Treating CTOs Is there evidence based data? Craig A. Thompson, M.D., MMSc. Director, Cardiovascular Catheterization and Intervention Yale University School of Medicine/Yale New Haven Hospital Consultant (Hon) Heart Hospital, London and London Chest Hospital

Craig A. Thompson, MD Consulting Fees: Abbott Vascular Terumo Cardiovascular Systems Group Ownership Interest (Stocks, Stock Options, or other Ownership Interest): Bridgepoint

The Onus is on us to prove utility? Single vessel CTO 1 or 2VD no proximal LAD Class 0 Class I/II Class III/IV High Risk Max Rx U A Int Risk Low Risk No Rx I Class 0 Class I/II Class III/IV High Risk Max Rx A Int Risk U Low Risk No Rx I Modified from Patel et al J Am Coll Cardiol 2009;53:530-553

Impact of Successful CTO PCI Effect of Successful CTO PCI on angina Effect of Successful CTO PCI on subsequent CABG Effect of Successful CTO PCI on Mortality Joyal, D., Afilalo J, Rinfret S. American Heart Journal 2010

SYNTAX CTO Subset Procedural characteristics Per lesion analysis CABG n=266 26.2% patients with CTO CTO accounted for 266 lesions (7.4%) 12 were not treated with CABG CABG n=254 Not Bypassed n=81 Not Bypassed n=173 Overall 68.1 % of TO were successfully bypassed 49.6% overall complete revascularization in CTO subset Would you have sent patient to surgery if CTO was not grafted? Would you ask a surgeon not to graft CTO because it “is collateralized and doesn’t matter”? “Let’s just see how they do…” ITT, Per Lesion Serruys P, CRT 2009 [modified]; courtesy Prof Serruys and the SYNTAX investigators 6

National Attempt Rates ACC-NCDR National Attempt Rate Over Time It is likely we are dramatically undertreating patients with CTO Courtesy J Aaron Grantham and ACC/NCDR

Clinical Indications why open a chronically occluded coronary artery? Symptom control Angina CHF Fatigue Improve LV function Regional Global Survival Improved tolerance of AMI Complete revascularization Ischemic Risk

Clinical Indications why open a chronically occluded coronary artery? Symptom control Angina CHF Fatigue Improve LV function Regional Global Survival Improved tolerance of AMI Complete revascularization Ischemic Risk

CTO Recanalization and Angina Control Series Successful PCI (n) Follow-up (months) Asymptomatic (%) Olivari 2003 248 12 88.7 Berger 1996 139 6 87 Stewart 1993 45 68 Ivanhoe 1992 264 36 69 Ruocco 1992 160 24 Bell 1991 234 32 76

CTO PCI Impact on Angina and Quality of Life FACTOR study Grantham JA et al., Circulation: Cardiovascular Quality and Outcomes 2009 (

Clinical Indications why open a chronically occluded coronary artery? Symptom control Angina CHF Fatigue Improve LV function Regional Global Survival Improved tolerance of AMI Complete revascularization Ischemic Risk

Long Term LV Function Improvement with CTO PCI Improvements in LV volume indices maintained at 3 years Degree of transmurality of scar by MRI predictor Kirschbaum SW et al. American Journal of Cardiology 2008

Clinical Indications why open a chronically occluded coronary artery? Symptom control Angina CHF Fatigue Improve LV function Regional Global Survival Improved tolerance of AMI Complete revascularization Ischemic Risk

False Assumptions about Coronary Chronic Total Occlusions The CTO is well collateralized and therefore minimal risk The CTO is a closed vessel and therefore not at risk for ACS/AMI CTO outcomes are more benign than non CTO coronary disease

Pressure Wire in Stenoses FAME Trial Inability to identify ischemia 1329 FFR-Guided Lesions in FAME 16% of 71-90% lesions were not physiologically significant 39% of 41-70% lesions were physiologically significant “5% reduction in 3 year MACE with Functionally complete revascularization” Pijls, TCT, 2008

Collaterals are Usually not Sufficient to Substantially Reduce Ischemia in CTO Modified from Werner GS et al, European Heart Journal 2006, courtesy Werner GS

Prognostic importance of complete revascularization Hannan et al., JACC:CI 2009

CTO as Predictor of Mortality and ICD Therapy Nombela-Franco et al. Circulation Arrhythmia and Electrophysiology 2011

CTO as Predictor of Mortality and ICD Therapy Nombela-Franco et al. Circulation Arrhythmia and Electrophysiology 2011

Prognostic importance of CTO in AMI Independent predictors of a fall in EF at follow up Age>60 CTO MVD without CTO 1.9 (1.0-3.4) p=.03 1.3 (0.6-2.6) p=.64 3.5 (1.6-7.8) p<.01 JACC:Cardiovasc Int, 2010

Survival Benefit with Revascularization Stratified by Ischemic Risk P <.0001 Cardiac Death Rate 1331 56 718 109 545 243 252 267 1- 5% 5-10% 11-20% >20% % Total Myocardium Ischemic Hachamovitch et al Circulation. 2003; 107:2900-2907

Concepts in Outcomes in CAD plaque destabilization and ischemic risk Unstable Coronary Disease Adverse Events Multivessel Disease with CTO LAD RCA Stable Coronary Disease LCx Ischemic Risk Minimal ischemia Nonviable Minimal territory at risk Time Thompson CA JACC CI 2009

Iterating for the US Environment Procedural success (%) Experienced operators Thompson CA JACC CI 2009

Revascularization for CTO what do we know CTO is associated with symptoms of angina, but also often with dyspnea, fatigue Patients minimize symptoms Often inappropriately labeled asymptomatic CTO has poor prognosis and is associated with higher mortality than most diseases we manage High fatal arrhythmia burden Poor tolerance for AMI in other territories Other cardiac mortality linked to ischemic burden index Patient cohorts with revascularized CTO have longevity benefit compared with unrevascularized CTO Better quality of life CTO territories are virtually all ischemic Consider them the true 95% lesions from clinical indications perspective We undertreat these patients

Treating CTO: Is there evidence based data? Conclusions I We all want randomized clinical trials But remember, RCT in and of itself does not sanctify therapy In the meantime, patients are suffering and dying The overwhemling wealth of current information supports revascularization of CTO in the majority of cases

Treating CTO: Is there evidence based data? Conclusions II ‘The new era of CTO revascularization in patients with symptoms and/or ischemic burden begins in which the question is not “why should we open the occluded vessel?”, but “what is the justification to leave the vessel closed?”. ‘ Thompson CA, JACC CI 2009