Coronary Artery Coronary Artery DiseaseDisease

Andrew C RankinAndrew C Rankin

Glasgow Royal InfirmaryGlasgow Royal Infirmary

AsymptomaticAsymptomatic Myocardial Myocardial InfarctionInfarction

AnginaAngina

UnstableUnstableanginaangina

Coronary Artery DiseaseCoronary Artery Disease

Atherosclerosis TimelineAtherosclerosis TimelineFoamFoamCells Cells

FattyFattyStreak Streak

IntermediateIntermediateLesion Lesion AtheromaAtheroma

FibrousFibrousPlaquePlaque

ComplicatedComplicatedLesion/Lesion/RuptureRupture

Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104).

From FirstDecade

From ThirdDecade

From FourthDecade

Endothelial DysfunctionEndothelial Dysfunction

Risk Factors for Atherosclerotic Disease

Hoeg JM. JAMA. 1997;277:1387–1390.

Non-modifiable

AgeFamily historySex

Modifiable

Cigarette smokingDiabetes mellitusHyperlipidemiaHypertensionObesityPhysical inactivity

Right Coronary Artery

Posterior Descending Artery

Left Main Coronary Artery

Diagonal Artery

Left Anterior Descending Artery

Coronary arteriesCoronary arteries

Coronary AngiographyCoronary Angiography

Left coronary arteryLeft coronary artery

Coronary AngiographyCoronary Angiography

Right coronary arteryRight coronary artery

JapanFrance

SpainPortugal

MexicoItaly

GreeceLuxembourg

NetherlandsCanada

AustraliaGermany

AustriaUSA

Sweden

DenmarkNorway

PolandUK

FinlandRomania

IrelandCzech Republic

HungaryLithuania

Russian FederationLatvia

0200400600800 200 4001000

Death rates from CHD, (per 100,000) men and women aged 35-74, 1994, selected countries

men

women

PP

QQ

RR

SS

T waveT wave

Mechanisms of Action of Mechanisms of Action of Anti-Anginal DrugsAnti-Anginal Drugs

Improve Blood SupplyImprove Blood Supply• Coronary VasodilatationCoronary Vasodilatation

Reduce Cardiac WorkloadReduce Cardiac Workload• Slow Heart RateSlow Heart Rate• Reduce Force of ContractionReduce Force of Contraction• Reduce Pre-load / After-loadReduce Pre-load / After-load

AntianginalsAntianginals Adalat LAAdalat LAAdipine MRAdipine MRAdizem-XLAdizem-XLAngiopine MRAngiopine MRAngitil SRAngitil SRBeta-AdalatBeta-AdalatBeta-PrograneBeta-PrograneBetalocBetalocBetimBetimBlocadrenBlocadrenBritiazimBritiazimCardeneCardeneCardilate MRCardilate MRCedocardCedocard

CoractenCoractenCordiloxCordiloxCorgardCorgardCoro-NitroCoro-NitroDeponitDeponitDilzem SRDilzem SRElantan Elantan LALAEmcorEmcor

GlytrinGlytrinIkorelIkorelImdurImdurInderal LAInderal LAIsib 60XLIsib 60XLIsmoIsmo

IsoketIsoketIsordilIsordilIstinIstinLopresorLopresorMCR-50MCR-50MinitranMinitranMonitMonitMono-CedocardMono-CedocardMonocorMonocorMonomaxMonomaxMyocardolMyocardolNitro-DurNitro-DurNitrocineNitrocineNitrolingualNitrolingual

NitronalNitronalPercutolPercutol

Probeta LAProbeta LASectralSectralSecuron SRSecuron SRSlow-TrasicorSlow-TrasicorSlozemSlozemSorbichewSorbichewSorbidSASorbidSASorbitrateSorbitrateSuscardSuscardSustacSustac

TenifTenifTenorminTenormin

Tildiem LATildiem LATotamolTotamolTrandateTrandateTransidermTransidermTrasicorTrasicorUniverUniver

ViskenVisken

EucardicEucardic

IsocardIsocard NitrominNitromin

PlendilPlendilPosicorPosicor

Syscor MRSyscor MR

Viazem XLViazem XL

Tensipine MRTensipine MR

Drug Therapy for AnginaDrug Therapy for Angina

Drug Therapy for AnginaDrug Therapy for AnginaBeta-blockersBeta-blockers CalciumCalcium NitratesNitrates KK++ Channel Channel

AntagonistsAntagonists ActivatorActivatorAcebutolol Acebutolol AtenololAtenololBisoprololBisoprololCarvedilolCarvedilolLabetololLabetololMetoprololMetoprololNadololNadololOxprenololOxprenololPindololPindololPropranololPropranololTimololTimolol

II VerapamilVerapamil

IIII AmlodipineAmlodipineFelodipineFelodipineNicardipineNicardipineNifedipineNifedipineNisoldipineNisoldipine

IIII DiltiazemDiltiazem

GTNGTN

IsosorbideIsosorbideDinitrateDinitrate

IsosorbideIsosorbideMononitrateMononitrate

NicorandilNicorandil

PCI / PTCA = AngioplastyPCI / PTCA = Angioplasty

Coronary stentsCoronary stents

Acute Coronary Acute Coronary SyndromesSyndromes

Acute Myocardial InfarctionAcute Myocardial Infarction Unstable anginaUnstable angina

• Rest painRest pain• Crescendo anginaCrescendo angina• New onset anginaNew onset angina

Role of Platelets in Thrombus Formation

in Acute Ischemic Events

MIMI

StrokeStroke

Vascular Vascular DeathDeath

ThromboticThromboticOcclusionOcclusion

AtheroscleroticAtheroscleroticVesselVessel

LipidCore

PlaquePlaqueRuptureRupture

Platelet Adhesion,Platelet Adhesion,Activation, and Activation, and

AggregationAggregation

ThrombusThrombusFormationFormation

ST depressionST depression

ST elevationST elevation

0 6 12 18 24 2 3 4 5 6 7 8 9 10

RE

LA

TIV

E C

ON

CE

NT

RA

TIO

N

DaysHours

TIME AFTER INFARCT

Normal

TroponinMyoglobin

CK, ASTLDH

Complications of Acute MI

Acute MIAcute MIExpansion / AneurysmExpansion / Aneurysm RV InfarctRV Infarct

PericarditisPericarditis

MechanicalMechanical Mural ThrombusMural Thrombus

ArrhythmiaArrhythmia

Heart FailureHeart Failure

Extension / IschemiaExtension / Ischemia

LVRV

ISIS-2.Lancet 1988;11:349–360

Acute coronary syndromeAcute coronary syndrome

No ST elevationNo ST elevationST elevationST elevation

Thrombolytic therapyThrombolytic therapyPCIPCI

??

Thrombolysis for ACS Thrombolysis for ACS without ST elevation?without ST elevation?

It doesn’t work!It doesn’t work!e.g. Fibrinolytic Therapy Trialist (1994)e.g. Fibrinolytic Therapy Trialist (1994)

• 3563 patients with suspected AMI• ST segment depression• Mortality 15.2% vs 13.8%

GUSTO IIbGUSTO IIb

0%

2%

4%

6%

8%

10%

0 30 60 90 120 150 180

Days from Randomization

Mo

rtal

ity

T-wave inversion

ST-segment depression

ST-segment elevation

0%

2%

4%

6%

8%

10%

0 30 60 90 120 150 180

Days from Randomization

Mo

rtal

ity

T-wave inversion

ST-segment depression

ST-segment elevation

T-wave inversionT-wave inversion

ST ST

ST ST

P 0.001P 0.001

ECG and outcome in ACSECG and outcome in ACS

1.01.7

3.4 3.7

6.0

7.5

0

1

2

3

4

5

6

7

8

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9.0

Cardiac troponin I (ng/ml)

1.01.7

3.4 3.7

6.0

7.5

0

1

2

3

4

5

6

7

8

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9.0

Cardiac troponin I (ng/ml)

Mo

rtal

ity

at 4

2 D

ays

Mo

rtal

ity

at 4

2 D

ays

831831 174174 148148 134134 5050 6767

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Troponin level and mortality in ACSTroponin level and mortality in ACS

Myocardial infarction redefinedMyocardial infarction redefinedWHO definition: (2 of 3)WHO definition: (2 of 3)

• Typical symptoms (chest pain)

• Typical ECG changes (Q waves)

• Enzyme riseESC/ACC redefinition 2000ESC/ACC redefinition 2000• Troponin rise, with one of:• Chest pain• ECG changes (Q waves or ST segment)• PCI

Acute coronary syndromeAcute coronary syndrome

No ST elevationNo ST elevationST elevationST elevation

Chest painChest painPresentationPresentation

WorkingWorkingDiagnosisDiagnosis

Myocardial InfarctionMyocardial Infarction

STEMISTEMI NSTEMINSTEMI

++

++

Unstable AnginaUnstable Angina

--

ECGECG

TroponinTroponin

Final Final diagnosidiagnosiss