Α-Δ. ΜΑΤΡΟΓΙΑΝΝΗ ΚΑΡΔΙΟΛΟΓΟ AIMOΔΤΝΑΜΙΚΟ ΕΡΓΑΣΗΡΙΟ Γ.Ν.Θ. Γ. ΠΑΠΑΝΙΚΟΛΑΟΤ ΘΕΑΛΟΝΙΚΗ

Transcription

1 Α-Δ. ΜΑΤΡΟΓΙΑΝΝΗ ΚΑΡΔΙΟΛΟΓΟ AIMOΔΤΝΑΜΙΚΟ ΕΡΓΑΣΗΡΙΟ Γ.Ν.Θ. Γ. ΠΑΠΑΝΙΚΟΛΑΟΤ ΘΕΑΛΟΝΙΚΗ

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5 Angiographic no reflow TIMI grade 0 No antegrade flow beyond the point of obstruction I Contrast material is able to pass through the area of obstruction but fails to opacify the distal coronary bed II III Contrast is able to penetrate the area of obstruction and fills the distal bed; however, it is perceptibly slower than other coronary vessels unaffected by the coronary obstruction Antegrade flow into distal coronary bed of the obstructed artery is as prompt as the flow in an uninvolved coronary vessel The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group. N Engl J Med.1985 Apr 4;312(14):932-6

6 Myocardial Blush Score TIMI Blush Score 0 no blush or contrast density of myocardium supplied by infarctrelated vessel on postangioplasty angiogram I minimal blush or contrast density of myocardium supplied by infarct-related vessel on postangioplasty angiogram II moderate blush or contrast density density of myocardium supplied by infarct-related vessel on postangioplasty angiogram III normal blush or contrast density, comparable with blush obtained during angiography of contralateral or ipsilateral non infarct-related coronary artery van 't Hof AW.et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation.1998 Jun 16;97(23):2302-6

7 No reflow phenomenon Due to inadequate myocardial perfusion after successful mechanical opening of the IRA Diagnosis made - post procedural TIMI flow < 3 - TIMI flow 3 but MB grade < 2 - ST resolution within 4 hrs. of the procedure < 70% Topol E., Ternstein P. Textbook of Interventional Cardiology. Elsevier Saunders, 6 th Edition.

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9 Anatomical no reflow Reffelmann T., Kloner RA. The "no-reflow" phenomenon: basic science and clinical correlates. Heart Feb;87(2):162-8

10 Regional endothelial swelling Endothelial gap and extravasated RBC's Fibrin tactoids Swollen myocyte compressing vessel Micro -emboli Endothelial blebs platelets Capillary lumen Neutrophil plugs (release of oxygen radicals) Subsarcolemmal bleb Rouleaux formation Reffelmann T., Kloner RA. The "no-reflow" phenomenon: basic science and clinical correlates. Heart Feb;87(2):162-8

11 Mechanisms responsible for no reflow Distal embolization Ischemic injury Reperfusion injury Individual susceptibility Niccoli G. et al. Myocardial no-reflow in humans. J Am Coll Cardiol Jul 21;54(4):281-92

12 Coronary microembolization: Consequences Heusch G. et al. Coronary microembolization: from bedside to bench and back to bedside. Circulation Nov 3;120(18):

13 Micro vessels major damage lessons learnt from MRI Wu KC. et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation.1998 Mar 3;97(8):765-72

14 Prognostic value of no reflow according to Angiographic, Electrocardiographic, Echocontrastographi c Indexes OR 95% CI Author year No reflow index Niccoli G. et al. Myocardial no-reflow in humans.

15 Cumulative Survival (%) Myocardial Perfusion After Primary PCI is the Strongest Predictor of Mortality independently from IRA reopening PPCI Hardest point 100 Final Blush Score (patients with final TIMI 3 flow) Blush 1-Year Mortality 6.8% 13.2% 18.3% 3 2 0/1 P= /1 Open Artery...but Closed Myocardium!! Stone GW. et al. Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction. J Am Coll Cardiol 2002 Feb 20;39(4):591-7 ( Courtesy of M.Gibson)

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17 Thrombus burden in STEMI: impact < G4 Small Thrombus Burden = G4 Large Thrombus Burden (G0) no cineangiographic characteristics of thrombus are present (G1) possible thrombus is present (reduced contrast density/ haziness/ irregular lesion contour/ or smooth convex meniscus at the site of total occlusion suggestive but not diagnostic of thrombus (G2) definite thrombus, with greatest dimensions 1/2 the vessel diameter (G3) definite thrombus but with greatest linear dimension >1/2 but <2 vessel diameters (G4) definite thrombus, with the largest dimension 2 vessel diameters (G5) total occlusion (unable to assess thrombus burden due to total vessel occlusion Sianos G et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol.2007 Aug 14;50(7):573-83

18 Thrombus burden in STEMI: impact Sianos G et al. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol.2007 Aug 14;50(7):573-83

19 Mechanisms of and Targets for Prevention of No Reflow For pharmacological therapies For reperfusion no reflow Mechanisms Myonecrosis Reperfusion injury Distal embolization Vasoconstriction Mechanisms Primarily distal embolization Jaffe R. et al. Prevention and treatment of microvascular obstruction-related myocardial injury and coronary no-reflow following percutaneous coronary intervention: a systematic approach. JACC Cardiovasc Interv Jul;3(7):

20 Mechanical Approaches to Thrombus Thrombus aspiration (Rinspirator, Pronto, Export, Rescue, Diver CE, etc.) Thrombectomy (AngioJet, X-Sizer) Embolic protection (GuardWire, FilterWire, Proxis, etc.) GuardWire

21 Aspiration Thrombectomy Catheters Soft, beveled short tip Bevel cut Bevel cut Rounded bullnose tip with slot cut to prox tip Bevel cut with long tip and 3 side holes Bevel cut with long tip Convex cut Distal Lumen (inches) Flat cut Flat cut

22 TAPAS: 1-Year Results Trial design: Patients with ST-elevation myocardial infarction were randomized to thrombus aspiration prior to PCI (n = 535) or standard PCI without aspiration (n = 536) and followed for 1 year. % (p = 0.042) (p = 0.05) Results All-cause mortality: 4.7% vs. 7.6% (p = 0.042), respectively Cardiac death: 3.6% vs. 6.7% (p = 0.02), respectively Reinfarction: 2.2% vs. 4.3% (p = 0.05), respectively Conclusions All-cause mortality Thrombus aspiration Reinfarction Standard PCI In earlier presentation of TAPAS, thrombus aspiration during acute MI improved reperfusion Extended follow-up to 1 year demonstrates that this strategy reduces death and MI Vlaar PJ. et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet.2008 Jun 7;371(9628):

23 Manual thrombectomy devices in STEMI De Luca G. et al. Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials. Eur Heart J.2008 Dec;29(24):

24 ClinicalTrials.gov number: NCT Gregg W. Stone, MD Columbia University Medical Center NewYork-Presbyterian Hospital Cardiovascular Research Foundation Stone GW. et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA.2012 May 2;307(17):

25 INFUSE-AMI Trial 452 pts with anterior STEMI Anticipated Sx to PCI <5 hrs, TIMI 0-2 flow in prox or mid LAD Primary PCI with bivalirudin anticoagulation Pre-loaded with aspirin and clopidogrel 600 mg or prasugrel 60 mg Manual aspiration R 1:1 Stratified by symptoms to angio <3 vs 3 hrs, and prox vs mid LAD occlusion No aspiration R 1:1 R 1:1 IC Abcx No Abcx IC Abcx No Abcx Primary endpoint: Infarct size at 30 days (cmri) 2º endpoints: TIMI flow, blush, ST-resolution, MACE (30d, 1 yr)

26 Between November 28 th, 2009 and December 2 nd, 2011, 6,318 patients with STEMI were screened at 37 sites in 6 countries 5,866 Patients excluded 5,866 Non-anterior myocardial infarction 1,717 Not proximal or mid LAD, or not TIMI 0-2 flow 1,389 Symptom onset to treatment >5 hours 528 Patient declined consent 375 Cardiogenic shock 246 Research staff not available (after hours) 237 Prior myocardial infarction 131 PCI not indicated 104 Unwilling/unable to follow study procedure 100 Participation in another study Current use of thrombolytic therapy or GPI 70 Prior CABG 67 Prior PCI in LAD 63 Current use of warfarin 96 Major concomitant medical illness 68 Infarct due to stent thrombosis 42 Contraindication to CMRI 40 Treatment of 2 epicardial vessels required 39 CABG required within 30 days 723 Other or unspecified 452 patients (7.2%) randomized Aspiration + IC abciximab N = 118 Aspiration + no abciximab N = 111 No aspiration + IC abciximab N = 111 No aspiration + no IC abciximab N = day follow-up N = 112 (94.9%) Withdrew Lost to follow-up day follow-up N = 106 (95.5%) day follow-up N = 105 (94.6%) Withdrew Lost to follow-up day follow-up N = 109 (97.3%) 30-day CMRI N = 101 (85.6%) 30-day CMRI N = 91 (82.0%) 30-day CMRI N = 94 (84.7%) 30-day CMRI N = 96 (85.7%)

27 INFUSE-AMI Intracoronary abciximab N=229 No intracoronary abciximab N=223 Pooled across the aspiration randomization P value TIMI flow pre-pci 0/1* 72.5% 70.9% 0.70 Blush pre-pci 0/1* 84.2% 83.8% 0.90 Hospital - 1 st device, mins 45 [35, 66] 45 [32, 67] 0.84 Aspiration performed 52.0% 51.6% 0.93 Abciximab administered 97.4%** 2.2% <0.001 N lesions treated 1.1 ± ± DES implanted 74.7% 70.4% 0.31 Stent length (mm) 24 [18, 34] 23 [17, 33] 0.13 Max stent diameter (mm) 3.0 [3.0, 3.5] 3.0 [3.0, 3.5] 0.75

28 TIMI 0/1 TIMI 2 INFUSE-AMI: Reperfusion post-pci* 3.1% 5.7% IC abciximab N= % 7.6% No abciximab N=223 P=0.94 TIMI % 91.5% Corrected TIMI frame counts: [16, 26] vs. 20 [16, 26] P=0.62 MBG 0/1 19.3% 17.9% P=0.71 MBG 2/3 80.7% 82.1% *Core laboratory assessed

29 ST-segment resolution (%) INFUSE-AMI: STR 60 minutes post-pci* P=0.30 P=0.13 [46.0, 85.5] [52.6, 88.2] *Core laboratory assessed

30 Infarct size, %LV INFUSE-AMI: Infarct size at 30 days* - Primary endpoint - 50 Total LV mass, 40grams Infarct mass, grams 30 Intracoronary abciximab 15.1% N=188 Median [IQR] [6.8, 22.7] [106.6, 152.4] 18.7P=0.03 [7.4, 31.3] No intracoronary abciximab 17.9% N=184 Median [IQR] [10.3, 25.4] [109.9, 155.9] 24.0 [12.1, 34.2] P value Infarct mass (% of total LV mass) [6.8, 22.7] 17.9 [10.3, 25.4] 0.03 Total abnormal wall 10 motion score 7.0 [2.0, 10.0] 8.0 [3.0, 10.0] 0.08 LVEF (%) 0 IC abciximab 50.2 [44.2, 57.9] N=229 No abciximab 48.9 N=223 [42.3, 56.7] 0.22 *Core laboratory assessed

31 INFUSE-AMI Manual aspiration N=229 No aspiration N=223 Pooled across the abciximab randomization P value TIMI flow pre-pci 0/1* 73.4% 70.0% 0.42 Blush pre-pci 0/1* 85.5% 82.4% 0.37 Hospital - 1 st device, mins 43 [30, 63] 48 [35, 70] 0.02 Aspiration performed 98.3%** 4.0% <0.001 Abciximab administered 50.7% 50.2% 0.93 N lesions treated 1.1 ± ± DES implanted 74.2% 70.9% 0.42 Stent length (mm) 24 [18, 32] 24 [18, 35] 0.30 Max stent diameter (mm) 3.0 [3.0, 3.5] 3.0 [3.0, 3.5] 0.20

32 TIMI 0/1 TIMI 2 INFUSE-AMI: Reperfusion post-pci* 1.7% Manual aspiration 5.7% N= % 7.6% No aspiration N=223 P=0.36 TIMI % 90.1% Corrected TIMI frame counts: [16, 26] vs. 20 [16, 26] P=0.40 MBG 0/1 16.6% 20.7% P=0.26 MBG 2/3 83.4% 79.3% *Core laboratory assessed

33 ST-segment resolution (%) INFUSE-AMI: STR 60 minutes post-pci* P=0.37 [45.2, 87.2] [55.8, 87.4] P=0.23 *Core laboratory assessed

34 Infarct size, %LV INFUSE-AMI: Infarct size at 30 days* - Major secondary endpoint - 50 Total LV mass, grams 40 Manual aspiration Median [IQR] N= % [9.0, 22.8] [108.9, 149.8] No aspiration N=186 Median [IQR] 17.3% [7.1, 25.5] [107.6, 156.1] P value 0.50 Infarct mass, grams [9.7, 31.7] P= [9.1, 34.1] 0.36 Infarct mass (% of total LV mass) [9.0, 22.8] 17.3 [7.1, 25.5] 0.51 Total abnormal 10wall motion score 7.5 [2.0, 10.0] 7.5 [2.0, 10.0] 0.89 LVEF (%) Aspiration N=229 [43.3, 56.8] 49.5 No aspiration N=223 [41.8, 57.6] 0.66 *Core laboratory assessed. No interaction was present between the 2 randomization groups for the primary 30-day infarct size endpoint (p=0.46)

35 Infarct size (%LV) INFUSE-AMI: Infarct size at 30 days* - 4 group analysis % [7.1%, 20.6%] vs. 17.6% [8.1%, 25.1%] P= ,3 18,6 17, ,7 [6.3%, 24.6%] [12.5%, 23.9%] [9.7%, 26.0%] [7.1%, 20.6%] iration + IC abciximab No aspiration (n=101) + Aspiration IC abciximab + (n=94) no abciximab No aspiration + (n=91) no abciximab

36 UCR Uppsala Clinical Research Center Main results at 30 days Ole Fröbert, MD, PhD - on behalf of the TASTE investigators Departement of Cardiology Örebro University Hospital Sweden Fröbert O. et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med.2013 Oct 24;369(17):

37 TAPAS / Swedish registry data PCI alone (N=16 417) TA + PCI (N= 3 666) HR (95% CI): 1.21 ( ) Vlaar PJ. et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet.2008 Jun 7;371(9628): Fröbert O. et al. Thrombus aspiration in ST-elevation myocardial infarction in Sweden: a short report on real world outcome. Int J Cardiol.2010 Dec 3;145(3):572-3

38 TASTE trial enrollment flow chart Enrolled in Denmark N=247 All patients with STEMI in Sweden and Iceland undergoing primary or rescue PCI. N= * ) Erroneous enrollments N=15 Enrolled in TASTE N=7259 Randomized in TASTE N=7244 Not enrolled N=4697 N=3621 assigned to thrombus aspiration N=3623 assigned to conventional PCI N=3399 underwent thrombus aspiration N=222 underwent conventional PCI N=3445 underwent conventional PCI N=178 underwent thrombus aspiration N=1162 underwent thrombus aspiration N=3535 underwent conventional PCI N=3621 were followed up N=3623 were followed up N=1162 were followed up N=3535 were followed up

39 TASTE and previous studies TASTE TAPAS JETSTENT AIMI INFUSE-AMI VAMPIRE PREPARE Chevalier Kaltoft MUSTELA X AMINE ST PIHRATE EXPIRA DEAR-MI Liistro PCI only Thrombus Aspiration Symptom to PCI time min,(med {IQR}) 182 ( ) 185 ( ) Diagnostic ECG to PCI time, min (med {IQR}) 66 (47-93) 67 (48-94)

40 All-cause mortality at 30 days HR 0.94 ( ), P=0.63 Per protocol analysis based on actual treatment: HR 0.88 ( ), P=0.38

41 Reinfarction at 30 days Per protocol analysis based on actual treatment: HR 0.67 ( ), P=0.19 HR 0.61 ( ), P=0.09 PCI only Thrombus aspiration Point Estimate ( 95% CI ) P value Stent thrombosis-no.(%) 19 (0.5) 9 (0.2) HR 0.47 ( ) 0.06

42 TASTE vs. TAPAS

43 Cor. Angio vs OCT: more than meets the eye

44 pre post TASTE was an altogether NEGATIVE trial. WHY? YOU DO NOT GET ENOUGH THROMBUS OUT YOU SEND DEBRIE DISTALLY NO UTILIZATION IN THE SICK ENOUGH PTS. MT 180 MIN.THROMBUS NOT AMENABLE TO ASPIRATION

45 Jolly SS. et al. Design and rationale of the TOTAL trial: A randomized trial of routine aspiration ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in patients with ST-elevation myocardial infarction undergoing primary PCI. Am Heart J Mar;167(3): e1.

46 TOTAL: flow chart STEMI within 12 hours of symptom onset referred for PPCI R 1:1 Manual Aspiration Thrombectomy followed by PCI PCI Alone Primary outcome: CV death, MI, cardiogenic shock and Class IV CHF up to 180 days Final Follow up at 1 year Sample size for pilot phase 240 Sample size for full trial 4000

47 The MGuard and MGuard Prime Embolic Protection Stent (EPS) MGuard MGuard Prime Metallic frame 316L stainless steel L605 cobalt chromium Strut width 100 µm 80 µm Crossing profile mm mm Shaft dimensions mm mm Mesh sleeve PET** PET** - Fiber width 20 µm 20 µm - Net aperture size µm µm *InspireMD, Tel Aviv, Israel; **Polyethyleneterephthalate

48 MGUARD for Acute ST Elevation Reperfusion The MASTER Trial STEMI with symptom onset within 12 hours at 432 pts at 50 sites in 9 countries R Stratified by infarct vessel and thrombus aspiration PCI with BMS or DES PCI with MGuard Follow-up: 30 days, 6 months, 1 year Primary endpoint: ST-segment resolution at minutes Substudies: Cardiac MRI: 60 pts (30 pts in each arm) at 3-5 days Angio FU: 50 pts in MGuard arm at 13 months Stone GW. et al. Prospective, Randomized, Multicenter Evaluation of a Polyethylene Terephthalate Micronet Mesh Covered Stent (MGuard) in ST- Segment Elevation Myocardial Infarction: The MASTER Trial J Am Coll Cardiol. 2012;60(19):

49 Primary Endpoint: Complete ST-segment resolution MGuard (n=204) Control (n=206) 16.7% 17.0% 25.5% 57.8% 38.3% 44.7% Difference [95%CI] = 13.2% [3.1, 23.3] P=0.008

50 a non invasive, invasive approach Culprit Lesion Repair at a median follow-up of 753 days, all patients were asymptomatic, regardless of stent implantation 31 patients presenting with STEMI and FD-OCT assessment of plaque erosion after aspiration thrombectomy. Group 1: 12 patients with subcritically occlusive plaque treated with DAPT ONLY Group 2: 19 patients treated with stenting

51 to aspirate, or not to aspirate? reasonable strategy NOT in every case reduces thrombotic burden visualization of coronary anatomy helpful with trends: - short stenting - direct stenting cheap (?) safe

52 Algorithm for the treatment of no-reflow No reflow (Assessment ECG, TMPG) Exclude another cause Thrombus, Spasm, Dissection, Air embolism - NTG mcg to 4 bolus - Distal contrast injections Check ACT Hemodynamic stabilisation Pressors Agents IABP O2 delivery Pacemaker Target s UFH:UFH + 2b/3a Delivery system Guiding catheter Over-the-wire catheter Microcatheter Aspiration catheter Muller O. et al. Management of two major complications in the cardiac catheterisation laboratory: the no-reflow phenomenon and coronary perforations. First line management (each bolus can be given several times) 1. Adenosine up to 60 mcg bolus 2. Verapamil up to 200 mcg bolus or 100 mcg/min up to 1000 mcg total, with temporary pacer on standby Never give >200 mcg as bolus 3. Nitroprusside up to 200 mcg bolus, up to 1000 mcg total dose 4. Epinephrine ug 5. Nicardipine 200 ug 6. Nicorandil 2 ug 7. Diltiazem mg over 1 min up to 5 mcg Never shown to be effective 1. Nitroglycerin (arteriols > 100 mm)

53 <πάντα εἴρηκεν ἔκγονα ῥοῆς τε καὶ κινήσεως: ἢ οὐ δοκεῖ τοῦτο λέγειν; (Πλάτων, Θεαίτητος 152)