primary percutaneous coronary intervention for acute st elevation myocardial infarction outcomes and determinants of outcomes a tertiary care center study from north india

The overall in hospital mortality seen in our trial was significantlyhigherthanthe5–9%mortalityreportedfromlarge registriesfromwesterncountries18,19andfromIndianstudies.3,4,10 Thehighermo

Original Article

1 Introduction

Coronaryarterydisease(CAD)isoneoftheleadingcausesof

mortality worldwide with increasing incidence in developing

countrieslikeIndia.1AcuteSTEMIisthemostlethalpresentationof

CADwithmortalityratesincommunityrangingfrom15to20%.2

Acute STEMI accounted for 60% and 37% of acute coronary

syndromes in India as per CREATE3 and Kerala ACS registries4

respectivelyandwasassociatedwithhighestmortalityamongthe

ACSspectrum

Primarypercutaneouscoronaryintervention (PCI)hasbeen

established as thetreatment of choice for patients presenting

withacuteSTelevationmyocardialinfarction(STEMI).However

widespread availability and affordability of primary PCI is still an important consideration in our country As per the latest data from Kerala ACS registry,4 only 19.6% of STEMI patientsunderwentcoronaryangiographyand12.9%underwent primaryPCI

To achieve optimalresults withprimary PCI it needs to be performedinatimelymannerathighvolumecentersbyexpert operators.WhetherresultssimilartothosereportedfromWestcan

beachievedinoursettingsornot,isnotknown.So,thisstudywas conductedwithintenttolookintotheoutcomesofprimaryPCI performedatatertiarycarecenterinNorthIndia

2 Methods 2.1 Studydesign This was an observational prospective study of consecutive STEMIpatientsundergoingprimaryPCIattheAllIndiaInstituteof

Keywords:

STEMI

Background: Primarypercutaneouscoronaryintervention(PCI)isthecurrentstandardofcareforacute

STelevationmyocardialinfarction(STEMI).MostofthedataonprimaryPCIinacuteSTEMIisfrom westerncountries.WestudiedtheoutcomesofprimaryPCIforacuteSTEMIatatertiarycarecenterin NorthIndia

Methods:ConsecutivepatientsundergoingprimaryPCIforSTEMIwereprospectivelystudiedduringthe periodfromFebruary2103toMay2015.Theoutcomesassessedwereallcauseinhospitalmortality, factorsassociatedwithmortality,majoradversecardiacandcerebrovasculareventrate(compositeofall causeinhospitalmortality,non-fatalreinfarctionandstroke)andproceduralcomplications Results:371patientsunderwentprimaryPCIduringthestudyperiod.Themeanagewas54yearsand 82.7%weremales.Themeantotalischemiatimeanddoortoballoontimeswere6.8hand51min respectively.96.4%patientsunderwentsuccessfulprimaryPCI.Thetotalinhospitalmortalitywas12.9% Mortalitywithcardiogenicshockatpresentationwas66.7%whilenon-shockmortalitywas2.6%.In hospitalMACCEratewas13.5%.FactorssignificantlyassociatedwithmortalitywereKILLIPclass(OR: 8.4),doortoballoontime(OR1.02),finalTIMIflow(OR0.44)andsevereLVdysfunction(OR22.0) Procedurerelatedadverseeventswererareandtherewasnonon-CABGassociatedmajorTIMIbleeding Conclusion:PrimaryPCIforacuteSTEMIisfeasibleinoursetupandassociatedwithhighsuccessrate, lowmortalityinnon-shockpatientsandlowcomplicationrates

ß2016PublishedbyElsevierB.V.onbehalfofCardiologicalSocietyofIndia.Thisisanopenaccessarticle

undertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/)

ContentslistsavailableatScienceDirect

j our na l ho me p a ge : w ww e l se v i e r com / l oc a te / i h j

http://dx.doi.org/10.1016/j.ihj.2016.11.322

creativecommons.org/licenses/by-nc-nd/4.0/ ).

2013toMay2015.AllpatientspresentingwithacuteSTelevation

MIandundergoingprimaryPCIwereincludedinthestudy.STEMI

Patientsmanagedwiththrombolytictherapy,orpatients

under-goingrescueorfacilitatedPCIwereexcludedfromthestudy

Alltheincludedpatientswerefolloweduptilldischargefrom

the hospital or in hospital death and pertinent data were

prospectivelycollected.Thestudywasethicallyapprovedbythe

InstituteEthicsCommittee

2.2 PrimaryPCIprocedure

Selection of patients for primary PCI was as per guideline

recommendations.5Allpatientspresentingwithin12hofonsetof

symptomswereconsidered forprimaryPCI.Patientspresenting

between12and24hofonsetofsymptomswerealsotakenupfor

primaryPCIiftheyhadongoingischemicsymptoms

Catheterizationteamwasactivatedimmediatelyon

confirma-tion of STEMI diagnosis After loading with dual antiplatelets,

patientswereimmediatelyshiftedtocatheterizationlaboratory

Aftergainingvascularaccess,non-culpritvesselangiogramwas

done first followed by the culprit vessel angiogram Once the

decision togo ahead withangioplasty was taken, heparin was

administeredindosageof70–100U/kgtoachieveanACTof250–

300.GPIIb/IIIainhibitorusewaslefttooperator’sdiscretion.The

choiceofguidewire,balloon,stent,thrombusaspirationandIABP

wason operator’s discretion Manual thrombus aspiration was

done with the ‘‘Thrombuster’’ thrombus aspiration catheter

(Atrium,OsakaJapan)

Onlyculpritvesselangioplastywasdoneexceptincaseswith

cardiogenic shock where non-culprit angioplasty was also

considered.Postprocedurepatientswereimmediatelyshiftedto

CCU.SheathswereremovedonceACTwasbelow180

HemodynamicallystablepatientswerekeptinCCUfor24–48h

andsubsequentlyshiftedtostepdownunitandweredischarged

on4thor5thday.Atdischargestatinsindoseof40–80mgand

dualantiplatelet(DAPT)agents wereprescribedtoallpatients

ACEI/ARB and beta blockers were used in all patients without

contraindicationsfortheiruse

2.3 Outcomes

Theoutcomesstudiedwereallcauseinhospitalmortalityrate,

factors associated with mortality, Major adverse cardiac and

cerebrovascularevents(MACCE)andproceduralcomplicationrate

2.4 Definitions

STEMI:Itwasdefinedassymptomsofischemiaassociatedwith

ST-segmentelevationof1mminlimbleadsand/or2mmin

chestleads in 2 contiguous leads, or newleft bundlebranch

block,ortrueposteriormyocardialinfarctionwithSTdepressionof

1mmin2contiguousanteriorleads

Cardiogenicshock:Persistenthypotensionwithsystolicblood

pressurelessthan90mmHgforatleast30min,despiteadequate

fluid administration and associated with features of tissue

hypoperfusion

Severe LV dysfunction: It was defined as left ventricular

ejectionfraction30%byechocardiography

Dyslipidemia: Fastinglipidprofile valuesweretakenwithin

24hofpresentationwithdyslipidemiadefinedaspresenceofone

ormoreoffollowingcharacteristics:

Totalcholesterol200mg/dl,LDLcholesterol130mg/dl,HDL

cholesterol 40mg/dl in males, 50mg/dl in females and/or

triglycerides150mg/dl

Total ischemia time: Time fromthe onset of symptoms to revascularization

Doorto balloontime: Timefromarrival at theInstituteto revascularization

Successful PCI: PCI success wasdefined as achievement of vesselpatencywitharesidualstenosisof<20%

Re-infarction: It was defined as recurrence of ischemic symptomswithnewECGchangessuggestiveofre-infarction Majorbleeding:ItwasdefinedasperstandardTIMIcriteria6

fornonCABGandCABGassociatedbleeding

Significantnon-infarct relatedartery(IRA) disease:Itwas definedaspresenceof70%diseaseinepicardialvesselotherthan the culprit vessel Cut-off of 50% was used for diagnosis of significantleftmaindisease

MACCE:Itwasdefinedasacompositeofallcauseinhospital mortality,non-fatalreinfarctionandstroke

2.5 Statisticalanalysis The data analysis wasdone with ‘STATA 13’ (STATA CORP, Texas,USA).Quantitativevariablesarepresentedasmean stan-standarddeviation Categoricalvariablesare presentedas percen-tages The chi square test was used to analyze association of categoricalvariableswiththeprimaryoutcome.Logisticregression analysiswasusedtoanalyzetheassociationbetweenquantitative variablesandtheprimaryoutcome.Multivariatelogisticregression analysiswasusedtostudytheindependentassociationofvariables withtheprimaryoutcome

3 Results 3.1 Studypopulation Overall383patients presentedwithacute STEMIduringthe studyperiod.Ofthese,7patientsdiedin theemergencybefore beingshiftedforprimaryPCIand5didnotconsentforprimaryPCI and were thrombolysed The study included the remaining

371patients who underwent primaryPCI at theinstitutefrom February 2013 to May 2015 Baseline characteristics of these patientsarepresentedinTable1.Ofthe371patients,almost83% were males Mean ageof thepatients was 54 years with12% patientsbelow40yearsofage

Amongcoronaryrisk factorsnotablewashighprevalence of smoking (57%) and relatively lower prevalence of dyslipidemia (18.6%) Importantly 37 patients (10%) had no conventional coronaryriskfactors

Themeantotalischemiatimeanddoortoballoontimeswere 6.8h and 51min respectively Anterior wall MI was the commonestpresentationandalmosthalfofthepatientswerein KILLIP class I A relatively highpercentage of patients werein KILLIPIVatpresentation

3.2 Angiographicandproceduralvariables(Table2) Femoralwasthepreferredrouteinmajorityofcases.Significant non-infarctrelatedarterydiseasewaspresentin50%ofcaseswith 26% having triple vessel disease (TVD) and 24% double vessel disease(DVD)

PCIwassuccessfulinalmost96%ofcaseswithmajorityofthem receivingstents.GlycoproteinIIb/IIIainhibitorswereusedin83%

ofpatients,initiatedinthecatheterizationlaboratory

EmergencyCABGwasdonein5patients,indicationbeingleft main CAD in one,triple vesseldisease in one,failure tocross guidewireintwoandsevereMRinonepatient

3.3 Mortality

Totalall cause in hospital mortality was12.9% (48 deaths)

Meanduration of hospitalstayprior todeath was2.2 days.Of

these,almost60%diedwithin24hofadmission.Mortalityrates

variedsignificantlywithinthecohort.Thoseinwhomcardiogenic

shockwasinitialpresentationhadanin-hospitalmortalityrateof 66.7% as compared to 2.6% in those not in cardiogenic shock EmergencyCABGwasassociatedwithinhospitalmortalityof60% Cardiogenic shock was the most common cause of death accountingfor77%ofdeathsfollowedbyCHFin10%andVT/VFin 8% One patient died from hospital acquired pneumonia with severesepsisandonepatientdiedfromLVfreewallrupture Factors significantly associated with mortality (Table 3) on multivariateanalysisweretheKILLIPclass,doortoballoontime, thefinalTIMIflowandpresenceofsevereLVdysfunction.Thosein KILLIP class four had eight-fold higher risk of mortality as comparedtoothers.Increaseinthedoortoballoontimebyone minuteleadto2%increaseinmortalityrates.FinalTIMI3flowwas associatedwithalmost60%lowermortalityascomparedtothose withoutTIMI3flow.Theriskofdeathwas22-foldhigherinthose withsevereLVdysfunction

3.4 Complications(Table4) Complicationsrelatedtovascularaccesswereinfrequentwith only 2.7% having local hematomas.All of them weremanaged conservativelyandnonerequiredtransfusionorreinterventionfor thesame.TherewerenopseudoaneurysmorAVfistulas Twopatientshadre-infarctionsinthesameterritoryduringthe indexhospitalstayandwerecausedbysubacutestentthrombosis Bothweremanagedsuccessfullywithballoonangioplasty.There wasnonon-CABGrelatedTIMImajorbleeding,whiletwopatients had CABG related major bleeding namely requiring more than

5unitsofpackedRBCtransfusionsduring48h.ThetotalMACCE rate was13.5% including 48 mortalitiesand two re infarctions secondarytostentthrombosis.Therewerenostrokesinourstudy population

indicated.

3.5 Dischargemedications

The mean duration of hospital stay prior to discharge was

approximately5 days Guideline directed medical therapy was

providedtoallthepatientsatdischarge.Dualantiplatelettherapy

and statins were prescribed to all the discharged patients

(323,100%) Beta blockers were prescribed to 80% patients at

dischargewhileAcei/ARBswereprescribedto85%ofdischarged

patients

4 Discussion

ThisisthefirstlargescaleregistrydataonprimaryPCIforacute

STEMIfromourInstituteandNorthIndia.The247freeprimary

PCIprogramatourInstitutewasinitiatedinFebruary2013,and

overaperiodof2yearsand3months,almost97%ofacuteSTEMI

patients(371outof383)underwentprimaryPCI.Inthisstudy,we

havereportedthedemographic,clinicalandangiographicfeatures

andoutcomesofthesepatients

Themeanageofpatientsinthisstudy(54years)wasalmosta

decadelesserthan thewesternpopulation.7,8Theearlier

occur-renceofacuteMIinSouthEastAsianpopulationiswellestablished

fact.3,9,10The possible reasonsfor earlier occurrence ofCAD in

SouthEastAsianpatientsaremultipleincludinggenetic

predispo-sition,higher prevalence ofabdominal obesity, higher

Apolipo-protein(Apo)B/ApoA1ratioetc

Amongriskfactorssmokingwasthemostwidelyprevalentrisk

factor, especially among the younger population (less than

40 years), often being the sole risk factor The percentage of

current smokers in this study is higher than that seen in

American11 and European registries.12 This high prevalence of

smoking in Indians has been documented earlier also,13 with

stronger association with coronary artery disease in younger

individuals.14

Dyslipidemia was another risk factor which needs special

mention.Itwasseenin18.6%ofourpatientswhichissignificantly

lowerthanthatseeninwesternpopulation.15,16Howeverstudies

fromIndia10,17haveconsistentlyreportedalowerprevalenceof

dyslipidemiaasseeninourstudy.ThehigherriskofCADevenin

absenceofdyslipidemiaascurrentlydefined,signifiestheneedof

redefiningormodifyingthecutoffsfortheIndianpopulation

Meantotalischemiatime(6.9h)inourstudywassignificantly

longer than that reported in studies from South India10 and

westerncountries.1,11Onepossiblereasonforhighermeantotal

ischemia time was inclusion of patients with duration of

symptoms between 12 and 24h with ongoing ischemia or

cardiogenicshock Lackof awareness among patients and long

traveltimes alsoaccountedfor longer totalischemiatime The

KeralaACSregistry4alsoreportedthatadiagnosisofSTEMIwas

associatedwithhigher probabilityof symptom todoor time of

morethan6handlackofanyformaleducation

The mean door to balloon time, a measure of operational

efficacy of system, was 51min in our study, well below the

recommended limit of 90min This is comparable to door to

balloontimesachievedinstudiesfromwest8andothercentersin

ourcountry.10Wecouldachievegooddoortoballoontimesdueto

coordinatedeffortsoftheemergencymedicalteam,a247ready

to operate catheterizationlaboratory and a dedicated team of

experiencedinterventionalcardiologist

The overall in hospital mortality seen in our trial was

significantlyhigherthanthe5–9%mortalityreportedfromlarge

registriesfromwesterncountries18,19andfromIndianstudies.3,4,10

Thehighermortalityrateseemstobedrivenmainlybythehigh

percentage of patients with cardiogenic shock in this study

However,themortalityratesinpatientswhowerenotinshockat

initial presentation was only 2.6% which is compatible with mortalityseeninlargerandomizedcontrolledtrials.20,21

Asmentionedearlier,thepercentageofpatientswith cardio-genicshockatpresentation(16%)wassignificantlyhigherthan7– 10% incidence of shock reported in other studies on acute myocardial infarction.22,23 Longer total ischemia time, high percentage of anterior wall MIand inclusion of all patients in cardiogenicshock forprimary PCI irrespective oftime delay as endorsedbyrecent guidelines,5seem toberesponsibleforthis highpercentageofcardiogenicshockinourstudy

Thefactorsassociatedwithmortalityonmultivariateanalysis were door to balloon time, KILLIP class, final TIMI flow and presenceof severeLV dysfunction.This datais consistentwith findings ofotherstudieslookingintopredictors ofmortalityin patientsundergoingprimaryPCI.24,25

Amongcomplications,notablefeatureofourstudywaslackof anynon-CABGrelatedTIMImajorbleedingdespiteextensiveuse

of potent DAPT, heparin and GPIIb/IIIa inhibitors Careful monitoring of ACT, avoidance of GP IIb/IIIa in elderly patients andrestrictionoftheiruseinpatientswithACTabove300were keycomponentsinavoidingexcessivebleeding Alsoreassuring wasabsenceofanystrokeinourstudy.Thrombusaspirationina recent large trial26 showed increased risk of stroke (0.7%) at

30days.Thiswasnotseeninourstudy

4.1 Limitations Themainlimitationofthisstudywasitsobservationalnature The lack of randomization precludes assessment of impact of therapies like GPIIb/IIIa, thrombus aspiration, IABP etc on mortality.Also,thiswasasinglecenterstudyconductedatahigh volumetertiarycareteachingInstituteandresultsobtainedmay notbeapplicableatlessercenterswithlowercasevolumes.Finally, there wasno follow upin this study and long termoutcomes remainunknown

5 Conclusion Promptprimarypercutaneouscoronaryinterventionforacute STEMIisfeasibleinoursetupandisassociatedwithhighsuccess rate,lowmortalityratesinnon-shockpatientsandlow complica-tion rates The mortality associated with cardiogenic shock continuestobehigh.Importantpredictorssignificantlyassociated withmortalityarethedoortoballoontime,Killipclass,finalTIMI flowandsevereLVdysfunction

Conflictsofinterest Theauthorshavenonetodeclare

Acknowledgements

Wethankallourpatientsandtheentirecardiologydepartment

attheAllIndiaInstituteofMedicalSciencesfortheircooperation TheprimaryPCIprogrammewasgovernmentsponsoredandno specificgrantpersewasreceivedforthestudyitself

References

1 Fox KAA, Goodman SG, Klein W, et al Management of acute coronary syndromes Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE) Eur Heart J 2002;23(August (15)):1177–1189.

2 Canto JG, Rogers WJ, Chandra NC, et al The association of sex and payer status on management and subsequent survival in acute myocardial infarction Arch Intern Med 2002;162(March (5)):587–593.

3 Xavier D, Pais P, Devereaux PJ, et al Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data Lancet Lond Engl 2008;371(April (9622)):1435–1442.

4 Mohanan PP, Mathew R, Harikrishnan S, et al Presentation, management, and

outcomes of 25 748 acute coronary syndrome admissions in Kerala, India: results

from the Kerala ACS Registry Eur Heart J 2013;34(January (2)):121–129.

5 O’Gara PT, Kushner FG, Ascheim DD, et al 2013 ACCF/AHA guideline for the

management of ST-elevation myocardial infarction: executive summary: a report

of the American College of Cardiology Foundation/American Heart Association

Task Force on Practice Guidelines Circulation 2013;127(January (4)):529–555.

6 Mehran R, Rao SV, Bhatt DL, et al Standardized bleeding definitions for

cardiovas-cular clinical trials: a consensus report from the Bleeding Academic Research

Consortium Circulation 2011;123(June (23)):2736–2747.

7 Steg PG, Goldberg RJ, Gore JM, et al Baseline characteristics, management

prac-tices, and in-hospital outcomes of patients hospitalized with acute coronary

syndromes in the Global Registry of Acute Coronary Events (GRACE) Am J Cardiol.

2002;90(August (4)):358–363.

8 Gibson CM NRMI and current treatment patterns for ST-elevation myocardial

infarction Am Heart J 2004;148(November (5 suppl)):S29–S33.

9 Yusuf S, Hawken S, Ounpuu S, et al Effect of potentially modifiable risk factors

associated with myocardial infarction in 52 countries (the INTERHEART study):

case–control study Lancet Lond Engl 2004;364(September (9438)):937–952.

10 Subban V, Lakshmanan A, Victor SM, et al Outcome of primary PCI – an Indian

tertiary care center experience Indian Heart J 2014;66(January (1)):25–30.

11 Rogers WJ, Canto JG, Lambrew CT, et al Temporal trends in the treatment of over

1.5 million patients with myocardial infarction in the US from 1990 through 1999:

the National Registry of Myocardial Infarction 1, 2 and 3 J Am Coll Cardiol.

2000;36(December (7)):2056–2063.

12 Mandelzweig L, Battler A, Boyko V, et al The second Euro Heart Survey on acute

coronary syndromes: characteristics, treatment, and outcome of patients with ACS

in Europe and the Mediterranean Basin in 2004 Eur Heart J 2006;27(October

(19)):2285–2293.

13 Gupta R, Gupta VP, Sarna M, et al Prevalence of coronary heart disease and risk

factors in an urban Indian population: Jaipur Heart Watch-2 Indian Heart J.

2002;54(February (1)):59–66.

14 Sharma M, Ganguly NK Premature coronary artery disease in Indians and its

associated risk factors Vasc Health Risk Manag 2005;1(3):217–225.

15 Canto JG, Kiefe CI, Rogers WJ, et al Atherosclerotic risk factors and their association

with hospital mortality among patients with first myocardial infarction (from the

National Registry of Myocardial Infarction) Am J Cardiol 2012;110(November (9)):1256–1261.

16 Vedre A, Gurm HS, Froehlich JB, et al Impact of prior statin therapy on arrhythmic events in patients with acute coronary syndromes (from the Global Registry of Acute Coronary Events [GRACE]) Am J Cardiol 2009;104(December (12)):1613–1617.

17 Victor SM, Subban V, Alexander T, et al A prospective, observational, multicentre study comparing tenecteplase facilitated PCI versus primary PCI in Indian patients with STEMI (STEPP-AMI) Open Heart 2014;1(1):e000133.

18 Rogers WJ, Frederick PD, Stoehr E, et al Trends in presenting characteristics and hospital mortality among patients with ST elevation and non-ST elevation myo-cardial infarction in the National Registry of Myocardial Infarction from 1990 to

2006 Am Heart J 2008;156(December (6)):1026–1034.

19 Roe MT, Messenger JC, Weintraub WS, et al Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention J Am Coll Cardiol 2010;56(July (4)):254–263.

20 Grines CL, Browne KF, Marco J, et al A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction The Primary Angioplasty in Myocardial Infarction Study Group N Engl J Med 1993;328(March (10)):673–679.

21 Cannon CP, Gibson CM, Lambrew CT, et al Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction JAMA 2000;283(June (22)): 2941–2947.

22 Goldberg RJ, Gore JM, Alpert JS, et al Cardiogenic shock after acute myocardial infarction Incidence and mortality from a community-wide perspective, 1975 to

1988 N Engl J Med 1991;325(October (16)):1117–1122.

23 Killip T, Kimball JT Treatment of myocardial infarction in a coronary care unit.

A two year experience with 250 patients Am J Cardiol 1967;20(October (4)): 457–464.

24 Halkin A, Singh M, Nikolsky E, et al Prediction of mortality after primary percuta-neous coronary intervention for acute myocardial infarction: the CADILLAC risk score J Am Coll Cardiol 2005;45(May (9)):1397–1405.

25 Caixeta A, Lansky AJ, Mehran R, et al Abstract 20882: predictors of suboptimal TIMI flow after primary angioplasty for acute myocardial infarction: results from the HORIZONS-AMI trial Circulation 2010;122(November (21 suppl)):A20882.

26 Jolly SS, Cairns JA, Yusuf S, et al Randomized trial of primary PCI with or without routine manual thrombectomy N Engl J Med 2015;372(April (15)):1389–1398.