CORONORY ARTERY DISESASE

9th Semester Theory Class

Acute Corononary Syndomes(ACS)
 An umbrella term for any condition where
the blood supplied to the heart muscle is
reduced.
 the most feared complications of coronary
artery disease (CAD) and associated with
high mortality and morbidity
 Cardiovascular diseases (CVD) - presently
the leading causes of death in industrialized
countries
 Coronary artery disease(CAD) is the cause of
13% of deaths worldwide.
Cardiovascular Mortality
Definiton
The clinical presentations of CAD include:
 silent ischaemia
 stable angina pectoris
 heart failure
 unstable angina
 myocardial infarction (MI)
 sudden death
 CORONARY HEART DISEASE:
CLINICAL MANIFESTATIONS AND PATHOLOGY.
Clinical Problem Pathology
Stable angina Ischemia due to fixed atheromatous
stenosis of one or more coronary
arteries.
Unstable angina Ischaemia caused by dynamic
obstruction of a coronary artery due to
plaque rupture with superimposed
thrombosis and vaso-spasm.

Myocardial infarction Myocardial necrosis caused by actue

occlusion of a coronary artery due to
plaque rupture and thrombosis.

Heart failure Myocardial dysfunction due to infarction

or ischaemia.
Arrhythmia Altered conduction due to ischaemia or
infarction
Sudden Death Ventricular arrhythmia, asystole or
massive MI
 FACTORS INFLUENCING MYOCARDIAL OXYGEN
SUPPLY AND DEMAND.
Oxygen Demand
Cardiac work
* Heart Rate * Left ventricular hypertrophy
* Blood Pressure * Valve disease e.g, aortic stenosis.
* Myocardial Contractility
Oxygen supply
Coronary Blood Flow
* Duration of diastole * Coronary vasomotor tone
* Coronary perfusion pressure(aortic * Oxygenation,Haemoglonin,oxygen saturation
diastolic minus coronary sinus or right
atrial diastolic pressure)
N.B. Coronary blood flows occurs mainly in diastole
 Acute Coronary Syndromes
ACS are usually divided into:
 Unstable angina - only ischemia, lack of necrosis
 STEMI - ST - elevation MI
 NSTEMI - non-ST elevation MI
 Sudden death - due to cardiac arrhythmias

+
Stable Angina = Ischaemic Heart disesase
STABLE
ANGINA
 A GUIDE TO RISK STRATIFICATION IN STABLE ANGINA
HIGH RISK LOW RISK

* Post infarct angina Predictable exertional angina

* Poor effort tolerance Good effort tolerance

*Ischaemia at low Ischaemia only at high workload

workload
*Left main or three vessel Single vessel or minor two vessel
disease disease

* Poor LV function Good LV function

N.B. Patients may fall between these categories.

Acute coronary syndromes
 Definition
 ST-elevation ACS (STE-ACS):
 typical acute chest pain
and persistent (>20 min)
 ST-segment elevation
 generally reflects an
acute total coronary
occlusion
 most will ultimately
develop an ST-elevation
MI (STEMI).
ST elevation on the ECG
 Definition
 Non-STE-ACS
(NSTE-ACS):
 acute chest pain
 without persistent
ST-segment elevation
 persistent or transient ST
segment depression or
T-wave inversion
 further qualified into non-ST
elevation MI (NSTEMI) or
unstable angina.
ST depresion on the ECG
 Pathophysiology of ACS
Atherothrombosis
 Atherosclerosis - a fixed and barely reversible
process of gradual luminal narrowing
(slowly over decades)

 Thrombosis - a dynamic and potentially

reversible process causing rapid complete or
partial occlusion of the coronary artery
Vulnerable plaque

Hamm, Cardiovascular Medicine 2006

Vulnerable plaque…..contd.
Vulnerable patient
 Multiple sites of plaque rupture with or without
intracoronary thrombosis
 Elevated levels of various systemic markers
of inflammation, thrombosis and coagulation
system activation
 Hypercholesterolaemia
 Tobacco smoking
Diagnosis of ACS
 Clinical presentation
 History of patient
 Physical examination
 Electrocardiogram
 Biochemical markers - troponin
 Non-invasive imaging - Echo
 Imaging of coronary arteries - coronary
angiography
 CLINICAL EXAMINATION
* History
* Physical Examination:
 - frequently negative
 should include a careful search of:
 Aortic valve disease
 Important risk factors (HTN, DM)
 LV dysfunction (cardiomegaly, gallop rhythm)
 Other manifestations of arterial disease(carotid
bruits, PVD)
 Unrelated conditions that may exacerbrate
angina(anemia, thyrotoxicosis)
 INVESTIGATIONS
1) E.C.G.
 The resting 12-lead ECG is the first-line
diagnostic tool in the assessment of patients
with suspected ACS.
 Exercise E.C.G. (E.T.T.)
2) Other forms of stress testing (Echocardiography)

 Myocardial perfusion scanning Stress echocardiograpy

3) Biochemical markers
4) Corononory arteriography
Electrocardiogram
 The resting 12-lead ECG is the first-line
diagnostic tool in the assessment of
patients with suspected ACS.

 STE-ACS… ST-elevation

 NSTE-ACS…ST-segment shifts and T-

wave changes
But …. A completely normal ECG does not
exclude the possibility of ACS.
 Biochemical markers
Markers of myocardial injury:
 cardiac troponins (I and T)
 creatinine kinase (CK)
 CK isoenzyme MB (CK-MB)
 Myoglobin

 repeated blood sampling and measurements are required 6–12 hrs

after admission and after any further episodes of severe chest pain
Biochemical markers in ACS
 Other biomarkers
1) C-reactive protein - inflammation
long-term prognosis
2) Elevated ESR and Leucocytosis
3) Natriuretic peptides - heart failure
short-term prognosis
4) Serum creatinine - renal function
Short and long-term prognosis

*No role for the diagnosis of ACS, diagnosis but effect on

short- or long-term prognosis and differential diagnosis
Non-invasive myocardial imaging
 Echocardiography
- to evaluate LV systolic function, aortic
stenosis, aortic dissection, pulmonary
embolism, or hypertrophic cardiomyopathy
- should be routinely used in emergency units
for the risk stratification
 Stress echocardiography, stress scintigraphy -
evidence of ischaemia or myocardial viability (in
stabilized patients)
 Imaging of the coronary anatomy

 The imaging of the coronary anatomy is the

most important diagnostics method in
evaluation of acute coronary syndrome

 The gold standard of patients with ACS is

conventional invasive coronary
angiography
 Pre-hospital management
 Antiplatelet therapy
 Aspirin 75-150 mg (per oral)
 Clopidogrel 75mg
 Antithrombin therapy
 Heparin 5000 - 10000 IU i.v. or Enoxaparine 0.6 S/C
 Resolve pain and fear
 analgesic drugs (Morphine)
 benzodiazepine (Alprazolam, Clonazepam)
 Pre-hospital management
 Nitrate - pain, hypertension, heart failure
 Isosorbide dinitrate, GTN etc.
 Monitoring vital function and ECG
ventricular fibrilation
-terminated by cardioversion
 Pre-hospital management
 Betablockers - tachycardia, hypertension
 Metoprolol - dose 25-50mg oral or 2 mg i.v.
 ACE inhibitors - hypertension
 Telmisartan(40mg),Olmesaratan(20-40mg),Perindopril.
 Diuretics - heart failure
 Furosemide 20 - 40mg i.v.
 Anti-arrhythmic drugs –not for prophylaxis
 Mesocain 1% 10 ml i.v.
 Amiodarone 150 mg i.v. bolus
 Hospital and discharge therapy
 Antiplatelet therapy
 Aspirin - 75-150mg oral
 Clopidogrel -75mg oral
 Statins - benefit for all patients with MI
 Atorvastatin 40 - 80mg, rosuvastatin 20 - 40mg
 ACE inhibitors - benefit for all patient with MI, more
expressed in left ventricular dysfunction
 perindopril - dose 5-10 mg oral
 Betablockers - 1 to 3 years after MI, longer for pts. with left
ventricular dysfunction, tachyarrhythmia
 UNSTABLE ANGINA
It is a Clinical syndrome comprising of:
* New onset (within 6 weeks) or rapidly worsening
angina (crescendo angina)
* Angina at rest or on minimal exertion lasting >20min
* Post-infarct angina
The condition shares common pathophysiology with AMI and
the term ‘acute corononary syndrome’ is used to describe these
disorders collectively.
These entities comprise a spectrum of disease:
1) ischaemia
2) ischaemia with minimal myocardial damage
3) partial thickness (non-Q wave) MI
4) full thickness (Q wave) MI
 The Spectrum of acute coronary syndromes.
The relation between ECG changes, biochemical markers of damage and the extent of myocardial
necrosis.(CK=creatine kinase)
UNSTABLE ANGINA RISK STRATIFICATION
HIGH RISK LOW RISK
CLINICAL Post-infarct angina No history of MI
Recurrent pain at rest Rapid resolution of
Heart Failure symptoms
ECG Arrhythmia ST depression Minor or no ECG
Transient ST elevation changes
persistent deep T-wave
inversion

Biochemistry Troponin T>0.1 μ g/l Troponin T <0.1 μ g/l

 Unstable angina
NSTEMI
Low risk High risk
CK and troponin
Aspirin, β-blocker
Heparin, ECG
mobilise

Poor effort tolerance

Good effort
tolerance

Consider
'culprit
lesion’
PCI

Medical
Therapy

No
Myocardial infarction
 Epidemiology of NSTE and STEMI-ACS
 The annual incidence of NSTE-ACS is higher
than STEMI
 The annual incidence of hospital admissions for
NSTE-ACS is in the range of 3 per 1000
inhabitants
 Sex differences - men account for more than
90% of patients with AMI at the age under 40yrs
(protective effect of female hormones)
• Age differences - in patients aged under 40yrs
only one artery to heart is affected
Myocardial infarction
Aetiology:
1. Atherosclerotic aetiology
2. Non-atherosclerotic aetiology:
 arteritis
 trauma
 dissection
 congenital anomalies
 cocaine abuse
 complications of cardiac catheterization,
CABG
 Diagnosis of acute MI
At least 2 from 3 criteria must be fulfilled :
• Clinical symptoms
– Chest pain
• ECG changes
– ST elevation or depression
– negative T wave
• Elevated cardiac biomarkers
– Troponin I or T
– CK-MB
– Myoglobin
Clinical presentation
 Prolonged chest (retrosternal) pain
 Anxiety and fear of impending death
 Nausea, vomiting
 Breathlessness
 Collapse/syncope
 Clinical presentation(diagram rep.)
1) Typical chest pain

2) Nausea
3) Sweating
 Clinical presentation
 The presence of tachycardia, hypotension, or
heart failure needs rapid diagnosis and
management, often indicating a poor prognosis
of this patient with ACS
 It is important to identify the clinical
circumstances such as anaemia, infection,
inflammation, fever, and metabolic or endocrine
(in particular thyroid disorders)
(may exacerbate or precipitate ACS)
 Physical examination
 Frequently normal

 Diffuse apical impulse

S1 muffled, S3 present

 Systolic murmur (due to Mitral incompetence)

 Pericardial rub may be heard

 Signs of heart failure or haemodynamic instability

 Physical examination
 Heart failure
 Tachycardia, tachypnoea
 Pulmonary rales (pulmonary congestion)
 RV failure - ↑ jugular congestion,
hepatomegaly
 Hypotension: ↓ 100/60 mmhg
cardiogenic shock (tachycardia)
Bradycardia:↑ vagal nerve activity (bradycardia
- inferior MI)
* AV block
 Inferior MI - non-serious, frequent
 Anterior MI - serious, rare
Infarct expansion and
ventricular
remodelling:
Full Thickness myocardial
infarction causes thinning
and stretching of the
infarcted segment (infarct
expansion), which leads to
increased wall stress with
progressive dilatation and
hypertrophy of the
remaining ventricle
(ventricular remodelling)
Complications of MI
 Early complications
 Heart failure, cardiogenic shock
 Mechanical complications :
- rupture of free wall of left ventricle
- ventricular septal defect
- acute mitral regurgitation
 Arrhythmia
- ventricular (up to 48 hr)
- bradycardia (9-25% of pts)
 Late complications
 Pericarditis
 Aneurysm of left or right ventricle
 Dressler’s syndrome
COMMON ARRHYTHMIAS IN
ACUTE MYOCARDIAL INFARCTION
 Ventricular fibrillation
 Ventricular tachycardia
 Accelerated idioventricular rhythm
 Ventricular ectopics
 Atrial fibrillation
 Atrial tachycardia
 Sinus bradycardia (particularly after
inferior MI)
 Heart block
COMPLICATIONS
1)Tamponade
2) VSD
3)Aneurysm
 Location of MI
ST elevation only:
 Anteroseptal - V1-V3
 Anterolateral - V1-V6
 Inferior wall - II, III, aVF
 Lateral wall - I, aVL, V4-V6
 Right ventricular - RV4, RV5
 Posterior- R/S ratio >1 in
V1 and T wave inversion
Location of MI
Location of MI
Location of MI
Location of MI
 Management of STEMI
 open the occluded artery as soon as possible….
“ time is muscle ”

 check for complications and treat them

immediately:
- Arrythmia
- Heart failure
- Bleeding
 Management of angina
 STEMI is an urgent situation with turbulent C/F
 NSTEMI may have symptoms
much milder and above its immediate prognosis
is better
 Pts. should stay on coronary care unit - 2-3
days, than standard cardiology department
 the total length of hospitalization is around 1
week
 even after leaving the CCU patients are able to
move around the room and in the following days
rehabilitate and before discharge they are able to
walk up the stairs
 return to job possible approximately one month.
 EARLY MANAGEMENT OF ACUTE
MYOCARDIAL INFARCTION
Provide facilities for defibrillation
Immediate measures
 High- Flow Oxygen
 IVaccess
 ECG Monitoring
 12-lead ECG
 I V analgesia(opiates)
 Aspirin 300 mg
Reperfusion
 Primary PCI or thrombolysis
Detect and manage acute complications:
 Arrhythmias
 Ischaemia
 Heart Failure
 Antiplatelet therapy
1) Aspirin: low dose (75-150mg)
- reduces the risk of adverse patients such as
MI
- should be prescribed to all pts. Of CAD
indefinitely.
2) Clopidrogel (P2Y12 receptor antagonist)
– equally effective antiplatelet drug
– reserved for patients who have long term side
effects of aspirin.
3) Prasugrel (2nd P2Y12 receptor antagonist)
4) Ticagelor (3rd- P2Y12 receptor antagonist)
 Antithrombin therapy
1) Antothrombotic therapy in form of unfractionated
heparin-used before the completion of thrombolytic
therapy – initial bolus dose of 60IU/Kg followed by an
infusion of 12 IU/Kg/hr and adjusted to attain APTT
time at 1.5-2 times normal.

2) Low molecular wt. heparin better than the above

3) Direct thrombin inhibitors (hirudin etc.) – alternative

to heparin and Gp IIb/IIIa in pts. Undergoing PCI
* These agents should be continued at least 48 hrs
and preferably upto 8 days.
 Anti-anginal drug treatment
 Four groups of drugs are used to relieve or
prevent the symptoms of angina: Nitrates,
Bblockers, Ca+ channel antag.,& K+channel
activators

• 1)Nitrates: acts directly on vascular smooth

muscle – venous and arterolar dilation –benefits:
reduces myocardial O2 demands (preload and
afterload)

• Myocardial O2 supply (coronary vasodiatation)

2) B-blockers:
- They act by lower myocardial O2 demand by
lowering Pulse, BP and myocardial contractility
- - Unfortunately, they can excaberate the
suptoms of PVD and provoke bronchospasm of
obstuctive airway disease
- - in theory non-selective B blockers may
aggravate coronary vasospasm by blocking the
coronary artery B2 adrenoreceptors and
therefore used as once daily cardioselective
preparation(slow release metoprolol and
bisopropol(5-10mg daily)
- - B blockers should not be withdrawn abruptly –
“the B blocker withdrawal syndrome”
3) Calcium antagonists:
- -Mode of action:*inhibit the slow inward current
caused by entry of extracellular Ca+ through the
cell membrane of exitable cells,particularly
cardiac and arterolar smooth muscle
- * lower myocardial O2 demand by BP and
myocardial contactility
- * Dihydropyridine derivates (Nifedipine) often
cause a reflex tachycardia,and is often
counterproductive when a B blocker is used
concurrently.
- * Unwanted effects: headache,flushing,peripheral
oedema
4) Potassium channel activators:
- Has arterial and venous dilating effects and also
does not have the tolerance properities of Nitrates
(Nicorandil-10-30mg 12hrly orally- is the only
drug in this class currently available for clinical
use)
N.B.: No single group of dugs is is more effective
compared to other groups
* Conventional therapy:Goal: control of angina with
minimum of side effects and the simplest
possible regimen:low dose aspirin/clopidrogel
and a B blocker and then add a long acting
calcium channel antagonist or a long acting
nitrate if necessary.
 -
INVASIVE TREATMENT:
1) PCI AND PTCA
- fine guidewire is passed across a coronorary
stenosis under radiographic control and using
it to position a baloon which is then inflated to
dilate the stenosis. A coronary ‘stent’ is
deployed on a baloon used to maximise and
maitain dilatation of a stenosed vessel.
-the routine use of stents in appropriate
vessels reduces both acute complications and
the recurrence of clinically imp. restenosis.
STENT- coated metallic ‘scaffolding’
* PCI- only for single or two vessel disease;
stenosis in bypass grafts and as a palliative
therapy in reccurent andina after CABG.
Therapy
Meta-analysis of 23 trials (n=7739 pts.)

Keeley EC. Lancet 2003

Process of the percutaneous
coronary intervention
Process of the implantation of stent
Revascularization strategy
Conservative treatment
 non-significant stenosis on CAG
Percutaneous coronary intervention
 BMS - “bare metal stents“
 DES – “drug-eluting stent“
Surgical revascularization
 better long-term results
 diffuse coronary artery involvement
 diabetics
 RELATIVE CONTRAINDICATIONS TO
THROMBOLYTIC THERAPY(POTENTIAL
CANDIDATES FOR PRIMARY ANGIOPLASTY)

 Active internal bleeding

 Previous subarachnoid or intracerebral
haemorrhage.
 Uncontrolled hypertension
 Recent surgery (within 1 month)
 Recent trauma (including traumatic
resuscitation)
 High Probability of active peptic ulcer
 Pregnancy
 PRIMARY PERCUTANEOUS CORONARY
INTERVENTION IN ACUTE MYOCARDIAL
INFARCTION

‘ Primary PCI is more effective than

thrombolysis for the treatment of acute myocardial
infarction. Death, non-fatal reinfarction and stroke
are reduced from 14% with thrombolytic therapy to
8% with primary PCI’
Drugs used:
1) Streptokinase
2) Alteplase (human tissue plasminogen activator or tPA )
3)Tenecteplase (TNK)
4) Reteplase (rPA)
 -
Main long term copmlications of PCI:
1)Restenosis (1/3rd of cases)- this is due to elastic
recoil and smooth muscle proliferation (neo-intimal
hyperplasia)-within 3 months
* Stenting reduces this restenosis.
2)Drug eluting stents can further reduce this risk
even further by allowing an antiproliferative drug
(sirolimus or paclitaxel) to elute slowly from the
coating and prevent neo-intimal hyperplasia and in
stent restenosis
*Outcomes:
In combination with aspirin and heparin, adjunctive
therapy with potent atiplatelet inhibitors such as
clopidrogel or glycopretein IIb/IIIa receptor
antagonists- shown to improve outcome of PCI with
lower short- & long term-rates of death and MI
 -

CABG:

- The internal mammary arteries, radial

arteries or reversed segments of the
patient’s own saphenous vein can be
used as bypass in CABG.
 Antithrombin therapy
1) Antithrombotic therapy in form of unfractionated
heparin-used before the completion of thrombolytic
therapy – initial bolus dose of 60IU/Kg followed by an
infusion of 12 IU/Kg/hr and adjusted to attain APTT
time at 1.5-2 times normal.

2) Low molecular wt. heparin better than the above

3) Direct thrombin inhibitors (hirudin etc.) – alternative

to heparin and Gp IIb/IIIa in pts. Undergoing PCI
* These agents should be continued at least 48 hrs
and preferably upto 8 days.
Treatment of NSTE
ACS vs.STE
 thrombolysis is not used in NSTEMI

 the base of treatment is again antithrombotic

therapy and revascularization - mostly via PCI

 in patients with multiple coronary disease, CABG

is indicated
Prognosis of STE-ACS
• overall case fatality:
- about half of the deaths caused by acute
coronary syndromes
- occur during the first two hours - no
change in present time.
• in-hospital mortality:
- prior to the introduction of coronary care units
in the 1960s - 25 - 30%
- pre-reperfusion era of the mid-1980s - 16%
- at present ~ 10%
Thank you for your attention