The Occluded Artery Trial (OAT) Viability Ancillary Study(OAT-NUC): Influence of infarct zone viability on leftventricular remodeling after percutaneous coronaryintervention versus optimal medical therapy aloneJames E. Udelson, MD,a Camille A. Pearte, MD, MPH,b Carey D. Kimmelstiel, MD,a Mariusz Kruk, MD,e

Joseph A. Kufera, MA,c Sandra A. Forman, MA,d Anna Teresinska, MD,e Bartosz Bychowiec, MD,f

Jose Antonio Marin-Neto, MD,g Thomas Höchtl, MD,h Eric A. Cohen, MD,i Paulo Caramori, MD, PhD, j

Benita Busz-Papiez, MD,k Christopher Adlbrecht, MD, MBA, l Zygmunt P. Sadowski, MD,e Witold Ruzyllo, MD,e

Debra J. Kinan, RT(N),a Gervasio A. Lamas, MD,m and Judith S. Hochman, MDb Boston, MA; New York, NY;Monkton and Owings Mills, MD; Warsaw, Poznan and Szezecin, Poland; Ribeirao Preto and Porto Alegre, Brazil;Vienna, Austria; Ontario, Canada; and Miami Beach, FL

Background The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronaryintervention (PCI) versus optimal medical therapy (MED) in patients with persistent total occlusion of the infarct-related artery 3to 28 days post–myocardial infarction. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ)viability is unknown.

Methods and Results The OAT nuclear ancillary study hypothesized that (1) IZ viability influences left ventricular(LV) remodeling and that (2) PCI as compared with MED attenuates adverse remodeling in post–myocardial infarction patientswith preserved viability. Enrolled were 124 OAT patients who underwent resting nitroglycerin-enhanced technetium-99msestamibi single-photon emission computed tomography (SPECT) before OAT randomization, with repeat imaging at 1 year.All images were quantitatively analyzed for infarct size, IZ viability, LV volumes, and function in a core laboratory. At baseline,mean infarct size was 26% ± 18 of the LV, mean IZ viability was 43% ± 8 of peak uptake, and most patients (70%) had at leastmoderately retained IZ viability. There were no significant differences in 1-year end-diastolic or end-systolic volume changebetween those with severely reduced versus moderately retained IZ viability, or when compared by treatment assignment PCIversus MED. In multivariable models, increasing baseline viability independently predicted improvement in ejection fraction(P = .005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling.

Conclusions In the contemporary era of MED, PCI of the infarct-related artery compared with MED alone does notimpact LV remodeling irrespective of IZ viability. (Am Heart J 2011;161:611-21.)

The Occluded Artery Trial (OAT) demonstrated nodifference in clinical outcomes over 5 years betweenpatients randomized to percutaneous coronary interven-tion (PCI) versus optimal medical therapy alone (MED) in

rom the aTufts Medical Center, Boston, MA, bNew York University School of Medicine,ew York, NY, cKufera Consulting, Inc., Monkton, MD, dClinical Trials and Surveysorporation, Owings Mills, MD, eNational Institute of Cardiology, Warsaw, Poland,oznan University of Medical Sciences, Poznan, Poland, gHospital das Clínicas daaculdade de Medicina de Ribeirao Preto-USP, Ribeirao Preto, Brazil, hWilhelminenhos-ital, Vienna, Austria,

iSunnybrook Health Sciences Center, Toronto, Ontario, Canada,

ospital São Lucas-Pontifícia University Católica do Rio Grande do Sul, Porto Alegre,razil, kSP Wojewodzki Szpital Zespolony w Szczecinie, Szezecin, Poland, lMedicalniversity of Vienna, Vienna, Austria, and mColumbia University Division of Cardiology,ount Sinai Medical Center, Miami Beach, FL.unding sources: OAT was supported by National Heart, Lung, and Blood Institute Awards01HL062509 and U01HL062511; OAT-NUC was funded by National Institutes ofealth Grant R01 HL075456—Myocardial Viability & Remodeling in the Occluded Artery

Trial. Supplemental funding was received by Dr Camille A. Pearte, MD, between 2006 and2008 by a Research Supplement (Grant No. R01 HL 075456-04S1) to Promote Diversity inHealth-Related Research PA-05-015. Supplemental grant funds and product donationsequivalent to 6% of total study costs were received from Eli Lilly, MillenniumPharmaceuticals and Schering Plough, Guidant, Cordis/Johnson and Johnson, Medtronic,Merck, and Bristol Myers Squibb Medical Imaging.Submitted November 18, 2010; accepted November 20, 2010.Reprint requests: James E. Udelson, MD, Tufts Medical Center, 800 Washington Street,Box 70, Boston, MA 02111.E-mail: judelson@tuftsmedicalcenter.org0002-8703/$ - see front matter© 2011, Mosby, Inc. All rights reserved.doi:10.1016/j.ahj.2010.11.020

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stable patients with an occluded infarct-related artery(IRA) 3 to 28 days post–myocardial infarction (post-MI).1

Data from previous observational and small nonrando-mized studies have suggested that preservation of

Figure 1

Examples of horizontal long-axis view of resting SPECT images from 2 patients in the OAT-NUC trial illustrating the viability classification. Left: alateral wall infarct but with some preservation of uptake in the lateral wall (yellow dotted line and arrow), classified as moderately retained IZviability. Right: a lateral wall infarct but a very severe reduction in uptake in the lateral wall (white dotted line and arrow) consistent with severelyreduced IZ viability.

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myocardial viability within the infarct zone (IZ) isassociated with attenuation of adverse left ventricular(LV) remodeling months after MI.2-5 However, they havebeen limited by variable testing protocols, small samplesizes, short follow-up durations, and nonrandomizedtreatment designs. The potentially interactive effect ofrevascularization and IZ viability and whether PCI maybenefit a subset of OAT patients with relative preserva-tion of IZ viability are unknown.The aims of the OAT Nuclear Viability Ancillary Study

(OAT-NUC) were to (1) examine the influence of retainedIZ viability on extent of LV remodeling in post-MI patientswith occluded IRAs, (2) evaluate the influence ofrevascularization with PCI versus MED on the extent ofsubsequent LV remodeling, and (3) assess whether OATpatients assigned to PCI with more preserved viabilitywould have less adverse remodeling than similar patientsassigned to MED alone.

MethodsStudy populationPatients in OAT-NUC had identical screening procedures,

eligibility criteria, and clinical follow-up as the main OATprotocol previously described.6 Briefly, patients had to have aconfirmed indexMI (2 of 3 criteria: ischemic symptoms, elevatedcardiac markers, typical MI electrocardiogram changes), totalocclusion (thrombolysis in myocardial infarction [TIMI] 0 or 1

flow) of the IRA on angiography on calendar days 3 to 28(minimum 24 hours) post MI, and increased risk (ejectionfraction [EF] b50% and/or proximal occlusion of a major vesselwith a large LV risk region). Major exclusion criteria were as inOAT. Each participating center had institutional review boardapproval, and patients were provided separate additional writteninformed consent for the OAT-NUC study protocol. The trial isregistered as Clinical trials.gov identifier NCT00119847.

Single-photon emission computed tomographyimaging and outcome measuresPatients were administered 0.4 mg sublingual nitroglycerin

followed by 25 to 30 mCi of technetium-99m sestamibi 5 to 10minutes later, and then imaged at rest 1 hour later using standardalgorithms optimized for each camera and computer system. Allimages were analyzed centrally at the Cardiac Imaging CoreLaboratory at Tufts Medical Center, blinded both to OATtreatment assignment and to SPECT study timing (baseline vs 1year), using standard quantitative techniques from validatedcommercially available software (4DM SPECT).7,8 The IZ wasidentified by areas falling below 60% of peak myocardial uptakein the OAT IRA territory confirmed by the OAT AngiographicCore Laboratory. Infarct size was the percent of the total LVprofile falling b60% peak uptake, a measure previouslycorrelated with other clinically relevant measures.9-12 For IZviability, a severity index was calculated by the software basedon the counts within the IZ and prospectively classified as“moderately-retained” for areas with average IZ uptake ≥40% ofpeak uptake, and “severely reduced” for areas b40% (Figure 1).

Figure 2

Enrolled in OAT-NUCN = 124

Randomized to PCIN = 61

Randomized to MEDN = 63

Lost to follow-up=2Died=4

BL or 1-yr data unusable=0

Lost to follow-up=3Died=3

BL or 1-yr data unusable=1

Paired data for infarct size& viability (1-year-BL)

N = 56

Paired data for infarct size& viability (1-year-BL)

N = 55

Paired data for Wall Motion(1-year-BL)

N = 53

Paired data for Wall Motion(1-year-BL)

N = 53

Enrolled between May 2004 and June

2006

20 of 217 OAT sites

90%

85%

Paired data for LVED, LVES, andEjection Fraction, (1-year-BL)

N = 5385%

Paired data for LVED, LVES, andEjection Fraction, (1-year-BL)

N = 52

OAT-NUC study enrollment and patient flow.

Udelson et al 613American Heart JournalVolume 161, Number 3

Patients with no identifiable IZ region (ie, no regions with b60%peak uptake) were included as having moderately retainedviability. Left ventricular EF (%), LV end-diastolic (EDV), and end-systolic volumes (ESV) (in milliliters) were calculated with anautomated software program.8 The use of gated SPECT for thedetermination of LV EF and volumes has been extensivelyvalidated.13-15 Wall motion was scored by one observer blindedto randomization group, using the standard 17-segment model,assigning scores ranging from 0 to 4 for wall motion rangingfrom normal to akinetic.

Statistical analysisData management and statistical analyses were performed by

an independent data coordinating center. Baseline clinical andindex MI characteristics including medication use at baselinehospital discharge and 1 year were assessed as frequencies/proportions or mean ± SD and compared with the remainingmain OAT patients and by treatment group PCI versus MED usingχ2 or Fisher tests. The primary end point of LV remodeling wasassessed by change in LV EDV from baseline to 1 year. Toevaluate the influence of retained IZ viability on extent of LVremodeling, change in LV volumes and EF were compared bybaseline viability. To evaluate the influence of treatment on LVremodeling, changes in LV volumes were compared by

treatment assignment PCI versus MED. To examine theinteraction between baseline IZ viability and treatment onextent of remodeling, the effect of PCI versus MED on change inLV volumes was compared among those with moderatelyretained versus severely reduced viability. Post hoc analyseswere also performed with viability as a continuous function.Intention-to-treat principle was used for all treatment-relatedanalyses except for an as-treated sensitivity analysis. Two-sided 2-group t tests at a = .05 were done for comparisons of changesfrom baseline to 1 year. Student t test was used to determine ifthe change from baseline to 1 year was different from 0 withineach treatment and/or viability group. It was estimated that witha targeted total sample size of 200 patients and a 25-mL predictedSD for 1-year EDV change, there would be 80% power to detect a14-mL difference in EDV change between viability groups andbetween treatment groups, with up to a 25% crossover and a 15%dropout rate. As described below, this sample size target was notreached, and with the observed SD of 26.9 mL and final achievedsample size of 124, post hoc analysis estimated that there was80% power to detect a difference of −15.0 mL for the primaryoutcome of change in LV EDV from baseline to 1 year. Reasonsfor not achieving the projected sample size included (1) OAT-NUC ancillary study began recruitment well after the parent OATstudy, (1) study startup at many sites was more prolonged than

Table I. Baseline characteristics of study cohort

OAT-NUC (n = 124)Remaining OAT

(n = 2077) P

Demographics n nAge (mean; y) 124 59 ± 11 2077 59 ± 11 .95Female (%) 26 21.0 458 22.0 .78Race (%)Black 3 2.4 66 3.2Hispanic 17 13.7 260 12.5Other 5 4.0 87 4.2 .95

Clinical historyHypertension (%) 66 53.2 1005 48.4 .30Diabetes (%) 21 16.9 433 20.8 .30On insulin (%) 7 5.6 117 5.6 1.00

Hypercholesterolemia (%) 64 51.6 1078/2076 51.9 .95Angina (%) 27 21.8 468 22.5 .84Prior MI (%) 8 6.4 239 11.5 .08Prior CHF (%) 3 2.4 49/2075 2.4 1.00Cerebrovascular disease (%) 11 8.9 71 3.4 .005Prior stroke (%) 9 7.3 54 2.6 .008Peripheral vascular disease (%) 2 1.6 81/2075 3.9 .33Family history of CAD (%) 52 41.9 831 40.0 .67Current smoker (%) 51 41.1 808 38.9 .62History of PCI (%) 3 2.4 102 4.9 .21Renal insufficiency (%) 2 1.6 28 1.4 .68

Clinical measuresBMI (kg/m2) 123 28 ± 5 2062 29 ± 5 .10Heart rate (beats/min) 124 70 ± 11 2074 72 ± 12 .12Systolic BP (mm Hg) 124 120 ± 15 2075 121 ± 18 .76Diastolic BP (mm Hg) 124 74 ± 10 2075 72 ± 11 .05

Index MIDays MI to randomization (median [IQR]) 124 14.5 [7-23] 2077 8.0 [5-16] b.001EF (mean; %) 122 48 ± 11 2063 48 ± 11 .61EF ≥50% (%) 53/122 43.4 962/2063 46.6 .49Highest Killip classes II-IV (%) 23 18.6 394/2068 19.0 .89STE/Q waves/R wave loss (%) 104 83.9 1801 86.7 .37

AngiographyIRALAD (%) 39 31.5 754 36.3LCX (%) 21 16.9 314 15.1RCA (%) 64 51.6 1009 48.6 .54

Multivessel disease (%) 25/123 20.3 354/2060 17.2 .37Collaterals: grade 1 or 2 (%) 108/123 87.8 1814/2050 88.5 .82Collaterals: grade 2 (%) 10/123 8.1 364/2050 17.8 .006

Values are presented as mean ± SD, unless otherwise indicated.CHF, Congestive heart failure; CAD, coronary artery disease; BMI, body mass index; BP, blood pressure; IQR, interquartile range; LAD, left anterior descending artery; LCX, leftcircumflex coronary artery; RCA, right coronary artery; STE, ST elevation.

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anticipated, (3) recruitment was slower than anticipated, and (4)the main OAT recruitment ended before the final OAT-NUCsample size was achieved; thus, recruitment in OAT-NUC wasrequired to stop as well.InOATand theOATancillary studies, aPb .01wasprespecified

for significance for all secondary analyses to limit type I error.Separate multivariable models were constructed for analysis ofthe change between baseline and 1 year in LV volumes and EF.The baseline values of ES Volume and EFwere included in the firststep of each corresponding stepwisemodel, and treatment group(PCI vs MED) was included in each step of the process. For EDV,the baseline measure was also included in each step. Baselineclinical and angiographic characteristics that were associated inunivariate analysis for each outcome measure (ie, P b .10) wereincluded in the corresponding multivariable model. For multivar-

iable models, stepwise linear regression with backward elimina-tionwas conducted,with a P value of .01 required for a variable tobe retained. Baseline infarct size and viability were tested forpossible inclusion in the models as both categorical andcontinuous functions. Because the models for 1-year change inLV volumes and EF had normally distributed residuals, thesemeasures were suitable for analysis with linear regression.Changes in EDV, ESV, wall motion (WM) index, andWM score

were not normally distributed andwerewinsorized then analyzedwith the t test.Winsorization is a method to control the variabilityintroduced by extreme values. This method typically identifiesthe top and bottom 5% and reduces them to the next highest (orlowest) value. This method permits the use of procedures thatrequire a normal distribution (ie, multiple regression) whilecontrolling the influence of these extreme values.16

Table II. OAT-NUC patient characteristics by treatment assignment

PCI (n = 61) MED (n = 63)

Pn % or mean ± SD n % or mean ± SD

DemographicsAge (y) 61 58.5 ± 11.5 63 58.6 ± 10.6 .93Female 15 24.6 11 17.5 .33Race black 1 1.6 2 3.2Hispanic (%) 9 14.8 8 12.7Other (%) 1 1.6 4 6.4 .65

Clinical historyHypertension 33 54.1 33 52.4 .85Diabetes 8 13.1 13 20.6 .26On insulin 1 1.6 6 9.5 .11

Hypercholesterolemia 29 47.5 35 55.6 .37Prior angina 12 19.7 15 23.8 .58Prior MI 3 4.9 5 7.9 .72Prior PCI 1 1.6 2 3.2 1.00Prior CHF 2 3.3 1 1.6 .62Cerebrovascular disease 5 8.2 6 9.5 .80Prior stroke 5 8.2 4 6.4 .74Peripheral vascular disease 2 3.3 0 0.0 .24Current smoker 24 39.3 27 42.9 .69Family history of CAD 22 36.1 30 47.6 .19

Clinical measuresBMI (kg/m2) 61 28.4 ± 4.6 62 27.2 ± 4.2 .16Heart rate (beats/min) 61 69.9 ± 10.9 63 70.4 ± 10.6 .77Systolic BP (mm Hg) 61 119.0 ± 15.2 63 121.7 ± 14.5 .31Diastolic BP (mm Hg) 61 73.4 ± 10.3 63 75.1 ± 9.4 .33Fasting glucose (mg/dL) 57 112.0 ± 48.7 62 109.3 ± 26.8 .72Estimated GFR30-59 7 11.5 7 11.160-89 35 57.4 34 54.0≥90 19 31.2 22 34.9 .90

Index MIDays from MI 61 14.7 ± 8.6 63 15.5 ± 7.8 .63EF (mean; %) 61 49.0 ± 12.1 61 47.4 ± 10.6 .44EF ≥50% 29 47.5 24/61 39.3 .36ST-elevation/Q wave/R loss 52 85.3 52 82.5 .68Killip classes II-IV 16 26.2 7 11.1 .03Mitral regurgitation 5/40 12.5 8/38 21.0 .31

AngiographyIRA

LAD 19 31.2 20 31.8LCX 11 18.0 10 15.9 .95RCA 31 50.8 33 52.4

Multivessel disease 9 14.8 16/62 25.8 .13Collaterals: grade 1 or 2 54 88.5 54/62 87.1 .81Collaterals: grade 2 5 8.2 5/62 8.1 1.00

Medications at hospital dischargeAspirin 59 96.7 60 95.2 1.00Thienopyridine (clopidogrel or ticlopidine) 52 85.2 26 41.3 b .001Warfarin 3 4.9 3 14.3 .08β-Blocker 56 91.8 62 98.4 .11Calcium-channel blocker 0 0.0 4 6.4 .12Lipid-lowering agent 56 91.8 62 98.4 .11Spironolactone 8 13.1 4 6.4 .20EF b40%: ACE inhibitor/ARB 12/12 100.0 13/13 100.0 1.00

Medications at 1 y (n = 41) (n = 47)Aspirin 39 95.1 38 80.8 .04Clopidogrel 8 19.5 6 12.8 .39Diuretic 10 24.4 15 31.9 .43β-Blocker 32 78.0 45 95.7 .01Ca blocker 1 2.4 4 8.5 .37

(continued on next page)

Udelson et al 615American Heart JournalVolume 161, Number 3

Table II (continued)

PCI (n = 61) MED (n = 63)

Pn % or mean ± SD n % or mean ± SD

Lipid-lowering agent 37 90.2 45 95.7 .41Spironolactone 4 9.8 5 10.6 1.00EF b40%: ACE inhibitor/ARB 7/9 77.8 7/8 87.5 1.00

CHF, Congestive heart failure; CAD, coronary artery disease; BMI, body mass index; BP, blood pressure;GFR, glomerular filtration rate; LAD, left anterior descending artery; LCX, leftcircumflex coronary artery; RCA, right coronary artery; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers.

616 Udelson et alAmerican Heart Journal

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ResultsBaseline characteristicsBetween May 2004 and June 2006, there were 124

patients enrolled in OAT-NUC at 20 sites in Australia,Austria, Brazil, Canada, Poland, and the United States(Figure 2). The patients in OAT-NUC were similar inclinical history to the rest of the main OAT studypopulation at baseline, except for a higher proportionof cerebrovascular disease (Table I).Among the OAT-NUC patients, those randomized to

PCI versus MED were also similar except for a trendtoward more Killip classes II to IV in the PCI group(Table II), more thienopyridine use among PCI patients,and more β-blockers use in the MED group at 1 year(Table II).At baseline, mean infarct size was 26% ± 18% of the

LV. Mean IZ viability was 43% ± 8% of peak uptake, andmost patients (70%; n = 87) had at least moderatelyretained viability with peak uptake ≥40%. Mean EF was48% ± 11%.Paired baseline and 1-year data were available for

infarct size and viability in 90% of the OAT-NUC studycohort and in 85% for LV volumes, EF, and wallmotion. Those with paired data were generally similarin clinical characteristics compared with those with-out paired data, though with less prior stroke (5% vs31%, P = .007) and cerebrovascular disease (5% vs38%, P = .002) and a trend toward fewer LCXinfarcts (P = .05).

Influence of baseline IZ viability on remodeling over1 yearThose with severely reduced IZ viability had signifi-

cantly larger mean EDV and ESV and lower EF atbaseline and 1 year, compared with those withmoderately retained viability (Figure 3, Table III).There were no significant changes in EDV or ESV foreither group. There was a trend toward greaterimprovement in EF among those with moderatelyretained viability compared with those with severelyreduced viability (between-group difference, P = .05)(Figure 3). Increasing baseline viability as a continuousvariable tended to predict improvement in EF (P = .05)but was not associated with 1-year EDV or ESV change.

Influence of treatment PCI versus MED on remodelingover 1 yearThere were no significant differences in 1-year change

in EDV, ESV, or EF when compared by treatment groupPCI versus MED (Figure 4, Table IV). There was similarimprovement in EF in both treatment groups (within-group changes, both P b .01). As-treated analysisaccounting for 12 failed PCIs, 1 PCI not done, and 2MED crossovers to PCI of IRA b30 days did not changethese estimates.

Interaction of treatment and baseline viability onremodeling over 1 yearNo significant interactions were found for any of the

measured remodeling changes; that is, treatment effectfor PCI versus MED did not differ by baseline viability(Table V). There was more improvement in EF amongthose with moderate compared with severely reducedviability in both PCI and MED groups. As-treated analysesdid not change these estimates, and there were nointeractions found with baseline viability analyzed as acontinuous function.

Multivariable analysesIn multivariable regression models predicting 1-year

change in ESV, EDV, and EF separately, treatmentassignment and baseline infarct size were not predictorsafter adjusting for all variables attaining significance levelsfor univariate associationwith the corresponding changesin outcome. However, increasing baseline viability as acontinuous variable was a significant predictor forincreasing change in EF following adjustment for clinicaland angiographic characteristics, but not for change inEDV or ESV. Treatment with PCI was not a significantpredictor in any of the multivariable models for remodel-ing changes in ESV, EDV, or EF (Table VI).

DiscussionThe results of this study suggest that in stable patients

studied in the subacute phase post-MI with a totallyoccluded IRA, there is no influence of baseline IZ viabilityon the extent of LV remodeling at 1 year. However, therewas an improvement in EF over 1 year in patients withmoderately retained viability. There was no benefit of PCI

Figure 3

One-year changes in end-diastolic (ED) and end-systolic (ES) volumes andEF, in patients with severe reduction in viability in the IZ (“b40%” of peaktracer uptake), compared with those patients with moderately preservedviability in the IZ (“≥40%” of peak tracer uptake). There were no significantbetween-group changes in ED or ES volume. Ejection fraction increasednominally more in the patients with moderately preserved viability.

Table III. Remodeling changes by baseline viability–paired data(winsorized for LV ED, LV ES, and WM)

Severelyreduced

viability <40%(n = 33)

Moderateretained

viability ≥40%(n = 79)

Pn Mean ± SD n Mean ± SD

LV ED volume (mL)Baseline 29 156.5 ± 44.6 76 114.0 ± 37.0 b.0011 y 29 148.1 ± 47.8 76 113.4 ± 37.7 b.001Change (1 y − baseline) 29 −8.3 ± 21.9 76 −0.57 ± 28.0 .18P value (within group) .05 .86

LV ES volume (mL)Baseline 29 95.5 ± 40.0 76 60.2 ± 29.7 b.0011 y 29 88.6 ± 41.0 76 55.7 ± 28.9 b.001Change (1 y − baseline) 29 −6.9 ± 20.3 76 −4.5 ± 20.6 .60P value (within group) 0.08 0.06

EF (%)Baseline 29 41.3 ± 11.5 76 49.2 ± 10.2 .0011 y 29 42.7 ± 13.3 76 53.6 ± 10.6 b.001Change (1 y − baseline) 29 1.4 ± 7.0 76 4.4 ± 7.0 .05P value (within group) .30 b.001

WM scoreBaseline 30 24.0 ± 6.9 76 15.3 ± 7.3 b.0011 y 30 18.8 ± 9.2 76 10.1 ± 8.1 b.001Change (1 y − baseline) 30 −5.2 ± 6.7 76 −5.2 ± 6.8 .98P value (within group) b.001 b.001

LV ED, Left ventricular end-diastolic dimension; LV ES, ventricular end-systolicdimension; WM, wall motion.

Udelson et al 617American Heart JournalVolume 161, Number 3

on 1-year change in EF or volumes and no interactionbetween the degree of retained viability and the extent ofremodeling in patients randomized to PCI versus MED.Thus, we did not find an important influence of IZ viabilityon remodeling, with or without revascularization, in thesetting of contemporary background therapy.The Open Artery Trial (TOAT) randomized 66 asymp-

tomatic, stable patients with an anterior MI, andproximal occlusion of the LAD to medical therapy orlate stenting—approximately 1 month post-MI. Theresults documented greater ESV and EDV at 1-yearfollow-up in the PCI group when compared withmedically treated patients.17 In contrast to the mainstudy findings, in a substudy of TOAT where viability wasassessed utilizing cardiac magnetic resonance imaging, asignificant relationship between viability and improve-ment in ESV and EF was seen in patients undergoing PCIbut not in medically treated patients.18

At baseline, patients in OAT-NUC had a high rate ofprescription of therapies documented to mitigate post-MILV remodeling when compared with prior trials.19

Importantly, OAT-NUC was a substudy of a randomizedtrial, with protocol-driven patient follow-up and optimi-zation of medical care. This approach likely led to areduction in the ability of nonpharmacologic factors toalter remodeling—a phenomenon previously reported.20

Factors other than IZ viability that may contribute to post-MI remodeling, such as enhanced sympathetic drive and

Figure 4

One-year changes in end-diastolic (ED) and end-systolic (ES) volumesand EF, in patients who were randomized to the OAT PCI strategycompared with those randomized to MED. There were no significantbetween-group changes in any of the parameters.

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β-adrenergic receptor down-regulation,21 could not bereadily assessed in this study. In addition, prior studiesand meta-analyses have shown a more profound impactof retained viability and revascularization on remodelingand clinical outcomes in those patients with the greatestdegree of LV functional impairment.5,22,23 It is plausiblethat the patient population in OAT-NUC with relativelypreserved baseline LV systolic function may have differedsignificantly from those in prior studies. The possibilityalso exists that the inability to detect an effect of IZviability or PCI on subsequent EDV and ESV could havebeen due to the relatively brief duration of follow-up inOAT-NUC. The time course of recovery of viablemyocardium can extend beyond 1 year,20 with someclinical trials documenting improvement in LV systolicfunction or clinical outcomes after N4 years.19,24-26

Several authors have suggested that IZ viability anddelayed revascularization have their greatest impact inthose patients with the most severe or extensiveischemia.19,27 Because OAT excluded patients with restangina and /or severe inducible ischemia, the patientpopulation in OAT-NUC differed from patients in priorstudies in this regard. In addition, it is not clear from priorstudies what proportion of patients actually had totalocclusion of the IRA, which was a critical inclusioncriterion of OAT.5,20,22,23,28

The Total Occlusion Study of Canada (TOSCA)-2 was amechanistic substudy of OAT that documented thatcoronary stenting resulted in significantly higher rates ofIRA patency at 1-year when compared with those patientssolely treated medically.29 Similar to OAT-NUC, bothstented and medically treated patients improved EF at1-year follow-up LV angiography with no between-groupdifference. In a subset of 42% of TOSCA 2 patients withpaired volumes measured 1 year apart, there was anapparent modest benefit of PCI on EDV index,29 althoughthere was no significant between-group difference whencompared with the medically treated group. Multivariableanalyses controlling for baseline LV volumes suggestedthat randomization to PCI therapy was an independentpredictor of a small absolute increase in EDV index.Whether this finding would have been verified in thewhole OAT cohort is unknown. This latter findingwas notobserved in the OAT-NUC data. Several variables werefound to be independently related to measures ofremodeling in multivariable analyses (Table VI). Potentialmechanisms underlying these noted associations arespeculative but would be of interest for generatingtestable hypotheses if confirmed in independent data sets.Strengths of OAT-NUC include a central core laborato-

ry, which performed systematic, standardized, blindedreadings. The population represents an important subsetof survivors of MI with the presented data providing themechanistic underpinnings to explain the outcome in themain trial.1 There are also important limitations to thepresent data set. The population sample represents a

Table IV. Remodeling changes by treatment group–paired data (winsorized for LV ED, LV ES, and WM)

PCI (n = 55) MED (n = 57) P value(betweengroups)n Mean ± SD n Mean ± SD

LV ED volume (mL)Baseline 53 118.9 ± 44.1 52 132.7 ± 42.7 .111 y 53 115.2 ± 43.5 52 131.0 ± 42.3 .06Change (1 y − baseline) 53 −3.7 ± 29.4 52 −1.7 ± 23.6 .70P value (within group) .36 .61

LV ES volume (mL)Baseline 53 64.3 ± 35.6 52 75.7 ± 36.5 .111 y 53 59.5 ± 35.3 52 70.1 ± 35.6 .13Change (1 y − baseline) 53 −4.8 ± 22.3 52 −5.6 ± 18.5 .84P value (within group) .13 .03

EF (%)Baseline 53 48.7 ± 11.0 52 45.2 ± 11.0 .111 y 53 51.8 ± 13.0 52 49.3 ± 11.8 .31Change (1 y − baseline) 53 3.1 ± 7.0 52 4.1 ± 7.2 .49P value (within group) .002 b.001

WM scoreBaseline 53 16.8 ± 8.5 53 18.7 ± 7.9 .261 y 53 11.6 ± 9.7 53 13.6 ± 8.7 .27Change (1 y − baseline) 53 −5.3 ± 7.5 53 −5.1 ± 5.8 .89P value (within group) b.001 b.001

LV ED, Left ventricular end-diastolic dimension; LV ES, ventricular end-systolic dimension; WM, wall motion.

Table V. Interaction—remodeling changes by baseline viability and treatment group–paired data (winsorized for LV ED, LV ES, and WM)

Severely reduced viability <40% Moderate retained viability ≥40%

InteractionP value

PCI (n = 13) MED (n = 20)

P

PCI (n = 42) MED (n = 37)

Pn Mean ± SD n Mean ± SD n Mean ± SD n Mean ± SD

LV ED volume (mL)Baseline 12 153.2 ± 52.2 17 158.8 ± 39.9 .75 41 108.9 ± 36.4 35 120.0 ± 37.4 .19 .751 y 12 142.6 ± 54.1 17 152.1 ± 44.2 .61 41 107.2 ± 36.9 35 120.7 ± 37.9 .12 .82Change (1 y − baseline) 12 −10.7 ± 26.1 17 −6.7 ± 19.2 .64 41 −1.7 ± 30.3 35 0.74 ± 25.3 .71 .90P value (within group) .18 .17 .72 .86

LV ES volume (mL)Baseline 12 88.4 ± 44.8 17 100.5 ± 36.7 .43 41 57.2 ± 29.5 35 63.7 ± 30.1 .35 .701 y 12 82.7 ± 48.0 17 92.8 ± 36.2 .52 41 52.7 ± 27.8 35 59.1 ± 30.0 .34 .80Change (1 y − baseline) 12 −5.8 ± 22.1 17 −7.7 ± 19.5 .80 41 −4.5 ± 22.7 35 −4.5 ± 18.2 .99 .84P value (within group) .39 .12 .21 .15

EF (%)Baseline 12 44.8 ± 12.6 17 38.9 ± 10.3 .18 41 49.9 ± 10.4 35 48.3 ± 10.1 .52 .351 y 12 45.9 ± 16.8 17 40.4 ± 10.2 .28 41 53.5 ± 11.3 35 53.6 ± 10.0 .96 .27Change (1 y − baseline) 12 1.2 ± 8.6 17 1.5 ± 5.9 .89 41 3.7 ± 6.5 35 5.3 ± 7.6 .32 .68P value (within group) .65 .30 b.001 b.001

WM scoreBaseline 12 23.2 ± 7.8 18 24.6 ± 6.5 .60 41 15.0 ± 7.8 35 15.6 ± 6.8 .71 .811 y 12 17.7 ± 10.4 18 19.6 ± 8.6 .59 41 9.8 ± 8.9 35 10.5 ± 7.2 .71 .75Change (1 y − baseline) 12 −5.5 ± 7.7 18 −5.0 ± 6.1 .84 41 −5.2 ± 7.6 35 −5.1 ± 5.8 .96 .89P value (within group) .03 .003 b.001 b.001

LV ED, Left ventricular end-diastolic dimension; LV ES, ventricular end-systolic dimension; WM, wall motion.

Udelson et al 619American Heart JournalVolume 161, Number 3

nonconsecutive series of patients enrolled in the mainOAT study who consented to participate in this substudy.Due to the limited number of enrolled patients in OAT-NUC (as well as the insufficient recruitment relative toinitial projections), there was not enough power to

detect small differences in remodeling between thecomparison groups if indeed the study hypothesis iscorrect. Finally, it is conceivable that between-groupdifferences may have become apparent had the patientsbeen followed for a longer period of time. However,

Table VI. Univariate and multivariable predictors of remodelingchanges (1 y − BL)

nParameterestimate P

LV ED volumeUnivariate predictorsPCI treatment 105 2.02 .70BL ED volume (continuous) 105 −0.19 .002BL viability (continuous) 105 0.44 .22BL infarct size (continuous) 105 −0.15 .35Prior CHF 105 40.49 .03Current smoker 105 −12.62 .02Systolic BP b140 mm Hg 105 −15.75 .05Killip class II-IV index MI 105 −18.21 .004Mitral regurgitation 1-4 66 12.39 .02IRA LAD 105 −17.99 .001Fasting glucose/10 102 1.31 .04

Multivariable modelPCI treatment 102 −4.98 .28BL ED volume (continuous) 102 −0.15 .01Current smoker 102 −14.95 .002Fasting glucose/10 102 1.76 .002IRA LAD 102 −14.81 .006

LV ES volumeUnivariate predictorsPCI treatment 105 −0.80 .84BL ES volume (continuous) 105 −0.18 .001BL viability (continuous) 105 0.21 .44BL infarct size (continuous) 105 −0.13 .27Killip class II-IV index MI 105 −11.39 .02IRA LAD 105 −13.06 .002

Multivariable modelPCI treatment 105 −1.25 .75BL ES volume (continuous) 105 −0.18 .001

EFUnivariate predictorsPCI treatment 105 0.96 .49BL EF (continuous) 105 −0.08 .19BL viability (continuous) 105 0.18 .05BL infarct size (continuous) 105 −0.03 .54Female 105 4.52 .008

Multivariable modelPCI treatment 105 −1.20 .36BL EF (continuous) 105 −0.20 .004BL viability (continuous) 105 0.29 .005Female 105 5.06 .003

Univariate predictors include those with P b .10 and forced BL variables. Allmultivariable models: P = .01 to remain. Mitral regurgitation NOT in initialmultivariable models. With mitral regurgitation in model, no significant predictorsfound. EDV: at P = .05 to remain in model, predictors also included prior CHF; ESV: atP = .05 to remain in model, predictors also included current smoking, fasting glucose,LAD IRA, and diastolic BP; EF: same results with P = .05.BL, Baseline; LV ED, left ventricular end-diastolic dimension; CHF, congestive heartfailure; BP, blood pressure; IRA LAD, infarct-related artery left anterior descendingcoronary artery; LV ES, ventricular end-systolic dimension.

620 Udelson et alAmerican Heart Journal

March 2011

there was no signal of an apparent effect on remodelingin this population sample. The findings presented hereare consistent with the absence of effect of PCI on clinicaloutcomes including heart failure hospitalization over 3.2-years average follow-up in the main OAT population.1

Hence, the data from the OAT-NUC study suggest thatin the contemporary era of comprehensive postinfarctionmedical therapy, IZ viability does not influence LV

remodeling nor the remodeling response to PCI, asopposed to medical therapy alone. The data also suggestthat residual IZ viability fails to identify a subgroup ofclinically stable post-MI patients with total occlusion ofthe IRA who will accrue a remodeling benefit over a1-year observation as a consequence of revascularizationduring the subacute phase of MI.

DisclosuresThe authors have no conflicts of interest to disclose

related to this work. The content is solely the responsi-bility of the authors and does not necessarily represent theofficial views of the National Heart, Lung, and BloodInstitute or the National Institutes of Health (NIH). Werequest the Journal to acknowledge that the authorretains the right to provide a copy of the final manuscriptto the NIH upon acceptance for journal publication, forpublic archiving in PubMedCentral as soon as possible butno later than 12 months after publication by the Journal.

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