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Oclusões crônicas: Impacto da intervenção percutânea na evolução clínica de longo prazo. Prof. Federico Piscione Federico II University Naples, Italy. Federico II University of Naples. Never convincingly shown! . Indisputably shown! . OPEN ARTERY HYPOTHESIS. TIME-DEPENDENT COMPONENT. - PowerPoint PPT Presentation

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  • Prof. Federico PiscioneFederico II University Naples, ItalyOcluses crnicas: Impacto da interveno percutnea na evoluo clnica de longo prazoFederico II University of Naples

  • OPEN ARTERY HYPOTHESISTIME-DEPENDENTCOMPONENTTIME-INDEPENDENTCOMPONENTIRA LATE RECANALIZATIONIRA EARLY RECANALIZATIONBENEFITS INDEPENDENT OFMYOCARDIAL SALVAGEIMPROVED SURVIVALMYOCARDIAL SALVAGELV FUNCTION PRESERVATIONIMPROVED SURVIVALFederico II University of Naples

  • Collateral VesselsElectrical StabilityAnti-Remodeling EffectsTime-independent Myocardial SalvagePotential Benefits by Time-Independent MechanismsOPEN ARTERY HYPOTHESISFederico II University of Naples

  • BENEFITS OF LATE PATENCY LINKED TO A TIME-INDEPENDENT MYOCARDIAL SALVAGE Restoration of blood flow to ischemic myocardium adjacent to endocardial scar

    Perfusion of hibernating myocardium

    Preservation of an epicardial rim of myocardiumFederico II University of Naples

  • LATE REPERFUSION AND ANTIREMODELING EFFECTSExtracellular matrix remodelingReduced collagen breakdownAccelleration of scar formation

    Stiffer and firmer infarcted tissue

    Scaffolding effect of the blood

    Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of NaplesOlivari Z, Rubartelli P, Piscione F et al. JACC 2003

  • Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of NaplesImproved LVF after Recanalization of CTO Piscione et al., Heart 2005 65 pts with CTO 6 monthsGroup 1: 35 TIMI 3Group 2: 30 TIMI 0-2

  • Federico II University of Naples

  • Federico II University of NaplesOlivari Z, Rubartelli P, Piscione F et al. JACC 2003

  • Federico II University of NaplesHoye et al. EHJ 2005

  • Federico II University of Naples

  • Federico II University of NaplesThree years Kaplan-Meier curves for cardiac death and MI, survival, and all MACE (cardiac death, AMI, TVR)Piscione et al., Heart 2005

  • Olivari Z, Rubartelli P, Piscione F et al. JACC 2003Federico II University of Naples

  • Federico II University of Naples

  • J. Moses CTO Summit 2011Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of Naples

  • J. Moses CTO Summit 2011Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of Naples

  • Thanks Federico II University of Naples

  • Federico II University of Naples

  • Federico II University of NaplesOlivari Z, Rubartelli P, Piscione F et al. JACC 2003

  • Federico II University of Naples

    Kirschbaumet al, Am J Cardiol 2008

  • What factors, if any, may have masked the benefit of late IRA recanalization?

  • THE SCIENTIFIC BACKGROUNG OF THE OPEN ARTERY HYPOTHESISEXPERIMENTAL STUDIESOBSERVATIONAL RETROSPECTIVE STUDIESOBSERVATIONAL PROSPECTIVE STUDIES RANDOMIZED STUDIES

  • Federico II University of NaplesJeffrey W. Moses, CTO Summit 2008

  • Federico II University of Naples

  • Federico II University of NaplesJeffrey W. Moses, CTO Summit 2008

  • Federico II University of NaplesOAT patients in the real world(data from CUMC) Jeffrey W. Moses, CTO Summit 2008

  • POWER of the STUDY

  • The actual event rate in the medical arm at 3 years was 14.8% not 25% !!!

    The number of observed events required was nearly 508. The study includes only 301 study events (60% of the expected rate)POWER of the STUDY

  • The PCI succes rate was relatively low considering subacute occlusions (NOT CTO!)The definition of anatomic success after PCI was too liberal in OAT given it included patients with less than TIMI 3 epicardial flow and even those with grade 1 antegrade flow perceived to be exclusively related to suboptimal microvascular coronary flow.

    Successful PCI87%TIMI Flow 0-218%Stent utilization87%

  • To have lasting benefit, late reperfusion of an occluded IRA must result in sustained long-term patencyTOSCA-2 Trial

    Reocclusion rate17%Restenosis rate45.7%Stent utilization99%

  • The secondary end-point of changes in LVEDVI was drawn from a subset of a subset since only 42% of the TOSCA-2 cohort underwent volume determination studies.

    This subset of patients is enriched by patients who survive for 1 year and may reflect a lower risk population

  • Coronary and LV angiography was performed one year after randomization. Since much of the healing and remodelling after infarction occurs within the first week, a quicker ascertainment and intervention might well have yielded a different result as has been the case with angiotensin inhibitors.

  • Mechanical reperfusion of chronically occluded vessels is not without hazards. Thus, the overall risk-benefit ratio may be not favourable

    IRA closure may be the result of poor flow caused by high microvascular resistance, which in turn is caused by severe ischemic injury. Thus, it conceivable that IRA patency does not improve LV remodelling but that minor infarction and improved ventricular remodeling enhance patency

    Late reperfusion may be detrimental because collateral vessels may be forced to regress, thus, precipitating further ischemia and reinfarctionDoes late mechanical recanalization confer the same benefits of spontaneous late recanalization?

  • The OAT trial found a non-significant but disturbing trend toward more new infarcts in the PCI group. A potential benefit of attenuation of left ventricular remodeling may be countered by excess nonfatal reinfarctions.Microvascular damage may occur when the artery is reopened

    Delayed recanalization of the infarct related artery in this setting will lead to loss of previously recruited collateral flow, reexposing the once-protected distal vascular bed and viable myocardium to future upstream vascular events

    The majority of patients (>85%) in this trial had collaterals at baseline, a finding presumably responsible for the high prevalence of viability of the infarct zone (69% of patients in the viability substudy)

  • Federico II University of Naples

  • Federico II University of NaplesR. Moreno et al. J Invas Cardiology 2006

  • Federico II University of NaplesBates and HochmanHochmanAHJ 2007

  • Federico II University of NaplesShaw for the COURAGE investigators Circ 2008

  • Federico II University of Naples

  • Federico II University of NaplesShaw for the COURAGE investigators Circ 2008

  • Federico II University of Naples

  • Federico II University of NaplesHachamovitchet al Circulation. 2003

  • Federico II University of NaplesAbbate et al, JACC 2008

  • Federico II University of NaplesAbbate et al, JACC 2008

  • Federico II University of NaplesAbbate et al, JACC 2008

  • Federico II University of NaplesJeffrey W. Moses, CTO Summit 2008

  • Federico II University of Naples

  • Federico II University of Naples

  • Late mechanical reperfusion of the IRA in stable asymptomatic post-MI patients is deadBiological plausibility of the late open artery hypothesis might be still aliveCONCLUSIONS

  • TOSCA-2 Trial: Study DesignPrimary Endpoints: 1) Change in LVEF and 2) infarct-related artery patencySecondary Endpoints: Change in LVEDVI, LVESVI, and regional wall motion scorePCI with stentingn=195381 patients with the same characteristics of the OAT TrialMedical Therapyn=1861-year repeat coronary and LV angiography

  • TOSCA-2 Trial IRA Patency at One YearDzavik et al. Circulation 2006; 114:2449

  • TOSCA-2 Trial Changes in LVEFDzavik et al. Circulation 2006; 114:2449

  • TOSCA-2 Trial Changes in LVEDVI and LVESVIDzavik et al. Circulation 2006; 114:2449

  • OPEN ARTERY HYPOTHESISCLINICAL IMPLICATIONS OF TIME-INDEPENDENT COMPONENTTHE FIRST VERSIONTHE LAST VERSIONIRA RECANALIZATION FROM 6 TO 24 HRS AFTER AMIIRA RICANALIZATION DAYS AFTER AMILATE THROMBOLYSISRESCUE THROMBOLYSISPrImary and RESCUE PCIELECTIVE PTCA OF THE OCCLUDED IRA

  • Federico II University of Naples

  • The available nonrandomized and randomized data on very late reperfusion (>24 h) was inconclusive

    The epidemiologic link between late patency and survival might reflect an epiphenomenon

    There were no large randomized trial data that had convincingly shown the long-term benefit of very late reperfusionWhat did we know on late reperfusion before the OAT study?

  • Primary EndpointCovariate adjusted and as treated analyses demonstrated similar resultsHochman JS et al. NEJM 2006; 355:2395

  • Cumulative 4-year RatesP=NS for allHochman JS et al. NEJM 2006; 355:2395

  • LATE REPERFUSION AND EXTRACELLULAR MATRIX REMODELINGLate reperfusion attenuates the activity of a family of enzymes involved in collagen breakdown which leads to aggressive infarct expansion and remodeling

    Late reperfusion increases the speed with which the scar is matured

    Late reperfusion is associated with a more intense inflammatory reaction that enhances clearence of necrotis debris, improves wound healing and induces an earlier expression of fibroblasts within the infarct zoneExperimental evidenceFederico II University of Naples

  • Federico II University of NaplesJ Hug et al., AHA 2000

    **