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The “Code White” Team of Dr. William Ganz: 1979

The “Code White” Team of Dr. William Ganz: 1979. Goal of IC SK Before PCI: Get the artery open. Acute MI Treated with Distal Protection and IC tPA (8 mg). Pre PCI. After Percusurge / Angiojet. Clot. Clot. After 8 mg IC tPA. P atients and R andomization

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The “Code White” Team of Dr. William Ganz: 1979

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  1. The “Code White” Team of Dr. William Ganz: 1979 Goal of IC SK Before PCI: Get the artery open

  2. Acute MI Treated with Distal Protection and IC tPA (8 mg) Pre PCI After Percusurge / Angiojet Clot Clot After 8 mg IC tPA

  3. Patients and Randomization Immediately after diagnostic angiography eligible patients (n =41) were randomized to ICSK group (n=21) Control group (n=20) (Primary PCI + 250 kU intracoronary streptokinase) (primary PCI) All patients recieved: - 300 mg of aspirin, - A loading dose of 600 mg of clopidogrel, - Intracoronary unfractioned heparin at a dose of 100 U/kg during the procedure, - Tirofiban as a bolus of 0.1 μg/kg in 3 minutes followed by continuous infusion of 0.15μg/kg/min for 12 hours, and - Low molecular weight heparin initiated four to five hours after primary PCI and continuedfor at least 48 hours Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  4. Study Design • All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days after primary PCI to evaluate microvascular function • ST segment resolution • Diastolic deceleration time • Echocardiographic assessment of left ventricular volumes and function • Coronary flow reserve • Index of microvascular resistance • Coronary wedge pressure (mean ad systolic) • Pressure derived collateral flow index • Myocardial blush grades • Corrected TIMI frame count Pre/post PCI ECG Transthoracic echocardiography, 2 days after AMI Assesing microvascular perfusion and LV volumes in early phase of STEMI Second angiography and intracoronary hemodynamic measurements 2 days after AMI. Long term assesments (at 6 months) Control angiography (TIMI frame count, Myocardial blush grade) Infarct size measurement (SPECT), Echocardiographic assessment of left ventricular volumes and function Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  5. Pressure wire Microvasculature Guiding cath. Balloon CWP: mm Hg Pa: mm Hg Assessment of Microvascular Perfusion by Invasive Methods • Thermodilution-derived Coronary Flow Reserve (CFR)* = Resting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486 • Index of Microvascular Resistance (IMR)**: = Distal coronary pressure x hyperemic mean transit time **Fearon WF. et al.. Circulation. 2003;107:3129-3132 • Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  6. Univariate Multivariate Intracoronary Streptokinase Group n:21 Control Group n:20 Mean Difference 95% CI p Intracoronary Streptokinase Group, Mean (95% CI) Control Group, Mean (95% CI) p IMR (U) 16.29 + 5.06 32.49 +11.04 -16.20 (-21.75)(10.64) <0.001 11.73 (5.53)-(17.92) 29.05 (22.17)-(35.92) <0.001 CFR 2.01 + 0.57 1.39 + 0.31 0.62 (0.35)-(0.93) <0.001 2.29 (1.92)-(2.66) 1.66 (1.25)-(2.07) 0.002 CWP, mean (mmHg) 10.81 + 5.46 17.20 + 7.93 -6.39 (-10.73)-(-2.05) 0.004 7.98 (2.84)-(13.12) 12.54 (6.83)-(18.24) 0.04 CWP, systolic (mmHg) 18.24 + 6.07 33.80 + 11.0 -15.56 (-21.27)-(-9.85) <0.001 15.17 (8.26)-(22.08) 29.46 (21.80)-(37.12) <0.001 CFIp (mean, unitless) 0.08 + 0.05 0.17 + 0.07 -0.09 (--­­0.13)-(-0.06) <0.001 0.08 (0.05)-(0.11) 0.17 (0.14)-(0.21) 0.002 Intracoronary Hemodynamic Indices of Microvascular Perfusion Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  7. Angiographic(cTFC, MBG), ic (STR) and Echocardiographic (DDT) Indices of Microvascular Perfusion Univariate MultivariateICSK group Control Mean diff. pICSK group Control p cTFC mean Immediately after primary PCI 33.6 + 9.45 34.44 + 8.26 -0.79 (-6.66)-(5.08) 0.69 30.30 (23.14)-(37.46) 29.36 (21.48)-(37.25) 0.80 Two days after primary PCI 22.52 + 5.58 31.79 + 7.58 -9.27 (-13.50)-(-5.03) <0.001 19.10 (14.16)-(24.04) 27.51 (22.03)-(32.99) 0.001 Six months after primary PCI 21.42 + 4.98 27.62 + 6.46 -6.2 (-11.00)-(-1.39) 0.014 18.88 (13.57)-(24.18) 25.89 (18.76)-(33.02) 0.023 MBG Immediately after primary PCI 0/1 10 (50%) 13 (72%) - 0.16 - - 0.70 2/3 10 (50%) 5 (28%) - - - Two days after primary PCI 0/1 6 (29%) 13 (68%) - 0.012 - - 0.065 2/3 15 (71%) 6 (32%) - - - Six months after primary PCI 0/1 1 (8.3) 6 (46.2) - 0.035 - - 0.13 2/3 11 (91.7) 7 (53.8) - - - DDT in the LAD artery (milliseconds)# 828+258 360+292 468 (261)-(676) <0.001 750 (446)-(1054) 257 (-65)-(580) 0.001 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  8. Left Ventricular End Systolic(ESV) and End Diastolic Volumes (EDV), Ejection Fraction (LVEF) and Infarct Size (%) Comparisons Univariate Multivariate ICSK (+) Control p (two tailed) ICSK (+), mean, 95%CI Control, mean 95%CI p (two tailed) ESV ml Two days after primary PCI 58.16 + 17.02 (n: 21) 78.65 + 30.55 (n: 20) 0.013 50.81 (31.25-66.37) 65.03 (47.76-82.30) 0.063 Six months after primary PCI 50.64 + 18.23 (n: 17) 83.73 + 39.32 (n: 15) 0.004 36.08 (9.07-63.10) 58.68 (25.10-92.27) 0.068 Change in ESV % -13.27 + 25.40 (n: 17) 12.67 + 30.75 (n: 15) 0.014 -12.32 (-47.47)-(-22.83) 15.30 (-28.40)-(59.01) 0.055 EDV ml Two days after primary PCI 119.88 + 23.36 (n: 21) 137.75 + 36.82 (n: 20) 0.07 111.22 (88.52-133.91) 118.53 (93.35-143.71) 0.50 Six months after primary PCI 115.70 + 29.67 (n: 17) 150.13 + 49.28 (n: 15) 0.021 92.72 (59.11-126.33) 118.77 (76.98-160.56) 0.089 Change in EDV, % -4.60 + 22.01 (n: 17) 11.90 + 23.50 (n: 15) 0.04 -11.19 (-37.95)-(15.58) 14.97 (-18.31)-(48.24) 0.036 LVEF % Two days after primary PCI 51.52 + 10.76 (n: 21) 44.51 + 12.40 (n: 20) 0.06 54.25 (46.95-61.55) 47.96 (39.86-56.06) 0.078 Six months after primary PCI 56.18 + 10.69 (n: 17) 46.19 + 12.21 (n: 15) 0.020 57.68 (45.88-69.47) 51.56 (36.90-66.23) 0.24 Change in LVEF, % 14.37 + 31.14 3.46 + 19.02 0.24 5.97 (-27.32)-(39.26) 2.71 (-37.75)-(43.16) 0.82 Infarct size %, SPECT 23 + 13.37 (n: 18) 37.05 + 13.84 (n: 18) 0.005 27.84 (14.35-41.32) 37.28 (21.57-52.99) 0.17 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

  9. Following NEJM Publication in 2007 Goal of IC SK After PCI: Get the microvasculature open

  10. IC Compared to IV Abciximab Reduces MACE in ACS Pts Undergoing PCI UA and MI P<0.0008 P<0.09 20.2 N = 403 pts IC – 294 IV – 109 49% 15.6 10.2 P<0.002 9.5 P<0.04 4.6 2.8 0.3 0.3 Urgent Revascularization Recurrent MI Death MACE IC abciximab IV abciximab Wöhrle J et al. Circulation 2003;107:1840.

  11. Clot Disaggregation Following IC Eptifibatide: Pre-PCI Angiogram Pinto et al, Am J Cardiol 2006

  12. Retrospective Experience with IC Eptifibatide • 59 patients treated with unbuffered IC eptifibatide: • TIMI Grade 3 flow in >90% of patients following PCI • Normal TIMI myocardial perfusion grade 3 flow (TMPG 3) present in 54.4% of patients following PCI (range 20%-25% in past) • There were no in-hospital deaths, reinfarctions, or TIMI major bleeding events • No arrhythmias during IC eptifibatide administration Pinto et al, Am J Cardiol 2006

  13. Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCA Placebo Adenosine 4 mg in 2 ml via central lumen of PTCA balloon p < 0.02 p < 0.03 p < 0.04 % of Patients % Developing Q Waves % Death, MI, CHF, Recurrent Angina Marzilli et al, Circulation 2000; 101:2154-2159

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