Atherosclerosis and IHD

1. ATHEROSCELEROSIS
PATHOGENESIS

2. Introduction
• Atherosclerosis remains the major cause of death and
premature disability
• predicted to be leading cause of global cause of total disease
burden by 2020
• Atherogenesis in humans typically occurs over a period of
many years, usually many decades
• Stenosis due to atherosclerosis tend to occur focally, typically
in certain predisposed regions
• The clinical expressions of atherosclerosis
– Asymptomtic
– Chronic event
– Acute event

3. INITIATION OF ATHEROSCLEROSIS
The initial lesion in atherosclerosis involves the
intima of the artery and begins in childhood
with the development of fatty streaks
1. Intimal lipoprotein accumulation and lipid oxidation
2. Leukocyte recruitment
3. Foam cell formation

4. INITIATION OF ATHEROSCLEROSIS

5. ATHEROMA EVOLUTION
• fatty streak commonly precedes the
development of a more advanced
atherosclerotic plaque, but not all fatty
streaks progress to form complex atheromata

6. Atheroma evolution
•Lipid removal
by
•Macroph
ages
• HDL chol
Lipid
accumulation
Atheroma
evolution

7. Atheroma evolution

8. Atheroma evolutio
a complex balance between entry and regress
of lipoproteins and leukocytes, cell
proliferation and cell death, extracellular
matrix production, and remodeling, as well as
calcification and neovascularization, contribute
to lesion formation

9. CLINICAL SYNDROMES OF ATHEROSCLEROSIS
• Most atheromata produce no
symptoms, and many never cause
clinical manifestations
• What accounts for this variability
in the clinical expression of
atherosclerotic disease?
i. Arterial remodeling
ii. Collateral circulation
iii. Plaque Instability and
Rupture: plaques that have
caused fatal thromboses tend
to have thin fibrous caps,
relatively large lipid cores,
and a high content of
macrophages

10. PLAQUE RUPTURE, THROMBOSIS, AND HEALING

11. CONVENTIONAL RISK FACTORS FOR ATHEROSCLEROSIS
 Cigarette smoking
 Hypertension (BP ≥140/90 mmHg or on antihypertensive
medication)
 Dyslipidemia ( low HDL< 40mg/dl, High LDL)
 Diabetes mellitus , insulin resistance and metabolic
syndrome
 Family history of premature CHD
 CHD in male first-degree relative <55 years
 CHD in female first-degree relative <65 years
 Age (men >45 years; women >55 years)
 Lifestyle risk factors
 Obesity (BMI 30 kg/m2)
 Physical inactivity
 Atherogenic diet
• CKD

12. Clinical Identification of the Metabolic Syndrome-
Any Three Risk Factors
˃100mg/dl

13. EMERGING RISK FACTORS
• Albuminuria
• Lipoprotein(a)
• Homocysteine
• Prothrombotic factors
• Proinflammatory factors
• Impaired fasting glucose
• Subclinical atherogenesis

14. ISCHEMIC HEART DISEASE

15. Ischemic Heart disease(IHD):introduction
• IHD is a condition in which there is an imbalance
between myocardial oxygen supply and demand
• IHD causes significant deaths and disability
• With urbanization in the developing world, the
prevalence of risk factors for IHD is increasing rapidly
in these regions such that a majority of the global
burden of IHD is now occurring in low-income and
middle-income countries

16. PATHOGENESIS: Concept of Myocardial O2 Supply and
Demand
 Determinants of myocardial oxygen demand are heart rate,
myocardial contractility, and myocardial wall tension
 met by the ability of the coronary vascular bed to vary its
resistance considerably while the myocardium extracts a high
and relatively fixed percentage of oxygen
 Atherosclerosis, coronary spasm, arterial thrombi, ,coronary
emboli and osteal narrowing due to aoritis decrease coronary
blood flow
 An adequate supply of oxygen to the myocardium requires a
satisfactory level of oxygen-carrying capacity of the blood
and an adequate level of coronary blood flow
 Anemia,high altitude,pulmonary disorders,poisoning and anomalous
origine of the coronary artery from the pulmonary artery decrease
oxygen carrying capacity of the blood

17. SPECTRUM OF PRESENTATION
• Asymptomatic: ~25% of patients who
survive acute MI may not come to
medical attention, and these patients
carry the same adverse prognosis as
those who present with the classic
clinical picture of acute MI
• Suden cardiac death
• Ischemic Cardiomyopathy
• Angina/myocardial infarction

18. ISCHEMIC HEART DISEASE
STABLE ANGINA PECTORIS

19. History
• Present with chest discomfort (angina)
• usually described as heaviness, pressure, squeezing,
smothering, or choking
– retrosternal with radiation to either shoulder and to both arms
(especially the ulnar surfaces of the forearm and hand).
– It can also arise in or radiate to the back, interscapular region, root of
the neck, jaw, teeth, and epigastrium
– Myocardial ischemic discomfort does not radiate to the trapezius
muscles; such a radiation pattern is more typical of pericarditis
– Angina is rarely localized below the umbilicus or above the mandible
– When the patient is asked to localize the sensation, he or she typically
places a hand over the sternum, sometimes with a clenched fist, to
indicate a squeezing, central, substernal discomfort (Levine's sign).

20. History cont
• Excertional angina is typically relieved by slowing or
ceasing activities in 1–5 min and even more rapidly by
rest and sublingual nitroglycerin
• Angina occurs more commonly in the morning due to a
diurnal increase in sympathetic tone

21. HISTORY
Chest discomfort
 lasts 2–5 min
 episodes of angina are typically caused by exertion
(e.g., exercise, hurrying, or sexual activity) or
emotion (e.g., stress, anger, fright, or frustration)
and are relieved by rest,
 may also occur at rest and while the patient is
recumbent (angina decubitus)
 Angina may also be precipitated by unfamiliar
tasks, a heavy meal, exposure to cold, or a
combination

22. HISTORY
 Anginal "equivalents“
 are symptoms of myocardial ischemia other than
angina.
 include dyspnea, nausea, fatigue, and faintness,
and are more common in the elderly and in
diabetic patients

23. History cont
coronary atherosclerosis is often accompanied
by similar lesions in other arteries, so look for
PAD, stroke and TIA
shortness of breath is commonly associated
 reflecting mild pulmonary congestion, resulting from
ischemia-mediated diastolic dysfunction
look for DM, hyperlipidemia, hypertension,
cigarette smoking, and other risk factors for
coronary atherosclerosis

24. P/E
• Often normal in patients with stable angina when
they are asymptomatic
• Evidence of atherosclerotic disease at other sites
• Risk factors for atherosclerosis, such as
xanthelasmas, xanthomas and hypertension
• Examination during an anginal attack is useful
– since ischemia can cause transient LV failure with the
appearance of a 3rd and/or 4th heart sound, a
dyskinetic cardiac apex, mitral regurgitation, and even
pulmonary edema
• AS, AR, pulmonary hypertension and HCM must
be excluded

25. INVESTIGATIONS
• FBS,lipid profile,RFT,serum electrolyte,U/A,Hgb,
CRP, Hgb, TFT
• Resting ECG
• Stress testing
• ECHO
• PET scan, SPECT, CT/MRI scan
• Angiography

26. STRESS TESTING

27. TREATMENT OF ANGINA
1. Explanation of the problem and reassurance
about the ability to formulate a treatment plan
2. Identification and treatment of aggravating
conditions
3. Recommendations for adaptation of activity as
needed
4. Treatment of risk factors that will decrease the
occurrence of adverse coronary outcomes
5. Drug therapy for angina
6. Consideration of revascularization

28. DRUG THERAPY FOR ANGINA
1. Nitrates: when metabolized release nitric oxide (NO)
 Systemic venodilation and reduction in LV end-diastolic volume and
pressurereducing myocardial wall tension and O2 requirements
 Dilation of epicardial coronary vessels
 Increased blood flow in collateral vessels
 Sublingual nitrates: It is given at a dose of 0.3-0.6 mg every 5-10
minute for three doses
 Chronic nitrate therapy: none of the long-acting nitrates are as
effective as sublingual nitroglycerin for the acute relief of angina
 It can prevent or reduce the frequency of recurrent anginal episodes
and improve exercise tolerance
 The major side effects associated with nitrate use are headache,
lightheadedness, and flushing which are due to the vasodilatation

29. DRUG THERAPY FOR ANGINA
2. -Adrenergic Blockers
 reduce myocardial O2 demand by inhibiting the increases in HR, BP, and myocardial
contractility caused by adrenergic activation
 reduces these variables most strikingly during exercise while causing only small
reductions at rest
 Side effects include
 fatigue, reduced exercise tolerance, nightmares, impotence, cold extremities,
intermittent claudication, bradycardia, impaired AV conduction, LV failure, bronchial
asthma, worsening claudication, & intensification of hypoglycemia produced by oral
hypoglycemic agents & insulin
 Relative contraindications:
 asthma and reversible airway obstruction in patients with chronic lung disease, AV
conduction disturbances, severe bradycardia, Raynaud's phenomenon, and a history of
mental depression
 Target therapy:
 resting HR b/n 50 & 60 bpm, blunting of peak HR and BP during exercise and reduction in
the frequency and severity of angina and in the use of sublingual nitroglycerin

30. DRUG THERAPY FOR ANGINA
3. Calcium Channel Blockers
When to use
oIn combination with ßB when initial treatment with ßB is
not successful.
o may be a substitute for a beta blocker when beta blockers
are contraindicated or cause side effects.
oare effective in patients with vasospastic or variant
(Prinzmetal) angina; they are the preferred agents in this
setting
Potential side effects include symptomatic bradycardia,
heart block, worsening HF, constipation, flushing,
headache, dizziness, and pedal edema

31. DRUG THERAPY FOR ANGINA
4. Antiplatelate agents
In the absence of a contraindication, all patients
should be treated with aspirin (81 to 325 mg/day)
Patients who have a gastrointestinal bleed on low
dose aspirin should, after the episode is
controlled, be treated with aspirin (81 mg/day)
plus PPI
Clopidogrel is an alternative in patients who are
allergic to aspirin

32. Revascularization
• Considered in
– Low exercise capacity
– Large area of ischemia
– EF<40 %
– Suitable coronary artery

33. ACUTE CORONARY SYNDROME
UNSTABLE ANGINA AND NON-ST-ELEVATION
MYOCARDIAL INFARCTION

34. INTRODUCTION
• Ischemic heart disease:
1. Chronic coronary artery disease (CAD):
Stable angina
2. Acute coronary syndrome
 ST-segement elevation MI(STEMI)
 Non-ST-segement elevation MI(NSTEMI)
 Unstable angina(UA)

35. THE VULNERABLE PLAQUE AND
CONSEQUENCES OF PLAQUE RUPTURE
Coronary heart disease is a slowly coming
disease, that may lead to acute myocardial
infarction.
Lipid core Plaque rupture Acute closure of the
artery by a thrombus

36. CLASSIFICATION OF ACS

37. DEFINITIONS OF UA/NSTEMI
UA is defined as angina pectoris or equivalent ischemic
discomfort with at least one of three features:
1. It occurs at rest (or with minimal exertion), usually
lasting >10 min
2. It is severe and of new onset (i.e., within the prior
4–6 weeks)
3. It occurs with a crescendo pattern (i.e., distinctly
more severe, prolonged, or frequent than
previously)
 NSTEMI is defined with the clinical features of UA
develops evidence of myocardial necrosis, as
reflected in elevated cardiac biomarkers

38. PATHOPHYSIOLOGY
1. Plaque rupture or erosion with
superimposed nonocclusive thrombus(the
most common cause)
2. Dynamic obstruction
3. Progressive mechanical obstruction (e.g.,
rapidly advancing coronary atherosclerosis)
4. Secondary UA related to increased
myocardial oxygen demand and/or
decreased supply (e.g., tachycardia, anemia)
 More than one pathogenetic mechanism can work at
a time

39. CLINICAL FEATURES
• clinical hallmark of UA/NSTEMI is chest pain
• or Anginal "equivalents’’

40. Clinical features
• The examination resembles that in patients with
stable angina and may be unremarkable
• If the patient has a large area of myocardial
ischemia or a large NSTEMI, the physical findings
can include diaphoresis, pale and cool skin, sinus
tachycardia, a 3rd and/or 4th heart sound, basilar
rales, and sometimes hypotension, resembling
the findings of large STEMI

41. INVESTIGATIONS
• ECG :ST-segment depression, transient ST-
segment elevation, and/or T-wave inversion occur
in 30 to 50% of patients
• Cardiac enzymes: CKMB, troponin
• CBC, RFT, blood glucose, lipid profile, serum
electrolyte
• CXR
• ECHO
• Stress test
• Angiography

43. TIMI RISK STRATIFICATION

45. ANTITHROMBOTIC THERAPY
All patients should receive uncoated aspirin as
soon as possible after the onset of symptoms,
in a dose of 162 to 325 mg. The first tablet
should be chewed to establish a high blood
level quickly
Clopidogrel given in combination with aspirin
In patients with a non-ST elevation ACS
UFH/LMWH should be added to antiplatelet
therapy
Thrombolytic therapy should not be
administered to patients with UA or NSTEMI

46. Additional treatment
• Beta blockers has mortality benefit
• Nitrates if chest pain
• CCB if beta blockers not tolerated
• Morphine: persistent symptom or pulmonary
edema

47. ADDITIONAL TREATEMENTS
 ACEIs/ARBs
 Recommended in pts with UA/NSTEMI and with diabetes,
heart failure, a LV EF <40%t, and hypertension.
 there may be benefit in all patients after an MI
 are started in-hospital but not necessarily in the first 24
hours
 Statin : atorvastatin 80mg irrespective lipid profile
 Aldosterone antigosnt
Are receiving an ACE inhibitor
Have an LVEF 40 percent
 Have either symptomatic heart failure or diabetes
Have a creatinine clearance >30 ml/min
Have a serum potassium <=5.0 meq/L

48. ACUTE CORONARY SYNDROME
ST-SEGEMENT ELEVATION MYOCARDIAL INFARCTION(STEMI)

49. pathogenesis

50. CLINICAL PRESENTATION
 Up to 50% of cases have precipitating factors( e.g. vigorous
physical exercise, emotional stress, or a medical or surgical
illness)
 The time of onset of STEMI has a pronounced circadian
periodicity, with peak incidence of events between 6 am
and noon
• Increase in catecholamines and cortisol
• Increases in platelet aggregability
 the characteristic circadian peak is absent in patients
receiving ßB or aspirin before their presentation with STEMI
 history crucial to establishing a diagnosis

51. CLINICAL PRESENTATION:the chest pain in STEMI
 varies in intensity; in most patients, it is
severe and in some instances intolerable
• Pain described as heavy, squeezing, and
crushing, although occasionally it is described
as stabbing or burning
The duration of pain is prolonged, usually
lasting for more than 30 minutes and
frequently for a number of hours

52. CLINICAL PRESENTATION:the chest
pain in STEMI
Typically involves the central portion of the chest
and/or the epigastrium, and on occasion it radiates
to the arms. Less common sites of radiation include
the abdomen, back, lower jaw, and neck
The pain of STEMI may radiate as high as the
occipital area but not below the umbilicus
The pain may commence when the patient is at rest,
but when it begins during a period of exertion, it
does not usually subside with cessation of activity, in
contrast to angina pectoris
It is often accompanied by weakness, sweating,
nausea, vomiting, anxiety, and a sense of impending
doom

53. CLINICAL PRESENTATION
 Atypical presentations of STEMI include the following:
1. Heart failure (i.e., dyspnea without pain beginning de novo or worsening of
established failure)
2. Classic angina pectoris without a particularly severe or prolonged episode
3. Atypical location of the pain
4. Central nervous system manifestations, resembling those of stroke,
secondary to a sharp reduction in cardiac output in a patient with cerebral
arteriosclerosis
5. Apprehension and nervousness
6. Sudden mania or psychosis
7. Syncope
8. Overwhelming weakness
9. Acute indigestion
10. Peripheral embolization
 SILENT STEMI: occurs more commonly in patients without antecedent
angina pectoris and in patients with diabetes and hypertension
 The prognoses of patients with silent and symptomatic presentations of
STEMI appear quite similar

54. CLINICAL PRESENTATION
 General appearance: anxious,restless and may be in cardiopulmonary
distress
 Vital signs:
o PR: can vary from a marked bradycardia to a rapid regular or irregular
tachycardia
o BP:
o It is determined by the degree and sited of infarction and presence of
hypertension prior to the infarction
o The majority of patients with uncomplicated STEMI are normotensive.
o It is common for previously hypertensive patients to become normotensive
without treatment after STEMI, although many of these previously hypertensive
patients eventually regain their elevated levels of blood pressure, generally 3 to
6 months after infarction
o T0 : Most patients with extensive STEMI develop fever, a nonspecific
response to tissue necrosis, within 24 to 48 hours of the onset of
infarction. Body temperature often begins to rise within 4 to 8 hours
after the onset of infarction, and rectal temperature may reach 38.3° to
38.9° C (101° to 102° F). Fever usually resolves by the fourth or fifth day
after infarction
o RR

55. CLINICAL PRESENTATION
 Chest
 JVP
 Arterial pulse character:
 a small pulse suggests a reduced stroke volume, whereas a sharp, brief
upstroke is often observed in patients with mitral regurgitation or
ruptured ventricular septum with a left-to-right shunt. Pulsus alternans
reflects severe left ventricular dysfunction
 Precordium:
 the precordium is usually quiet, and the apical impulse may be difficult
to palpate. In patients with transmural infarction systolic and presystolic
pulsations may be felt.On auscultation one may hear S3 and S4 heart sounds
and murmur of MR and friction rub
 Abdomen
 Integumentary system:
 in the presence of cardiogenic shock the skin is cool and clammy, with a
bluish or mottled color over the extremities, and there is marked facial
pallor with severe cyanosis of the lips and nailbeds
 CNS: include funduscopic examination

56. KILLIP CLASSIFICATION OF ACUTE MYOCARDIAL INFARCTION
• Class I - no evidence of HF
• Class II - findings consistent with mild to
moderate HF (S3, lung rales less than
one-half way up the posterior lung fields,
or jugular venous distension)
• Class III - overt pulmonary edema
• Class IV - cardiogenic shock

57. INVESTIGATIONS
 ECG
 Cardiac biomarkers(cardiac enzymes)
 Cardiac imaging: ECHO,radionuclide imaging techniques,
cardiac magnetic resonance imaging and angiography
 Nonspecific indices of tissue necrosis and inflammation
 CBC with platelet count
 PT and INR
 aPTT
 Electrolytes
 Magnesium
 BUN
 Creatinine
 Blood glucose
 Serum lipid profile

58. ECG IN STEMI
• STEMI diagnosed in patients in ACS and with with
• ST elevation,
• new or presumably new left bundle branch block
• a true posterior MI
• Localaization
o Leads V1 to V3 with anteroseptal ischemia
o Leads I and aVL with lateral ischemia
o Leads V4 to V6 with apical or lateral ischemia
o Leads II, III, and aVF with inferior wall ischemia
o Right-sided precordial leads with right ventricular
ischemia

59. ECG FINDINGS (e.g. Acute Lateral Transmural Myocardial Infarction)

60. CARDIAC ENZYMES

61. TIME COURSE OF SERUM MARKERS IN ACUTE MI

62. TIME COURSE OF SERUM MARKERS IN ACUTE MI

63. GOALS OF THERAPY IN STEMI
• Relief of ischemic pain
• Assessment of the hemodynamic state and correction of abnormalities that are
present
• Initiation of reperfusion therapy with primary percutaneous coronary intervention
(PCI) or fibrinolysis
• Antithrombotic therapy to prevent rethrombosis or subtotal stenosis at the site of
an ulcerated plaque
• Antiplatelet therapy to reduce the risk of recurrent coronary artery thrombosis or,
with PCI, coronary artery stent thrombosis
• Prevention of left ventricular remodeling with ACEI
• Prevention of recurrent ischemia and life-threatening ventricular arrhythmias with
beta blockers
• Cholesterol lowering with a statin to prevent or slow disease progression; the
benefit of statins may be mediated by pleiotropic effects in addition to its effect on
serum lipids

64. Most out-of-hospital deaths from STEMI are due to the sudden development of
ventricular fibrillation. The vast majority of deaths due to ventricular fibrillation occur
within the first 24 h of the onset of symptoms, and of these, over half occur in the first
hour.

65. STEMI
MANAGEMENT IN THE EMERGENCY DEPARTEMENT

66. ALGORITHM FOR INITIAL MANAGEMENT OF PATIENTS WITH AN ACUTE
ST ELEVATION MYOCARDIAL INFARCTION
 Initial clopidogrel loading dose is 600 mg if patient going to primary PCI and 300 mg if
thrombolysis and 75 years of age or if no reperfusion therapy. Among patients >75 years of age given
thrombolytic therapy, most receive 75 mg loading dose

67. REPERFUSION THERAPY
1. PCI
– Primary PCI preferred
– Better done within 12hrs of onset and within 90min of
presentation
2. Fibrinolysis ;
– better done within 30min of presentation if no containdication
– Benefit within first 1-3 hrs of symptom onset, but can be used upto 12 hrs of
symptoms onset.

68. ANTICOAGULATION
1. Use of heparine in STEMI:
Patients with an STEMI undergoing percutaneous
or surgical revascularization
Patients treated with thrombolytic therapy with
alteplase, reteplase, or tenecteplase
Patients who receive no reperfusion therapy
2. Use of warfarine in STEMI:
• Left ventricular thrombus
• A history of a thromboembolism
• Chronic atrial fibrillation, in which warfarin therapy
is continued for an indefinite period of time

69. STEMI
HOSPITAL PHASE MANAGEMENT

70. GENERAL MEASURES
 A calm, quiet atmosphere and the “laying on of hands” with a gentle but
confident touch help allay anxiety and reduce sympathetic tone, ultimately
leading to a reduction in hypertension, tachycardia, and arrhythmias
 Activity
• patients with STEMI should be kept at bed rest for the first 12 h
• patients should be encouraged, under supervision, to resume an upright
posture by dangling their feet over the side of the bed and sitting in a chair
within the first 24 h
• In the absence of hypotension and other complications, by the second or third
day patients typically are ambulating in their room with increasing duration and
frequency, and they may shower or stand at the sink to bathe
• By day 3 after infarction, patients should be increasing their ambulation
progressively to a goal of 185 m (600 ft) at least three times a day
 Diet: Because of the risk of emesis and aspiration soon after STEMI,
patients should receive either nothing or only clear liquids by mouth for
the first 4–12 h
 Bowels
 Sedation

71. PHARMACOTHERAPY
 Antithrombotic agents: ASA, clopedogrel, heparin
 Beta-Adrenoceptor Blockers
 ACEIs
 Statins
 Aldosterone antagonists
• Are receiving an ACE inhibitor
• Have an LVEF<= 40 percent
• Have either symptomatic HF or diabetes
• Have a serum creatinine <=2.5 mg/dL [221 µmol/L] in men and<= 2.0
mg/dL [177 µmol/L] in women
• Have a serum potassium <=5.0 meq/L
blood glucose control
maintaining the serum potassium concentration above 4.0 meq/L
and a serum magnesium concentration above 2.0 meq/L (2.4
mg/dL or 1 mmol/L)

72. COMPLICATIONS OF STEMI
 Mechanical
• Rupture of the left ventricular free wall
• Rupture of IVS
• Mitral regurgitation
• Left ventricular dysfunction
• LV aneurysm
• Pericarditis
• Electrical complications
• Complications which can be as a result of both mechanical
and electrical disturbances
Heart failure
Cardiogenic shock
Thromboembolism