National Medical Policy

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1 National Medical Policy Subject: Policy Number: Ventricular Assist Devices NMP104 Effective Date*: January 2004 Updated: April 2016 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate State s Medicaid manual(s), publication(s), citation(s), and documented guidance for coverage criteria and benefit guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link X National Coverage Determination (NCD) Artificial Hearts and Related Devices (20.9): National Coverage Manual Citation Local Coverage Determination (LCD)* Article (Local)* X Other Decision Memo for Ventricular Assist Devices as Destination Therapy (CAG-00119R2) (November 2010) tricular+assist+devices+as+destination+thera py+(2nd+recon)&bc=beaaaaaaeaaa&&fromdb =true MLN Matters Number: MM7888. Implementation Date: April 1, New Healthcare Common Procedure Coding System (HCPCS) Code for External Ventricular Assist Devices or Any Ventricular Assist Device (VAD) For Which Ventricular Assist Devices Apr 16 1

2 Payment Was Not Made Under Medicare Part A: Education/Medicare-Learning-Network- MLN/MLNMattersArticles/Downloads/MM7888.pd f MLN Matters Number: MM8803. Implementation Date September 30, Ventricular Assist Devices for Bridge-to-Transplant and Destination Therapy: Education/Medicare-Learning-Network- MLN/MLNMattersArticles/downloads/MM8803.pdf None Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Current Policy Statement : Health Net, Inc. considers FDA approved ventricular assist devices (VAD) or left ventricular assist devices (LVAD) medically necessary for any of the following indications: 1) Post-cardiotomy VADs may be used for support of blood circulation during the period following open-heart surgery. 2) Bridge-to-Transplant VADs may be used for bridge-to-transplant for individuals waiting for heart transplant 3) Destination Therapy (long term/permanent placement) Destination therapy is for patients that require permanent mechanical cardiac support. VADs used for destination therapy in patients who have chronic endstage heart failure (New York Heart Association Class IV end-stage left ventricular failure) for at least 90 days with a life expectancy of less than 2 years), who are not candidates for heart transplantation, and meet all of the following conditions: Ventricular Assist Devices Apr 16 2

3 The patient's Class IV heart failure symptoms have failed to respond to optimal medical management, including dietary salt restriction, diuretics, digitalis, beta-blockers, and ACE inhibitors (if tolerated) according to either of the following device specific parameters: for at least 60 of the last 90 days (HeartMate XVE-LVAS) or for at least 45 of the last 60 days, or have been balloon pumpdependent for 7 days, or IV inotrope-dependent for 14 days (HeartMate II); and The patient has a left ventricular ejection fraction (LVEF) < 25%; and The patient has demonstrated functional limitation with a peak oxygen consumption of <14 ml/kg/min; or the patient has a continued need for intravenous inotropic therapy owing to symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion; and (Medicare <12) The patient has the appropriate body size to support the VAD. (No longer noted in CMS, since these devices are now bigger). Note: Health Net does not consider this device medically necessary when used as an artificial heart. There is no authoritative evidence substantiating the safety and effectiveness of a VAD used as a replacement for the human heart. Percutaneous Left Ventricular Assist Devices Health Net, Inc. considers FDA approved percutaneous left ventricular assist devices* (LVADs) (e.g. Tandem Heart Percutaneous Ventricular Assist Device; Impella Recover LP 2.5 Percutaneous Cardiac Support System) medically necessary for partial circulatory support, for periods up to 6 hours, for any of the following indications: 1. To provide short-term circulatory support in patients with Windecker et al., 2014). after ST segment elevation myocardial infarction (STEMI) who do not quickly stabilize with pharmacological therapy; or 2. Refractory cardiogenic shock unresponsive to revascularization to allow for myocardial recovery or subsequent cardiac transplantation in suitable patients; or 3. As an adjunct to PCI in carefully selected high-risk patients (e.g. those undergoing unprotected left main or last-remaining-conduit PCI, those with severely depressed EF undergoing PCI of a vessel supplying a large territory, and/or those with cardiogenic shock. *Note: Patient risk, hemodynamic support, ease of application/removal, and operator and laboratory expertise are all factors involved in consideration of use of these devices. With devices that require large cannula insertion, the risk of vascular injury and related complications are important considerations regarding necessity and choice of device. Ventricular Assist Devices Apr 16 3

4 Definitions PCI Percutaneous coronary intervention IABP Intraaortic balloon pump STEMI ST segment elevation myocardial infarction HR-PCI High-risk percutaneous coronary intervention PLVADs Percutaneous left ventricular assist devices TH TandemHeart LVAD Left ventricular assist device DT Destination therapy BTT Bridge to transplant OMM Optimal medical management CF Continuous-flow RV Right ventricle CVP Central venous pressure PAP Pulmonary artery pressures PCWP Pulmonary capillary wedge pressure CI Cardiac index RVEF RV ejection fraction RVEDD RV end-diastolic dimension RVSWI RV stroke work index TAPSE Tricuspid annular plane systolic excursion TR Tricuspid regurgitation Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures have been replaced by ICD-10 code sets. ICD-9 Codes Acute myocardial infarction Fibrotic left ventricle after aneurysmectomy; left ventricular rupture Acute myocarditis in diseases classified elsewhere Acute myocarditis, unspecified Idiopathic myocarditis Septic myocarditis Mitral valve disruption Cardiomyopathy Atrial fibrillation Ventricular fibrillation End-stage, intractable congestive heart failure Left heart failure Combined systolic and diastolic heart failure, unspecified Combined systolic and diastolic heart failure, acute Congenital heart defects Acute cardiogenic shock Ventricular Assist Devices Apr 16 4

5 ICD-10 Codes I21.01-I21.4 I22.0-I22.9 ST elevation (STEMI) and non-st elevation (NSTEMI) myocardial infarction Subsequent ST elevation (STEMI) and non-st elevation (NSTEMI) myocardial infarction Chronic ischemic heart disease Acute myocarditis Myocarditis in diseases classified elsewhere Nonrheumatic mitral valve disorders Cardiomyopathy I25.1-I25.9 I40.0-I49 I41 I34.0-I34.9 I42.0-I42.9 I48.1 Persistant atrial fibrillation I48.2 Chronic atrial fibrillation I48.91 Unspecified atrial fibrillation I49.01 Ventricular fibrillation I50.1 Left ventricular failure I50.40-I50.43 Combined systolic (congestive) and diastolic (congestive) heart failure Q20-Q28 Congenital malformations of the circulatory system R57.0 Cardiogenic shock CPT Codes Removal of ventricular assist device, extracorporeal single ventricle Removal of ventricular assist device, extracorporeal, biventricular Insertion of a ventricular assist device, implantable intracorporeal, single ventricle Removal of a ventricular assist device, implantable interacorporeal, single ventricle Insertion of ventricular assist device, percutaneous including radiological supervision and interpretation; arterial access only Insertion of ventricular assist device, percutaneous including radiological supervision and interpretation; both arterial and venous access, with transseptal puncture Removal of percutaneous ventricular assist device at separate and distinct session from insertion Repositioning of percutaneous ventricular assist device with imaging guidance at separate and distinct session from insertion HCPCS Codes Q0480 Driver for use with pneumatic ventricular assist device, replacement only Q0481 Microprocessor control unit for use with pneumatic ventricular assist device, replacement only Q0482 Microprocessor control unit for use with electric/pneumatic combination ventricular assist device, replacement only Q0483 Monitor/display module for use with pneumatic ventricular assist device, replacement only Q0484 Monitor/display module for use with electric or electric/pneumatic ventricular assist device, replacement only Q0485 Monitor control cable for use with electric ventricular assist device, replacement only Ventricular Assist Devices Apr 16 5

6 Q0486 Q0487 Q0488 Monitor control cable for use with electric/pneumatic ventricular assist device, replacement only Leads (pneumatic/electrical) for use with any type electric/pneumatic ventricular assist device, replacement only Power pack base for use with electric ventricular assist device, Replacement only Scientific Rationale Update April 2016 Rihal et al. (2015) notes that the Society for Cardiovascular Angiography and Interventions, American College of Cardiology, Heart Failure Society of America, and the Society for Thoracic Surgeons (SCAI/ACC/HFSA/STS, 2015) have a consensus statement on the use of percutaneous mechanical circulatory support (MCS). It states that percutaneous MCS, particularly with the Impella and TandemHeart, is superior to pharmacologic therapy for providing hemodynamic support and these devices should be available. One of the suggested indications for percutaneous MCS is for patients undergoing high-risk percutaneous coronary intervention (PCI), especially if the patient is inoperable or has a low LVEF (< 20% to 30%) and complex CAD involving a large territory (i.e. sole remaining vessel, left main disease, or 3-vessel disease). Windecker et al. (2014), notes a guideline by the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS), that supports use of LVADs for cardiogenic shock (CS), as a bridge to transplantation, or as destination therapy, but does not discuss use of LVADs for high-risk percutaneous coronary intervention (PCI). The LVAD Impella 5.0 System (Abiomed Inc.) has been proposed for emergent hemodynamic support in patients with cardiogenic shock (CS) and requires surgical cutdown of the femoral or axillary artery, therefore it is not truly percutaneous. This system received U.S. Food and Drug Administration approval in September 2012 and is based on the Impella 2.5 platform, but can provide flow up to 4.0 l/min. However, there is a paucity of quality peer-reviewed comparative studies on the Impella 5.0 System in patients with CS, to determine the benefits and harms of the Impella 5.0 as emergent hemodynamic support in patients with CS. The increase in vascular access related issues and the propensity for hemolysis due to the high rotational speed of the axial flow pump do not appear to be outweighed by any significant gains in survival. There is a Clinical Trial on MOMENTUM 3 IDE Clinical Study Protocol (HM3), that is currently recruiting participants. The ClinicalTrials.gov Identifier is NCT , and it was last verified on March 24, The objective of the study is to evaluate the safety and effectiveness of the HeartMate 3 Left Ventricular Assist device (HM3 LVAS) by demonstrating non-inferiority to the HeartMate 2 Left Ventricular Assist device (HMII LVAS) when used for the treatment of advanced, refractory, left ventricular heart failure. The estimated study completion date is November Scientific Rationale Update April 2014 The 2013 Guidelines from the ACCF/AHA on the management of heart failure (Yancey et al 2013) report that a subset of patients with chronic HF will continue to progress and develop persistently severe symptoms despite maximum guideline- Ventricular Assist Devices Apr 16 6

7 directed medical therapy (GDMT.) Various terminologies have been used to describe this group of patients who are classified with ACCF/AHA stage D HF, including advanced HF, end-stage HF, and refractory HF. The guidelines make the following recommendations regarding mechanical circulatory support (MCS): CLASS IIa (i.e., Recommendation in favor of treatment or procedure being useful/effective. Some conflicting evidence from a single randomized trial or nonrandomized study) MCS is beneficial in carefully selected patients with stage D HF with reduced ejection fraction (HFrEF) in whom definitive management (e.g., cardiac transplantation) or cardiac recovery is anticipated or planned. (Level of Evidence: B) Nondurable MCS, including the use of percutaneous and extracorporeal ventricular assist devices (VADs), is reasonable as a bridge to recovery or bridge to decision for carefully selected patients with HFrEF with acute, profound hemodynamic compromise. (Level of Evidence: B) Durable MCS is reasonable to prolong survival for carefully selected patients with stage D HFrEF. (Level of Evidence: B) Per the guideline, MCS has emerged as a viable therapeutic option for patients with advanced stage D HFrEF refractory to optimal GDMT and cardiac device intervention. Since its initial use 50 years ago for postcardiotomy shock, the implantable VAD continues to evolve. Designed to assist the native heart, VADs are differentiated by the implant location (intracorporeal versus extracorporeal), approach (percutaneous versus surgical), flow characteristic (pulsatile versus continuous), pump mechanism (volume displacement, axial, centrifugal), and the ventricle(s) supported (left, right, biventricular). VADs are effective in both the short-term (hours to days) management of acute decompensated, hemodynamically unstable HFrEF that is refractory to inotropic support, and the long-term (months to years) management of stage D chronic HFrEF. Nondurable or temporary, MCS provides an opportunity for decisions about the appropriateness of transition to definitive management such as cardiac surgery or durable, that is, permanent, MCS or, in the case of improvement and recovery, suitability for device removal. Nondurable MCS thereby may be helpful as either a bridge to decision or a bridge to recovery. More common scenarios for MCS, however, are long-term strategies, including 1) bridge to transplantation, 2) bridge to candidacy, and 3) destination therapy. Bridge to transplant and destination therapy have the strongest evidence base with respect to survival, functional capacity, and HRQOL benefits. Data from INTERMACS provides valuable information on risk factors and outcomes for patients undergoing MCS. The greatest risk factors for death among patients undergoing bridge to transplant include acuity and severity of clinical condition and evidence of right ventricular failure. MCS may also be used as a bridge to candidacy. Retrospective studies have shown reduction in pulmonary pressures with MCS therapy in patients with HF considered to have fixed pulmonary hypertension. Thus, patients who may be transplant-ineligible due to irreversible severe pulmonary hypertension may become eligible with MCS support over time. Other bridge-to-candidacy indications may include obesity and tobacco use in patients who are otherwise candidates for cardiac transplantation. Ventricular Assist Devices Apr 16 7

8 Taghavi et al (2014) reported bridge to transplantation patients with continuous flow left ventricular assist devices (cflvads) are assigned United Network for Organ Sharing status 1A or 1B priority while awaiting orthotopic heart transplantation. They investigated the influence of cflvad on the waitlist times and organ allocation. The United Network for Organ Sharing database was examined from 2005 to 2012 for patients with cflvad and pulsatile flow LVAD (plvad). These 2 cohorts were compared with patients who did not receive LVAD. Of 16,476 total orthotopic heart transplantations, 3270 (19.8%) were performed on patients with an LVAD as a bridge to transplantation. The cflvad group had the longest total waitlist time (259.6 days) compared with the plvad (134.6 days) and non-lvad (121.7 days) groups (P <.001). The cflvad group spent more time in status 1A (44.7 days) than did the plvad (32.1 days) and non-lvad (16.4 days) cohorts (P <.001). The median waitlist survival was better for the cflvad group ( days) than in the plvad (441.0 days) and non-lvad (471.0 days) groups (P <.001). The cflvad recipients were older, had a greater body mass index, and more often had diabetes than did plvad and non-lvad patients. The cflvad cohort received hearts from older, more often male donors, with a greater body mass index. Post-transplant survival was not significantly different among the 3 groups on Kaplan-Meier analysis (P =.12). Investigators concluded despite being older, less favorable recipients, the cflvad patients spent more time in status 1A and had greater waitlist survival. This might allow cflvad patients to receive preferred donor hearts, which might allow for better post-transplant survival. De Rita et al (2014) reported a significant number of children affected by congenital heart disease (CHD) develop heart failure early or late after surgery, and heart transplantation (OHTx) remains the last treatment option. Due to shortage of donor organs in pediatric group, mechanical circulatory support (MCS) is now routinely applied as bridging strategy to increase survival on the waiting list for OTHx. The authors sought to assess the impact of MCS as intention to bridge to OHTx in patients with CHD less than 16 years of age. From 1998 to 2013, 106 patients received 113 episodes of MCS with paracorporeal devices as intention to bridge to OHTx. Twenty-nine had CHD, 15 (52%) with two-ventricle (Group A) and 14 (48%) with single-ventricle physiology (Group B). In Group A, 5 children had venoarterial extracorporeal membrane oxygenation (VA ECMO), 6 left ventricular assist device (LVAD), 2 biventricular assist device (BIVAD), 1 VA ECMO followed by BIVAD and 1 BIVAD followed by VA ECMO. In Group B, VA ECMO was used in 7 children, univentricular assist device (UVAD) changed to VA ECMO in 4, UVAD in 2 and surgical conversion to two-ventricles physiology with BIVAD support changed to VA ECMO in 1. Twenty-one of 29 (72%) children survived to recovery/ohtx. Seven of 29 (59%) survived to discharge. In Group A, 11/15 (73%) survived to recovery/ohtx and 9/15 (60%) survived to discharge. Four of 15 (27%) died awaiting OHTx. One child had graft failure requiring VA ECMO and was bridged successfully to retransplantation. One child dying after OHTx had acute rejection, was supported with VA ECMO and then BIVAD but did not recover. One patient had an unsuccessful second run on BIVAD 1 year after recovery from VA ECMO. In Group B, 10/14 (71%) survived to recovery/ohtx and 8/14 (57%) survived to discharge. Four of 14 (29%) died awaiting OHTx. Of deaths after OHTx, 1 occurred intraoperatively and 1 was consequent to graft failure and had an unsuccessful second run with VA ECMO. Authors concluded children with CHD can be successfully bridged with MCS to heart transplantation. Single-ventricle circulation compared with biventricular physiology does not increase the risk of death before transplant or before hospital discharge. Ventricular Assist Devices Apr 16 8

9 Boyle et al (2014) sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. The authors noted that adverse events in LVAD patients remain high. It is unclear whether preoperative characteristics influence the likelihood of the development of postoperative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative hematocrit ( 31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m(2) increase) were also multivariable risk factors for pump thrombosis. Reviewers concluded the risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups. Smedira et al (2013) sought to identify potential areas for quality improvement and cost containment. They investigated readmissions after HeartMate II left ventricular assist device (LVAD) implantation by characterizing their type, temporal frequency, causative factors, and resource use and survival after readmission. From October 2004 to January 2010, 118 patients received a HeartMate II, of whom 92 were discharged on device support. Subsequent readmissions were analyzed using prospectively maintained clinical and financial databases. Forty-eight patients (52%) had 177 unplanned hospital readmissions, 87 non-lvad- and 90 LVAD-associated. Reasons for non-lvad-associated readmissions included medical management of comorbidities and progression of cardiac pathology (n = 48), neuropsychiatric/psychosocial issues (n = 22), and infections (n = 17). Those for LVAD-associated readmissions included device component infection (n = 51), management of nontherapeutic anticoagulation or device malfunction (n = 22), and bleeding (n = 15). Cumulative incidence of unplanned readmissions was higher (p < ) for destination therapy than bridge-to-transplant patients (9/patient vs. 4/patient at 24 months). Cumulative hospital days overall were 25 and 42 at 12 and 18 months, respectively, and the costs were 18% and 29% of initial implantation costs. Increased number of unplanned readmissions was predictive of mortality. Authors concluded unplanned readmissions are common during HeartMate II support and negatively affect resource use and survival. Refining patient selection, especially in destination therapy patients, reducing infectious and bleeding complications, and increasing awareness about these devices might reduce unnecessary readmissions. Scientific Rationale Update April 2013 Ventricular Assist Devices Apr 16 9

10 Left ventricular assist devices (LVADs) have been approved by the U.S. Food and Drug Administration (FDA) for use in patients awaiting transplant (a bridge to transplant) and as a last resort in patients with refractory heart failure who are not eligible for a heart transplant (destination therapy). LVADs have evolved over the years and are still rapidly evolving. At this time, several LVADs have received FDA approval for short-term use as a bridge to transplant (BTT) in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular failure. These include the HeartMate Sutures Not Applied Vented Electric Left Ventricular Assist System (SNAP VE LVAS) and its enhanced version, the HeartMate Extended Lead Vented Electric Left Ventricular Assist System (XVE LVAS), as well as earlier versions, such as the HeartMate Implantable Pneumatic (IP) LVAS and the HeartMate VE LVAS (Thoratec Corp.); the Thoratec Ventricular Assist Device (VAD) System (Thoratec Corp.); and the Novacor LVAS. In addition to approval for use as BTT, three Thoratec devices have been approved for use as destination therapy (DT): the HeartMate SNAP VE LVAS, the HeartMate XVE LVAS, and the HeartMate II. According to approvals for HeartMate VE/XVE, DT is indicated as an alternative to optimal medical therapy for end-stage HF patients who are not eligible for cardiac transplantation (patients with NYHA Class IV end-stage left ventricular failure who have received optimal medical management (OMM) for at least 60 of the last 90 days, have a life expectancy of < 2 years, and are not eligible for cardiac transplantation). These systems are approved for use both inside and outside of the hospital. FDA approval was based on the results of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial, which compared the experience of patients supported by the HeartMate SNAP VE LVAS with those being treated with OMM. Thoratec HeartMate II Left Ventricular Assist System is intended for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular failure. It is also indicated for use in patients with New York Heart Association (NYHA) Class 111B or IV end-stage left ventricular failure who have received optimal medical therapy for at least 45 of the last 60 days, and are not candidates for cardiac transplantation. The HeartMate II LVAS is intended for use both inside and outside the hospital, or for transportation of ventricular assist device patients via ground ambulance, fixed-wing aircraft, or helicopter. Third generation VADs have been designed for long durability, compact size, optimization of blood flow through the device to minimize the risk of thrombus formation and hemolysis, and simplified surgical implantation. These devices are just starting to be used, and they are anticipated to last for 5 to 10 years. The HeartWare Ventricular Assist System is a third generation device which was recently approved by the FDA in November The device is indicated for use as a bridge to cardiac transplantation in patients who are at risk of death from refractory endstage left ventricular heart failure. This device is designed for in-hospital and out-ofhospital settings, including transportation via fixed wing aircraft or helicopter. The device is being evaluated for clinical use as destination therapy in clinical trial. In March 2011, the US FDA approved the Berlin Heart EXCQR Pediatric Ventricular Assist Device through the humanitarian device exemption (HDE) process. The device Ventricular Assist Devices Apr 16 10

11 is intended to provide mechanical circulatory support as a bridge to cardiac transplantation for pediatric patients. Pediatric candidates with severe isolated left ventricular or biventricular dysfunction who are candidates for cardiac transplant and require circulatory support may be treated using the EXCOR. According to 2012 guidelines from the European Society of Cardiology in collaboration with the Heart Failure Association on treatment of acute and chronic heart failure: Patients potentially eligible for implantation of a ventricular assist device include: Patients with >2 months of severe symptoms despite optimal medical and device therapy and more than one of the following: LVEF <25% and, if measured, peak VO2 < 12 ml/kg/min 3 HF hospitalizations in previous 12 months without an obvious precipitating cause Dependence on i.v. inotropic therapy Progressive end-organ dysfunction (worsening renal and/or hepatic function) due to reduced perfusion and not to inadequate ventricular filling pressure (PCWP 20 mm Hg and SBP mmhg or CI 2 L/min/m2) Deteriorating right ventricular function CLASS IIa recommendations from the American College of Cardiology guidelines on heart failure in adults (2005 updated 2009) state: Consideration of an LV assist device as permanent or destination therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy. (Level of Evidence: B) Morgan et al (2013) reported that continuous-flow (CF) pumps have yielded improvements in short- and long-term survival and quality of life, and have reduced the number of left ventricular assist device (LVAD)-related complications. However, their ability to unload the right ventricle (RV) and improve RV function has not been as clearly defined. We evaluated the short- and mid-term effects of CF-LVADs on central venous pressure (CVP), pulmonary artery pressures (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), RV ejection fraction (RVEF), RV end-diastolic dimension (RVEDD), RV stroke work index (RVSWI), tricuspid annular plane systolic excursion (TAPSE) and severity of tricuspid regurgitation (TR). From March 2006 through June 2012, 130 patients with chronic heart failure underwent implantation of a CF-LVAD (122 HeartMate II and 8 HeartWare devices) as a bridge to transplant (n = 76) or as destination therapy (n = 54). Patients with pre-operative long-term LVADs (n = 4) and patients who underwent concomitant tricuspid valve repairs during their LVAD implant (n = 21) were excluded from the analysis. Echocardiograms and right heart catheterizations of the remaining 105 patients were reviewed pre-operatively and at 1 and 6 months post-lvad implantation. At 1 month post-lvad implantation, CVP decreased from 12.4 ± 5.9 mm Hg to 8.7 ± 4.5 mm Hg (p < 0.001), systolic PAP decreased from 52.3 ± 14.1 mm Hg to 36.8 ± 11.3 mm Hg (p < 0.001), PCWP decreased from 23.0 ± 9.4 mm Hg to 12.9 ± 8.0 mm Hg (p < 0.001), CI index increased from 1.8 ± 0.5 liters/min m(2) to 2.4 ± 0.5 liters/min m(2) (p < 0.001), RVEF increased from 33.1 ± 4.9% to 40.4 ± 6.2% (p < 0.001), RVEDD decreased from 36 mm to 31 mm (p = 0.020), RVSWI improved Ventricular Assist Devices Apr 16 11

12 from ± mm Hg ml m(2) to ± mm Hg ml m(2) (p < 0.001), and mean TAPSE increased from 1.1 ± 0.4 cm to 1.9 ± 0.4 cm (p = 0.004). Similarly, qualitative RV function on echocardiography improved from 57.1% moderately or severely reduced pre-operatively to 38.1% at 1 month (p = 0.008). Severity of TR decreased from 11.4% moderate or severe pre-operatively to 4.8% at 1 month (p < 0.001). These improvements were maintained at 6 months post-lvad. Investigators concluded CF-LVAD support significantly decreased CVP and RVEDD, with concomitant improvement in RV function, as measured by increases in RVEF, RVSWI and TAPSE, as well as improvements in the qualitative echocardiographic appearance of RV contractility and a reduction in TR. Cowger et al (2012) sought to derive and validate a model to predict survival in candidates for HeartMate II (HMII) (Thoratec, Pleasanton, California) LVAD support. The authors note that LVAD mortality risk prediction is important for candidate selection and communicating expectations to patients and clinicians. With the evolution of LVAD support, prior risk prediction models have become less valid. Patients enrolled into the HMII bridge to transplantation and destination therapy trials (N = 1,122) were randomly divided into derivation (DC) (n = 583) and validation cohorts (VC) (n = 539). Pre-operative candidate predictors of 90-day mortality were examined in the DC with logistic regression, from which the HMII Risk Score (HMRS) was derived. The HMRS was then applied to the VC. There were 149 (13%) deaths within 90 days. In the DC, mortality (n = 80) was higher in older patients (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1 to 1.7 per 10 years), those with greater hypoalbuminemia (OR: 0.49, 95% CI: 0.31 to 0.76 per mg/dl of albumin), renal dysfunction (OR: 2.1, 95% CI: 1.4 to 3.2 per mg/dl creatinine), coagulopathy (OR: 3.1, 95% CI: 1.7 to 5.8 per international normalized ratio unit), and in those receiving LVAD support at less experienced centers (OR: 2.2, 95% CI: 1.2 to 4.4 for <15 trial patients). Mortality in the DC low, medium, and high HMRS groups was 4%, 16%, and 29%, respectively (p < 0.001). In the VC, corresponding mortality was 8%, 11%, and 25%, respectively (p < 0.001). HMRS discrimination was good (area under the receiver-operating characteristic curve: 0.71, 95% CI: 0.66 to 0.75). The authors concluded the HMRS might be useful for mortality risk stratification in HMII candidates and may serve as an additional tool in the patient selection process. Park et al (2012) reported the HeartMate II (HMII) DT trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes. Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year, P<0.001), sepsis (0.38 versus 0.27, P=0.025), device-related infections (0.47 versus 0.27, P<0.001), and hemorrhagic stroke (0.07 versus 0.03, P=0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year, P=0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group (P=0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke (P=0.01). Quality of life improvements were significant in both Ventricular Assist Devices Apr 16 12

13 the groups (P<0.001). Investigators concluded the benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival. John et al (2011) reported the outcomes in patients receiving the HeartMate II LVAD at a single center and review the lessons learned from this experience. From June 2005 to June 2010, 130 consecutive patients received the HeartMate II LVAD. Of these, 102 were bridge-to-transplant (BTT), 17 destination therapy, and 11 exchanges for failed HeartMate XVE. This study focuses on the 102 BTT patients. The HeartMate II was approved by the US Food and Drug Administration (FDA) as BTT in April 2008 and 64 patients received this device as BTT since that date. We review our experience with the device as BTT and report on patient survival and adverse events as well as the impact of FDA approval on outcomes. Overall, mean age was 52.6 ± 12.8 years; 26 (25.5%) were female. Disease etiology was ischemic in 58, nonischemic in 36, and other in 8. Overall, 30-day, 6-month, and 1-year survival for the BTT patients was 95.1%, 83.5%, and 78.8%, respectively. The 6-month survival in 38 patients in the clinical trial (pre-fda) was 88.8% and was not statistically significant compared with the 76.2% 6-month survival in the 64 patients in the post- FDA approval period (p value = 0.1). Major adverse events among the 102 BTT patients included right ventricular failure in 5 (4.9%), LVAD driveline infections in 25 (24.5%), neurologic events in 10 (9.8%), and gastrointestinal bleeding in 18 (17.6%) patients. In addition, 1 patient (0.98%) had pump thrombus requiring device replacement. Investigators concluded despite significant morbidity, use of the HeartMate II LVAD as BTT provides excellent hemodynamic support and is associated with excellent survival and low mortality. In addition, there needs to be improvement and focused strategies in the areas of gastrointestinal bleeding, driveline infections, and adverse neurologic events for these devices to be able to provide a real longterm alternative to heart transplantation. Adamson et al (2011) sought to to determine outcomes in left ventricular assist device (LVAD) patients older than age 70 years. Fifty-five patients received the HeartMate II LVAD between October 5, 2005, and January 1, 2010, as part of either the bridge to transplantation or destination therapy trials at a community hospital. Patients were divided into 2 age groups: 70 years of age (n = 30) and < 70 years of age (n = 25). Outcome measures including survival, length of hospital stay, adverse events, and quality of life were compared between the 2 groups. Preoperatively, all patients were in New York Heart Association functional class IV refractory to maximal medical therapy. Kaplan-Meier survival for patients 70 years of age (97% at 1 month, 75% at 1 year, and 70% at 2 years) was not statistically different from patients <7 0 years of age (96% 1 month, 72% at 1 year, and 65% at 2 years, p = 0.806). Average length of hospital stay for the 70-year age group was 24 ± 15 days, similar to that of the < 70-year age group (23 ± 14 days, p = 0.805). There were no differences in the incidence of adverse events between the 2 groups. Quality of life and functional status improved significantly in both groups. Investigators concluded the LVAD patients 70 years of age have good functional recovery, survival, and quality of life at 2 years. Advanced age should not be used as an independent contraindication when selecting a patient for LVAD therapy at experienced centers. Scientific Rationale Update April 2012 Many patients who have an MI or who develop cardiogenic shock require treatment of the coronary arteries and undergo percutaneous coronary intervention (PCI) Ventricular Assist Devices Apr 16 13

14 procedures. For PCI performed during cardiogenic shock, hemodynamics can be stabilized with an intra-aortic balloon counterpulsation pump (IABP). Some studies have shown that patient survival of patients undergoing PCI during cardiogenic shock, the survival rate has been only 20% despite use of an IABP. In addition, IABP use has been associated with major complications in 4% to 14% of patients. As a result, other types of ventricular assist devices (VADs) have been developed in an attempt to improve patient survival and reduce the incidence of serious complications. Despite recent advances in the treatment of cardiogenic shock, mortality is still high at approximately 50%. Current therapeutic approaches include early revascularization, fluid resuscitation, inotropic and vasopressor therapy, and mechanical circulatory support using intra-aortic balloon counterpulsation or percutaneous left ventricular assist devices. The Impella Recover LP 2.5 System (Abiomed, Aachen, Germany/Danvers, Massachusetts) is a 12.5 Fr catheter that is inserted percutaneously through a 13 Fr femoral artery sheath and placed across the aortic valve into the left ventricle, through which a transaxial blood pump provides flows of up to 2.5 L/min. This has been used in patients with cardiogenic shock as well as elective PCI. The effects of the Impella 2.5 have been studied in high-risk PCI patients, demonstrating beneficial LV unloading effect (decreased end-diastolic pressure and wall stress) with no change in global or systolic LV function. The TandemHeart (CardiacAssist, Inc, Pittsburgh, PA) is a left atrial to aorta catheter-based system that includes a centrifugal blood pump providing flows of up to 4 L/min. This device uses a 21 Fr cannula percutaneously inserted into the femoral vein for transseptal access of the left atrium with a 15 Fr catheter placed in the contralateral femoral artery and positioned above the aortic bifurcation. An extracorporeal pump then returns oxygenated blood from the left atrium to the arterial system, thereby unloading the left ventricle. The hemodynamic effects have been studied in patients undergoing high-risk PCI. Temporary mechanical support with left ventricular assist devices may allow time for recovery of stunned or hibernating myocardium. Small randomized trials have not revealed any outcomes advantage compared with intraaortic balloon counterpulsation, but hemodynamic improvement is greater with the percutaneous left ventricular assist device. Left ventricular assist devices may be considered for patients with refractory shock after revascularization. According to the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions, Percutaneous coronary intervention (PCI) is recommended for patients with acute MI who develop cardiogenic shock and are suitable candidates. A hemodynamic support device is recommended for patients with cardiogenic shock after ST segment elevation myocardial infarction (STEMI) who do not quickly stabilize with pharmacological therapy. (Class I recommendations) The guidelines state further, Hemodynamic support is available with intra-aortic balloon pump (IABP) counterpulsation or percutaneous left ventricular assist devices, although no data support a reduction in mortality rates. Refractory cardiogenic shock unresponsive to revascularization may necessitate institution of more intensive cardiac support with a ventricular assist device or other Ventricular Assist Devices Apr 16 14

15 hemodynamic support devices to allow for myocardial recovery or subsequent cardiac transplantation in suitable patients. Regarding patients with multivessel disease, the guidelines note, Refractory cardiogenic shock unresponsive to revascularization may necessitate institution of more intensive cardiac support with a ventricular assist device or other hemodynamic support devices to allow for myocardial recovery or subsequent cardiac transplantation in suitable patients. The guidelines states further, Elective insertion of an appropriate hemodynamic support device as an adjunct to PCI may be reasonable in carefully selected high-risk patients. (Class IIb recommendation) IABP counterpulsation is frequently used as an adjunct to PCI in hemodynamically unstable patients. In single-center series, the routine prophylactic use of IABP during PCI in high-risk patients was associated with lower mortality and fewer major complications compared with rescue use of IABP. In the only RCT in high-risk PCI patients (BCIS-1 [Balloon Pump-Assisted Coronary Intervention Study]), there was no difference in the primary composite outcome between routine and provisional use of IABP. There were also no differences in major secondary endpoints except major procedural complications. The effects of the Impella 2.5 have been studied in highrisk PCI patients, demonstrating beneficial LV unloading effect (decreased enddiastolic pressure and wall stress) with no change in global or systolic LV function. The PROTECT I (A Prospective Feasibility Trial Investigating the Use of the IMPELLA Recover LP 2.5 System in Patients Undergoing High-Risk PCI) trial in 20 patients undergoing high-risk PCI with the Impella 2.5 system concluded that this device was safe, easy to implant, and hemodynamically effective. The Europella Registry included 144 patients undergoing highrisk PCI and reported the safety, feasibility, and potential usefulness of the device and that RCTs were warranted. The randomized PROTECT II (A Prospective, Multicenter, Randomized Controlled Trial of the IMPELLA Recover LP 2.5 System Versus Intra Aortic Balloon Pump in Patients Undergoing Non Emergent High Risk PCI) trial, which was designed to demonstrate superiority of Impella over IABP in terms of 1-month adverse events, was halted for futility after interim analysis of study results. The hemodynamic effects of the TandemHeart have been studied in patients undergoing high-risk PCI. Several small studies have addressed the clinical efficacy of the TandemHeart in high risk patients undergoing PCI. In a single-center report of 68 patients undergoing high-risk PCI using either TandemHeart or Impella Recover 2.5, success rates (>90%) and vascular complications (7%) were similar. High-risk patients may include those undergoing unprotected left main or last-remainingconduit PCI, those with severely depressed EF undergoing PCI of a vessel supplying a large territory, and/or those with cardiogenic shock. Patient risk, hemodynamic support, ease of application/removal, and operator and laboratory expertise are all factors involved in consideration of use of these devices. With devices that require large cannula insertion, the risk of vascular injury and related complications are important considerations regarding necessity and choice of device. Shah et al (2012) investigated seventy-four consecutive patients undergoing highrisk PCI and those with cardiogenic shock (CS) receiving intraaortic balloon pump (IABP), TandemHeart (TH), or Impella device (IMP) were enrolled. Patient undergoing high-risk PCI (n=57) and those treated for CS (n=17) were analyzed as separate cohorts. Patients undergoing IABP-assisted PCI were compared to those Ventricular Assist Devices Apr 16 15

16 undergoing PLVAD (TH and IMP)-assisted PCI. The primary end point was in-hospital major adverse cardiovascular events, and the secondary end point was in-hospital vascular complications. For the high-risk PCI cohort (n=57), 22 received PLVAD and 35 received IABP. Patients receiving IABP were younger and less likely to have a prior myocardial infarction (MI) and less likely to be on dialysis compared to those receiving PLVAD support. Patients receiving PLVAD support had a higher baseline Syntax score, had a higher prevalence of unprotected left main disease, underwent treatment of more coronary lesions, received more coronary stents, and more likely received drug-eluting stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. For the CS cohort (n=17), 4 received PLVAD and 13 received IABP. Patients receiving PLVAD support were more likely to have a prior MI, had a lower ejection fraction, underwent treatment of more coronary lesions, and received more coronary stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. Investigators concluded IABP compared with PLVAD use for high-risk PCI and CS is associated with significantly different baseline patient, clinical, procedural, and angiographic characteristics. In-hospital clinical outcome was similar between both groups in both the high-risk PCI and the CS cohorts. When physicians have access to each of these devices, short-term clinical outcome appears to be similar. Schwartz et al 2011 reported that intra-aortic balloon pumps (IABPs) are indicated during high-risk percutaneous coronary intervention (HR-PCI) to reduce major procedural complications. They sought to determine the baseline characteristics, hemodynamics, and outcomes of patients treated with prophylactic percutaneous left ventricular assist devices (PLVADs) during HR-PCI, noting that the clinical utility of the newer Impella and TandemHeart devices is not clear. A retrospective analysis at a private, tertiary referral hospital was conducted of all cases involving prophylactic PLVAD during HR-PCI between January 1, 2008 and June 30, General practice in this institution involved a tiered approach to PLVAD whereby patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or TandemHeart, respectively. Fifty cases were identified (5 IABP, 13 Impella, 32 TandemHeart). Mean ejection fraction was 31 ± 17%. All devices (100%) were initiated successfully. Angiographic success was achieved in 96% (80% IABP, 100% Impella, 97% TandemHeart). Of the 38 patients not in cardiogenic shock, death occurred in 1 (2.6%), recurrent ischemia in 3 (8%), and stroke in 0%. Shortly after device removal, systolic blood pressure (mean increase, +5 ± 22 mmhg) and ejection fraction (mean increase, +7.4 ± 11%; p = ) increased in all 3 groups, suggesting a beneficial effect on the myocardium. Investigators concluded in patients undergoing HR-PCI with Impella and TandemHeart support, angiographic success was high and major complication rates were low. A tiered approach where patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or Tandem- Heart, respectively, theoretically maximizes appropriate hemodynamic support and minimizes complications. Further studies are warranted. Alasnag et al (2011) reported that patients undergoing percutaneous coronary intervention (PCI) who are at high risk for cardiovascular collapse during the procedure may benefit from prophylactic circulatory support. They sought to evaluate the safety and feasibility of prophylactic use of the Impella 2.5 during highrisk PCI, using the Impella 2.5 for partial circulatory support during 60 consecutive elective high-risk PCI cases over 20 months. All patients either were deemed inoperable by the cardiac surgeons or were offered bypass surgery but declined. The Ventricular Assist Devices Apr 16 16