Prof. Federico Piscione Federico II University Naples, Italy

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 TIME-INDEPENDENT COMPONENT IRA LATE RECANALIZATION IRA EARLY RECANALIZATION MYOCARDIAL SALVAGE BENEFITS INDEPENDENT OF MYOCARDIAL SALVAGE LV FUNCTION PRESERVATION IMPROVED SURVIVAL IMPROVED SURVIVAL Federico II University of Naples

OPEN ARTERY HYPOTHESIS • Potential Benefits by Time-Independent Mechanisms • Collateral Vessels • Electrical Stability • Anti-Remodeling Effects • Time-independent Myocardial Salvage Federico 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 myocardium Federico II University of Naples

LATE REPERFUSION AND ANTIREMODELING EFFECTS • Extracellular matrix remodeling • Reduced collagen breakdown • Accelleration of scar formation • Stiffer and firmer infarcted tissue • Scaffolding effect of the blood Federico II University of Naples

Federico II University of Naples

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

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

Hoye et al. EHJ 2005 Federico II University of Naples

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

J. Moses CTO Summit 2011 Federico II University of Naples

Thanks Federico II University of Naples

Kirschbaumet al, Am J Cardiol 2008 Federico II University of Naples

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

THE SCIENTIFIC BACKGROUNG OF THE OPEN ARTERY HYPOTHESIS • EXPERIMENTAL STUDIES • OBSERVATIONAL RETROSPECTIVE STUDIES • OBSERVATIONAL PROSPECTIVE STUDIES • RANDOMIZED STUDIES

Jeffrey W. Moses, CTO Summit 2008 Federico II University of Naples

“OAT” patients in the real world (data from CUMC) Jeffrey W. Moses, CTO Summit 2008 Federico II University of Naples

90% power to detect 25% reduction in PE rate assuming PE rate of 25% with med Rx, 25% cross-over rate and a 5% loss at FU Estimated sample size 3200 pts Recruitment challenges and cross-over rate less than expected New estimated sample size 2400 pts 90% target population 94% power to detect anticipated difference in PE Final enrollment 2166 pts POWER of the STUDY

79% 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)

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.

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

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.

Does late mechanical recanalization confer the same benefits of spontaneous late recanalization? • 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 reinfarction

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)

R. Moreno et al. J Invas Cardiology 2006 Federico II University of Naples

Bates and HochmanHochmanAHJ 2007 Federico II University of Naples

Shaw for the COURAGE investigators Circ 2008 Federico II University of Naples

Prof. Federico Piscione Federico II University Naples, Italy