21taXR0ZWUgZm9yIFByYWN0aWNlIEd1aWRl

bGluZXMgKFdyaXRpbmcgQ29tbWl0dGVlIHRvIERldmVsb3AgR3VpZGVsaW5lcyBmb3IgTWFuYWdl

bWVudCBvZiBQYXRpZW50cyBXaXRoIFZlbnRyaWN1bGFyIEFycmh5dGhtaWFzIGFuZCB0aGUgUHJl

dmVudGlvbiBvZiBTdWRkZW4gQ2FyZGlhYyBEZWF0aCk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

SiBBbSBDb2xsIENhcmRpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkpvdXJuYWwgb2Yg

dGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxh

bHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNhbiBDb2xsZWdl

IG9mIENhcmRpb2xvZ3k8L2Z1bGwtdGl0bGU+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+ZTI0Ny0z

NDY8L3BhZ2VzPjx2b2x1bWU+NDg8L3ZvbHVtZT48bnVtYmVyPjU8L251bWJlcj48ZWRpdGlvbj4y

MDA2LzA5LzA1PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbnRpLUFycmh5dGhtaWEgQWdl

bnRzL3RoZXJhcGV1dGljIHVzZTwva2V5d29yZD48a2V5d29yZD5DYXJkaWFjIE91dHB1dCwgTG93

PC9rZXl3b3JkPjxrZXl3b3JkPkNhcmRpb215b3BhdGhpZXMvY29tcGxpY2F0aW9uczwva2V5d29y

ZD48a2V5d29yZD5DYXRoZXRlciBBYmxhdGlvbjwva2V5d29yZD48a2V5d29yZD5EZWF0aCwgU3Vk

ZGVuLCBDYXJkaWFjLypldGlvbG9neS8qcHJldmVudGlvbiAmYW1wOyBjb250cm9sPC9rZXl3b3Jk

PjxrZXl3b3JkPkRlZmlicmlsbGF0b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD5F

bGVjdHJvY2FyZGlvZ3JhcGh5PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IEFycmVzdC9ldGlvbG9n

eS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IEZ1bmN0aW9uIFRlc3RzPC9rZXl3b3Jk

PjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJpY3Vs

YXIvKmNvbXBsaWNhdGlvbnMvKmRydWcgdGhlcmFweS9waHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+

PGtleXdvcmQ+VmVudHJpY3VsYXIgRmlicmlsbGF0aW9uLypjb21wbGljYXRpb25zLypkcnVnIHRo

ZXJhcHkvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIw

MDY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5TZXAgNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVz

Pjxpc2JuPjA3MzUtMTA5NzwvaXNibj48YWNjZXNzaW9uLW51bT4xNjk0OTQ3ODwvYWNjZXNzaW9u

LW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMTYvai5qYWNj

LjIwMDYuMDcuMDEwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXBy

b3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1

YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkVwc3RlaW48L0F1dGhvcj48WWVhcj4y

MDA4PC9ZZWFyPjxSZWNOdW0+MTA8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjEwPC9yZWMt

bnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDll

emR3OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMwOTQxOTAiPjEwPC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5FcHN0ZWluLCBBLiBFLjwvYXV0aG9yPjxh

dXRob3I+RGltYXJjbywgSi4gUC48L2F1dGhvcj48YXV0aG9yPkVsbGVuYm9nZW4sIEsuIEEuPC9h

dXRob3I+PGF1dGhvcj5Fc3RlcywgTi4gQS4sIDNyZDwvYXV0aG9yPjxhdXRob3I+RnJlZWRtYW4s

IFIuIEEuPC9hdXRob3I+PGF1dGhvcj5HZXR0ZXMsIEwuIFMuPC9hdXRob3I+PGF1dGhvcj5HaWxs

aW5vdiwgQS4gTS48L2F1dGhvcj48YXV0aG9yPkdyZWdvcmF0b3MsIEcuPC9hdXRob3I+PGF1dGhv

cj5IYW1taWxsLCBTLiBDLjwvYXV0aG9yPjxhdXRob3I+SGF5ZXMsIEQuIEwuPC9hdXRob3I+PGF1

dGhvcj5IbGF0a3ksIE0uIEEuPC9hdXRob3I+PGF1dGhvcj5OZXdieSwgTC4gSy48L2F1dGhvcj48

YXV0aG9yPlBhZ2UsIFIuIEwuPC9hdXRob3I+PGF1dGhvcj5TY2hvZW5mZWxkLCBNLiBILjwvYXV0

aG9yPjxhdXRob3I+U2lsa2EsIE0uIEouPC9hdXRob3I+PGF1dGhvcj5TdGV2ZW5zb24sIEwuIFcu

PC9hdXRob3I+PGF1dGhvcj5Td2VlbmV5LCBNLiBPLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRy

aWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5BQ0MvQUhBL0hSUyAyMDA4IGd1aWRlbGluZXMgZm9yIERl

dmljZS1CYXNlZCBUaGVyYXB5IG9mIENhcmRpYWMgUmh5dGhtIEFibm9ybWFsaXRpZXM6IGV4ZWN1

dGl2ZSBzdW1tYXJ5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkhlYXJ0IFJoeXRobTwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwg

b2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGlj

YWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9mdWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5

dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9h

YmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5IZWFydCBSaHl0

aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5h

bCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxw

YWdlcz45MzQtNTU8L3BhZ2VzPjx2b2x1bWU+NTwvdm9sdW1lPjxudW1iZXI+NjwvbnVtYmVyPjxl

ZGl0aW9uPjIwMDgvMDYvMDc8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFtZXJpY2FuIEhl

YXJ0IEFzc29jaWF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJkaWFjL3Bo

eXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5BdHJpb3ZlbnRyaWN1bGFy

IEJsb2NrL3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlhYyBQYWNpbmcsIEFydGlmaWNp

YWw8L2tleXdvcmQ+PGtleXdvcmQ+Q2FyZGlvbXlvcGF0aGllcy90aGVyYXB5PC9rZXl3b3JkPjxr

ZXl3b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+KkVs

ZWN0cmljIENvdW50ZXJzaG9jazwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtl

eXdvcmQ+U2lub2F0cmlhbCBOb2RlL3BoeXNpb3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5T

b2NpZXRpZXMsIE1lZGljYWw8L2tleXdvcmQ+PGtleXdvcmQ+VGhvcmFjaWMgU3VyZ2VyeTwva2V5

d29yZD48a2V5d29yZD5Vbml0ZWQgU3RhdGVzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5

ZWFyPjIwMDg8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PC9k

YXRlcz48aXNibj4xNTQ3LTUyNzE8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTg1MzQzNzc8L2FjY2Vz

c2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ou

aHJ0aG0uMjAwOC4wNC4wMTU8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJh

c2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwv

bGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE.DATA (Epstein et al., 2008; Zipes et al., 2006).A patient with chronic heart failure is also susceptible to malignant ventricular arrhythmias. Further, the prevalence and complexity of ventricular arrhythmias such as premature depolarisations and non-sustained ventricular tachycardia (NSVT) increases as left ventricular function deteriorates. In patients with LVEF less than 40%, the prevalence of NSVT rises from 15-20% in patients with NYHA class I-II symptoms of heart failure to 40-55% in patients with NYHA class II-III symptoms, and 50-70% in patients with NYHA class III-IV symptoms ADDIN EN.CITE <EndNote><Cite><Author>Packer</Author><Year>1992</Year><RecNum>29</RecNum><DisplayText>(Packer, 1992)</DisplayText><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183887">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Packer, M.</author></authors></contributors><auth-address>Department of Medicine, Mount Sinai School of Medicine, City University of New York, N.Y. 10029.</auth-address><titles><title>Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>I50-6</pages><volume>85</volume><number>1 Suppl</number><edition>1992/01/01</edition><keywords><keyword>Arrhythmias, Cardiac/*complications/epidemiology/etiology</keyword><keyword>Cardiac Output, Low/*complications</keyword><keyword>Chronic Disease</keyword><keyword>Death, Sudden, Cardiac/*etiology</keyword><keyword>Heart Ventricles</keyword><keyword>Humans</keyword><keyword>Prevalence</keyword></keywords><dates><year>1992</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0009-7322 (Print)&#xD;0009-7322</isbn><accession-num>1728505</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Packer, 1992). Therefore there is a complex interaction between electrical and mechanical performance of the heart, and it is impossible to determine which factor may play a primary factor in terminal heart failure ADDIN EN.CITE <EndNote><Cite><Author>MSAC</Author><Year>2006</Year><RecNum>35</RecNum><DisplayText>(MSAC, 2006)</DisplayText><record><rec-number>35</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383260284">35</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>MSAC</author></authors></contributors><titles><title>“Implantable cardiac defibrillators for prevention of sudden cardiac death, Reference 32”</title></titles><dates><year>2006</year></dates><urls><related-urls><url>[Internet] Available from: $File/MSAC%20Ref%2032%20-%20ICDs.pdf [accessed 15 October 2013]</url></related-urls></urls></record></Cite></EndNote>(MSAC, 2006). The risk of sudden death is higher in patients with chronic heart failure than in any other identifiable subset of patients in cardiovascular medicine and five times higher than in the general population ADDIN EN.CITE <EndNote><Cite><Author>Packer</Author><Year>1992</Year><RecNum>29</RecNum><DisplayText>(Packer, 1992)</DisplayText><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383183887">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Packer, M.</author></authors></contributors><auth-address>Department of Medicine, Mount Sinai School of Medicine, City University of New York, N.Y. 10029.</auth-address><titles><title>Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>I50-6</pages><volume>85</volume><number>1 Suppl</number><edition>1992/01/01</edition><keywords><keyword>Arrhythmias, Cardiac/*complications/epidemiology/etiology</keyword><keyword>Cardiac Output, Low/*complications</keyword><keyword>Chronic Disease</keyword><keyword>Death, Sudden, Cardiac/*etiology</keyword><keyword>Heart Ventricles</keyword><keyword>Humans</keyword><keyword>Prevalence</keyword></keywords><dates><year>1992</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0009-7322 (Print)&#xD;0009-7322</isbn><accession-num>1728505</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Packer, 1992).In summary, acute ventricular arrhythmias and chronic heart failure are common risk factors for sudden cardiac arrest (SCA) and SCD. Subcutaneous ICD therapy is indicated to treat ventricular arrhythmias and SCA, and prevent SCD.Australian Pathway to Identify Patients at Risk of SCDIndividuals at the highest risk of ventricular arrhythmia and SCD are those with a history of myocardial infarction, coronary artery disease, left ventricular dysfunction and cardiomyopathies. Individuals with a family history of SCD or genetic defects such as long QT syndrome are also at a high risk of SCD ADDIN EN.CITE <EndNote><Cite><Author>Lopshire</Author><Year>2006</Year><RecNum>33</RecNum><DisplayText>(Lopshire &amp; Zipes, 2006)</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383185710">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lopshire, J. C.</author><author>Zipes, D. P.</author></authors></contributors><titles><title>Sudden cardiac death: better understanding of risks, mechanisms, and treatment</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title></periodical><alt-periodical><full-title>Circulation</full-title></alt-periodical><pages>1134-6</pages><volume>114</volume><number>11</number><edition>2006/09/13</edition><keywords><keyword>Angina, Unstable/physiopathology</keyword><keyword>Arrhythmias, Cardiac/complications/physiopathology</keyword><keyword>Death, Sudden, Cardiac/*etiology/pathology/*prevention &amp; control</keyword><keyword>Electrocardiography</keyword><keyword>Humans</keyword><keyword>Ion Channels/genetics/physiopathology</keyword><keyword>Long QT Syndrome/genetics/physiopathology</keyword><keyword>Mutation/genetics</keyword><keyword>Myocardial Infarction/pathology</keyword><keyword>Risk Factors</keyword><keyword>Tachycardia, Ventricular/complications/physiopathology</keyword><keyword>Ventricular Dysfunction, Left/complications/physiopathology</keyword><keyword>Ventricular Fibrillation/*complications/genetics/*physiopathology</keyword></keywords><dates><year>2006</year><pub-dates><date>Sep 12</date></pub-dates></dates><isbn>0009-7322</isbn><accession-num>16966594</accession-num><urls></urls><electronic-resource-num>10.1161/circulationaha.106.647933</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Lopshire & Zipes, 2006). Common clinical presentations of patients with ventricular arrhythmia and SCD are presented in REF _Ref387409738 \h Table 7.Table SEQ Table \* ARABIC 7 Clinical Presentations of Patients with Ventricular Arrhythmias and Sudden Cardiac DeathAsymptomatic individuals with or without electrocardiographicAbnormalitiesPersons with symptoms potentially attributable to ventricular arrhythmiasPalpitationsDyspneaChest painSyncope and presyncopeVentricular tachycardia that is hemodynamically stableVentricular tachycardia that is not hemodynamically stableCardiac arrestAsystolic (sinus arrest, atrioventricular block)Ventricular tachycardiaVentricular fibrillationPulseless electrical activitySource: Zipes, et al., 2006Currently available treatment options for patients at risk of SCDThe most common methods for treating ventricular arrhythmia are antiarrhythmic medications, ICDs and cardiac ablation surgery. With the exception of beta blockers, the currently available antiarrhythmic drugs have not been shown in RCTs to be effective in the prevention of sudden cardiac death. More specifically, the overall long-term benefit from amiodarone does not appear to have a clear advantage over placebo (Epstein, et al., 2008).Depending on the patient’s clinical need, commercially available transvenous ICDs include: Single chamber ICD: A single lead connected to a pulse generator is placed using a transvenous approach into the right ventricle at a site that can pace and also defibrillate the heart. Dual-chamber ICD: the defibrillation lead is placed using a transvenous approach in the right ventricle and a pacing lead is placed in the right atrium and is connected to a pulse generator. The defibrillation lead delivers an electrical shock to the heart. Cardiac resynchronisation therapy defibrillators (CRT-Ds): The CRT-D device operates very similarly to an ICD system, but it involves three leads with the purpose of the third lead when introduced into the left ventricle to coordinate or resynchronise, ventricular contractions.Note that pacemakers (MBS item 38353) are generally designed to correct bradycardia and are not relevant to this protocol.Cardiac Ablation Surgery: Evidence suggests that standard radiofrequency (RF) ablation carries a relatively low success rate and is recommended for patients who are not or cannot receive appropriate therapy from an ICD or antiarrhythmic drugs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FcHN0ZWluPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjEwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihFcHN0ZWluIGV0IGFsLiwgMjAwOCk8L0Rp

c3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MTA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5

cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVw

NWEiIHRpbWVzdGFtcD0iMTM4MzA5NDE5MCI+MTA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0

aG9ycz48YXV0aG9yPkVwc3RlaW4sIEEuIEUuPC9hdXRob3I+PGF1dGhvcj5EaW1hcmNvLCBKLiBQ

LjwvYXV0aG9yPjxhdXRob3I+RWxsZW5ib2dlbiwgSy4gQS48L2F1dGhvcj48YXV0aG9yPkVzdGVz

LCBOLiBBLiwgM3JkPC9hdXRob3I+PGF1dGhvcj5GcmVlZG1hbiwgUi4gQS48L2F1dGhvcj48YXV0

aG9yPkdldHRlcywgTC4gUy48L2F1dGhvcj48YXV0aG9yPkdpbGxpbm92LCBBLiBNLjwvYXV0aG9y

PjxhdXRob3I+R3JlZ29yYXRvcywgRy48L2F1dGhvcj48YXV0aG9yPkhhbW1pbGwsIFMuIEMuPC9h

dXRob3I+PGF1dGhvcj5IYXllcywgRC4gTC48L2F1dGhvcj48YXV0aG9yPkhsYXRreSwgTS4gQS48

L2F1dGhvcj48YXV0aG9yPk5ld2J5LCBMLiBLLjwvYXV0aG9yPjxhdXRob3I+UGFnZSwgUi4gTC48

L2F1dGhvcj48YXV0aG9yPlNjaG9lbmZlbGQsIE0uIEguPC9hdXRob3I+PGF1dGhvcj5TaWxrYSwg

TS4gSi48L2F1dGhvcj48YXV0aG9yPlN0ZXZlbnNvbiwgTC4gVy48L2F1dGhvcj48YXV0aG9yPlN3

ZWVuZXksIE0uIE8uPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPkFDQy9BSEEvSFJTIDIwMDggZ3VpZGVsaW5lcyBmb3IgRGV2aWNlLUJhc2VkIFRoZXJhcHkg

b2YgQ2FyZGlhYyBSaHl0aG0gQWJub3JtYWxpdGllczogZXhlY3V0aXZlIHN1bW1hcnk8L3RpdGxl

PjxzZWNvbmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGht

IFNvY2lldHk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5IZWFy

dCBSaHl0aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8L2FiYnItMT48L3BlcmlvZGljYWw+

PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkhlYXJ0IFJoeXRobTwvZnVsbC10aXRsZT48YWJi

ci0xPkhlYXJ0IHJoeXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFsIG9mIHRoZSBIZWFydCBSaHl0

aG0gU29jaWV0eTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjkzNC01NTwvcGFnZXM+

PHZvbHVtZT41PC92b2x1bWU+PG51bWJlcj42PC9udW1iZXI+PGVkaXRpb24+MjAwOC8wNi8wNzwv

ZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb248L2tl

eXdvcmQ+PGtleXdvcmQ+QXJyaHl0aG1pYXMsIENhcmRpYWMvcGh5c2lvcGF0aG9sb2d5Lyp0aGVy

YXB5PC9rZXl3b3JkPjxrZXl3b3JkPkF0cmlvdmVudHJpY3VsYXIgQmxvY2svdGhlcmFweTwva2V5

d29yZD48a2V5d29yZD5DYXJkaWFjIFBhY2luZywgQXJ0aWZpY2lhbDwva2V5d29yZD48a2V5d29y

ZD5DYXJkaW9teW9wYXRoaWVzL3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmlsbGF0

b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD4qRWxlY3RyaWMgQ291bnRlcnNob2Nr

PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5TaW5vYXRyaWFsIE5v

ZGUvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlNvY2lldGllcywgTWVkaWNhbDwv

a2V5d29yZD48a2V5d29yZD5UaG9yYWNpYyBTdXJnZXJ5PC9rZXl3b3JkPjxrZXl3b3JkPlVuaXRl

ZCBTdGF0ZXM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwODwveWVhcj48cHVi

LWRhdGVzPjxkYXRlPkp1bjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NDctNTI3

MTwvaXNibj48YWNjZXNzaW9uLW51bT4xODUzNDM3NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3Vy

bHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMTYvai5ocnRobS4yMDA4LjA0LjAxNTwv

ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3Jl

bW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48

L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FcHN0ZWluPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjEwPC9SZWNOdW0+PERpc3BsYXlUZXh0PihFcHN0ZWluIGV0IGFsLiwgMjAwOCk8L0Rp

c3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MTA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5

cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVw

NWEiIHRpbWVzdGFtcD0iMTM4MzA5NDE5MCI+MTA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0

aG9ycz48YXV0aG9yPkVwc3RlaW4sIEEuIEUuPC9hdXRob3I+PGF1dGhvcj5EaW1hcmNvLCBKLiBQ

LjwvYXV0aG9yPjxhdXRob3I+RWxsZW5ib2dlbiwgSy4gQS48L2F1dGhvcj48YXV0aG9yPkVzdGVz

LCBOLiBBLiwgM3JkPC9hdXRob3I+PGF1dGhvcj5GcmVlZG1hbiwgUi4gQS48L2F1dGhvcj48YXV0

aG9yPkdldHRlcywgTC4gUy48L2F1dGhvcj48YXV0aG9yPkdpbGxpbm92LCBBLiBNLjwvYXV0aG9y

PjxhdXRob3I+R3JlZ29yYXRvcywgRy48L2F1dGhvcj48YXV0aG9yPkhhbW1pbGwsIFMuIEMuPC9h

dXRob3I+PGF1dGhvcj5IYXllcywgRC4gTC48L2F1dGhvcj48YXV0aG9yPkhsYXRreSwgTS4gQS48

L2F1dGhvcj48YXV0aG9yPk5ld2J5LCBMLiBLLjwvYXV0aG9yPjxhdXRob3I+UGFnZSwgUi4gTC48

L2F1dGhvcj48YXV0aG9yPlNjaG9lbmZlbGQsIE0uIEguPC9hdXRob3I+PGF1dGhvcj5TaWxrYSwg

TS4gSi48L2F1dGhvcj48YXV0aG9yPlN0ZXZlbnNvbiwgTC4gVy48L2F1dGhvcj48YXV0aG9yPlN3

ZWVuZXksIE0uIE8uPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPkFDQy9BSEEvSFJTIDIwMDggZ3VpZGVsaW5lcyBmb3IgRGV2aWNlLUJhc2VkIFRoZXJhcHkg

b2YgQ2FyZGlhYyBSaHl0aG0gQWJub3JtYWxpdGllczogZXhlY3V0aXZlIHN1bW1hcnk8L3RpdGxl

PjxzZWNvbmRhcnktdGl0bGU+SGVhcnQgUmh5dGhtPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGht

IFNvY2lldHk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5IZWFy

dCBSaHl0aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCByaHl0aG0gOiB0aGUgb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8L2FiYnItMT48L3BlcmlvZGljYWw+

PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkhlYXJ0IFJoeXRobTwvZnVsbC10aXRsZT48YWJi

ci0xPkhlYXJ0IHJoeXRobSA6IHRoZSBvZmZpY2lhbCBqb3VybmFsIG9mIHRoZSBIZWFydCBSaHl0

aG0gU29jaWV0eTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjkzNC01NTwvcGFnZXM+

PHZvbHVtZT41PC92b2x1bWU+PG51bWJlcj42PC9udW1iZXI+PGVkaXRpb24+MjAwOC8wNi8wNzwv

ZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW1lcmljYW4gSGVhcnQgQXNzb2NpYXRpb248L2tl

eXdvcmQ+PGtleXdvcmQ+QXJyaHl0aG1pYXMsIENhcmRpYWMvcGh5c2lvcGF0aG9sb2d5Lyp0aGVy

YXB5PC9rZXl3b3JkPjxrZXl3b3JkPkF0cmlvdmVudHJpY3VsYXIgQmxvY2svdGhlcmFweTwva2V5

d29yZD48a2V5d29yZD5DYXJkaWFjIFBhY2luZywgQXJ0aWZpY2lhbDwva2V5d29yZD48a2V5d29y

ZD5DYXJkaW9teW9wYXRoaWVzL3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmlsbGF0

b3JzLCBJbXBsYW50YWJsZTwva2V5d29yZD48a2V5d29yZD4qRWxlY3RyaWMgQ291bnRlcnNob2Nr

PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5TaW5vYXRyaWFsIE5v

ZGUvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlNvY2lldGllcywgTWVkaWNhbDwv

a2V5d29yZD48a2V5d29yZD5UaG9yYWNpYyBTdXJnZXJ5PC9rZXl3b3JkPjxrZXl3b3JkPlVuaXRl

ZCBTdGF0ZXM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwODwveWVhcj48cHVi

LWRhdGVzPjxkYXRlPkp1bjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NDctNTI3

MTwvaXNibj48YWNjZXNzaW9uLW51bT4xODUzNDM3NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3Vy

bHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMTYvai5ocnRobS4yMDA4LjA0LjAxNTwv

ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3Jl

bW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48

L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE.DATA (Epstein et al., 2008).Proposed MBS listingThe proposed MBS item for the insertion, replacement or removal of subcutaneous ICD lead is presented in REF _Ref387409840 \h Table 8. The proposed item descriptor specifies that the use of subcutaneous ICD should be limited to patients who do not have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently occurring VT that is reliably terminated with anti-tachycardia pacing. The applicant estimates the time and skill required for extraction of a subcutaneous ICD lead is similar to the insertion of a subcutaneous ICD lead. Therefore, the proposed MBS item includes both insertion and removal/replacement of subcutaneous ICD leads. This is in contrast the current funding arrangement for transvenous ICD whereby a separate MBS item for lead removal (item?38358) is required due to the complexity of the procedure.It should be noted that the applicant is not requesting reimbursement in a new population, but rather a subpopulation of patients already eligible for transvenous ICD. Subcutaneous electrode implantation is not indicated for other conditions; therefore there is a low risk of use of the proposed service outside this patient population. Table SEQ Table \* ARABIC 8 Proposed MBS item descriptor for insertion, removal or replacement of subcutaneous ICD lead Category 3 – Therapeutic ProceduresSUBCUTANEOUS DEFIBRILLATOR LEAD, insertion, removal or replacement of, for prevention of sudden cardiac death in patients who do not have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently occurring ventricular tachycardia that is reliably terminated with anti-tachycardia pacing.Multiple Services Rule (Anaes.) (Assist.) Fee: $TBDA comparison of time and complexity for the two procedures will be undertaken in the submission based assessment e.g. appropriate lead placement to reduce over sensing, lead migration and local infection. Patient PopulationMSAC Assessment Report 32 ADDIN EN.CITE <EndNote><Cite><Author>MSAC</Author><Year>2006</Year><RecNum>35</RecNum><DisplayText>(MSAC, 2006)</DisplayText><record><rec-number>35</rec-number><foreign-keys><key app="EN" db-id="ea0rept09ptvp9ezdw8xw5xr022ta0fvep5a" timestamp="1383260284">35</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>MSAC</author></authors></contributors><titles><title>“Implantable cardiac defibrillators for prevention of sudden cardiac death, Reference 32”</title></titles><dates><year>2006</year></dates><urls><related-urls><url>[Internet] Available from: $File/MSAC%20Ref%2032%20-%20ICDs.pdf [accessed 15 October 2013]</url></related-urls></urls></record></Cite></EndNote>(2006) assessed ICDs for the prevention of SCD. A review of cardiac services for implantable cardioverter defibrillators is currently in development. The purpose of the assessment for subcutaneous ICD therapy is to address whether the proposed service is safe, effective and cost-effective for patients currently indicated for a transvenous ICD who will be eligible for subcutaneous ICD in clinical practice. The applicant suggests that, as subcutaneous ICD is indicated for a sub-group of the current patient population receiving transvenous ICD technology, a description of epidemiology for the proposed service is not required. Clinical place for proposed interventionThe subcutaneous ICD system cannot provide long-term bradycardia pacing or antitachycardia pacing PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BeWRpbjwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl

Y051bT4yNTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQXlkaW4gZXQgYWwuLCAyMDEyOyBEYWJpcmkg

QWJrZW5hcmkgZXQgYWwuLCAyMDExOyBMb2JvZHppbnNraSwgMjAxMSk8L0Rpc3BsYXlUZXh0Pjxy

ZWNvcmQ+PHJlYy1udW1iZXI+MjU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFt

cD0iMTM4MzEzMzMxOCI+MjU8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91

cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9y

PkF5ZGluLCBBLjwvYXV0aG9yPjxhdXRob3I+SGFydGVsLCBGLjwvYXV0aG9yPjxhdXRob3I+U2No

bHV0ZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5CdXR0ZXIsIEMuPC9hdXRob3I+PGF1dGhvcj5Lb2Jl

LCBKLjwvYXV0aG9yPjxhdXRob3I+U2VpZmVydCwgTS48L2F1dGhvcj48YXV0aG9yPkdvc2F1LCBO

LjwvYXV0aG9yPjxhdXRob3I+SG9mZm1hbm4sIEIuPC9hdXRob3I+PGF1dGhvcj5Ib2ZmbWFubiwg

TS48L2F1dGhvcj48YXV0aG9yPlZldHRvcmF6emksIEUuPC9hdXRob3I+PGF1dGhvcj5XaWxrZSwg

SS48L2F1dGhvcj48YXV0aG9yPldlZ3NjaGVpZGVyLCBLLjwvYXV0aG9yPjxhdXRob3I+UmVpY2hl

bnNwdXJuZXIsIEguPC9hdXRob3I+PGF1dGhvcj5FY2thcmR0LCBMLjwvYXV0aG9yPjxhdXRob3I+

U3RldmVuLCBELjwvYXV0aG9yPjxhdXRob3I+V2lsbGVtcywgUy48L2F1dGhvcj48L2F1dGhvcnM+

PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIEVsZWN0cm9waHlzaW9s

b2d5LCBVbml2ZXJzaXR5IEhlYXJ0IENlbnRlciwgSGFtYnVyZywgR2VybWFueS4gYXlkaW5AdWtl

LmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+U2hvY2sgZWZmaWNhY3kgb2Ygc3ViY3V0

YW5lb3VzIGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1kZWZpYnJpbGxhdG9yIGZvciBwcmV2ZW50

aW9uIG9mIHN1ZGRlbiBjYXJkaWFjIGRlYXRoOiBpbml0aWFsIG11bHRpY2VudGVyIGV4cGVyaWVu

Y2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2lyY3VsYXRpb24uIEFycmh5dGhtaWEgYW5kIGVs

ZWN0cm9waHlzaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0

bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1

bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5c2lvbG9neTwvYWJici0xPjwvcGVyaW9k

aWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5

c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVj

dHJvcGh5c2lvbG9neTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjkxMy05PC9wYWdl

cz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjU8L251bWJlcj48ZWRpdGlvbj4yMDEyLzA4LzI4

PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2Vk

PC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvKnByZXZlbnRpb24gJmFt

cDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxl

PC9rZXl3b3JkPjxrZXl3b3JkPkVjaG9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+RmVt

YWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3Jk

Pkdlcm1hbnk8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkxvZ2lz

dGljIE1vZGVsczwva2V5d29yZD48a2V5d29yZD5NYWduZXRpYyBSZXNvbmFuY2UgSW1hZ2luZzwv

a2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3

b3JkPjxrZXl3b3JkPlBhdGllbnQgU2VsZWN0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByaW1hcnkg

UHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TZWNvbmRhcnkgUHJldmVudGlvbjwva2V5d29y

ZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBW

ZW50cmljdWxhci9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJl

YXRtZW50IE91dGNvbWU8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMjwveWVh

cj48cHViLWRhdGVzPjxkYXRlPk9jdDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE5

NDEtMzA4NDwvaXNibj48YWNjZXNzaW9uLW51bT4yMjkyMzI3NDwvYWNjZXNzaW9uLW51bT48dXJs

cz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjExNjEvY2lyY2VwLjExMi45NzMz

Mzk8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+Tmxt

PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv

cmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+RGFiaXJpIEFia2VuYXJpPC9BdXRob3I+PFllYXI+MjAx

MTwvWWVhcj48UmVjTnVtPjI0PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yNDwvcmVjLW51

bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpk

dzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTMzMjQ3Ij4yNDwva2V5PjwvZm9y

ZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48

Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9y

PjxhdXRob3I+VGhldW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+VmFsaywgUy4gRC48L2F1dGhv

cj48YXV0aG9yPlZhbiBCZWxsZSwgWS48L2F1dGhvcj48YXV0aG9yPmRlIEdyb290LCBOLiBNLjwv

YXV0aG9yPjxhdXRob3I+SGFpdHNtYSwgRC48L2F1dGhvcj48YXV0aG9yPk11c2tlbnMtSGVlbXNr

ZXJrLCBBLjwvYXV0aG9yPjxhdXRob3I+U3ppbGktVG9yb2ssIFQuPC9hdXRob3I+PGF1dGhvcj5K

b3JkYWVucywgTC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz

cz5EZXBhcnRtZW50IG9mIENhcmRpb2xvZ3ksIEVyYXNtdXMgTUMsIFJvdHRlcmRhbSwgVGhlIE5l

dGhlcmxhbmRzLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNsaW5pY2FsIGV4cGVyaWVu

Y2Ugd2l0aCBhIG5vdmVsIHN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBkZWZpYnJpbGxhdG9yIHN5

c3RlbSBpbiBhIHNpbmdsZSBjZW50ZXI8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2xpbiBSZXMg

Q2FyZGlvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2xpbmljYWwgcmVzZWFyY2ggaW4g

Y2FyZGlvbG9neSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2ll

dHk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DbGluIFJlcyBD

YXJkaW9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9n

eSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FiYnIt

MT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRp

b2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDog

b2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwv

YWx0LXBlcmlvZGljYWw+PHBhZ2VzPjczNy00NDwvcGFnZXM+PHZvbHVtZT4xMDA8L3ZvbHVtZT48

bnVtYmVyPjk8L251bWJlcj48ZWRpdGlvbj4yMDExLzAzLzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48

a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFy

cmh5dGhtaWFzLCBDYXJkaWFjL3BoeXNpb3BhdGhvbG9neS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3

b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGUvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3Jk

PjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5

d29yZD48a2V5d29yZD5IZWFydCBEaXNlYXNlcy9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tl

eXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtl

eXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+UmVjdXJyZW5jZS9wcmV2ZW50aW9u

ICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxr

ZXl3b3JkPlZlbnRyaWN1bGFyIEZpYnJpbGxhdGlvbi9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8

L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxk

YXRlPlNlcDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE4NjEtMDY4NDwvaXNibj48

YWNjZXNzaW9uLW51bT4yMTQxNjE5MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3Rv

bTI+UG1jMzE2NzA0MDwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAwNy9z

MDAzOTItMDExLTAzMDMtNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFz

ZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9s

YW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5Mb2JvZHppbnNraTwvQXV0aG9y

PjxZZWFyPjIwMTE8L1llYXI+PFJlY051bT4yMjwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjI8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0

MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzExODk5MyI+MjI8

L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwv

cmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkxvYm9kemluc2tpLCBTLiBT

LjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1l

bnQgb2YgRWxlY3RyaWNhbCBhbmQgQmlvbWVkaWNhbCBFbmdpbmVlcmluZywgQ2FsaWZvcm5pYSBT

dGF0ZSBVbml2ZXJzaXR5IExvbmcgQmVhY2gsIENBLCBVU0EuIHNsb2JvQGNzdWxiLmVkdTwvYXV0

aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBjYXJkaW92

ZXJ0ZXItZGVmaWJyaWxsYXRvciAoUy1JQ0QpPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNhcmRp

b2wgSjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2FyZGlvbG9neSBqb3VybmFsPC9hbHQt

dGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2FyZGlvbCBKPC9mdWxsLXRp

dGxlPjxhYmJyLTE+Q2FyZGlvbG9neSBqb3VybmFsPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYXJkaW9sIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5DYXJk

aW9sb2d5IGpvdXJuYWw8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4zMjYtMzE8L3Bh

Z2VzPjx2b2x1bWU+MTg8L3ZvbHVtZT48bnVtYmVyPjM8L251bWJlcj48ZWRpdGlvbj4yMDExLzA2

LzExPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5EZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2Vw

aWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVm

aWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlL2FkdmVyc2UgZWZmZWN0cy9zdGF0aXN0aWNzICZhbXA7

IG51bWVyaWNhbCBkYXRhLyp0cmVuZHM8L2tleXdvcmQ+PGtleXdvcmQ+RGV2aWNlIEFwcHJvdmFs

PC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9kZXMsIEltcGxhbnRlZC9hZHZlcnNlIGVmZmVjdHMv

c3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YS8qdHJlbmRzPC9rZXl3b3JkPjxrZXl3b3Jk

PkV1cm9wZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+KlByb3N0

aGVzaXMgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPlByb3N0aGVzaXMgSW1wbGFudGF0aW9uLypt

ZXRob2RzL3RyZW5kczwva2V5d29yZD48a2V5d29yZD5SaXNrIEZhY3RvcnM8L2tleXdvcmQ+PGtl

eXdvcmQ+VGFjaHljYXJkaWEsIFZlbnRyaWN1bGFyLyp0aGVyYXB5PC9rZXl3b3JkPjwva2V5d29y

ZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRlcz48aXNibj4xODk4LTAxOHg8L2lzYm4+

PGFjY2Vzc2lvbi1udW0+MjE2NjA5Mjg8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1

YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BeWRpbjwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl

Y051bT4yNTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQXlkaW4gZXQgYWwuLCAyMDEyOyBEYWJpcmkg

QWJrZW5hcmkgZXQgYWwuLCAyMDExOyBMb2JvZHppbnNraSwgMjAxMSk8L0Rpc3BsYXlUZXh0Pjxy

ZWNvcmQ+PHJlYy1udW1iZXI+MjU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJlYTByZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFt

cD0iMTM4MzEzMzMxOCI+MjU8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91

cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9y

PkF5ZGluLCBBLjwvYXV0aG9yPjxhdXRob3I+SGFydGVsLCBGLjwvYXV0aG9yPjxhdXRob3I+U2No

bHV0ZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5CdXR0ZXIsIEMuPC9hdXRob3I+PGF1dGhvcj5Lb2Jl

LCBKLjwvYXV0aG9yPjxhdXRob3I+U2VpZmVydCwgTS48L2F1dGhvcj48YXV0aG9yPkdvc2F1LCBO

LjwvYXV0aG9yPjxhdXRob3I+SG9mZm1hbm4sIEIuPC9hdXRob3I+PGF1dGhvcj5Ib2ZmbWFubiwg

TS48L2F1dGhvcj48YXV0aG9yPlZldHRvcmF6emksIEUuPC9hdXRob3I+PGF1dGhvcj5XaWxrZSwg

SS48L2F1dGhvcj48YXV0aG9yPldlZ3NjaGVpZGVyLCBLLjwvYXV0aG9yPjxhdXRob3I+UmVpY2hl

bnNwdXJuZXIsIEguPC9hdXRob3I+PGF1dGhvcj5FY2thcmR0LCBMLjwvYXV0aG9yPjxhdXRob3I+

U3RldmVuLCBELjwvYXV0aG9yPjxhdXRob3I+V2lsbGVtcywgUy48L2F1dGhvcj48L2F1dGhvcnM+

PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIEVsZWN0cm9waHlzaW9s

b2d5LCBVbml2ZXJzaXR5IEhlYXJ0IENlbnRlciwgSGFtYnVyZywgR2VybWFueS4gYXlkaW5AdWtl

LmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+U2hvY2sgZWZmaWNhY3kgb2Ygc3ViY3V0

YW5lb3VzIGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1kZWZpYnJpbGxhdG9yIGZvciBwcmV2ZW50

aW9uIG9mIHN1ZGRlbiBjYXJkaWFjIGRlYXRoOiBpbml0aWFsIG11bHRpY2VudGVyIGV4cGVyaWVu

Y2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2lyY3VsYXRpb24uIEFycmh5dGhtaWEgYW5kIGVs

ZWN0cm9waHlzaW9sb2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0

bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1

bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVjdHJvcGh5c2lvbG9neTwvYWJici0xPjwvcGVyaW9k

aWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2lyYyBBcnJoeXRobSBFbGVjdHJvcGh5

c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkNpcmN1bGF0aW9uLiBBcnJoeXRobWlhIGFuZCBlbGVj

dHJvcGh5c2lvbG9neTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjkxMy05PC9wYWdl

cz48dm9sdW1lPjU8L3ZvbHVtZT48bnVtYmVyPjU8L251bWJlcj48ZWRpdGlvbj4yMDEyLzA4LzI4

PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2Vk

PC9rZXl3b3JkPjxrZXl3b3JkPkRlYXRoLCBTdWRkZW4sIENhcmRpYWMvKnByZXZlbnRpb24gJmFt

cDsgY29udHJvbDwva2V5d29yZD48a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxl

PC9rZXl3b3JkPjxrZXl3b3JkPkVjaG9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+RmVt

YWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3Jk

Pkdlcm1hbnk8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkxvZ2lz

dGljIE1vZGVsczwva2V5d29yZD48a2V5d29yZD5NYWduZXRpYyBSZXNvbmFuY2UgSW1hZ2luZzwv

a2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3

b3JkPjxrZXl3b3JkPlBhdGllbnQgU2VsZWN0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByaW1hcnkg

UHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TZWNvbmRhcnkgUHJldmVudGlvbjwva2V5d29y

ZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBW

ZW50cmljdWxhci9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJl

YXRtZW50IE91dGNvbWU8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMjwveWVh

cj48cHViLWRhdGVzPjxkYXRlPk9jdDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE5

NDEtMzA4NDwvaXNibj48YWNjZXNzaW9uLW51bT4yMjkyMzI3NDwvYWNjZXNzaW9uLW51bT48dXJs

cz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjExNjEvY2lyY2VwLjExMi45NzMz

Mzk8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+Tmxt

PC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNv

cmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+RGFiaXJpIEFia2VuYXJpPC9BdXRob3I+PFllYXI+MjAx

MTwvWWVhcj48UmVjTnVtPjI0PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yNDwvcmVjLW51

bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpk

dzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTMzMjQ3Ij4yNDwva2V5PjwvZm9y

ZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48

Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9y

PjxhdXRob3I+VGhldW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+VmFsaywgUy4gRC48L2F1dGhv

cj48YXV0aG9yPlZhbiBCZWxsZSwgWS48L2F1dGhvcj48YXV0aG9yPmRlIEdyb290LCBOLiBNLjwv

YXV0aG9yPjxhdXRob3I+SGFpdHNtYSwgRC48L2F1dGhvcj48YXV0aG9yPk11c2tlbnMtSGVlbXNr

ZXJrLCBBLjwvYXV0aG9yPjxhdXRob3I+U3ppbGktVG9yb2ssIFQuPC9hdXRob3I+PGF1dGhvcj5K

b3JkYWVucywgTC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz

cz5EZXBhcnRtZW50IG9mIENhcmRpb2xvZ3ksIEVyYXNtdXMgTUMsIFJvdHRlcmRhbSwgVGhlIE5l

dGhlcmxhbmRzLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNsaW5pY2FsIGV4cGVyaWVu

Y2Ugd2l0aCBhIG5vdmVsIHN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBkZWZpYnJpbGxhdG9yIHN5

c3RlbSBpbiBhIHNpbmdsZSBjZW50ZXI8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2xpbiBSZXMg

Q2FyZGlvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2xpbmljYWwgcmVzZWFyY2ggaW4g

Y2FyZGlvbG9neSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2ll

dHk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DbGluIFJlcyBD

YXJkaW9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2xpbmljYWwgcmVzZWFyY2ggaW4gY2FyZGlvbG9n

eSA6IG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEdlcm1hbiBDYXJkaWFjIFNvY2lldHk8L2FiYnIt

MT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRp

b2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDog

b2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwv

YWx0LXBlcmlvZGljYWw+PHBhZ2VzPjczNy00NDwvcGFnZXM+PHZvbHVtZT4xMDA8L3ZvbHVtZT48

bnVtYmVyPjk8L251bWJlcj48ZWRpdGlvbj4yMDExLzAzLzE5PC9lZGl0aW9uPjxrZXl3b3Jkcz48

a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFy

cmh5dGhtaWFzLCBDYXJkaWFjL3BoeXNpb3BhdGhvbG9neS90aGVyYXB5PC9rZXl3b3JkPjxrZXl3

b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGUvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3Jk

PjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5

d29yZD48a2V5d29yZD5IZWFydCBEaXNlYXNlcy9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8L2tl

eXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtl

eXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+UmVjdXJyZW5jZS9wcmV2ZW50aW9u

ICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxr

ZXl3b3JkPlZlbnRyaWN1bGFyIEZpYnJpbGxhdGlvbi9waHlzaW9wYXRob2xvZ3kvKnRoZXJhcHk8

L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVhcj48cHViLWRhdGVzPjxk

YXRlPlNlcDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE4NjEtMDY4NDwvaXNibj48

YWNjZXNzaW9uLW51bT4yMTQxNjE5MTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3Rv

bTI+UG1jMzE2NzA0MDwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAwNy9z

MDAzOTItMDExLTAzMDMtNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFz

ZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9s

YW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5Mb2JvZHppbnNraTwvQXV0aG9y

PjxZZWFyPjIwMTE8L1llYXI+PFJlY051bT4yMjwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjI8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTByZXB0

MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzExODk5MyI+MjI8

L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwv

cmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkxvYm9kemluc2tpLCBTLiBT

LjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1l

bnQgb2YgRWxlY3RyaWNhbCBhbmQgQmlvbWVkaWNhbCBFbmdpbmVlcmluZywgQ2FsaWZvcm5pYSBT

dGF0ZSBVbml2ZXJzaXR5IExvbmcgQmVhY2gsIENBLCBVU0EuIHNsb2JvQGNzdWxiLmVkdTwvYXV0

aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlN1YmN1dGFuZW91cyBpbXBsYW50YWJsZSBjYXJkaW92

ZXJ0ZXItZGVmaWJyaWxsYXRvciAoUy1JQ0QpPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNhcmRp

b2wgSjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2FyZGlvbG9neSBqb3VybmFsPC9hbHQt

dGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2FyZGlvbCBKPC9mdWxsLXRp

dGxlPjxhYmJyLTE+Q2FyZGlvbG9neSBqb3VybmFsPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYXJkaW9sIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5DYXJk

aW9sb2d5IGpvdXJuYWw8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4zMjYtMzE8L3Bh

Z2VzPjx2b2x1bWU+MTg8L3ZvbHVtZT48bnVtYmVyPjM8L251bWJlcj48ZWRpdGlvbj4yMDExLzA2

LzExPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5EZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2Vw

aWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+RGVm

aWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlL2FkdmVyc2UgZWZmZWN0cy9zdGF0aXN0aWNzICZhbXA7

IG51bWVyaWNhbCBkYXRhLyp0cmVuZHM8L2tleXdvcmQ+PGtleXdvcmQ+RGV2aWNlIEFwcHJvdmFs

PC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0cm9kZXMsIEltcGxhbnRlZC9hZHZlcnNlIGVmZmVjdHMv

c3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YS8qdHJlbmRzPC9rZXl3b3JkPjxrZXl3b3Jk

PkV1cm9wZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+KlByb3N0

aGVzaXMgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPlByb3N0aGVzaXMgSW1wbGFudGF0aW9uLypt

ZXRob2RzL3RyZW5kczwva2V5d29yZD48a2V5d29yZD5SaXNrIEZhY3RvcnM8L2tleXdvcmQ+PGtl

eXdvcmQ+VGFjaHljYXJkaWEsIFZlbnRyaWN1bGFyLyp0aGVyYXB5PC9rZXl3b3JkPjwva2V5d29y

ZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRlcz48aXNibj4xODk4LTAxOHg8L2lzYm4+

PGFjY2Vzc2lvbi1udW0+MjE2NjA5Mjg8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1

YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Aydin et al., 2012; Dabiri Abkenari et al., 2011; Lobodzinski, 2011). Rather, the subcutaneous ICD system is an alternative option for patients indicated for a single- or dual- chamber ICD who do not require pacing therapy i.e. patients indicated for ICD therapy that do not have symptomatic bradycardia or ventricular tachycardia that is reliably terminated with anti-tachycardia pacing. As such, subcutaneous ICD technology does not introduce a new patient population in addition to patients indicated for single or dual-chamber ICD. Subcutaneous ICD therapy is suitable for a subset of patients who are currently indicated for transvenous ICD: those that do not require pacing. Expert clinical opinion estimates that ~75-80% of patients receiving an ICD would not have a bradycardia pacing indication at the time of implantation and be eligible to receive a subcutaneous ICD instead of a transvenous ICD. Both the number of patients suitable for subcutaneous ICD and the number of those patients expected to develop a need for pacing overtime (expected to be small) will be investigated in the submission based assessment. Subcutaneous ICD is a direct substitute for patients who have an indication for a transvenous ICD and do not require pacing therapy. The management algorithm for treatment of ventricular arrhythmia is presented in REF _Ref378688629 \h Figure 1.Figure SEQ Figure \* ARABIC 1: Proposed clinical management pathway for patients with ventricular arrhythmia at risk of sudden cardiac deathComparatorThe proposed comparator for the subcutaneous ICD system is single and dual-chamber transvenous ICD in patients who do not have bradycardia pacing indications. ICD therapy is standard of care for patients at risk of SCD and is subject to a current MSAC Review. The proposed application will focus on establishing non-inferiority of subcutaneous ICD to transvenous ICD with respect to safety and effectiveness.Subcutaneous ICD is proposed to be a direct substitute for transvenous ICD systems programmed for defibrillation only as the subcutaneous ICD is not suitable for patients with symptomatic bradycardia, incessant VT, or spontaneous, frequently recurring VT that is reliably terminated with anti-tachycardia pacing. The proportion of subcutaneous ICD systems that will be utilised in place of transvenous ICD systems will be provided in the submission based assessment. A comparison of the physical characteristics and clinical capabilities of subcutaneous and transvenous ICD is provided in REF _Ref387242024 \h Table 9 below.Table SEQ Table \* ARABIC 9 Comparison of physical and clinical characteristics of subcutaneous and transvenous ICD devicesDevice CharacteristicSubcutaneous ICDTransvenous ICD(based on typical single or dual chamber device)PhysicalSize (HxWxD)MassVolumePositioning78.2 × 65.5 × 15.7 mm145g69.9ccSubcutaneous device and lead placement61.7 x 6.90 x 9.9 mm*72g*30.5cc*Subcutaneous device and transvenous lead placementDefibrillation capabilitiesRhythm discriminationDFT testing energyDelivered energyNumber of ShocksShock ZoneSensing configurationPolarityYes; morphology template matching10-80 joules programmable80 joules; non programmable5Yes; programmableYes; manual and automaticSelected based on history of successful shocks with ability to manually override.Yes; two available options – Onset and Stability & Morphology template matching*.1-37 joules; programmable*1-37 joules; programmable*5 to 8Yes; programmableYes; manual and automaticProgrammable; Initial or ReversedPacing capabilitiesPost-shock pacing; programmable ON or OFF onlyNo Antitachycardia pacingPost-shock pacing; programmableVarious device specific tachy and brady pacing capabilities Storing and analyzing dataPatient, hospital and treating physician detailsStores up to 24 treated and 20 untreated tachyarrythmia episodes (74 mins total)Patient, hospital and treating physician details17mins storage of event episodes*CommunicationWireless communication with programmerNo remote monitoringWireless communication with programmerRemote monitoring capabilitySystem DiagnosticsShock electrode impedance Device integrity checkBattery PerformanceInternal warning systemMagnet ResponseYes, weekly and post-shock deliveryYes, daily and on connection with programmerOngoing battery status, Elective replacement indicator and end of lifeTone alerts patient if anything requires attentionInhibits Tachy therapy Yes; manually, daily and post shockYes; manually, daily and post shockOngoing battery status, Elective replacement indicator and end of lifeTone alerts patient if anything requires attentionOff, Store EGM, Inhibit Therapy* Specifications for INCEPTA? single-chamber ICD provided as an exampleClinical claimThe application considers subcutaneous ICD is non-inferior to transvenous ICD and offers some important safety advantages because subcutaneous ICD does not require transvenous lead implantation. As such, it is proposed that Section D of the submission based assessment will take a cost-minimisation approach.The submission based assessment will undertake a literature review to identify the best available clinical data for subcutaneous ICD and transvenous ICD.Outcomes and health care resources affected by introduction of proposed interventionOutcomesThe highest-quality clinical evidence available will be used to support the efficacy and safety of subcutaneous ICD. This will likely include data from both single arm trials PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZWlzczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl

Y051bT4xMzwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQmFyZHkgZXQgYWwuLCAyMDEwOyBCdXJrZSwg

MjAxMjsgRGFiaXJpIEFia2VuYXJpIGV0IGFsLiwgMjAxMTsgT2xkZSBOb3Jka2FtcCBldCBhbC4s

IDIwMTI7IFdlaXNzIGV0IGFsLiwgMjAxMyk8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1i

ZXI+MTM8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTBy

ZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzEwMTg0NSI+

MTM8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPldlaXNzLCBSLjwvYXV0

aG9yPjxhdXRob3I+S25pZ2h0LCBCLiBQLjwvYXV0aG9yPjxhdXRob3I+R29sZCwgTS4gUi48L2F1

dGhvcj48YXV0aG9yPkxlb24sIEEuIFIuPC9hdXRob3I+PGF1dGhvcj5IZXJyZSwgSi4gTS48L2F1

dGhvcj48YXV0aG9yPkhvb2QsIE0uPC9hdXRob3I+PGF1dGhvcj5SYXNodGlhbiwgTS48L2F1dGhv

cj48YXV0aG9yPktyZW1lcnMsIE0uPC9hdXRob3I+PGF1dGhvcj5Dcm96aWVyLCBJLjwvYXV0aG9y

PjxhdXRob3I+TGVlLCBLLiBMLjwvYXV0aG9yPjxhdXRob3I+U21pdGgsIFcuPC9hdXRob3I+PGF1

dGhvcj5CdXJrZSwgTS4gQy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgt

YWRkcmVzcz5PaGlvIFN0YXRlIFVuaXZlcnNpdHksIENvbHVtYnVzLCBPSCwgVVNBLjwvYXV0aC1h

ZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlNhZmV0eSBhbmQgZWZmaWNhY3kgb2YgYSB0b3RhbGx5IHN1

YmN1dGFuZW91cyBpbXBsYW50YWJsZS1jYXJkaW92ZXJ0ZXIgZGVmaWJyaWxsYXRvcjwvdGl0bGU+

PHNlY29uZGFyeS10aXRsZT5DaXJjdWxhdGlvbjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+

Q2lyY3VsYXRpb248L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5D

aXJjdWxhdGlvbjwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxs

LXRpdGxlPkNpcmN1bGF0aW9uPC9mdWxsLXRpdGxlPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjk0

NC01MzwvcGFnZXM+PHZvbHVtZT4xMjg8L3ZvbHVtZT48bnVtYmVyPjk8L251bWJlcj48ZWRpdGlv

bj4yMDEzLzA4LzI4PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48

a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkNvaG9ydCBTdHVkaWVzPC9rZXl3b3JkPjxr

ZXl3b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+RXF1

aXBtZW50IFNhZmV0eTwva2V5d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+

Rm9sbG93LVVwIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3

b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+

UHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJp

Y3VsYXIvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJlYXRtZW50IE91dGNvbWU8L2tleXdv

cmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMzwveWVhcj48cHViLWRhdGVzPjxkYXRlPkF1

ZyAyNzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMDktNzMyMjwvaXNibj48YWNj

ZXNzaW9uLW51bT4yMzk3OTYyNjwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjEwLjExNjEvY2lyY3VsYXRpb25haGEuMTEzLjAwMzA0MjwvZWxlY3Ry

b25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1k

YXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+

PENpdGU+PEF1dGhvcj5CYXJkeTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJlY051bT40PC9S

ZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj40PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtl

eSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0

aW1lc3RhbXA9IjEzODMwODYyMTMiPjQ8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48

YXV0aG9yPkJhcmR5LCBHLiBILjwvYXV0aG9yPjxhdXRob3I+U21pdGgsIFcuIE0uPC9hdXRob3I+

PGF1dGhvcj5Ib29kLCBNLiBBLjwvYXV0aG9yPjxhdXRob3I+Q3JvemllciwgSS4gRy48L2F1dGhv

cj48YXV0aG9yPk1lbHRvbiwgSS4gQy48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLjwvYXV0

aG9yPjxhdXRob3I+VGhldW5zLCBELjwvYXV0aG9yPjxhdXRob3I+UGFyaywgUi4gRS48L2F1dGhv

cj48YXV0aG9yPldyaWdodCwgRC4gSi48L2F1dGhvcj48YXV0aG9yPkNvbm5lbGx5LCBELiBULjwv

YXV0aG9yPjxhdXRob3I+RnlubiwgUy4gUC48L2F1dGhvcj48YXV0aG9yPk11cmdhdHJveWQsIEYu

IEQuPC9hdXRob3I+PGF1dGhvcj5TcGVyemVsLCBKLjwvYXV0aG9yPjxhdXRob3I+TmV1em5lciwg

Si48L2F1dGhvcj48YXV0aG9yPlNwaXR6ZXIsIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5BcmRhc2hl

diwgQS4gVi48L2F1dGhvcj48YXV0aG9yPk9kdXJvLCBBLjwvYXV0aG9yPjxhdXRob3I+Qm9lcnNt

YSwgTC48L2F1dGhvcj48YXV0aG9yPk1hYXNzLCBBLiBILjwvYXV0aG9yPjxhdXRob3I+VmFuIEdl

bGRlciwgSS4gQy48L2F1dGhvcj48YXV0aG9yPldpbGRlLCBBLiBBLjwvYXV0aG9yPjxhdXRob3I+

dmFuIERlc3NlbCwgUC4gRi48L2F1dGhvcj48YXV0aG9yPktub3BzLCBSLiBFLjwvYXV0aG9yPjxh

dXRob3I+QmFyciwgQy4gUy48L2F1dGhvcj48YXV0aG9yPkx1cG8sIFAuPC9hdXRob3I+PGF1dGhv

cj5DYXBwYXRvLCBSLjwvYXV0aG9yPjxhdXRob3I+R3JhY2UsIEEuIEEuPC9hdXRob3I+PC9hdXRo

b3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+U2VhdHRsZSBJbnN0aXR1dGUgZm9yIENh

cmRpYWMgUmVzZWFyY2gsIFNlYXR0bGUsIFdBLCBVU0EuIGdiYXJkeUBzaWNyLm9yZzwvYXV0aC1h

ZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkFuIGVudGlyZWx5IHN1YmN1dGFuZW91cyBpbXBsYW50YWJs

ZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxsYXRvcjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5OIEVu

Z2wgSiBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlRoZSBOZXcgRW5nbGFuZCBqb3Vy

bmFsIG9mIG1lZGljaW5lPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0

bGU+TiBFbmdsIEogTWVkPC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIE5ldyBFbmdsYW5kIGpvdXJu

YWwgb2YgbWVkaWNpbmU8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxs

LXRpdGxlPk4gRW5nbCBKIE1lZDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBq

b3VybmFsIG9mIG1lZGljaW5lPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MzYtNDQ8

L3BhZ2VzPjx2b2x1bWU+MzYzPC92b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGVkaXRpb24+MjAx

MC8wNS8xNDwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdv

cmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BZ2VkLCA4MCBhbmQgb3Zlcjwva2V5d29yZD48a2V5

d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0

cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+RWxlY3Ryb2RlcywgSW1wbGFudGVkPC9r

ZXl3b3JkPjxrZXl3b3JkPkVxdWlwbWVudCBEZXNpZ248L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxl

PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IERpc2Vhc2VzL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFw

eTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29y

ZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5QaWxvdCBQcm9qZWN0czwv

a2V5d29yZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3JkPjxrZXl3b3JkPllvdW5nIEFk

dWx0PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTA8L3llYXI+PHB1Yi1kYXRl

cz48ZGF0ZT5KdWwgMTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjgtNDc5Mzwv

aXNibj48YWNjZXNzaW9uLW51bT4yMDQ2MzMzMTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+

PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwNTYvTkVKTW9hMDkwOTU0NTwvZWxlY3Ryb25p

Yy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRh

YmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENp

dGU+PEF1dGhvcj5EYWJpcmkgQWJrZW5hcmk8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNO

dW0+MjQ8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjI0PC9yZWMtbnVtYmVyPjxmb3JlaWdu

LWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEw

ZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMzMyNDciPjI0PC9rZXk+PC9mb3JlaWduLWtleXM+PHJl

Zi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+

PGF1dGhvcnM+PGF1dGhvcj5EYWJpcmkgQWJrZW5hcmksIEwuPC9hdXRob3I+PGF1dGhvcj5UaGV1

bnMsIEQuIEEuPC9hdXRob3I+PGF1dGhvcj5WYWxrLCBTLiBELjwvYXV0aG9yPjxhdXRob3I+VmFu

IEJlbGxlLCBZLjwvYXV0aG9yPjxhdXRob3I+ZGUgR3Jvb3QsIE4uIE0uPC9hdXRob3I+PGF1dGhv

cj5IYWl0c21hLCBELjwvYXV0aG9yPjxhdXRob3I+TXVza2Vucy1IZWVtc2tlcmssIEEuPC9hdXRo

b3I+PGF1dGhvcj5TemlsaS1Ub3JvaywgVC48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLjwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQg

b2YgQ2FyZGlvbG9neSwgRXJhc211cyBNQywgUm90dGVyZGFtLCBUaGUgTmV0aGVybGFuZHMuPC9h

dXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Q2xpbmljYWwgZXhwZXJpZW5jZSB3aXRoIGEgbm92

ZWwgc3ViY3V0YW5lb3VzIGltcGxhbnRhYmxlIGRlZmlicmlsbGF0b3Igc3lzdGVtIGluIGEgc2lu

Z2xlIGNlbnRlcjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5DbGluIFJlcyBDYXJkaW9sPC9zZWNv

bmRhcnktdGl0bGU+PGFsdC10aXRsZT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDog

b2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWx0LXRpdGxl

PjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRpb2w8L2Z1bGwt

dGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDogb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwvcGVyaW9kaWNh

bD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2xpbiBSZXMgQ2FyZGlvbDwvZnVsbC10aXRs

ZT48YWJici0xPkNsaW5pY2FsIHJlc2VhcmNoIGluIGNhcmRpb2xvZ3kgOiBvZmZpY2lhbCBqb3Vy

bmFsIG9mIHRoZSBHZXJtYW4gQ2FyZGlhYyBTb2NpZXR5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNh

bD48cGFnZXM+NzM3LTQ0PC9wYWdlcz48dm9sdW1lPjEwMDwvdm9sdW1lPjxudW1iZXI+OTwvbnVt

YmVyPjxlZGl0aW9uPjIwMTEvMDMvMTk8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0

PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+QXJyaHl0aG1pYXMsIENh

cmRpYWMvcGh5c2lvcGF0aG9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmls

bGF0b3JzLCBJbXBsYW50YWJsZS9hZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+RmVt

YWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3Jk

PkhlYXJ0IERpc2Vhc2VzL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29y

ZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUg

QWdlZDwva2V5d29yZD48a2V5d29yZD5SZWN1cnJlbmNlL3ByZXZlbnRpb24gJmFtcDsgY29udHJv

bDwva2V5d29yZD48a2V5d29yZD5UaW1lIEZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+VmVudHJp

Y3VsYXIgRmlicmlsbGF0aW9uL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48L2tl

eXdvcmRzPjxkYXRlcz48eWVhcj4yMDExPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+U2VwPC9kYXRl

PjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTg2MS0wNjg0PC9pc2JuPjxhY2Nlc3Npb24tbnVt

PjIxNDE2MTkxPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48Y3VzdG9tMj5QbWMzMTY3MDQw

PC9jdXN0b20yPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA3L3MwMDM5Mi0wMTEtMDMw

My02PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5s

bTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPk9sZGUgTm9yZGthbXA8L0F1dGhvcj48WWVhcj4yMDEy

PC9ZZWFyPjxSZWNOdW0+MTg8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjE4PC9yZWMtbnVt

YmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3

OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMTQ4NDIiPjE4PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5PbGRlIE5vcmRrYW1wLCBMLiBSLjwvYXV0aG9y

PjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9yPjxhdXRob3I+Qm9lcnNtYSwgTC4g

Vi48L2F1dGhvcj48YXV0aG9yPk1hYXNzLCBBLiBILjwvYXV0aG9yPjxhdXRob3I+ZGUgR3Jvb3Qs

IEouIFIuPC9hdXRob3I+PGF1dGhvcj52YW4gT29zdHJvbSwgQS4gSi48L2F1dGhvcj48YXV0aG9y

PlRoZXVucywgRC4gQS48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLiBKLjwvYXV0aG9yPjxh

dXRob3I+V2lsZGUsIEEuIEEuPC9hdXRob3I+PGF1dGhvcj5Lbm9wcywgUi4gRS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIENhcmRp

b2xvZ3ksIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBOZXRoZXJsYW5k

cy48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5UaGUgZW50aXJlbHkgc3ViY3V0YW5lb3Vz

IGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1kZWZpYnJpbGxhdG9yOiBpbml0aWFsIGNsaW5pY2Fs

IGV4cGVyaWVuY2UgaW4gYSBsYXJnZSBEdXRjaCBjb2hvcnQ8L3RpdGxlPjxzZWNvbmRhcnktdGl0

bGU+SiBBbSBDb2xsIENhcmRpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkpvdXJuYWwg

b2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNhbiBDb2xs

ZWdlIG9mIENhcmRpb2xvZ3k8L2Z1bGwtdGl0bGU+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTkz

My05PC9wYWdlcz48dm9sdW1lPjYwPC92b2x1bWU+PG51bWJlcj4xOTwvbnVtYmVyPjxlZGl0aW9u

PjIwMTIvMTAvMTY8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkb2xlc2NlbnQ8L2tleXdv

cmQ+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29y

ZD5BZ2VkLCA4MCBhbmQgb3Zlcjwva2V5d29yZD48a2V5d29yZD5BcnJoeXRobWlhcywgQ2FyZGlh

Yy8qZXBpZGVtaW9sb2d5L3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29y

ZD5DaGlsZDwva2V5d29yZD48a2V5d29yZD5Db2hvcnQgU3R1ZGllczwva2V5d29yZD48a2V5d29y

ZD5EZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2VwaWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNv

bnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmlsbGF0b3JzLCBJbXBsYW50YWJsZTwva2V5

d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+Rm9sbG93LVVwIFN0dWRpZXM8

L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+

PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+TmV0aGVybGFuZHMvZXBpZGVt

aW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlJldHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48

a2V5d29yZD4qU3ViY3V0YW5lb3VzIFRpc3N1ZS9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3Jk

PlRyZWF0bWVudCBPdXRjb21lPC9rZXl3b3JkPjxrZXl3b3JkPllvdW5nIEFkdWx0PC9rZXl3b3Jk

Pjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3Yg

NjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjA3MzUtMTA5NzwvaXNibj48YWNjZXNz

aW9uLW51bT4yMzA2MjUzNzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMt

cmVzb3VyY2UtbnVtPjEwLjEwMTYvai5qYWNjLjIwMTIuMDYuMDUzPC9lbGVjdHJvbmljLXJlc291

cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXBy

b3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0

aG9yPkJ1cmtlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVjTnVtPjM4PC9SZWNOdW0+PHJl

Y29yZD48cmVjLW51bWJlcj4zODwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJF

TiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1w

PSIxMzgzMjgwODk5Ij4zODwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3Vy

bmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+

QnVya2UsIE0uIEMuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPlNhZmV0eSBhbmQgRWZmaWNhY3kgb2YgYSBTdWJjdXRhbmVvdXMgSW1wbGFudGFibGUgRGVm

aWJyaWxsYXRvciAoUy1JQ0QpPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkhlYXJ0IFJoeXRobSBT

b2NpZXR5IExhdGUgQnJlYWtpbmcgQ2xpbmljYWwgVHJpYWxzPC9zZWNvbmRhcnktdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtIFNvY2lldHkgTGF0ZSBC

cmVha2luZyBDbGluaWNhbCBUcmlhbHM8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxkYXRlcz48

eWVhcj4yMDEyPC95ZWFyPjwvZGF0ZXM+PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48L0Vu

ZE5vdGU+AG==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XZWlzczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl

Y051bT4xMzwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQmFyZHkgZXQgYWwuLCAyMDEwOyBCdXJrZSwg

MjAxMjsgRGFiaXJpIEFia2VuYXJpIGV0IGFsLiwgMjAxMTsgT2xkZSBOb3Jka2FtcCBldCBhbC4s

IDIwMTI7IFdlaXNzIGV0IGFsLiwgMjAxMyk8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1i

ZXI+MTM8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlYTBy

ZXB0MDlwdHZwOWV6ZHc4eHc1eHIwMjJ0YTBmdmVwNWEiIHRpbWVzdGFtcD0iMTM4MzEwMTg0NSI+

MTM8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPldlaXNzLCBSLjwvYXV0

aG9yPjxhdXRob3I+S25pZ2h0LCBCLiBQLjwvYXV0aG9yPjxhdXRob3I+R29sZCwgTS4gUi48L2F1

dGhvcj48YXV0aG9yPkxlb24sIEEuIFIuPC9hdXRob3I+PGF1dGhvcj5IZXJyZSwgSi4gTS48L2F1

dGhvcj48YXV0aG9yPkhvb2QsIE0uPC9hdXRob3I+PGF1dGhvcj5SYXNodGlhbiwgTS48L2F1dGhv

cj48YXV0aG9yPktyZW1lcnMsIE0uPC9hdXRob3I+PGF1dGhvcj5Dcm96aWVyLCBJLjwvYXV0aG9y

PjxhdXRob3I+TGVlLCBLLiBMLjwvYXV0aG9yPjxhdXRob3I+U21pdGgsIFcuPC9hdXRob3I+PGF1

dGhvcj5CdXJrZSwgTS4gQy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgt

YWRkcmVzcz5PaGlvIFN0YXRlIFVuaXZlcnNpdHksIENvbHVtYnVzLCBPSCwgVVNBLjwvYXV0aC1h

ZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlNhZmV0eSBhbmQgZWZmaWNhY3kgb2YgYSB0b3RhbGx5IHN1

YmN1dGFuZW91cyBpbXBsYW50YWJsZS1jYXJkaW92ZXJ0ZXIgZGVmaWJyaWxsYXRvcjwvdGl0bGU+

PHNlY29uZGFyeS10aXRsZT5DaXJjdWxhdGlvbjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+

Q2lyY3VsYXRpb248L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5D

aXJjdWxhdGlvbjwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxs

LXRpdGxlPkNpcmN1bGF0aW9uPC9mdWxsLXRpdGxlPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjk0

NC01MzwvcGFnZXM+PHZvbHVtZT4xMjg8L3ZvbHVtZT48bnVtYmVyPjk8L251bWJlcj48ZWRpdGlv

bj4yMDEzLzA4LzI4PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48

a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkNvaG9ydCBTdHVkaWVzPC9rZXl3b3JkPjxr

ZXl3b3JkPipEZWZpYnJpbGxhdG9ycywgSW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+RXF1

aXBtZW50IFNhZmV0eTwva2V5d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+

Rm9sbG93LVVwIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3

b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+

UHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48a2V5d29yZD5UYWNoeWNhcmRpYSwgVmVudHJp

Y3VsYXIvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+VHJlYXRtZW50IE91dGNvbWU8L2tleXdv

cmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMzwveWVhcj48cHViLWRhdGVzPjxkYXRlPkF1

ZyAyNzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMDktNzMyMjwvaXNibj48YWNj

ZXNzaW9uLW51bT4yMzk3OTYyNjwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjEwLjExNjEvY2lyY3VsYXRpb25haGEuMTEzLjAwMzA0MjwvZWxlY3Ry

b25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1k

YXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+

PENpdGU+PEF1dGhvcj5CYXJkeTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJlY051bT40PC9S

ZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj40PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtl

eSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEwZnZlcDVhIiB0

aW1lc3RhbXA9IjEzODMwODYyMTMiPjQ8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48

YXV0aG9yPkJhcmR5LCBHLiBILjwvYXV0aG9yPjxhdXRob3I+U21pdGgsIFcuIE0uPC9hdXRob3I+

PGF1dGhvcj5Ib29kLCBNLiBBLjwvYXV0aG9yPjxhdXRob3I+Q3JvemllciwgSS4gRy48L2F1dGhv

cj48YXV0aG9yPk1lbHRvbiwgSS4gQy48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLjwvYXV0

aG9yPjxhdXRob3I+VGhldW5zLCBELjwvYXV0aG9yPjxhdXRob3I+UGFyaywgUi4gRS48L2F1dGhv

cj48YXV0aG9yPldyaWdodCwgRC4gSi48L2F1dGhvcj48YXV0aG9yPkNvbm5lbGx5LCBELiBULjwv

YXV0aG9yPjxhdXRob3I+RnlubiwgUy4gUC48L2F1dGhvcj48YXV0aG9yPk11cmdhdHJveWQsIEYu

IEQuPC9hdXRob3I+PGF1dGhvcj5TcGVyemVsLCBKLjwvYXV0aG9yPjxhdXRob3I+TmV1em5lciwg

Si48L2F1dGhvcj48YXV0aG9yPlNwaXR6ZXIsIFMuIEcuPC9hdXRob3I+PGF1dGhvcj5BcmRhc2hl

diwgQS4gVi48L2F1dGhvcj48YXV0aG9yPk9kdXJvLCBBLjwvYXV0aG9yPjxhdXRob3I+Qm9lcnNt

YSwgTC48L2F1dGhvcj48YXV0aG9yPk1hYXNzLCBBLiBILjwvYXV0aG9yPjxhdXRob3I+VmFuIEdl

bGRlciwgSS4gQy48L2F1dGhvcj48YXV0aG9yPldpbGRlLCBBLiBBLjwvYXV0aG9yPjxhdXRob3I+

dmFuIERlc3NlbCwgUC4gRi48L2F1dGhvcj48YXV0aG9yPktub3BzLCBSLiBFLjwvYXV0aG9yPjxh

dXRob3I+QmFyciwgQy4gUy48L2F1dGhvcj48YXV0aG9yPkx1cG8sIFAuPC9hdXRob3I+PGF1dGhv

cj5DYXBwYXRvLCBSLjwvYXV0aG9yPjxhdXRob3I+R3JhY2UsIEEuIEEuPC9hdXRob3I+PC9hdXRo

b3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+U2VhdHRsZSBJbnN0aXR1dGUgZm9yIENh

cmRpYWMgUmVzZWFyY2gsIFNlYXR0bGUsIFdBLCBVU0EuIGdiYXJkeUBzaWNyLm9yZzwvYXV0aC1h

ZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkFuIGVudGlyZWx5IHN1YmN1dGFuZW91cyBpbXBsYW50YWJs

ZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxsYXRvcjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5OIEVu

Z2wgSiBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlRoZSBOZXcgRW5nbGFuZCBqb3Vy

bmFsIG9mIG1lZGljaW5lPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0

bGU+TiBFbmdsIEogTWVkPC9mdWxsLXRpdGxlPjxhYmJyLTE+VGhlIE5ldyBFbmdsYW5kIGpvdXJu

YWwgb2YgbWVkaWNpbmU8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxs

LXRpdGxlPk4gRW5nbCBKIE1lZDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBOZXcgRW5nbGFuZCBq

b3VybmFsIG9mIG1lZGljaW5lPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MzYtNDQ8

L3BhZ2VzPjx2b2x1bWU+MzYzPC92b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGVkaXRpb24+MjAx

MC8wNS8xNDwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdv

cmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BZ2VkLCA4MCBhbmQgb3Zlcjwva2V5d29yZD48a2V5

d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3b3JkPjxrZXl3b3JkPkVsZWN0

cm9jYXJkaW9ncmFwaHk8L2tleXdvcmQ+PGtleXdvcmQ+RWxlY3Ryb2RlcywgSW1wbGFudGVkPC9r

ZXl3b3JkPjxrZXl3b3JkPkVxdWlwbWVudCBEZXNpZ248L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxl

PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IERpc2Vhc2VzL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFw

eTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29y

ZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5QaWxvdCBQcm9qZWN0czwv

a2V5d29yZD48a2V5d29yZD5TdHJva2UgVm9sdW1lPC9rZXl3b3JkPjxrZXl3b3JkPllvdW5nIEFk

dWx0PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTA8L3llYXI+PHB1Yi1kYXRl

cz48ZGF0ZT5KdWwgMTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjgtNDc5Mzwv

aXNibj48YWNjZXNzaW9uLW51bT4yMDQ2MzMzMTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+

PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwNTYvTkVKTW9hMDkwOTU0NTwvZWxlY3Ryb25p

Yy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRh

YmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENp

dGU+PEF1dGhvcj5EYWJpcmkgQWJrZW5hcmk8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNO

dW0+MjQ8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjI0PC9yZWMtbnVtYmVyPjxmb3JlaWdu

LWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIydGEw

ZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMzMyNDciPjI0PC9rZXk+PC9mb3JlaWduLWtleXM+PHJl

Zi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+

PGF1dGhvcnM+PGF1dGhvcj5EYWJpcmkgQWJrZW5hcmksIEwuPC9hdXRob3I+PGF1dGhvcj5UaGV1

bnMsIEQuIEEuPC9hdXRob3I+PGF1dGhvcj5WYWxrLCBTLiBELjwvYXV0aG9yPjxhdXRob3I+VmFu

IEJlbGxlLCBZLjwvYXV0aG9yPjxhdXRob3I+ZGUgR3Jvb3QsIE4uIE0uPC9hdXRob3I+PGF1dGhv

cj5IYWl0c21hLCBELjwvYXV0aG9yPjxhdXRob3I+TXVza2Vucy1IZWVtc2tlcmssIEEuPC9hdXRo

b3I+PGF1dGhvcj5TemlsaS1Ub3JvaywgVC48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLjwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQg

b2YgQ2FyZGlvbG9neSwgRXJhc211cyBNQywgUm90dGVyZGFtLCBUaGUgTmV0aGVybGFuZHMuPC9h

dXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Q2xpbmljYWwgZXhwZXJpZW5jZSB3aXRoIGEgbm92

ZWwgc3ViY3V0YW5lb3VzIGltcGxhbnRhYmxlIGRlZmlicmlsbGF0b3Igc3lzdGVtIGluIGEgc2lu

Z2xlIGNlbnRlcjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5DbGluIFJlcyBDYXJkaW9sPC9zZWNv

bmRhcnktdGl0bGU+PGFsdC10aXRsZT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDog

b2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWx0LXRpdGxl

PjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNsaW4gUmVzIENhcmRpb2w8L2Z1bGwt

dGl0bGU+PGFiYnItMT5DbGluaWNhbCByZXNlYXJjaCBpbiBjYXJkaW9sb2d5IDogb2ZmaWNpYWwg

am91cm5hbCBvZiB0aGUgR2VybWFuIENhcmRpYWMgU29jaWV0eTwvYWJici0xPjwvcGVyaW9kaWNh

bD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2xpbiBSZXMgQ2FyZGlvbDwvZnVsbC10aXRs

ZT48YWJici0xPkNsaW5pY2FsIHJlc2VhcmNoIGluIGNhcmRpb2xvZ3kgOiBvZmZpY2lhbCBqb3Vy

bmFsIG9mIHRoZSBHZXJtYW4gQ2FyZGlhYyBTb2NpZXR5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNh

bD48cGFnZXM+NzM3LTQ0PC9wYWdlcz48dm9sdW1lPjEwMDwvdm9sdW1lPjxudW1iZXI+OTwvbnVt

YmVyPjxlZGl0aW9uPjIwMTEvMDMvMTk8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0

PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+QXJyaHl0aG1pYXMsIENh

cmRpYWMvcGh5c2lvcGF0aG9sb2d5L3RoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmls

bGF0b3JzLCBJbXBsYW50YWJsZS9hZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+RmVt

YWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZvbGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3Jk

PkhlYXJ0IERpc2Vhc2VzL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29y

ZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUg

QWdlZDwva2V5d29yZD48a2V5d29yZD5SZWN1cnJlbmNlL3ByZXZlbnRpb24gJmFtcDsgY29udHJv

bDwva2V5d29yZD48a2V5d29yZD5UaW1lIEZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+VmVudHJp

Y3VsYXIgRmlicmlsbGF0aW9uL3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48L2tl

eXdvcmRzPjxkYXRlcz48eWVhcj4yMDExPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+U2VwPC9kYXRl

PjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTg2MS0wNjg0PC9pc2JuPjxhY2Nlc3Npb24tbnVt

PjIxNDE2MTkxPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48Y3VzdG9tMj5QbWMzMTY3MDQw

PC9jdXN0b20yPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA3L3MwMDM5Mi0wMTEtMDMw

My02PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5s

bTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPk9sZGUgTm9yZGthbXA8L0F1dGhvcj48WWVhcj4yMDEy

PC9ZZWFyPjxSZWNOdW0+MTg8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjE4PC9yZWMtbnVt

YmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3

OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMTQ4NDIiPjE4PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5PbGRlIE5vcmRrYW1wLCBMLiBSLjwvYXV0aG9y

PjxhdXRob3I+RGFiaXJpIEFia2VuYXJpLCBMLjwvYXV0aG9yPjxhdXRob3I+Qm9lcnNtYSwgTC4g

Vi48L2F1dGhvcj48YXV0aG9yPk1hYXNzLCBBLiBILjwvYXV0aG9yPjxhdXRob3I+ZGUgR3Jvb3Qs

IEouIFIuPC9hdXRob3I+PGF1dGhvcj52YW4gT29zdHJvbSwgQS4gSi48L2F1dGhvcj48YXV0aG9y

PlRoZXVucywgRC4gQS48L2F1dGhvcj48YXV0aG9yPkpvcmRhZW5zLCBMLiBKLjwvYXV0aG9yPjxh

dXRob3I+V2lsZGUsIEEuIEEuPC9hdXRob3I+PGF1dGhvcj5Lbm9wcywgUi4gRS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIENhcmRp

b2xvZ3ksIEFjYWRlbWljIE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBOZXRoZXJsYW5k

cy48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5UaGUgZW50aXJlbHkgc3ViY3V0YW5lb3Vz

IGltcGxhbnRhYmxlIGNhcmRpb3ZlcnRlci1kZWZpYnJpbGxhdG9yOiBpbml0aWFsIGNsaW5pY2Fs

IGV4cGVyaWVuY2UgaW4gYSBsYXJnZSBEdXRjaCBjb2hvcnQ8L3RpdGxlPjxzZWNvbmRhcnktdGl0

bGU+SiBBbSBDb2xsIENhcmRpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkpvdXJuYWwg

b2YgdGhlIEFtZXJpY2FuIENvbGxlZ2Ugb2YgQ2FyZGlvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNhbiBDb2xs

ZWdlIG9mIENhcmRpb2xvZ3k8L2Z1bGwtdGl0bGU+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTkz

My05PC9wYWdlcz48dm9sdW1lPjYwPC92b2x1bWU+PG51bWJlcj4xOTwvbnVtYmVyPjxlZGl0aW9u

PjIwMTIvMTAvMTY8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFkb2xlc2NlbnQ8L2tleXdv

cmQ+PGtleXdvcmQ+QWR1bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29y

ZD5BZ2VkLCA4MCBhbmQgb3Zlcjwva2V5d29yZD48a2V5d29yZD5BcnJoeXRobWlhcywgQ2FyZGlh

Yy8qZXBpZGVtaW9sb2d5L3BoeXNpb3BhdGhvbG9neS8qdGhlcmFweTwva2V5d29yZD48a2V5d29y

ZD5DaGlsZDwva2V5d29yZD48a2V5d29yZD5Db2hvcnQgU3R1ZGllczwva2V5d29yZD48a2V5d29y

ZD5EZWF0aCwgU3VkZGVuLCBDYXJkaWFjL2VwaWRlbWlvbG9neS9wcmV2ZW50aW9uICZhbXA7IGNv

bnRyb2w8L2tleXdvcmQ+PGtleXdvcmQ+KkRlZmlicmlsbGF0b3JzLCBJbXBsYW50YWJsZTwva2V5

d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+Rm9sbG93LVVwIFN0dWRpZXM8

L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+

PGtleXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+TmV0aGVybGFuZHMvZXBpZGVt

aW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlJldHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48

a2V5d29yZD4qU3ViY3V0YW5lb3VzIFRpc3N1ZS9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3Jk

PlRyZWF0bWVudCBPdXRjb21lPC9rZXl3b3JkPjxrZXl3b3JkPllvdW5nIEFkdWx0PC9rZXl3b3Jk

Pjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3Yg

NjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjA3MzUtMTA5NzwvaXNibj48YWNjZXNz

aW9uLW51bT4yMzA2MjUzNzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMt

cmVzb3VyY2UtbnVtPjEwLjEwMTYvai5qYWNjLjIwMTIuMDYuMDUzPC9lbGVjdHJvbmljLXJlc291

cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5sbTwvcmVtb3RlLWRhdGFiYXNlLXBy

b3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0

aG9yPkJ1cmtlPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVjTnVtPjM4PC9SZWNOdW0+PHJl

Y29yZD48cmVjLW51bWJlcj4zODwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJF

TiIgZGItaWQ9ImVhMHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1w

PSIxMzgzMjgwODk5Ij4zODwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3Vy

bmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+

QnVya2UsIE0uIEMuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPlNhZmV0eSBhbmQgRWZmaWNhY3kgb2YgYSBTdWJjdXRhbmVvdXMgSW1wbGFudGFibGUgRGVm

aWJyaWxsYXRvciAoUy1JQ0QpPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkhlYXJ0IFJoeXRobSBT

b2NpZXR5IExhdGUgQnJlYWtpbmcgQ2xpbmljYWwgVHJpYWxzPC9zZWNvbmRhcnktdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtIFNvY2lldHkgTGF0ZSBC

cmVha2luZyBDbGluaWNhbCBUcmlhbHM8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxkYXRlcz48

eWVhcj4yMDEyPC95ZWFyPjwvZGF0ZXM+PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48L0Vu

ZE5vdGU+AG==

ADDIN EN.CITE.DATA (Bardy et al., 2010; Burke, 2012; Dabiri Abkenari et al., 2011; Olde Nordkamp et al., 2012; Weiss et al., 2013) and comparative studies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb2xkPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj

TnVtPjEyPC9SZWNOdW0+PERpc3BsYXlUZXh0PihHb2xkIGV0IGFsLiwgMjAxMjsgS29iZSBldCBh

bC4sIDIwMTMpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEyPC9yZWMtbnVtYmVy

Pjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3

NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMwOTQzNDciPjEyPC9rZXk+PC9mb3JlaWdu

LWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250

cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Hb2xkLCBNLiBSLjwvYXV0aG9yPjxhdXRob3I+VGhl

dW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+S25pZ2h0LCBCLiBQLjwvYXV0aG9yPjxhdXRob3I+

U3R1cmRpdmFudCwgSi4gTC48L2F1dGhvcj48YXV0aG9yPlNhbmdoZXJhLCBSLjwvYXV0aG9yPjxh

dXRob3I+RWxsZW5ib2dlbiwgSy4gQS48L2F1dGhvcj48YXV0aG9yPldvb2QsIE0uIEEuPC9hdXRo

b3I+PGF1dGhvcj5CdXJrZSwgTS4gQy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+

PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBDYXJkaW9sb2d5LCBNZWRpY2FsIFVuaXZlcnNpdHkg

b2YgU291dGggQ2Fyb2xpbmEsIENoYXJsZXN0b24sIFNvdXRoIENhcm9saW5hIDI5NDI1LCBVU0Eu

IGdvbGRtckBtdXNjLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkhlYWQtdG8taGVh

ZCBjb21wYXJpc29uIG9mIGFycmh5dGhtaWEgZGlzY3JpbWluYXRpb24gcGVyZm9ybWFuY2Ugb2Yg

c3ViY3V0YW5lb3VzIGFuZCB0cmFuc3Zlbm91cyBJQ0QgYXJyaHl0aG1pYSBkZXRlY3Rpb24gYWxn

b3JpdGhtczogdGhlIFNUQVJUIHN0dWR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogQ2FyZGlv

dmFzYyBFbGVjdHJvcGh5c2lvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBv

ZiBjYXJkaW92YXNjdWxhciBlbGVjdHJvcGh5c2lvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxw

ZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogQ2FyZGlvdmFzYyBFbGVjdHJvcGh5c2lvbDwvZnVsbC10

aXRsZT48YWJici0xPkpvdXJuYWwgb2YgY2FyZGlvdmFzY3VsYXIgZWxlY3Ryb3BoeXNpb2xvZ3k8

L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogQ2FyZGlv

dmFzYyBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkpvdXJuYWwgb2YgY2FyZGlv

dmFzY3VsYXIgZWxlY3Ryb3BoeXNpb2xvZ3k8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdl

cz4zNTktNjY8L3BhZ2VzPjx2b2x1bWU+MjM8L3ZvbHVtZT48bnVtYmVyPjQ8L251bWJlcj48ZWRp

dGlvbj4yMDExLzExLzAxPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZ2VkPC9rZXl3b3Jk

PjxrZXl3b3JkPipBbGdvcml0aG1zPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJk

aWFjLypkaWFnbm9zaXMvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+Q29tcHV0ZXIgU2ltdWxh

dGlvbjwva2V5d29yZD48a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3

b3JkPjxrZXl3b3JkPkVsZWN0cmljIENvdW50ZXJzaG9jay8qaW5zdHJ1bWVudGF0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHkvKmluc3RydW1lbnRhdGlvbjwva2V5d29y

ZD48a2V5d29yZD5FbGVjdHJvcGh5c2lvbG9naWMgVGVjaG5pcXVlcywgQ2FyZGlhYzwva2V5d29y

ZD48a2V5d29yZD5FcXVpcG1lbnQgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5

d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5

d29yZD5NYXRlcmlhbHMgVGVzdGluZzwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5

d29yZD48a2V5d29yZD5QcmVkaWN0aXZlIFZhbHVlIG9mIFRlc3RzPC9rZXl3b3JkPjxrZXl3b3Jk

PlByb3NwZWN0aXZlIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+U2Vuc2l0aXZpdHkgYW5kIFNw

ZWNpZmljaXR5PC9rZXl3b3JkPjxrZXl3b3JkPipTaWduYWwgUHJvY2Vzc2luZywgQ29tcHV0ZXIt

QXNzaXN0ZWQ8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48cHVi

LWRhdGVzPjxkYXRlPkFwcjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjEwNDUtMzg3

MzwvaXNibj48YWNjZXNzaW9uLW51bT4yMjAzNTA0OTwvYWNjZXNzaW9uLW51bT48dXJscz48L3Vy

bHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjExMTEvai4xNTQwLTgxNjcuMjAxMS4wMjE5

OS54PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5s

bTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPktvYmU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS

ZWNOdW0+MTQ8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjE0PC9yZWMtbnVtYmVyPjxmb3Jl

aWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIy

dGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMDIwMzgiPjE0PC9rZXk+PC9mb3JlaWduLWtleXM+

PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRv

cnM+PGF1dGhvcnM+PGF1dGhvcj5Lb2JlLCBKLjwvYXV0aG9yPjxhdXRob3I+UmVpbmtlLCBGLjwv

YXV0aG9yPjxhdXRob3I+TWV5ZXIsIEMuPC9hdXRob3I+PGF1dGhvcj5TaGluLCBELiBJLjwvYXV0

aG9yPjxhdXRob3I+TWFydGVucywgRS48L2F1dGhvcj48YXV0aG9yPkthYWIsIFMuPC9hdXRob3I+

PGF1dGhvcj5Mb2hlciwgQS48L2F1dGhvcj48YXV0aG9yPkFtbGVyLCBTLjwvYXV0aG9yPjxhdXRo

b3I+TGljaHRlbmJlcmcsIEEuPC9hdXRob3I+PGF1dGhvcj5XaW50ZXIsIEouPC9hdXRob3I+PGF1

dGhvcj5FY2thcmR0LCBMLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1h

ZGRyZXNzPkRpdmlzaW9uIG9mIEVsZWN0cm9waHlzaW9sb2d5LCBEZXBhcnRtZW50IG9mIENhcmRp

b2xvZ3kgYW5kIEFuZ2lvbG9neSwgVW5pdmVyc2l0eSBIb3NwaXRhbCBvZiBNdWVuc3RlciwgR2Vy

bWFueS4ga29lYmVqdUBtZWRuZXQudW5pLW11ZW5zdGVyLmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxl

cz48dGl0bGU+SW1wbGFudGF0aW9uIGFuZCBmb2xsb3ctdXAgb2YgdG90YWxseSBzdWJjdXRhbmVv

dXMgdmVyc3VzIGNvbnZlbnRpb25hbCBpbXBsYW50YWJsZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxs

YXRvcnM6IGEgbXVsdGljZW50ZXIgY2FzZS1jb250cm9sIHN0dWR5PC90aXRsZT48c2Vjb25kYXJ5

LXRpdGxlPkhlYXJ0IFJoeXRobTwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SGVhcnQgcmh5

dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9h

bHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9m

dWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2Yg

dGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9k

aWNhbD48ZnVsbC10aXRsZT5IZWFydCBSaHl0aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCBy

aHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8

L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4yOS0zNjwvcGFnZXM+PHZvbHVtZT4xMDwv

dm9sdW1lPjxudW1iZXI+MTwvbnVtYmVyPjxlZGl0aW9uPjIwMTIvMTAvMDQ8L2VkaXRpb24+PGtl

eXdvcmRzPjxrZXl3b3JkPkNhc2UtQ29udHJvbCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkNo

aS1TcXVhcmUgRGlzdHJpYnV0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPipEZWZpYnJpbGxhdG9ycywg

SW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZv

bGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29y

ZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPlBv

c3RvcGVyYXRpdmUgQ29tcGxpY2F0aW9uczwva2V5d29yZD48a2V5d29yZD5QcmltYXJ5IFByZXZl

bnRpb248L2tleXdvcmQ+PGtleXdvcmQ+UHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48a2V5

d29yZD5TZWNvbmRhcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TdGF0aXN0aWNzLCBO

b25wYXJhbWV0cmljPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci8q

cGh5c2lvcGF0aG9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PC9rZXl3

b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMzwveWVhcj48cHViLWRhdGVzPjxkYXRlPkphbjwvZGF0ZT48

L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NDctNTI3MTwvaXNibj48YWNjZXNzaW9uLW51bT4y

MzAzMjg2NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2Ut

bnVtPjEwLjEwMTYvai5ocnRobS4yMDEyLjA5LjEyNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+

PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48

bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb2xkPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj

TnVtPjEyPC9SZWNOdW0+PERpc3BsYXlUZXh0PihHb2xkIGV0IGFsLiwgMjAxMjsgS29iZSBldCBh

bC4sIDIwMTMpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEyPC9yZWMtbnVtYmVy

Pjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3

NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMwOTQzNDciPjEyPC9rZXk+PC9mb3JlaWdu

LWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250

cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Hb2xkLCBNLiBSLjwvYXV0aG9yPjxhdXRob3I+VGhl

dW5zLCBELiBBLjwvYXV0aG9yPjxhdXRob3I+S25pZ2h0LCBCLiBQLjwvYXV0aG9yPjxhdXRob3I+

U3R1cmRpdmFudCwgSi4gTC48L2F1dGhvcj48YXV0aG9yPlNhbmdoZXJhLCBSLjwvYXV0aG9yPjxh

dXRob3I+RWxsZW5ib2dlbiwgSy4gQS48L2F1dGhvcj48YXV0aG9yPldvb2QsIE0uIEEuPC9hdXRo

b3I+PGF1dGhvcj5CdXJrZSwgTS4gQy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+

PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBDYXJkaW9sb2d5LCBNZWRpY2FsIFVuaXZlcnNpdHkg

b2YgU291dGggQ2Fyb2xpbmEsIENoYXJsZXN0b24sIFNvdXRoIENhcm9saW5hIDI5NDI1LCBVU0Eu

IGdvbGRtckBtdXNjLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkhlYWQtdG8taGVh

ZCBjb21wYXJpc29uIG9mIGFycmh5dGhtaWEgZGlzY3JpbWluYXRpb24gcGVyZm9ybWFuY2Ugb2Yg

c3ViY3V0YW5lb3VzIGFuZCB0cmFuc3Zlbm91cyBJQ0QgYXJyaHl0aG1pYSBkZXRlY3Rpb24gYWxn

b3JpdGhtczogdGhlIFNUQVJUIHN0dWR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogQ2FyZGlv

dmFzYyBFbGVjdHJvcGh5c2lvbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBv

ZiBjYXJkaW92YXNjdWxhciBlbGVjdHJvcGh5c2lvbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxw

ZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogQ2FyZGlvdmFzYyBFbGVjdHJvcGh5c2lvbDwvZnVsbC10

aXRsZT48YWJici0xPkpvdXJuYWwgb2YgY2FyZGlvdmFzY3VsYXIgZWxlY3Ryb3BoeXNpb2xvZ3k8

L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogQ2FyZGlv

dmFzYyBFbGVjdHJvcGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkpvdXJuYWwgb2YgY2FyZGlv

dmFzY3VsYXIgZWxlY3Ryb3BoeXNpb2xvZ3k8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdl

cz4zNTktNjY8L3BhZ2VzPjx2b2x1bWU+MjM8L3ZvbHVtZT48bnVtYmVyPjQ8L251bWJlcj48ZWRp

dGlvbj4yMDExLzExLzAxPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZ2VkPC9rZXl3b3Jk

PjxrZXl3b3JkPipBbGdvcml0aG1zPC9rZXl3b3JkPjxrZXl3b3JkPkFycmh5dGhtaWFzLCBDYXJk

aWFjLypkaWFnbm9zaXMvKnRoZXJhcHk8L2tleXdvcmQ+PGtleXdvcmQ+Q29tcHV0ZXIgU2ltdWxh

dGlvbjwva2V5d29yZD48a2V5d29yZD4qRGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlPC9rZXl3

b3JkPjxrZXl3b3JkPkVsZWN0cmljIENvdW50ZXJzaG9jay8qaW5zdHJ1bWVudGF0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPkVsZWN0cm9jYXJkaW9ncmFwaHkvKmluc3RydW1lbnRhdGlvbjwva2V5d29y

ZD48a2V5d29yZD5FbGVjdHJvcGh5c2lvbG9naWMgVGVjaG5pcXVlcywgQ2FyZGlhYzwva2V5d29y

ZD48a2V5d29yZD5FcXVpcG1lbnQgRGVzaWduPC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5

d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5

d29yZD5NYXRlcmlhbHMgVGVzdGluZzwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5

d29yZD48a2V5d29yZD5QcmVkaWN0aXZlIFZhbHVlIG9mIFRlc3RzPC9rZXl3b3JkPjxrZXl3b3Jk

PlByb3NwZWN0aXZlIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+U2Vuc2l0aXZpdHkgYW5kIFNw

ZWNpZmljaXR5PC9rZXl3b3JkPjxrZXl3b3JkPipTaWduYWwgUHJvY2Vzc2luZywgQ29tcHV0ZXIt

QXNzaXN0ZWQ8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48cHVi

LWRhdGVzPjxkYXRlPkFwcjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjEwNDUtMzg3

MzwvaXNibj48YWNjZXNzaW9uLW51bT4yMjAzNTA0OTwvYWNjZXNzaW9uLW51bT48dXJscz48L3Vy

bHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjExMTEvai4xNTQwLTgxNjcuMjAxMS4wMjE5

OS54PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5s

bTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPktvYmU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS

ZWNOdW0+MTQ8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjE0PC9yZWMtbnVtYmVyPjxmb3Jl

aWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3OHh3NXhyMDIy

dGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMxMDIwMzgiPjE0PC9rZXk+PC9mb3JlaWduLWtleXM+

PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRv

cnM+PGF1dGhvcnM+PGF1dGhvcj5Lb2JlLCBKLjwvYXV0aG9yPjxhdXRob3I+UmVpbmtlLCBGLjwv

YXV0aG9yPjxhdXRob3I+TWV5ZXIsIEMuPC9hdXRob3I+PGF1dGhvcj5TaGluLCBELiBJLjwvYXV0

aG9yPjxhdXRob3I+TWFydGVucywgRS48L2F1dGhvcj48YXV0aG9yPkthYWIsIFMuPC9hdXRob3I+

PGF1dGhvcj5Mb2hlciwgQS48L2F1dGhvcj48YXV0aG9yPkFtbGVyLCBTLjwvYXV0aG9yPjxhdXRo

b3I+TGljaHRlbmJlcmcsIEEuPC9hdXRob3I+PGF1dGhvcj5XaW50ZXIsIEouPC9hdXRob3I+PGF1

dGhvcj5FY2thcmR0LCBMLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1h

ZGRyZXNzPkRpdmlzaW9uIG9mIEVsZWN0cm9waHlzaW9sb2d5LCBEZXBhcnRtZW50IG9mIENhcmRp

b2xvZ3kgYW5kIEFuZ2lvbG9neSwgVW5pdmVyc2l0eSBIb3NwaXRhbCBvZiBNdWVuc3RlciwgR2Vy

bWFueS4ga29lYmVqdUBtZWRuZXQudW5pLW11ZW5zdGVyLmRlPC9hdXRoLWFkZHJlc3M+PHRpdGxl

cz48dGl0bGU+SW1wbGFudGF0aW9uIGFuZCBmb2xsb3ctdXAgb2YgdG90YWxseSBzdWJjdXRhbmVv

dXMgdmVyc3VzIGNvbnZlbnRpb25hbCBpbXBsYW50YWJsZSBjYXJkaW92ZXJ0ZXItZGVmaWJyaWxs

YXRvcnM6IGEgbXVsdGljZW50ZXIgY2FzZS1jb250cm9sIHN0dWR5PC90aXRsZT48c2Vjb25kYXJ5

LXRpdGxlPkhlYXJ0IFJoeXRobTwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SGVhcnQgcmh5

dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2YgdGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9h

bHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SGVhcnQgUmh5dGhtPC9m

dWxsLXRpdGxlPjxhYmJyLTE+SGVhcnQgcmh5dGhtIDogdGhlIG9mZmljaWFsIGpvdXJuYWwgb2Yg

dGhlIEhlYXJ0IFJoeXRobSBTb2NpZXR5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9k

aWNhbD48ZnVsbC10aXRsZT5IZWFydCBSaHl0aG08L2Z1bGwtdGl0bGU+PGFiYnItMT5IZWFydCBy

aHl0aG0gOiB0aGUgb2ZmaWNpYWwgam91cm5hbCBvZiB0aGUgSGVhcnQgUmh5dGhtIFNvY2lldHk8

L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4yOS0zNjwvcGFnZXM+PHZvbHVtZT4xMDwv

dm9sdW1lPjxudW1iZXI+MTwvbnVtYmVyPjxlZGl0aW9uPjIwMTIvMTAvMDQ8L2VkaXRpb24+PGtl

eXdvcmRzPjxrZXl3b3JkPkNhc2UtQ29udHJvbCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkNo

aS1TcXVhcmUgRGlzdHJpYnV0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPipEZWZpYnJpbGxhdG9ycywg

SW1wbGFudGFibGU8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3b3JkPkZv

bGxvdy1VcCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29y

ZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPlBv

c3RvcGVyYXRpdmUgQ29tcGxpY2F0aW9uczwva2V5d29yZD48a2V5d29yZD5QcmltYXJ5IFByZXZl

bnRpb248L2tleXdvcmQ+PGtleXdvcmQ+UHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48a2V5

d29yZD5TZWNvbmRhcnkgUHJldmVudGlvbjwva2V5d29yZD48a2V5d29yZD5TdGF0aXN0aWNzLCBO

b25wYXJhbWV0cmljPC9rZXl3b3JkPjxrZXl3b3JkPlRhY2h5Y2FyZGlhLCBWZW50cmljdWxhci8q

cGh5c2lvcGF0aG9sb2d5LypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+PC9rZXl3

b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMzwveWVhcj48cHViLWRhdGVzPjxkYXRlPkphbjwvZGF0ZT48

L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NDctNTI3MTwvaXNibj48YWNjZXNzaW9uLW51bT4y

MzAzMjg2NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2Ut

bnVtPjEwLjEwMTYvai5ocnRobS4yMDEyLjA5LjEyNjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+

PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5ObG08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48

bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==

ADDIN EN.CITE.DATA (Gold et al., 2012; Kobe et al., 2013), as well as larger longer-term registry data PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2Vyc21hPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

UmVjTnVtPjM5PC9SZWNOdW0+PERpc3BsYXlUZXh0PihCb2Vyc21hLCAyMDEyOyBQZWRlcnNlbiBl

dCBhbC4sIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjM5PC9yZWMtbnVt

YmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3

OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMyODExNTUiPjM5PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2Vyc21hLCBMLjwvYXV0aG9yPjwvYXV0aG9y

cz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5Mb25nIFRlcm0gT3V0Y29tZSBPZiBQYXRp

ZW50cyBSZWNlaXZpbmcgVGhlIFN1YmN1dGFuZW91cyBJQ0QgQWZ0ZXIgVHJhbnN2ZW5vdXMgSUNE

IEV4dHJhY3Rpb248L3RpdGxlPjwvdGl0bGVzPjxkYXRlcz48eWVhcj4yMDEyPC95ZWFyPjwvZGF0

ZXM+PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlBlZGVyc2VuPC9B

dXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVjTnVtPjE5PC9SZWNOdW0+PHJlY29yZD48cmVjLW51

bWJlcj4xOTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVh

MHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTE0OTM2

Ij4xOTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUi

PjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+UGVkZXJzZW4sIFMu

IFMuPC9hdXRob3I+PGF1dGhvcj5MYW1iaWFzZSwgUC48L2F1dGhvcj48YXV0aG9yPkJvZXJzbWEs

IEwuIFYuPC9hdXRob3I+PGF1dGhvcj5NdXJnYXRyb3lkLCBGLjwvYXV0aG9yPjxhdXRob3I+Sm9o

YW5zZW4sIEouIEIuPC9hdXRob3I+PGF1dGhvcj5SZWV2ZSwgSC48L2F1dGhvcj48YXV0aG9yPlN0

dWFydCwgQS4gRy48L2F1dGhvcj48YXV0aG9yPkFkcmFnYW8sIFAuPC9hdXRob3I+PGF1dGhvcj5U

aGV1bnMsIEQuIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJl

c3M+Q29SUFMgLSBDZW50ZXIgb2YgUmVzZWFyY2ggb24gUHN5Y2hvbG9neSBpbiBTb21hdGljIGRp

c2Vhc2VzLCBUaWxidXJnIFVuaXZlcnNpdHksIFRpbGJ1cmcsIHRoZSBOZXRoZXJsYW5kcy4gcy5z

LnBlZGVyc2VuQHV2dC5ubDwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkV2YWx1YXRpb24g

b0YgRmFjdE9ScyBJbXBhY1RpbmcgQ0xpbmljYWwgT3V0Y29tZSBhbmQgQ29zdCBFZmZlY3RpdmVu

ZVNTIG9mIHRoZSBTLUlDRDogZGVzaWduIGFuZCByYXRpb25hbGUgb2YgdGhlIEVGRk9SVExFU1Mg

Uy1JQ0QgUmVnaXN0cnk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ry

b3BoeXNpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlBhY2luZyBhbmQgY2xpbmljYWwg

ZWxlY3Ryb3BoeXNpb2xvZ3kgOiBQQUNFPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+

PGZ1bGwtdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ryb3BoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5QYWNpbmcgYW5kIGNsaW5pY2FsIGVsZWN0cm9waHlzaW9sb2d5IDogUEFDRTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ry

b3BoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5QYWNpbmcgYW5kIGNsaW5pY2FsIGVsZWN0cm9w

aHlzaW9sb2d5IDogUEFDRTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjU3NC05PC9w

YWdlcz48dm9sdW1lPjM1PC92b2x1bWU+PG51bWJlcj41PC9udW1iZXI+PGVkaXRpb24+MjAxMi8w

My8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWRvbGVzY2VudDwva2V5d29yZD48a2V5

d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQs

IDgwIGFuZCBvdmVyPC9rZXl3b3JkPjxrZXl3b3JkPkNvc3QtQmVuZWZpdCBBbmFseXNpcy9lY29u

b21pY3Mvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwva2V5d29yZD48a2V5d29yZD5E

ZWF0aCwgU3VkZGVuLCBDYXJkaWFjLypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+

PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlLyplY29ub21pY3MvKnN0YXRpc3Rp

Y3MgJmFtcDsgbnVtZXJpY2FsIGRhdGE8L2tleXdvcmQ+PGtleXdvcmQ+RXVyb3BlPC9rZXl3b3Jk

PjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5IZWFsdGggQ2FyZSBDb3N0cy8qc3Rh

dGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tl

eXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29y

ZD48a2V5d29yZD5OZXcgWmVhbGFuZDwva2V5d29yZD48a2V5d29yZD5QYXRpZW50IFNhdGlzZmFj

dGlvbi8qZWNvbm9taWNzL3N0YXRpc3RpY3MgJmFtcDsgbnVtZXJpY2FsIGRhdGE8L2tleXdvcmQ+

PGtleXdvcmQ+KlF1YWxpdHkgb2YgTGlmZTwva2V5d29yZD48a2V5d29yZD5SZWdpc3RyaWVzLypz

dGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxrZXl3b3JkPlJlc2VhcmNo

IERlc2lnbjwva2V5d29yZD48a2V5d29yZD5UcmVhdG1lbnQgT3V0Y29tZTwva2V5d29yZD48a2V5

d29yZD5Zb3VuZyBBZHVsdDwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDEyPC95

ZWFyPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+

MDE0Ny04Mzg5PC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIyMzYwNjc3PC9hY2Nlc3Npb24tbnVtPjx1

cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTExMS9qLjE1NDAtODE1OS4y

MDEyLjAzMzM3Lng8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2Vyc21hPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

UmVjTnVtPjM5PC9SZWNOdW0+PERpc3BsYXlUZXh0PihCb2Vyc21hLCAyMDEyOyBQZWRlcnNlbiBl

dCBhbC4sIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjM5PC9yZWMtbnVt

YmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZWEwcmVwdDA5cHR2cDllemR3

OHh3NXhyMDIydGEwZnZlcDVhIiB0aW1lc3RhbXA9IjEzODMyODExNTUiPjM5PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2Vyc21hLCBMLjwvYXV0aG9yPjwvYXV0aG9y

cz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5Mb25nIFRlcm0gT3V0Y29tZSBPZiBQYXRp

ZW50cyBSZWNlaXZpbmcgVGhlIFN1YmN1dGFuZW91cyBJQ0QgQWZ0ZXIgVHJhbnN2ZW5vdXMgSUNE

IEV4dHJhY3Rpb248L3RpdGxlPjwvdGl0bGVzPjxkYXRlcz48eWVhcj4yMDEyPC95ZWFyPjwvZGF0

ZXM+PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlBlZGVyc2VuPC9B

dXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVjTnVtPjE5PC9SZWNOdW0+PHJlY29yZD48cmVjLW51

bWJlcj4xOTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVh

MHJlcHQwOXB0dnA5ZXpkdzh4dzV4cjAyMnRhMGZ2ZXA1YSIgdGltZXN0YW1wPSIxMzgzMTE0OTM2

Ij4xOTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUi

PjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+UGVkZXJzZW4sIFMu

IFMuPC9hdXRob3I+PGF1dGhvcj5MYW1iaWFzZSwgUC48L2F1dGhvcj48YXV0aG9yPkJvZXJzbWEs

IEwuIFYuPC9hdXRob3I+PGF1dGhvcj5NdXJnYXRyb3lkLCBGLjwvYXV0aG9yPjxhdXRob3I+Sm9o

YW5zZW4sIEouIEIuPC9hdXRob3I+PGF1dGhvcj5SZWV2ZSwgSC48L2F1dGhvcj48YXV0aG9yPlN0

dWFydCwgQS4gRy48L2F1dGhvcj48YXV0aG9yPkFkcmFnYW8sIFAuPC9hdXRob3I+PGF1dGhvcj5U

aGV1bnMsIEQuIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJl

c3M+Q29SUFMgLSBDZW50ZXIgb2YgUmVzZWFyY2ggb24gUHN5Y2hvbG9neSBpbiBTb21hdGljIGRp

c2Vhc2VzLCBUaWxidXJnIFVuaXZlcnNpdHksIFRpbGJ1cmcsIHRoZSBOZXRoZXJsYW5kcy4gcy5z

LnBlZGVyc2VuQHV2dC5ubDwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkV2YWx1YXRpb24g

b0YgRmFjdE9ScyBJbXBhY1RpbmcgQ0xpbmljYWwgT3V0Y29tZSBhbmQgQ29zdCBFZmZlY3RpdmVu

ZVNTIG9mIHRoZSBTLUlDRDogZGVzaWduIGFuZCByYXRpb25hbGUgb2YgdGhlIEVGRk9SVExFU1Mg

Uy1JQ0QgUmVnaXN0cnk8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ry

b3BoeXNpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlBhY2luZyBhbmQgY2xpbmljYWwg

ZWxlY3Ryb3BoeXNpb2xvZ3kgOiBQQUNFPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+

PGZ1bGwtdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ryb3BoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5QYWNpbmcgYW5kIGNsaW5pY2FsIGVsZWN0cm9waHlzaW9sb2d5IDogUEFDRTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+UGFjaW5nIENsaW4gRWxlY3Ry

b3BoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5QYWNpbmcgYW5kIGNsaW5pY2FsIGVsZWN0cm9w

aHlzaW9sb2d5IDogUEFDRTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjU3NC05PC9w

YWdlcz48dm9sdW1lPjM1PC92b2x1bWU+PG51bWJlcj41PC9udW1iZXI+PGVkaXRpb24+MjAxMi8w

My8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWRvbGVzY2VudDwva2V5d29yZD48a2V5

d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQs

IDgwIGFuZCBvdmVyPC9rZXl3b3JkPjxrZXl3b3JkPkNvc3QtQmVuZWZpdCBBbmFseXNpcy9lY29u

b21pY3Mvc3RhdGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwva2V5d29yZD48a2V5d29yZD5E

ZWF0aCwgU3VkZGVuLCBDYXJkaWFjLypwcmV2ZW50aW9uICZhbXA7IGNvbnRyb2w8L2tleXdvcmQ+

PGtleXdvcmQ+RGVmaWJyaWxsYXRvcnMsIEltcGxhbnRhYmxlLyplY29ub21pY3MvKnN0YXRpc3Rp

Y3MgJmFtcDsgbnVtZXJpY2FsIGRhdGE8L2tleXdvcmQ+PGtleXdvcmQ+RXVyb3BlPC9rZXl3b3Jk

PjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5IZWFsdGggQ2FyZSBDb3N0cy8qc3Rh

dGlzdGljcyAmYW1wOyBudW1lcmljYWwgZGF0YTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tl

eXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29y

ZD48a2V5d29yZD5OZXcgWmVhbGFuZDwva2V5d29yZD48a2V5d29yZD5QYXRpZW50IFNhdGlzZmFj

dGlvbi8qZWNvbm9taWNzL3N0YXRpc3RpY3MgJmFtcDsgbnVtZXJpY2FsIGRhdGE8L2tleXdvcmQ+

PGtleXdvcmQ+KlF1YWxpdHkgb2YgTGlmZTwva2V5d29yZD48a2V5d29yZD5SZWdpc3RyaWVzLypz

dGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxrZXl3b3JkPlJlc2VhcmNo

IERlc2lnbjwva2V5d29yZD48a2V5d29yZD5UcmVhdG1lbnQgT3V0Y29tZTwva2V5d29yZD48a2V5

d29yZD5Zb3VuZyBBZHVsdDwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDEyPC95

ZWFyPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+

MDE0Ny04Mzg5PC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIyMzYwNjc3PC9hY2Nlc3Npb24tbnVtPjx1

cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTExMS9qLjE1NDAtODE1OS4y

MDEyLjAzMzM3Lng8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TmxtPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Boersma, 2012; Pedersen et al., 2012). Where available, the submission will report patient-relevant endpoints, such as all-cause mortality and SCD. Where such data are not reported, surrogate efficacy endpoints such as accurate ventricular arrhythmia detection and treatment will be presented. Studies of subcutaneous ICD are likely to be underpowered to detect differences between treatments in the rate of major clinical events. Therefore it is proposed that the assessment of non-inferiority is based on surrogate efficacy endpoints. The validity of these endpoints and the identification of appropriate non-inferiority margins will be key research questions in the submission. The submission will also present a detailed assessment of safety, including short term safety data from comparative studies and long term safety outcomes from single-arm trials. A list of relevant efficacy and safety endpoints is provided below. Primary Efficacy OutcomesSensitivity and Specificity of Induced Arrhythmia DetectionInduced VF ConversionSpontaneous VF Detection and ConversionSecondary Efficacy OutcomesAll-cause mortalitySudden Cardiac DeathSafety OutcomesPeri-procedural Adverse EventsPost-procedural Adverse EventsAppropriate/Inappropriate ShocksLead FailurePneumothoraxMajor infection e.g. lead re-intervention, pneumothorax, cardiac perforationMinor infection i.e. only requiring antibioticsHealth care resourcesPatient identification costsSubcutaneous ICD will provide physicians and patients with an alternative treatment option; the initial tests to establish if a patient is indicated for an ICD will remain unchanged. When deciding if a patient is suitable for subcutaneous ICD, physicians will need to ensure that patients with any need for pacing are excluded. Since pacing requirements are already taken into consideration by physicians when selecting and configuring a patient’s ICD, this will have no impact on the costs associated with patient identification.Device and procedure costsIf MBS listing is recommended by MSAC, the applicant intends to seek a comparable price for subcutaneous ICD to a single chamber ICD device on the Prostheses List. Based on the clinical claim of non-inferiority (supported by clinical evidence presented in Section B of the submission) and the similarity in the procedure complexity and resources used, a cost-minimisation analysis is considered appropriate. Since the reimbursement of subcutaneous ICD is unlikely to lead to any growth in the market for ICDs, the applicant considers subcutaneous ICD will be cost-neutral to the health system. It is more likely that the new service will be cost-saving as subcutaneous ICD is associated with a decreased need for fluoroscopic imaging, which is associated with its own MBS item fee and substantial infrastructure requirements. The duration and complexity of the procedure relative to the implantation of transvenous ICD will be evaluated in the SBA to determine an appropriate fee. Subcutaneous ICD devices need replacing approximately every 5 years. Conventional transvenous ICD devices need replacing approximately every 5-8 years, and leads have a lifetime of approximately 10 years. The implications of any differences in battery-life on lifetime costs will be considered in the economic evaluation.In terms of how the service is to be provided, the insertion of a subcutaneous ICD lead will need to be performed by a surgeon, cardiologist or electrophysiologist. The current listing for ICD lead insertion does not limit the insertion, removal, or replacement of the device to cardiologists. The proposed listing is not expected to lead to any incremental training requirements. Manufacturers of subcutaneous ICD technology provide training to hospital staff.As stated in the MSAC Assessment Report 32, the average length of stay for implantation of an transvenous-ICD device in Australia is likely to be the same as for implantation of a standard cardiac pacemaker (National Hospital Cost Data Collection Cost Weights for AR-DRG Versions 5.1 [private] and 5.2 [public] 2008-09, AR-DRG F12Z estimate this to be 4.65 days in public hospitals and 3.9 days in private hospitals), except in cases where there are complications associated with implantation of the device. The length of stay for subcutaneous ICD lead and generator insertion is expected to be similar to insertion of transvenous ICD (Kobe, 2013). The subcutaneous ICD System is designed to be implanted using anatomical landmarks only, with the pulse generator placed in the lateral thoracic region and the electrode placed in a subcutaneous sinus along the sternum. As the electrode and pulse generator are placed subcutaneously, there is no need for fluoroscopy or other medical imaging systems found in an electrophysiology laboratory. The patient is required to be admitted to hospital for access to a sterile environment, device programmer and resuscitation equipment. Similar to transvenous ICD insertion, an x-ray is often performed after implanting the subcutaneous ICD pulse generator and lead to confirm accurate placement.Implantation of transvenous leads can be difficult for certain patients who have compromised or abnormal venous structures. In such cases, implanting physicians must firstly locate and access a suitable vein, then navigate through structures under fluoroscopy using a variety of single-use accessories with different shapes and sizes, until they can access the correct location where they wish to secure the lead. In contrast, there is less variability when tunnelling subcutaneously. While the time taken to make incisions, tunnel between them, draw the electrode through and close incisions may be similar to the time taken to perform a transvenous lead implant, the steps are predictable and require less equipment to perform the procedure. Comparing the insertion of transvenous and subcutaneous ICD leads is somewhat subjective, as the two procedures require a different set of skills to ensure appropriate lead placement to reduce over sensing, lead migration and local infection. The skill and time required for the implantation of subcutaneous ICD leads will be examined in the submission based assessment to determine an appropriate fee for the service. A list of the resource items that will be considered in the cost-minimisation analysis is presented in REF _Ref387242503 \h Table 10.Table SEQ Table \* ARABIC 10 List of resources to be considered in the economic analysisProvider of resourceSetting in which resource is providedProportion of patients receiving resourceNumber of units of resource per relevant time horizon per patient receiving resourceDisaggregated unit costMBSSafety nets*Other govt budgetPrivate health insurerPatientTotal costResources provided to identify eligible population No changeResources provided to deliver proposed interventionInsertion of generatorSurgeon/specialistPrivate hospital100%1$287.85 Acquisition of generatorManufacturersPrivate hospital100%1$42,640Insertion of leadsSurgeon/specialistPrivate hospital100%1$TBDAcquisition of leadsManufacturersPrivate hospital100%1$4,680Hospital stay / Operating roomsPrivate hospitalPrivate hospital100%1 (65 days)TBDAnaesthetistsPrivate hospitalPrivate hospitalTBD1TBDImaging (fluoroscopy and X-ray)Private hospitalPrivate hospitalTBD1TBDResources provided in association with proposed interventionOptimal medical management no change, not includedResources provided to deliver main comparator Insertion of generatorSurgeon/specialistPrivate hospital100%1$287.85 Acquisition of generatorManufacturersPrivate hospital100%1$42,640 (Billing Code BS208)Insertion of leadsSurgeon/specialistPrivate hospital100%1$1,052.6Acquisition of leadsManufacturersPrivate hospital100%1$4,680 (Billing Code MC251)Hospital stay / Operating roomsPrivate hospitalPrivate hospital100%1 (65 days)TBDAnaesthetistsPrivate hospitalPrivate hospitalTBD1TBDImaging (fluoroscopy and X-ray)Private hospitalPrivate hospitalTBD1TBDResources provided in association with main comparatorOptimal medical management no change, not included* Include costs relating to both the standard and extended safety net.MBS: Medicare Benefits Schedule; ICD: implantable cardioverter defibrillator; RA: right atrial; RV: right ventricular; CRT-D: cardiac resynchronisation therapy device capable of defibrillation; LV: left ventricular.Clinical advice has suggested that tests prior to subcutaneous ICD implantation are the same as those prior to transvenous ICD implant:Electrocardiogram and cardiac echocardiogramPossibly cardiac catheterisation, cardiac MRI, cardiac biopsyPatients with a cardiac device will require testing at least every 6 monthsIn some cases testing may require echocardiographic optimisation of the ICD deviceOverall, resources for the population without a requirement for pacing and are eligible for subcutaneous ICD are expected to be similar to the patient population currently indicated for a transvenous ICD on the MBS. This will be assessed in the submission based assessment using a cost-minimisation analysis.Proposed structure of economic evaluationThe clinical claim in this submission is likely to be non-inferiority compared to transvenous ICD in terms of clinical efficacy and safety. Therefore the most appropriate form of economic evaluation is a cost-minimisation analysis. A decision analytic economic evaluation is therefore not proposed for this assessment. The PICO criteria for the cost-minimisation analysis are provided in REF _Ref387242524 \h Table 11.Table SEQ Table \* ARABIC 11 Summary of extended PICO to define research question that assessment will investigatePatientsInterventionComparatorOutcomes to be assessedHealthcare resources to be consideredPatients indicated for ICD for the treatment of life-threatening ventricular arrhythmia and who do not require pacing therapy i.e. do not have symptomatic bradycardia or ventricular tachycardia that is reliably terminated with anti-tachycardia pacing.Subcutaneous ICDTransvenous ICDPrimary Efficacy OutcomesSensitivity and Specificity of Induced Arrhythmia DetectionInduced VF ConversionSpontaneous VF Detection and ConversionSecondary Efficacy OutcomesAll-cause mortalitySudden Cardiac DeathSafety OutcomesPeri-procedural Adverse EventsPost-procedural Adverse EventsAppropriate/Inappropriate ShocksLead FailurePneumothoraxMajor infection e.g. lead re-intervention, pneumothorax, cardiac perforationMinor infection i.e. only requiring antibioticsInsertion of generatorAcquisition of generatorInsertion of leadsAcquisition of leadsHospital stay / Operating roomsAnaesthetistsImaging (fluoroscopy and X-ray)Monitoring and follow up visitsICD: implantable cardioverter defibrillator Appendix A: Device Overview and Anatomical Landmarks for Lead InsertionThe S-ICD? System includes the S-ICD? pulse generator, a subcutaneous electrode which requires an insertion tool for proper electrode placement and a programmer for device analysis and defibrillation testing. The S-ICD? System components are extremely similar to those of a single-chamber transvenous ICD system that includes a pulse generator, electrode, insertion tool, and programmer. S-ICD Pulse Electrode Insertion ToolS-ICD Pulse Electrode Insertion ToolS-ICD Pulse Generator and Subcutaneous electrodeS-ICD Pulse Generator and Subcutaneous electrodeS-ICD ProgrammerS-ICD ProgrammerAnatomical landmarks for lead insertion.Illustrative representation of device and lead placement One month post operativeOne month post operativeReferences ADDIN EN.REFLIST Ahmed, A. (2003). American College of Cardiology/American Heart Association Chronic Heart Failure Evaluation and Management guidelines: relevance to the geriatric practice. J Am Geriatr Soc, 51(1), 123-126. Aydin, A., Hartel, F., Schluter, M., Butter, C., Kobe, J., Seifert, M., . . . Willems, S. (2012). Shock efficacy of subcutaneous implantable cardioverter-defibrillator for prevention of sudden cardiac death: initial multicenter experience. Circ Arrhythm Electrophysiol, 5(5), 913-919. doi: 10.1161/circep.112.973339Bardy, G. H., Smith, W. M., Hood, M. A., Crozier, I. G., Melton, I. C., Jordaens, L., . . . Grace, A. A. (2010). An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med, 363(1), 36-44. doi: 10.1056/NEJMoa0909545Boersma, L. (2012). Long Term Outcome Of Patients Receiving The Subcutaneous ICD After Transvenous ICD Extraction. Burke, M. C. (2012). Safety and Efficacy of a Subcutaneous Implantable Defibrillator (S-ICD). Heart Rhythm Society Late Breaking Clinical Trials. Charles, R. D., & Gammage, M. D. (2007). Heart Rhythm Management Devices: Guidance for Commissioners. National Heart Rhythm Management Device Taskforce. Cowie, M. R., & Zaphiriou, A. (2002). Management of chronic heart failure. Bmj, 325(7361), 422-425. Dabiri Abkenari, L., Theuns, D. A., Valk, S. D., Van Belle, Y., de Groot, N. M., Haitsma, D., . . . Jordaens, L. (2011). Clinical experience with a novel subcutaneous implantable defibrillator system in a single center. Clin Res Cardiol, 100(9), 737-744. doi: 10.1007/s00392-011-0303-6Dickstein, K., Vardas, P. E., Auricchio, A., Daubert, J. C., Linde, C., McMurray, J., . . . van Veldhuisen, D. J. (2010). 2010 Focused Update of ESC Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC Guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Europace, 12(11), 1526-1536. doi: 10.1093/europace/euq392DiMarco, J. P. (2003). Implantable cardioverter-defibrillators. N Engl J Med, 349(19), 1836-1847. doi: 10.1056/NEJMra035432Epstein, A. E., Dimarco, J. P., Ellenbogen, K. A., Estes, N. A., 3rd, Freedman, R. A., Gettes, L. S., . . . Sweeney, M. O. (2008). ACC/AHA/HRS 2008 guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: executive summary. Heart Rhythm, 5(6), 934-955. doi: 10.1016/j.hrthm.2008.04.015FDA. (2012). Device Approvals and Clearances: subcutaneous Implantable Defibrillator (S-ICD) - P110042. Gold, M. R., Theuns, D. A., Knight, B. P., Sturdivant, J. L., Sanghera, R., Ellenbogen, K. A., . . . Burke, M. C. (2012). Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the START study. J Cardiovasc Electrophysiol, 23(4), 359-366. doi: 10.1111/j.1540-8167.2011.02199.xHare, J. M. (2002). Cardiac-resynchronization therapy for heart failure. N Engl J Med, 346(24), 1902-1905. doi: 10.1056/NEJMed020028Huikuri, H. V., Castellanos, A., & Myerburg, R. J. (2001). Sudden death due to cardiac arrhythmias. N Engl J Med, 345(20), 1473-1482. doi: 10.1056/NEJMra000650Kobe, J., Reinke, F., Meyer, C., Shin, D. I., Martens, E., Kaab, S., . . . Eckardt, L. (2013). Implantation and follow-up of totally subcutaneous versus conventional implantable cardioverter-defibrillators: a multicenter case-control study. Heart Rhythm, 10(1), 29-36. doi: 10.1016/j.hrthm.2012.09.126Krum, H., Jelinek, M. V., Stewart, S., Sindone, A., & Atherton, J. J. (2011). 2011 update to National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines for the prevention, detection and management of chronic heart failure in Australia, 2006. Med J Aust, 194(8), 405-409. Lobodzinski, S. S. (2011). Subcutaneous implantable cardioverter-defibrillator (S-ICD). Cardiol J, 18(3), 326-331. Lopshire, J. C., & Zipes, D. P. (2006). Sudden cardiac death: better understanding of risks, mechanisms, and treatment. Circulation, 114(11), 1134-1136. doi: 10.1161/circulationaha.106.647933MSAC. (2006). “Implantable cardiac defibrillators for prevention of sudden cardiac death, Reference 32”. Myerburg, R. J., Interian, A., Jr., Mitrani, R. M., Kessler, K. M., & Castellanos, A. (1997). Frequency of sudden cardiac death and profiles of risk. Am J Cardiol, 80(5b), 10f-19f. Olde Nordkamp, L. R., Dabiri Abkenari, L., Boersma, L. V., Maass, A. H., de Groot, J. R., van Oostrom, A. J., . . . Knops, R. E. (2012). The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large Dutch cohort. J Am Coll Cardiol, 60(19), 1933-1939. doi: 10.1016/j.jacc.2012.06.053Packer, M. (1992). Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation, 85(1 Suppl), I50-56. Pedersen, S. S., Lambiase, P., Boersma, L. V., Murgatroyd, F., Johansen, J. B., Reeve, H., . . . Theuns, D. A. (2012). Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD: design and rationale of the EFFORTLESS S-ICD Registry. Pacing Clin Electrophysiol, 35(5), 574-579. doi: 10.1111/j.1540-8159.2012.03337.xWeiss, R., Knight, B. P., Gold, M. R., Leon, A. R., Herre, J. M., Hood, M., . . . Burke, M. C. (2013). Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator. Circulation, 128(9), 944-953. doi: 10.1161/circulationaha.113.003042Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., . . . Zamorano, J. L. (2006). ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol, 48(5), e247-346. doi: 10.1016/j.jacc.2006.07.010Zipes, D. P., & Wellens, H. J. (1998). Sudden cardiac death. Circulation, 98(21), 2334-2351. ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download