Coronary Heart Disease, Co o a y ea t sease,Angina, MI, Embolism

Year 1 Cardiovascular System

Ranil de Silva FRCP PhDSenior Lecturer in Clinical Cardiology

r.desilva@imperial.ac.uk@ p

How does coronary artery disease present?

o Sudden cardiac deatho Sudden cardiac deatho Acute coronary syndrome

– Acute myocardial infarction– Unstable anginag

o Stable angina pectorisfo Heart failure

o Arrhythmiao Arrhythmia

Epidemiology – Determinants of Risk

o Tobacco use, physical inactivity, harmful p y yuse of alcohol, unhealthy diet accounts results in:results in:– Hypertension

Ob it– Obesity– Diabetes mellitus– Hyperlipdaemia

o Responsible for ~80% of CHD

Global Burden of CVD

o Cardiovascular diseaseo Cardiovascular disease accounts for ~17M deaths per year.deaths per year.

o Leading cause of death in both developed and plow/medium income countries

o Leading cause of death in age <70yL di f d th io Leading cause of death in women

WHO Global Status Report on Non-communicable disease 2010

UK Burden of CHD

88 000 CHD d th t fo 88,000 CHD deaths per year, commonest cause of death

o CHD accounts for 18% deaths in men and 10% deaths in women <75y commonest cause of premature deathin women <75y, commonest cause of premature death

o While rates are falling UK mortality still greater thano While rates are falling, UK mortality still greater than most of Western Europe

Coronary Heart Disease Statistics 2010

UK MI Statistics (2009-10)( )

o 124,000 MI’s per yr, p y

o ~99,000 hospital , padmissions per year

o ~33,000 deaths per year (~6% of all deaths in UK)

o £3.6 billion per year

Epidemiology of Stable Anginap gy g

o Incidence increasingo Incidence increasing

o 2M cases in UKo ~2M cases in UK

o Age 55-64y– Affects 8% ♂ and 3% ♀♀

o Age 65-74yo Age 65-74y– Affects 14% ♂ and 8% ♀

Epidemiology of Stable Anginap gy g

o In 2009/10 ~45K admission → ~65K bed dayso In 2009/10 45K admission → 65K bed days

67 000 l ti PCI’o ~67,000 elective PCI’s per year

o ~50% of patients undergoing PCI are on no or suboptimal medical Rxp

o In 2009/10 ~300K angina patients attendedo In 2009/10, ~300K angina patients attended Cardiology Outpatient appointments

Myocardial Ischaemiay

o Mismatch between myocardial oxygeno Mismatch between myocardial oxygen supply and demand

o Primary reduction in blood flowo Primary reduction in blood flow

o Inability to increase blood flow to match increased metabolic demandincreased metabolic demand

Functional Anatomy of Coronary Circulation

Capillary Bed

I t di lIntramyocardial

Effect of Epicardial Stenosis on Resting Coronary Resistance and FlowCoronary Resistance and Flow

Capillary Bed

Intramyocardial

R2R1 R2=

Capillary Bed

Intramyocardialy

R1 R2>R1 R2>Gould, Lipscomb, Calvert Circulation 1975

Effect of Coronary Stenosis on Flow Response to VasodilatorsResponse to Vasodilators

Gould and Lipscomb Am Heart J 1974 Uren et al. N Engl J Med 1994

Angina PectorisAngina Pectoriso Angina pectoris is a clinical diagnosiso Angina pectoris is a clinical diagnosis

o Discomfort in the chest, jaw, shoulders, arms, or back.arms, or back.

o Provoked by exertion or emotional stress

o Relieved by rest or s.l. GTN in < 5min

I ti ti f St bl CHDInvestigation for Stable CHD

o To confirm the clinical diagnosisDemonstrate myocardial ischaemia– Demonstrate myocardial ischaemia

o To assess risk of future adverse cardiovascular eventso To assess risk of future adverse cardiovascular events– Burden of myocardial ischaemia– Anatomic severity coronary artery diseaseAnatomic severity coronary artery disease– LV function

o Choice of test dependent on clinical probability of CHD

Investigation of CHDInvestigation of CHD

Functional Anatomical

E i ECG

Non-invasive

Exercise ECGStress echo

Stress cardiac MRIPET/CT

CT coronary calcium scoreCT coronary angiogramPET/CT

Stress nuclear MPSFFRCT

CT coronary angiogram

Invasive

CFRPressure wire (FFR)

iFR Coronary angiogramIVUSOCT

Coronary angiogram

I l t i i i di tiInvolves exposure to ionising radiation

How do we diagnose CHD?gAnatomical Functional

Treatment Strategiesg

o Improve blood supplyo Improve blood supply– Revascularisation (PCI, CABG)– Vasodilators

o Reduce myocardial oxygen demando Reduce myocardial oxygen demand– HR (b blockers, Ca antagonists, If blockers)

ll t (ACE i hibit C t i t )– wall stress (ACE inhibitors, Ca antagonists)– Metabolic modifiers

o Prevent atherosclerosis progression and risk of death/MIrisk of death/MI

…a man with …a man with severe chest pain severe chest pain going down thegoing down theSpelling

mistake

going down the going down the arms: Death is arms: Death is near …near …

The Ebers Papyrus 2600 B.C.with kind permission from J.C. Kaski

Definition of MI

o Myocardial cell death arising fromo Myocardial cell death arising from interrupted blood flow to the heart

Coronary plaque rupture– Coronary plaque rupture– Coronary plaque erosion– Coronary dissection

o Mechanisms of myocardial cell death– Oncosis– Apoptosisp p

Universal Definition Acute MI

Acute MI

Acute Coronary Syndromesy yo Inflammation

– Systemic– Local

o Plaqueo Plaque– Rupture– Erosion– Erosion

Th b io Thrombosis

Hansson N Engl J Med 2005

“Man lives with atherosclerosis but dies from thrombosis”

ACSACS Didischem 1957ACSACS Didischem 1957

THROMBOSISTHROMBOSIS

70-80 % 20-30 %PLAQUE RUPTUREPLAQUE EROSION

Thrombosis - Virchow’s Triado Abnormal vessel wall (endothelial dysfunction,

inflammation atherosclerosis)inflammation, atherosclerosis)

o Abnormal blood flow (endothelial dysfunction, turbulent flow at bifurcations and stenoses, stasis)

o Abnormal blood constitutents (endothelial dysfunction hypercoagulability abnormaldysfunction, hypercoagulability, abnormal platelet function, altered fibrinolysis, metabolic, hormonal factors)hormonal factors)

Thrombosis

White Thrombuso Platelet rich

Red Thrombuso Fibrin rich, with trapped

o Common in arterial thrombosis (high

pperythrocytes

o Common in venous or pressure/turbulent circulation)B fit f ti l t l t

low pressure situations (stasis)B fit fo Benefit from antiplatelet

therapyo Benefit from

anticoagulant or anti-fibrinolytic therapyfibrinolytic therapy

Effect of Coronary Stenosis on Haemodynamics

HSSHSS

LSS OSS

Kern et al. JACC 2010

BLOODHEART

TF Circulates in Blood: Possible Cellular Sources

BLOODHEARTmyocardial

ischaemia

monocytemyocyte

TF PMNfibroblast

macrophage

AT plaqueEndothelial cellEndothelial cell

VESSEL WALL

AT plaque

SMClipid core

VESSEL WALLAdapted from Badimon JJ

Tissue Factor as a Determinant of Thrombosis

TF/VIIaTF/VIIa

XX IXIX

IXaIXaVIIIaVIIIa

IXaIXa

VaVa

XaXa ATAT

IIII

XaXa

IIaIIa

Fibrinogen → FibrinFibrinogen → Fibrin

Adapted from Adapted from WeitzWeitz JI: JI: J J ThromThrom HaemostHaemost. 2007 Jul 5 . 2007 Jul 5 SupplSuppl 1:651:65--77

PPCI for STEMI

Development of Infarction

Reperfusion Injuryp j y

Yellon & Hausenloy NEJM 2007

Post-MI LV Remodellingg

Mechanisms Underlying LV Remodelling

o Infarct thinning, elongation, expansiono LV dilatation

– reduce wall tension– maintains cardiac output

o Non-infarcted myocardiumo Non infarcted myocardium– LVH + myofilament dysfunction– Altered electromechanical couplingAltered electromechanical coupling– Myocardial fibrosis– ApoptosisApoptosis– Inflammation

Consequences of Adverse LV Remodelling

o Increased systolic wall tension/stressyo Increased MVO2o Reduced myocyte shorteningo Reduced myocyte shorteningo Increased diastolic wall tension/stresso Reduced subendocardial perfusiono Dysynchronous depolarization/contractiony yo Mitral regurgitationo Ventricular arrhythmiaso Ventricular arrhythmiaso Ventricular fibrillation

Manage Thrombotic Burden/Riskg

Acute RecurrentAcuteo Thrombectomy

D

Recurrento Oral antiplatelet drugs

A ti l to Drugs– Oral antiplatelets: Aspirin,

clopidogrel, prasugrel,

o Anticoagulants– Direct thrombin inhibition– Factor Xa inhibitorsclopidogrel, prasugrel,

ticagrelor– SC anticoagulants: LMWH,

fondaparinux

– Factor Xa inhibitors

fondaparinux– IV antiplatelets: GpIIb/IIIa

inhibitors – IV anticaogulants:

Bivalirudin,, fibrinolytics, Factor Xa inhibitorsFactor Xa inhibitors

Plaque Stabilisationq

Mechanicalo Stent

Drugso Statins (high dose)( g )o ACE inhibitors

Manage LV Remodellingg g

Non-Drug DrugsNon Drugo CRT-P/Do Progenitor cells

Drugsο β blockerso ACE inhibitorso Progenitor cells o ACE inhibitorso Angiotensin receptor

blockersblockerso Aldosterone receptor

antagonistsg

Embolism

o An obstruction in a blood vessel due to a thrombus or other foreign matter that gets stuck while travelling through thestuck while travelling through the bloodstream.A t i l (th b [ACS TIA t k ] io Arterial (thrombus [ACS, TIA, stroke], air, fat, amniotic, foreign body/material)

o Venous (thrombus [DVT, PE])

TIA/Strokeo Embolic o Haemorrhagic

– ICA plaque rupture– Intracardiac (e.g. AF, old

MI valve disease)

– Vascular malformation– Hypertension

TMI, valve disease)– Intracardiac communication

o Treatment

– Tumor– Iatrogenic

o Treatmento Treatment– Fibrinolysis– Clot extraction

o Treatment– Coil/clip aneurysm– Withdraw pro-haemorrhagic

– Antiplatelet drugs– Modify atherosclerotic risk

factors

p gmedication

– Control hypertensionfactors

– Endarterectomy, stent– Hole closure

Venous ThromboembolismDeep Vein Thrombosis

o Incidence: 1.6/1000/yr

Pulmonary Embolism

o Symptoms: Dyspnoea, chest pain, h potension shocko Aetiology:

– Trauma– Orthopaedic surgery

Malignancy

hypotension, shocko Diagnosis: clinical, ECG, D-dimer,

echo, CTPA, MRI, VQ scan, pulmonary arteriogram– Malignancy

– Autoimmune disease– Thrombophilia– Immobility

pulmonary arteriogramo Complications: death, shock,

pulmonary hypertension, RV failureo Treatment: anticoagulation,y

o Diagnosis: Clinical (Wells Score), D-Dimer, Duplex ultrasound, CT, MRI, Venography

o Complications:

o Treatment: anticoagulation, fibrinolysis, mechanolysis, IVC filter

– PE (in 50% if symptomatic DVT untreated)– Post-thrombotic syndrome (in ~45% within 1

year of symptomatic DVT’s)– Venous ulcerVenous ulcer

o Prevention– TEDS, sc LMWH/Anti-Xa

o Treatment– Anticoagulation, Fibrinolysis, Thrombectomy

Embolism - Othero Air embolism

– Iatrogenic– Decompression sickness– Trauma

o Fat embolism– Trauma

A i ti fl id b lio Amniotic fluid embolism– Pulmonary vasoconstriction, inflammation– ~1:54,000 deliveries, CFR 13-30%

Sudden CV collapse: Pulmonary HTN + RV failure > LV failure– Sudden CV collapse: Pulmonary HTN + RV failure -> LV failure– DIC– Rx: pulmonary vasodilators, FVIIa, ITU support

o Cholesterol embolism– Showers of microemboli from within plaque of large calibre artery– Plaque rupture (spontaneous, traumatic, iatrogenic)– Embolization of plaque debris (cholesterol crystals, platelets, fibrin)– Lodging of emboli in arterioles 100-200μm diam.– Foreign body inflammatory response– End-organ damage due to microvascular plugging and inflammation