Late Open ArteryLate Open ArteryHypothesisHypothesis

Jason S. Finkelstein, M.D.Jason S. Finkelstein, M.D.Tulane University Medical Tulane University Medical

CenterCenter2/24/032/24/03

Acute Myocardial infarctionAcute Myocardial infarction• Early Reperfusion BenefitsEarly Reperfusion Benefits

– Infarct size reductionInfarct size reduction

– Preservation of LV functionPreservation of LV function

– Increased survivalIncreased survival

Post Myocardial infarctionPost Myocardial infarction• Late reperfusion benefitsLate reperfusion benefits

– Beyond the window of myocardial salvage Beyond the window of myocardial salvage remains controversial and inconclusiveremains controversial and inconclusive

– However, despite lack of consensus, late However, despite lack of consensus, late mechanical reperfusion after MI seems to mechanical reperfusion after MI seems to be a common treatment strategybe a common treatment strategy

HypothesisHypothesis

• That late mechanical reperfusion in That late mechanical reperfusion in patients with asymptomatic occluded patients with asymptomatic occluded IRA’s will improve long-term clinical IRA’s will improve long-term clinical outcomesoutcomes

• Remains to be proved by clinical trialsRemains to be proved by clinical trials

The Open Artery TrialThe Open Artery Trial

(TOAT)(TOAT)

ObjectiveObjective

• To conduct a randomized trial To conduct a randomized trial comparing late revascularization with comparing late revascularization with conservative therapy in symptom-conservative therapy in symptom-free patients after AMIfree patients after AMI

MethodsMethods• Patient selection criteriaPatient selection criteria

– Age Age << 75 75– Uncomplicated hospital courseUncomplicated hospital course– Sinus rhythm without BBBSinus rhythm without BBB– Ejection fraction < 50% or Ejection fraction < 50% or >> 3 3

pathological Q waves in 3 precordial leadspathological Q waves in 3 precordial leads– Absence of chest pain or hemodynamic Absence of chest pain or hemodynamic

disturbance during modified Bruce disturbance during modified Bruce treadmill exercise testingtreadmill exercise testing

AngiographyAngiography• ScreeningScreening

– Coronary angiography was performed Coronary angiography was performed between 3 days and 4 weeks of MIbetween 3 days and 4 weeks of MI

– Patients with an occluded LAD and non-Patients with an occluded LAD and non-significant disease elsewheresignificant disease elsewhere

((<< 50% stenosis) were randomized 50% stenosis) were randomized

RandomizationRandomization• 223 patients enrolled with Q-wave anterior MI223 patients enrolled with Q-wave anterior MI• 66 patients with isolated occlusion of LAD 66 patients with isolated occlusion of LAD

were randomized to 2 groupswere randomized to 2 groups

– Medical therapy ( n=34)Medical therapy ( n=34)– Late PCI plus stent to the LAD + medical therapy Late PCI plus stent to the LAD + medical therapy

( n=32) ( n=32)

– Very similar baseline characteristics in both groupsVery similar baseline characteristics in both groups

Medical therapyMedical therapy• ASAASA• B-blockersB-blockers• ACE-IACE-I• Lipid-lowering agentsLipid-lowering agents

• Stented patients received plavix for 2 Stented patients received plavix for 2 weeks post procedureweeks post procedure

End PointsEnd Points• To compareTo compare

– LV functionLV function– LV sizeLV size– Quality of Life Quality of Life – Exercise Tolerance Exercise Tolerance

• Between the 2 groups at 12 months post AMIBetween the 2 groups at 12 months post AMI

Patient Follow-upPatient Follow-up• 6 weeks6 weeks• 3 months3 months• 6 months6 months• 12 months12 months

• For 2-D echo estimates of LV function, For 2-D echo estimates of LV function, size, assessments of exercise size, assessments of exercise tolerance and quality of lifetolerance and quality of life

ResultsResults• LV ESV, EDV, and EF were similar in both LV ESV, EDV, and EF were similar in both

groups at 6 weeks post MIgroups at 6 weeks post MI

• No significant changes were observed in the No significant changes were observed in the medical therapy group over 12 months, but medical therapy group over 12 months, but the LV ESV significantly increased in the the LV ESV significantly increased in the open artery groupopen artery group LV ESV (106LV ESV (106++ 37.5 ml vs. 79.7 37.5 ml vs. 79.7++34.4 ml) p<0.0134.4 ml) p<0.01– LV EDV (162.0 LV EDV (162.0 ++ 51.4 ml vs. 130.1 51.4 ml vs. 130.1 ++ 46.1 ml) 46.1 ml)

p<0.01p<0.01

ResultsResults• Exercise toleranceExercise tolerance

– Exercise duration increased in both Exercise duration increased in both groups, but was greater in the open artery groups, but was greater in the open artery group at 12 monthsgroup at 12 months

• Quality of lifeQuality of life– At 12 months, late intervention was At 12 months, late intervention was

associated with less functional impairmentassociated with less functional impairment

DiscussionDiscussion• Late intervention to open occluded Late intervention to open occluded

IRA’s is associated with greater LV IRA’s is associated with greater LV dilation than a non-invasive strategydilation than a non-invasive strategy

• However, late PCI may lead to an However, late PCI may lead to an improved quality of life and exercise improved quality of life and exercise tolerancetolerance

Possible adverse effects of Late Possible adverse effects of Late PCIPCI• Distal micro-circulation has high Distal micro-circulation has high

resistance leading to low-reflow and resistance leading to low-reflow and stasis within the epicardial vesselstasis within the epicardial vessel

• Collateral circulation may become Collateral circulation may become embolized contributing to the embolized contributing to the regression of collateral supportregression of collateral support

LimitationsLimitations• Small study, only 66 patientsSmall study, only 66 patients

• Did not assess microinfarction by routinely Did not assess microinfarction by routinely checking cardiac enzymeschecking cardiac enzymes

• Study population was highly selected, limiting Study population was highly selected, limiting the generalizability of the findingsthe generalizability of the findings

• Role of microvascular circulation was Role of microvascular circulation was inadequately addressedinadequately addressed

Clinical implicationsClinical implications• Late PCI after MI is technically feasible and Late PCI after MI is technically feasible and

compellingcompelling

• Associated with an adverse effect on LV Associated with an adverse effect on LV remodeling when compared to medical therapyremodeling when compared to medical therapy

• Patients may not derive objective benefits from Patients may not derive objective benefits from late PCIlate PCI

• More ongoing clinical trials are neededMore ongoing clinical trials are needed

Occluded Artery TrialOccluded Artery Trial

(OAT)(OAT)

OATOAT• Sponsored by the National Heart, Sponsored by the National Heart,

Lung, and Blood InstituteLung, and Blood Institute

• Currently recruiting patients for an Currently recruiting patients for an ongoing trialongoing trial

• Not yet publishedNot yet published

PurposePurpose• To determine whether opening an To determine whether opening an

occluded infarcted artery 3-28 days occluded infarcted artery 3-28 days post AMI in high risk asymptomatic post AMI in high risk asymptomatic patients reduces the composite patients reduces the composite endpoint of mortality, recurrent MI, endpoint of mortality, recurrent MI, and hospitalization for Class IV CHF and hospitalization for Class IV CHF over a 3 year follow upover a 3 year follow up

DesignDesign• Multi-center randomized, controlled trialMulti-center randomized, controlled trial• 3200 patients are allocated to 2 3200 patients are allocated to 2

treatment groupstreatment groups

– Medical therapy: ASA, Medical therapy: ASA, B- B- blockers, ACE-I, blockers, ACE-I, and risk factor modificationand risk factor modification

– PCI plus stent with medical therapyPCI plus stent with medical therapy

EndpointEndpoint• Primary composite endpoint is Primary composite endpoint is

mortality, recurrent MI, and mortality, recurrent MI, and hospitalization of Class IV CHFhospitalization of Class IV CHF

• Costs of the 2 treatmentsCosts of the 2 treatments

• Health related quality of lifeHealth related quality of life

Clinical ImplicationClinical Implication

To Late PCI or Not to Late To Late PCI or Not to Late PCI?PCI?

We shall see!!!!We shall see!!!!