Conflict of Interest Disclosure

Transcription

1 Conflict of Interest Disclosure Abiomed Personal: None Sponsor of PROTECT-II trial and EBC travel

2 Pathophysiology When a critical mass of LV is necrotic and fails to pump, stoke volume and CO falls Myocardial and coronary perfusion are compromised causing tachycardia and hypotension Increased LVEDP further decreases coronary perfusion Increase LV wall stress increases myocardial oxygen demand Lactic acidosis worsens myocardial performance Hollenberg Ann Int Med 1999; 131:47-99

3 Reducing the Work of the Heart Muscle Ventricular Unloading 3 PV Loop of the Cardiac Cycle Work = Pressure x Volume Pressure C B Ventricular Work = Area of PV Loop Unloading Work = Reducing Area of PV Loop D A Volume A. End Diastole Mitral Valve Closure B. Aortic Valve Opening C. End Systole - Aortic Valve Closure D. Mitral Valve Opening

4 Shock Steps to be followed STABILIZE the patient as rapidly as possible Pressors, fluids, WHATEVER to prevent the downward spiral Hemodynamic support!! Selection based upon risk-benefit assessment Revascularization as appropriate Make sure the revascularization targets the lesion(s) that are causing the shock

5 Cardiac Power Is The Most Important Mortality Predictor in the SHOCK Trial Estimated In-hospital Mortality (%) Cardiac Power = (Mean Arterial Pressure x Cardiac Output) Cardiac Power Output Finke et al JACC 2004; 44:340

6 Why are hemodynamics so essential? Catheters can obstruct native aorto-ostial flow (especially larger catheters). Wires, balloons, stents, devices can obstruct flow and when inflated by definition are producing ischemia Contrast does not contain hemoglobin and is a myocardial depressant Patient smay have acute or longstanding LV dysfuction and CHF Adverse hemodynamics will make it difficult to do the case and can worsen short and long term outcomes ignore them at your peril..

7 High Risk PCI Patients (bifurcations) Heart failure, diabetes, advanced age, peripheral vascular disease, complex lesions, unstable angina/ NSTEMI, prior surgery Patient Comorbidities Protected PCI Patients Complex Coronary Artery Disease Multi-vessel disease, Left Main disease Hemodynamic Compromise Depressed ejection fraction (LVEF<35%)

8 Patients Most Appropriate for Revascularization Coronary Revascularization Appropriateness Guidelines ACCF/ SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 1 Heart Failure Angina High Risk Findings on Noninvasive Study CCS Class III or IV Angina Symptoms Symptoms Med. Rx Class III or IV Max Rx A A A A A Class I or II Max Rx A A A A A Asymptoma tic Max Rx U A A A A Class III or IV No/min Rx A A A A A Class I or II No/min Rx U A A A A Asymptoma tic No/min Rx U U A A A Protected PCI Patients = More Heart Failure More Angina More Complex = More likely to be appropriate Symptoms Stress Test Med. Rx High Risk Max Rx A A A A A High Risk No/min Rx A A A A A Int. Risk Max Rx A A A A A Int. Risk No/min Rx U U A A A Low Risk Max Rx U A A A A Low Risk No/min Rx I U A A A Coronary Anatomy CTO of 1 vz.; no other disease 1-2 vz. disease; no Prox. LAD 1 vz. disease of Prox. LAD 2 vz. disease with Prox. LAD A = Appropriate, U = Uncertain, I= Inappropriate Complexity 3 vz. disease; no Left Main Coronary Anatomy CTO of 1-vz; no other disease 1-2-vz. disease; no prox. LAD 1-vz. disease of prox. LAD Complexity 2-vz. disease with prox. LAD 3-vz. disease; no left main A = Appropriate, U = Uncertain, I= Inappropriate 1. Patel MR, et al, J AM Coll Cardiol. 2012;59(9);

9 Revascularization Strategy by Risk Category Surgical Risk Low Medium High Often inoperable Low PCI PCI PCI Anatomic Risk Medium High CABG or PCI CABG PCI or CABG CABG or PCI Support & PCI Support & PCI Protected PCI FDA Indicated Safe & Effective ACC/AHA PCI Guidelines 1,2 SYNTAX Study 1. Levine GN, et al. J Am Coll Cardiol, 2011 Dec 6;58(24):e44-122, 2 Amsterdam EA, et al. Circulation Dec 23; 130(25):e

10 Intra-Aortic Balloon Pump PROs: Well known technology Increases coronary perfusion Mild increase in cardiac output Ease of use Cost CONs: Requires a minimum of cardiac function Requires a stable rhythm Modest unloading Negative studies

11 IABP History History: 1962 Animal studies Moulopoulos et al, Am Heart J 1962;63: Clinical description in shock Kantrowitz et al, JAMA 1968;203: Hemodynamic effects in shock, Mortality unchanged Scheidt et al, NEJM 1973;288: >40 yrs >1 Million patients treated, low complication rate, Benchmark registry Ferguson et al, JACC 2001;38: c/o H. Thiele

12 BCIS-1 Trial Design DESIGN: Prospective, randomized, control trial 301 patients enrolled between December 2005 an January 2009 in 17 clinical sites in the United Kingdom OBJECTIVE: To evaluate all cause long term mortality in patients with LV impairment (EF <30%) and severe CAD receiving elective IABP support during PCI. PRINCIPAL INVESTIGATOR Divika Perera, MD Kings College London, London, UK 50% No Planned IABP Use (N=151) 12% Required Bailout IABP Use (N=18) 50% Planned IABP Use (N=150)

13 BCIS-1: Inclusion Criteria Impaired LV function (EF < 30%) and Extensive Myocardium at Risk BCIS-1 Jeopardy Score > 8 or...target vessel supplying occluded vessel which supplies >40% of myocardium Perera et al, Am Heart J 2009;158:

14 BCIS-1: Major Outcomes Adverse Events (%) HR 0.94 ( ) HR 0.11 ( ) HR 1.86 ( ) OR 0.61 ( ) Perera et al, JAMA 2010; 304(8):

15 BCIS-1: All Cause Mortality 50% IABP No IABP 40% 30% 20% 10% Hazard ratio 0.66 (95% CI 0.44 to 0.98) 0% IABP No IABP 0 6 m 1 year 2 years 3 years 4 years 5 years Time since randomisation Perera et al, Circulation 2013; 127(2):207-12

16 IABP SHOCK-2 Design DESIGN: Prospective, multicenter, randomized, openlabel controlled trial comparing IABP vs. medical therapy. 790 patients enrolled between June 2009 and March 2012 in 37 clinical sites in Germany 600 patients randomized 190 patients excluded OBJECTIVE: To compare the efficacy and safety of the IABP vs. early medical therapy on the background of early revascularization by PCI or CABG. Medical Therapy Clinical follow-up at 30 days in 99.7% (N=298) IABP Clinical follow-up at 30 days in 99.7% (N=300) Thiele H. et al, NEJM 2012

17 IABP SHOCK II Primary Study Endpoint (30-Day Mortality) 50 Mortality (%) Control IABP P=0.92 by log-rank test Relative risk 0.96; 95% CI ; P=0.69 by Chi 2 -Test 41.3% 39.7% Time after Randomization (Days) Thiele et al NEJM 2012

18 Impella: FDA approved for High risk PCI Impella hemodynamic support device has been proven safe and effective at reducing peri-procedural and post-procedure adverse events in elective and urgent High Risk PCI patients

19 Randomized Trial of Impella vs. IABP in AMI with Shock (ISAR-SHOCK) N=25 (primary endpoint) Adapted from Seyfarth et al., JACC 2008

20 Hemodynamic Support Effectiveness: PROTECT II Cardiac Power Output Maximal Decrease in CPO on device Support from Baseline (in x0.01 Watts) IABP Impella N=138 N= ± 24 p= ± 27 CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x (Fincke R, Hochman J et al JACC 2004; 44: )

21 PROTECT-II Trial Design Patients Requiring Prophylactic Hemodynamic Support During Non-Emergent High Risk PCI on Unprotected LM/Last Patent Conduit and LVEF 35% OR 3 Vessel Disease and LVEF 30% IABP + PCI R 1:1 IMPELLA PCI Primary Endpoint = 30-day Composite MAE* rate Follow-up of the Composite MAE* rate at 90 days *Major Adverse Events (MAE) : Death, Stroke/TIA, MI (>3xULN CK-MB or Troponin), Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

22 Impella Reduces Peri & Post Procedural MACCE MACCE MACCE (%) MACCE = Death, Stroke, MI, Repeat revasc. IABP N=211 Impella N=216 29% reduction In MACCE 10 p= Time Post Procedure (day) Dangas et al, Am. Journ of Cardiol. 2014: 113(2):222-8 FDA Approved Randomized Controlled Trial Protect II

23 PROTECT II Multivariate analysis predictors of MACCE at 90 days Per-Protocol Population Odds Ratio Estimate 95% confidence interval P-Value Use of atherectomy rotablation during index procedure Renal Insufficiency Baseline worst TIMI flow: Device: IMPELLA Intention-To-treat Population Use of atherectomy rotablation during index procedure Renal Insufficiency Baseline worst TIMI flow: Device: IMPELLA American Journal of Cardiology 2014

24 Clinical Guidelines for Impella 2014 AHA/ACC Guideline for the Management of Patients With Non ST- Elevation Acute Coronary Syndromes. Circulation Revascularization in Heart Failure: Class I Revascularization strategy based on degree, severity, & extent of CAD; cardiac lesions; extent of LV dysfunction; prior revascularization. PVADS: Large amount of ischemic territory/poor LV function 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC Protected PCI High risk patients: Class IIb CLASS III: HARM without Hemodynamic support; for PCI at hospitals without on-site cardiac surgery Additional Guidelines 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC PCI and Cardiogenic Shock: Class I Use of Mechanical Circulatory Support: American Heart Association. Circulation 2012 Acutely decompensated heart failure patients: Class IIa 2013 Int l Society for Heart & Lung Transplantation Guidelines for Mechanical Circulatory Support. Jnl of Heart & Lung Transplantation Temporary mechanical support for patients with multi-organ failure: Class I 2013 ACCF/AHA Guideline for the Management of Heart Failure, JACC Bridge to Recovery or Bridge to Decision for patients with acute, profound hemodynamic compromise: Class IIa 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation STEMI and Cardiogenic Shock: Class IIb STEMI and urgent CABG: Class IIa Categories referencing Impella include Percutaneous LVAD, PVAD, Nondurable MCS, TCS and percutaneous MCSD Reimbursement and coding information: Inpatient Hospital = ICD.9 Code 37.68, commonly MS-DRG 216/217 Physician = CPT codes (insertion), (removal), (repositioning)

25 FDA Indications for Use Impella 2.5 The Impella 2.5 is a temporary ( 6 hours) ventricular support device indicated for use during high risk percutaneous coronary interventions (PCI) performed in elective or urgent, hemodynamically stable patients with severe coronary artery disease and depressed left ventricular ejection fraction, when a heart team, including a cardiac surgeon, has determined high risk PCI is the appropriate therapeutic option. Use of the Impella 2.5 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 product labeling allows for the clinical decision to leave Impella 2.5 in place beyond the intended duration of <6 hours due to unforeseen circumstances.

26 Open Questions in Hemodynamic Support How much support is necessary? What is the role of IABP / Do we believe IABP SHOCK II? Which patients should get upfront treatment with an LVAD? What is the optimal use for Impella LVAD support? Relevance of cost/complications vs. benefit of active LVADs How do we manage biventricular failure?

27 Certain limitations of evidence-based medicine Umbrellas protect from rain randomized studies not useful There are no randomized, controlled studies on the efficacy of parachutes Courtesy H. Thiele (left) & A. DeMaria (right)