Recovering Hearts. Saving Lives ṬM The Door to Unload (DTU) STEMI Safety & Feasibility Pilot Trial November 218 Recovering Hearts. Saving Lives.
LEGAL DISCLAIMERS This presentation includes select slides presented by Navin Kapur, MD, executive director of the CardioVascular Center for Research and Innovation at Tufts Medical Center, at the American Heart Association Scientific Sessions 218 in Chicago. The complete slide presentation, Door to Unload (DTU) STEMI Safety & Feasibility Pilot Trial, is available in the Abiomed investor website at http://investors.abiomed.com/events-presentations. Impella heart pumps are not FDA approved for use in STEMI patients without cardiogenic shock. This presentation contains forward-looking statements, including statements regarding development of Abiomed's existing and new products, the Company's progress toward commercial growth, and future opportunities, the Company s guidance for future financial performance and expected regulatory approvals. Each forward-looking statement contained in this presentation is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statement, including uncertainties associated with development, testing and related regulatory approvals; the potential for future losses; the impact of complex manufacturing processes and high quality requirements; dependence on limited sources of supply; competition; technological change; government regulation; third-party reimbursement to the Company s customers; litigation matters; future capital needs and uncertainty of additional financing, and other risks and challenges detailed in the Company's filings with the Securities and Exchange Commission, including the most recently filed Annual Report on Form 1-K and Quarterly Report on Form 1-Q. Readers are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this presentation. The Company undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this presentation or to reflect the occurrence of unanticipated events, whether as a result of new information, future events or otherwise, unless otherwise required by law. U.S. Food and Drug Administration Approvals The Impella 2.5 and Impella CP are indicated for providing temporary (< 6 hours) ventricular support during elective or urgent high risk percutaneous coronary interventions (PCI) performed in hemodynamically stable patients with severe coronary artery disease, when a heart team, including a cardiac surgeon, has determined high risk PCI is the appropriate therapeutic option. Use of the Impella 2.5 and the Impella CP in these patients may prevent hemodynamic instability which can result from repeat episodes of reversible myocardial ischemia that occur during planned temporary coronary occlusions and may reduce peri- and post-procedural adverse events. The Impella 2.5, Impella CP, Impella 5., and Impella LD Catheters, in conjunction with the Automated Impella Controller, are temporary ventricular support devices intended for short term use ( 4 days for the Impella 2.5 and Impella CP, and 6 days for the Impella 5. and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (<48 hours) following acute myocardial infarction or open heart surgery, or in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures.* The intent of the Impella Support Systems therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function. The Impella RP is indicated for providing circulatory assistance for up to 14 days with a body surface area 1.5 m2 who develop acute right heart failure or decompensation following left ventricular assist device implantation, myocardial infarction, heart transplant, or open-heart surgery. For safety information associated with Abiomed s technologies, visit www.protectedpci.com/hcp/information/isi and www.cardiodenicshock.com/hcp/information/isi. The ABIOMED logo, ABIOMED, Impella 2.5, Impella CP, Impella RP, Impella 5., Impella LD and Symphony are registered trademarks of Abiomed, Inc. in the U.S.A. and certain foreign countries. Impella ECP, Impella 5.5, Impella BTR, cvad Registry and Recovering hearts. Saving lives. is a trademark of Abiomed, Inc. Recovering Hearts. Saving Lives.
Loaded heart during AMI Unloaded heart during AMI 3 CO CO MAP LA Stretch MAP LA Stretch pvad Support LVEDP LVEDV Wall Stress MVO2 AAR LVEDP LVEDV Wall Stress MVO2 AAR Cardioprotective Effects of Unloading Decreased myocardial oxygen consumption Reduced acute infarct size and subsequent scar size Activation of cardioprotective signaling (i.e., SDF1a/CXCR4 and RISK pathway) Hemodynamic stabilization through reperfusion-dependent arrhythmia Increased cardiac microvascular perfusion into infarct zone Bridge through reperfusion-induced myocardial stunning
Preclinical Development of the DTU Concept 212 218 TandemHeart Delayed Reperfusion (Circulation 213) Impella CP Delayed Reperfusion (JACC HF 215) Impella CP Cardioprotective Biology (JACC 218) Impella CP Preclinical Pilot (JACC 218) Impella CP DTU-STEMI Pilot Trial (Circulation 218) Trans-valvular LV Unloading Limits Myocardial Ischemia and Promotes a Cardioprotective Shift in Myocardial Biology Esposito, Zhang, Qiao and Kapur et al JACC 218 4
Infarct Size / Area at Risk (%) The Rationale for the DTU Pilot Before the Pivotal 1 8 6 4 DTU Pivotal DTU? Pilot 2 Reperfusion Alone Esposito, Zhang, Qiao and Kapur et al JACC 218 15 min 3 min Unloading + Delayed Reperfusion Unloading After Reperfusion 5
Door To Unload: STEMI Pilot Trial: Central Hypothesis Compared to LV unloading and immediate reperfusion, LV unloading followed by a 3 minute delay to reperfusion is feasible and safe as defined by: o Successful enrollment and protocol completion (Feasibility) o No increase in major adverse cardiovascular or cerebral events (MACCE Safety) o No increase in infarct size between groups (Safety) 6
Results: Procedural Characteristics Clinical Variable U-IR (n=25) U-DR (n=25)* p-value LAD Culprit, n (%) 25 (1) 24 (1) NS Proximal LAD Lesion Location, n (%) 17 (68) 19 (76) NS Mid LAD Lesion Location, n (%) 8 (32) 5 (21) NS Successful Impella CP Implant, n (%) 25 (1) 25 (1) NS Pre-PCI TIMI Flow (After Impella CP Activation) NS Pre-Intervention TIMI Flow -1, n (%) 16 (64) 1 (4) NS Pre-Intervention TIMI Flow 2-3, n (%) 9 (36) 15 (6) NS Post-Intervention TIMI Flow NS Post-Intervention TIMI Flow 3, n (%) 25 (1) 24 (1) NS * 1 patient had no coronary obstruction LAD = Left anterior descending artery TIMI = Thrombolysis In Myocardial Infaction 7
Unload to Balloon Time (Minutes) Results: Successful enrollment & protocol completion Zero Bailout PCI in the U-DR Group 45 4 35 3 25 2 15 1 5 Enrolled Patients U-DR U-IR 3 minutes of LV Unloading 8
DTU-STEMI Results: 3-5 Day CMR Parameters Infarct Size vs Total LV Mass (%) Myocardial Salvage Index (%) Microvascular Obstruction (%) 4 35 3 25 2 15 1 5 U-IR U-DR CRISP AMI 8 7 6 5 4 3 2 1 U-IR U-DR CRISP AMI 1 9 8 7 6 5 4 3 2 1 U-IR U-DR CRISP AMI Unloading and delaying reperfusion for 3 minutes did not increase infarct size 9
DTU-STEMI Results: Exploratory Subgroup Analysis Infarct Size / Total LV Mass (%) Infarct Size / Area at Risk (%) 4 3 1 8 * 2 6 4 15 19 16 1 2 Total STE>4 STE>5 STE>6 Total STE>4 STE>5 STE>6 U-DR U-IR 1
What did we learn from this Pilot Study? The Door-To-Unload in STEMI Pilot Trial demonstrates for the first time that LV unloading using the Impella CP device with a 3-minute delay before reperfusion is safe and feasible within a relatively short DTB Time. No prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading and delaying reperfusion for 3 minutes were identified. Compared to LV unloading and immediate reperfusion, LV unloading and delaying reperfusion for 3 minutes does not increase infarct size. Among patients with sum STE>6mm, infarct size normalized to the area at risk was significantly lower with 3 minutes of LV unloading before reperfusion compared to LV unloading and immediate reperfusion. 11
TERMS AND ACRONYMS: STEMI-DTU PRESENTATION 12 STEMI ST segment Elevation Myocardial Infarction an EKG pattern that identifies acute coronary occlusion, sometimes referred to as a tombstone pattern U-IR Unloading with immediate reperfusion - Impella placed for ventricular unloading in the setting of STEMI care followed immediately by PPCI U-DR Unloading with delayed reperfusion - Impella placed for ventricular unloading in the setting of STEMI care followed by a longer period of unloading before PPCI (in STEMI DTU duration was prespecified as 3 minutes) Primary PCI or PPCI A coronary interventional procedure usually with coronary stenting (PCI) performed in the setting of a STEMI Unloading Reduction of mechanical power expenditure (PVA x HR) 1 of the ventricle to minimize myocardial oxygen consumption (MVO2) and reduce hemodynamic forces that lead to ventricular remodeling and, in MI, to reduce infarct size MACCE Major adverse cardiac and cerebral events (a composite endpoint of death, MI, stroke or repeat revascularization) Infarct Size /Total LV Mass (%) An imaging evaluation usually with CMR to assess the % of the entire heart which has sustained an infarction larger infarct % correlates with greater post MI sequela Infarct Size / Area at Risk (%) An imaging evaluation usually with CMR to assess the % of the portion of the heart that was ischemic or in jeopardy which has sustained an infarction - larger infarct % correlates with greater post MI sequela Myocardial Salvage Index (%) (MSI) A calculated assessment of the amount of heart salvaged calculated as 1- Infarct Size/ Area at risk a greater MSI correlates with greater amount of infarct area that was rescued from infarction by the intervention Microvascular Obstruction (%) Or no-reflow phenomenon is an established complication of coronary reperfusion therapy for acute myocardial infarction; recognized as a poor prognostic indicator and marker of subsequent adverse LV remodeling, evaluation by CMR is particularly useful in STE or STE Sum score of ST segment elevation a measurement made by adding the maximal ST segment elevation in mm on each of the 12 ECG leads to assess the extent of myocardium in jeopardy CMR Cardiac magnetic resonance imaging also Cardiac MR or Cardiac MRI TIMI Flow A scoring system from 3 of the coronary flow rates estimated visually on angiography developed by investigators at Thrombolysis in Myocardial Infarction Study Group. TIMI flow (no perfusion) refers to the absence of any antegrade flow beyond a coronary occlusion. TIMI 1 flow (penetration without perfusion) is faint antegrade coronary flow beyond the occlusion, with incomplete filling of the distal coronary bed. TIMI 2 flow (partial reperfusion) is delayed or sluggish antegrade flow with complete filling of the distal territory. TIMI 3 is normal flow which fills the distal coronary bed completely LVEF Left ventricular ejection fraction the amount of volume of blood ejected from the heart each beat expressed as a percent of the diastolic volume LVEDP Left ventricular end diastolic pressure in mmhg MAP Mean arterial pressure in mmhg CRISP-AMI A study evaluating use of Intra-aortic balloon pump (IABP) placed before reperfusion in Anterior STEMI results failed to show a benefit compared to PPCI alone with a trend toward larger infarcts with IABP published in JAMA. 211;36(12):1329-1337