I s c h a e m i a

(central)
I S C H A E M I A
Sayed Sileem, MSc. cardiologist
ICU – Kafr Saad central hospital
Damietta – Egypt
2014

4
Risk Factors
Uncontrollable
•Sex
•Hereditary
•Race
•Age
Controllable
•High blood pressure
•High blood cholesterol
•Smoking
•Physical activity
•Obesity
•Diabetes
•Stress and anger
-Fibrinogen
-Homocysteine
-Urine
microalbuminuria/creatinine ratio
-Hs CRP
-Markers of subclinical CVD
ABI
Exercise testing
EBCT/MRI
Carotid IMT

PREVENTION OF ATHEROMATOUS DISEASE
 ACE-Is improve endothelial function and prolong life
 Regular exercise increases circulating HDL.
 Antioxidants (e.g. vitamin C and vitamin E) improve endothelial
function.

LIPOPROTEIN TRANSPORT
 Lipids and cholesterol are transported in the bloodstream as
complexes of lipid and protein known as lipoproteins. These
consist of a central core of hydrophobic lipid encased in a
hydrophilic coat of polar phospholipid, free cholesterol
and apoprotein.
There are four main classes of lipoprotein
1. HDL particles (contain apoA1 and apoA2), diameter 7-20 nm
2. LDL particles (contain apoB-100), diameter 20-30 nm
3. VLDL particles (contain apoB-100), diameter 30-80 nm
4. chylomicrons (contain apoB-48), diameter 100-1000 nm.

 Ischaemic heart disease(IHD) is defined as acute or
chronic form of cardiac disability arising from
imbalances between the myocardial supply and
demand for oxygenated blood.
 Since, narrowing or obstruction of the coronary
arterial system is the most common cause of
myocardial anoxia, the alternate term coronary
artery disease(CAD) is used synonymously with IHD.

SIGNS AND SYMPTOMS
Ischaemic heart disease may be present with any of the following
problems:
 Angina pectoris
 Acute chest pain: ACS {unstable angina or MI}.("heart attack",
severe chest pain unrelieved by rest associated with evidence
of acute heart damage)
 Heart failure (dyspnoea or limb oedema).
 Heart burn.

 Angina occurs when the oxygen supply to the myocardium is
insufficient for its needs.
 The pain has a characteristic distribution in the
 chest,
 arm and
 neck,
It is brought on by
1. exertion,
2. cold or
3. excitement.

TYPES OF ANGINA stable=unstable=varient=MI
 Predictable
 Occurs on exercise, emotion or eating.
 Caused by increase demand of the heart and by a fixed narrowing
of coronary vessels, almost always by atheroma.
 Blood flow fails to increase during increased demand despite the
local factors mediated vasodilation and so ischemic pain.
 So, the diastolic pressure increases and this causes a endocrinal
crunch and thus causing Ischaematic pain in this region.
 Relieved by taking rest and reducing the myocardial workload.

 This is characterized by pain that occurs with less and less
exertion, culminating in pain at rest.
 The pathology is similar to that involved in myocardial
infarction, namely platelet-fibrin thrombus associated with a
ruptured atheromatous plaque, but without complete occlusion
of the vessel.

 Uncommon
 Occurs at rest generally during sleep
 Caused by Large Coronary artery spasm
 Therapy is with Coronary artery vasodilators.(e.g. organic
nitrates, calcium antagonists).

 Myocardial infarction occurs when a coronary artery has been
blocked by thrombus.
 This may be fatal and is a common cause of death, usually as a
result of mechanical failure of the ventricle or from arrhythmia.
 Cardiac myocytes rely on aerobic metabolism. If the supply of
oxygen remains below a critical value, a sequence of events
leading to cell death (by necrosis or apoptosis) detected
clinically by an elevation of circulating troponin.

Effects of myocardial ischaemia: This leads to cell death by one of two
pathways: Necrosis or apoptosis

Pathophysiology of myocardial ischemia
 Myocardial oxigen supply is decreased
 Narrowed coronary arteries (sclerosis, thrombus,
spasmus, coronary embolism, vasculitis)
 Hypotension
 Severe anemia
 Methemoglobinemia, increased carboxyhemoglobin
 Myocardial oxigen demand is increased
 Left ventricle hypertrophy
 Fever
 Hyperthyroidism
 Tachycardy

The clinical manifestations of ischemic heart disease
 Ischemic heart disease without clinical symptoms.
Sudden death can be the presenting manifestation.
 Cardiomegaly and heart failure that may have caused
no symptoms prior the development of heart failure –
ischemic cardiomyopathy.
 Angina pectoris. Stable angina pectoris.
 Unstable angina/Non ST-elevation myocardial
infarction (NSTEMI)/STEMI = acut coronary
syndromes

The typical clinical features of angina pectoris
 The typical location of pain is retrosternal.
 When the patient is asked to localize the sensation, he or
she will typically place their hand over the sternum,
somtetimes with a clenched fist, to indicate the
squezzing. The pain can not be localized with one finger.
 Usually described as heaviness, pressure, squezzing, or
choking.
 Usually associates with gradual intensification of
symptoms over a period of minutes.
 It lasts typically 2-5 min.
 It can radiate 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 neck, jaw, teeth, and epigastrium. Rarely
localized below the umbilicus or above the mandible.
 Exertional angina is typically relieved by rest and
nitroglycerin.

Associated symptoms and signs of angina pectoris
 Associated symptoms
 Dyspnoe
 Fatique, faintness
 Nausea, vomiting
 Sweating
 Sense of impending doom (mostly in case of
myocardial infarction)
 Physical signs
 Third and fourth heart sounds
 Apical systolic murmur due to mitral regurgitation
(impaired papillary muscle function)
 Pulmonary congestion

Summary of the characteristics of angina pectoris
 Typical angina pectoris:
 Retrosternal chest pain (discomfort)
 Complaints occur after exertion or emotional stress
 The pain is relieved by rest and nitroglycerin
 Atypical angina pectoris: especially in women and
diabetics, angina may be atypical in location and not
strictly related to provocing factors)
 Pseudoangina: Only one or no one out of three
characteristics.

Cardial and extracardial causes of chest discomfort
 CARDIOVASCULAR DIS.
 Ischemic heart disease
 Pericarditis
 Aortic dissection
 Congestive heart failure
 Aortic stenosis and
regurgitation
 Hypertrophic cardiomyopathy
 Pulmonary hypertension
 LUNG DISEASES
 Pulmonary embolism
 Pneumothorax
 Pleuro-pneumonia
 Pleuritis
 GASTROESOPHAGEAL DIS.
 Gastroesophageal reflux
 Esophageal motility disorders
 Paptic ulcer
 Gallstones
 NEUROMUSCULOSKELETAL DIS
 Fracture of sternum or rib
 Spondylarthrosis
 Periarthritis humeroscapularis
 Intercostal muscle cramp
 Tietze’ s syndrome
 MISCELLANEOUS
 Subphrenic abscess
 Herpes zoster
 Splenic infraction
 Psychiatric disease

Diagnostic tests in patients with chest discomfort
2.
 If the patient’s history or examination is consistent
 with pulmonary embolism
 D-dimer, CT-angiography or a lung scan, echocardiography combined with
lower extremity venous ultrasound
 With aortic dissection
 Chest CT scan with contrast, MRI, or transesophageal echocardiography
No evidence of life-threatening conditions, the clinician should
then focus on serious chronic conditions with the potential to
cause major complications, the most common of which is stable
angina
- exercise electrocradiography, stress echocardiography or
stress perfusion imaging
- Pericarditis (, blood pressure pattern, echocardiography)
If not, could the discomfort be due to an acute condition that
warrants specific therapy?
- Pneumonia – Chest X-ray
- Herpes zoster – physical examination
If not, another treatable chronic condition

Serum cardiac markers
Released into the circulation from necrotic heart muscle
CK (creatine kinase) rises 4-8 hrs after onset of MI
and normalize by 48-72 hrs
not specific for myocardial necrosis
MB isoenzyme of CK is more specific
Cardiac specific troponins: more sensitive and
specific than CK and CKMB for identification
of myocardial necrosis
Myoglobin- first serum marker to rise after MI, but
lacks specificity.

Diagnostic Decision Tree
for Coronary Artery Disease
NEGATIVE
Nuclear Medicine NEGATIVE
rule out CAD
POSITIVE
NON DIAGNOSTIC
POSITIVE
NON DIAGNOSTIC
~ 4.4 m
procedures/y
Stress ECG
Ultrasound
$ 400.-
rule out CAD
medication
Stress Perfusion Imaging
medication
~ 2.2 m
procedures/y
X-Ray Coronary
Angiography or IVUS
$ 300.-
$ 700.-
>$ 3,000.-
~ 13 m
procedures/y
Radiation
Invasive

MR Coronary Angiography after 0.125 mmol/kg
Injection of B-22956/1 [Res. : 0.7  0.7  0.7 mm3]
1 min
postcontrast
33 min
postcontrast
17 min
postcontrast
RCA RCA
RCA
RCA
LAD LAD

Diagnosis
 Electrocardiogram
 Echocardiograms
 Stress Tests
 Nuclear Imaging
 Angiography

Treatment
 Lifestyle changes:
Weight control
Smoking cessation
Exercise
Healthy diet

The main therapeutic drugs include drugs to
improve cardiac function by maintaining
oxygenation and reducing cardiac work as well as
treating pain and preventing further thrombosis.
Combinations of thrombolytic, antiplatelet and
antithrombotic (a heparin preparation) drugs to
open the blocked artery and prevent re-occlusion.

 Antiplatelet treatment. Clopidogrel 300mg if undergoing PCI- Glycoprotein IIb/IIIa inhibitors
(abciximab) if undergoing PCI
 Throbolytic therapy then, Heparin eg enoxaparin 1mg/kg 12 hourly
 ACEIs and ARBs also reduce cardiac work and improve survival, treat hypertension and may
lower the risk of recurrent myocardial infarction
 Aspirin : 160-325 mg chewable aspirin leads to rapid buccal absorption, inhibition of COX in
platelets and reduction of TXA2
 βB reduce cardiac work and thereby the metabolic needs of the heart, and are used as soon as
the patient is stable. Atenolol 5mg over 5 mins repeated after 10-15 mins
 CCB
 Cholesterol lowering medications, such as statins, are useful to decrease the amount of LDL.
 Nitroglycerin 0.4mg sublingual +- IV
 Oxygen if there is arterial hypoxia.
 Opioids (given with an antiemetic) to prevent pain
 Tight glycaemic control
 Optimise potassium and magnesium

Surgical intervention
Angioplasty
Stents
Coronary artery bypass grafting (CABG)

PCI Procedural refinements: Stents
Expandable metal mesh tubes that buttresses the dilated segment, limit
restenosis.
Drug eluting stents: further reduce cellular proliferation in response to the
injury of dilatation.

Coronary Artery Bypass Grafting (CABG)

STEMI
ASA, beta blockers, antithrombin therapy
<12 hrs >12 hrs
Eligible for
Lytic therapy
Lytic C/I Not a candidate
For reperfusion
Persistent
symptoms
Thrombolysis Primary PCI no yes
Other medical therapy Consider reperfusion
(ACEI, nitrates, beta blockers, antiplatelets, antithrombin,statins)

TThhee FFoouurr DDss
TTiimee ooff OOnnsseett
ED Time Point 1:
DOOR
ED Time Point 2:
DATA
ED Time Point 3:
DECISION
ED Time Point 4:
DRUG
Time Interval III
Decision to drug
Time Interval II
ECG to decision to treat
Time Interval I
Door to ECG
NHAAP Recommendations. U.S. Department of Health NIH Publication: 1997:97-3787.

Unstable angina/NSTEMI
Aspirin, antithrombin - nitrates - GP IIb-IIIa
antagonist- Betablockers (or CCB)
Assess clinical status
High risk/unstable Stable
(Recurrent ischemia, LV dysfunction
Widespread EKG changes, positive
enzyme markers)
Stress test
yes
Cardiac catheterization Severe ischemia
no
Revascularization (PCI/CABG) Medical therapy

DRUGS USED IN ANGINA AND THEIR SITE OF
ACTIONS

Effects of
nitrates and
nitrites on
smooth
muscle

Time to peak effect
and duration of
action for some
common organic
nitrate preparations

Mode of action
 Activate plasminogen to form plasmin which
degrades fibrin breaking up thrombi
 Streptokinase, alteplase, reteplase, tenecteplase
 Streptokinase – antibodies within 4 ds
 Alteplase, reteplase followed by heparin for 48 hs

Indications Contraindications
 Acute ST elevation
myocardial infarction
 Acute pulmonary
embolism
 Acute ischaemic stroke
within 3 hours
 Recent haemorrhage
trauma or surgery
 Recent dental extraction
 Coagulation defects;
bleeding disorders
 History of cerebrovascular
disease
 Active peptic ulceration
 Severe menorrhagia
 Severe hypertension
 Active cavitating lung
disease
 Acute pancreatitis
 Severe liver disease
 Oesophageal varices
 Previous reaction to
streptokinase
Relative contraindications
 Venepuncture (non-compressible
site)
 Recent invasive procedure
 External chest compressions
 Pregnancy
 Abdominal aortic aneurysm
 Diabetic retinopathy
 Anticoagulant therapy

Side effects
 Nausea and vomiting
 Bleeding
 Reperfusion arrhythmias
 Hypotension
 Back pain
 Allergic reactions (esp streptokinase)

العناية المركزة بكفر
سعد
ترجو لكم و منكم الفائدة

Differencial diagnosis of
chest discomfort
 Acute myocardial infarction
 The duration of the pain often more than 30 min
 Often more severe than angina
 Unrielived by nitroglicerin
 May be associated with evidence of heart failure or
arrhythmia
 Tearing, ripping pain with abrupt onset
 Associated with hypertension, and/or connective tissue
disorder
 Depending on the location of dissection:
 Loss of peripheral pulse
 Pericardial tamponad
 Murmur of aortic insufficiency

chest discomfort
 Pericarditis
 The duration of the pain is hours to days
 Sharp, retrosternal pain that is aggravated by coughing, deep
breath, or changes in body position (relieved by sitting and leaning
forward)
 Pulmonary embolism
 Abrupt onset of the pain. Location is often lateral
 Associated symptoms are dyspnea, tachycardy,and occasionally
hemoptysis
 Pneumothorax
 Sudden onset of pleuritic chest pain. Location:lateral to side of
pneumothorax
 Dyspnea, decreased breath sounds, tympanic percussion sound.
 Pneumonia or pleuritis
 Localized sharp, knifelike pain
 Pain is aggravated by inspiration and coughing
 Dyspnea, fever, rales, occasionally pleural rub

chest discomfort
 Esophageal reflux
 Deep, burning discomfort that may be exacerbated by
alcohol, aspirin, or some foods
 Worsened by postprandial recumbency, relieved by
antacids
 Ulcer disease
 Symptoms do not associated with exertion
 Prolonged burning pain
 Typically occurs 60 to 90 min after meals, when
postprandial acid production is no longer neutralized
by food in the stomach
 Gallbladder disease
 Prolonged colic pain
 Occurs an hour or more after meals

chest discomfort
 Neuromusculoskeletal diseases
 Cervical disk disease: compression of nerve roots –
dermatomal distribution (pain in dermatomal
distribution can also be caused by intercostal muscle
cramp and herpes zoster)
 The pain is aggravated by movement
 Costochondral and chondrosternal syndromes
(Tietze’s syndrome)
 direct pressure on the costochondral-costosternal junctions
may reproduce the pain.
 Psychiatric conditions
 Th symptoms are frquently described as visceral
tightness or aching that last more than 30 min.

Pathophysiology of acut
coronary syndrome
 UA/NSTEMI: Caused by a reduction in oxygen supply
and/or by an increase in myocardial oxygen demand
superimposed on an atherosclerotic coronary plaque.
 STEMI: coronary blood flow decreases abruptly after a
thrombotic occlusion of a coronary artery previously
affected by atherosclerosis.

Diagnosis
 Echocardiograms
 Stress Tests
 Nuclear Imaging
 Angiography
It is may be ordered if your doctor
suspects a problem with the heart muscle
or one of the valves that channel blood
through the heart.

Diagnosis
 Echocardiograms
 Stress Tests
 Nuclear Imaging
 Angiography
They are used to show how the heart
reacts to physical exertion. Exercise stress
tests are usually performed on a treadmill
or exercise bicycle.

Diagnosis
 Echocardiograms
 Stress Tests
 Nuclear Imaging
 Angiography
involves the use of small amounts of
short-lived radioactive material, which is
injected into the bloodstream.
A special camera (live-motion x-ray)
detects the radioactivity of these
materials, and the images displayed show
how your heart pumps blood.
This is useful in identifying any areas of
abnormal motion or for assessing the
blood supply to the heart muscle.

Diagnosis
 Echocardiograms
 Stress Tests
 Nuclear Imaging
 Angiography
Is the most accurate means by which to
examine the coronary arteries.
It requires a surgical procedure called
cardiac catheterization. During the
procedure, catheters (small thin plastic
tubes) are placed in the artery of the leg
or arm, and directed using an x-ray
machine to the opening of each of the
coronary arteries

Ten important treatment elements of stable angina include:
AA aspirin and anti-anginals
BB beta-blockers and blood pressure control
CC cholesterol and cigarettes
DD diet and diabetes
EE education and exercise

1. ORGANIC NITRATES
 It is used in the treatment of angina pectoris are simple nitric
and nitrous acid esters of glycerol. They differ in their
volatility, e.g. isosorbide dinitrate and isosorbide mononitrate
are solids at room temperature, nitroglycerin is only
moderately volatile, and amyl nitrite is extremely volatile.
 These compounds cause a rapid reduction in myocardial
oxygen demand, followed by rapid relief of symptoms.
 They are effective in stable and unstable angina as well as in
variant angina pectoris.

Mechanism of action
 Nitrates decrease coronary vasoconstriction or spasm and increase
perfusion of the myocardium by relaxing coronary arteries.
 In addition, they relax veins, decreasing preload and myocardial oxygen
consumption.
 Organic nitrates, such as nitroglycerin, which is also known as glyceryl
trinitrate, are thought to relax vascular smooth muscle by their intracellular
conversion to nitrite ions, and then to nitric oxide, which in turn activates
guanylate cyclase and increases the cells' cyclic guanosine monophosphate
(GMP). Elevated cGMP ultimately leads to dephosphorylation of the
myosin light chain, resulting in vascular smooth muscle relaxation.

Pharmacokinetics
 The time to onset of action varies from 1 minute for nitroglycerin to more
than 1 hour for isosorbide mononitrate .
 Significant first-pass metabolism of nitroglycerin occurs in the liver.
Therefore, it is common to take the drug either sublingually or via a
transdermal patch, thereby avoiding this route of elimination.
 Isosorbide mononitrate owes its improved bioavailability and long
duration of action to its stability against hepatic breakdown.
 Oral isosorbide dinitrate undergoes denitration to two mononitrates, both of
which possess antianginal activity.

Adverse effects
 The most common adverse effect of nitroglycerin, as well as of
the other nitrates, is headache.
 High doses of organic nitrates can also cause postural
hypotension, facial flushing, and tachycardia. Sildenafil
potentiates the action of the nitrates.
 To preclude the dangerous hypotension that may occur, this
combination is contraindicated.

2. β BLOCKERS
 The β blockers decrease the oxygen demands of the myocardium by lowering
both the rate and the force of contraction of the heart.
 They suppress the activation of the heart by blocking β receptors, and they
reduce the work of the heart by decreasing heart rate, contractility, cardiac
output, and blood pressure. With β blockers, the demand for oxygen by the
myocardium is reduced both during exertion and at rest.
 Propranolol is the prototype for this class of compounds, but it is not cardio
selective.
 Thus, other β blockers, such as metoprolol or atenolol, are preferred.
 Agents with intrinsic sympathomimetic activity (for example, pindolol) are
less effective and should be avoided in angina.

3. CALCIUM-CHANNEL BLOCKERS
Calcium channels
Three types of Ca2+ channel
(a ) Voltage sensitive channel : Activated when membrane potential drops
to around -40 m V or lower.
(b) Receptor operated channel : Activated by Adr and other agonists-independent
of membrane depolarization
(NA contracts even depolarized aortic smooth me bypromoting influx of
Ca2+ through this channel and releasing Ca2+ from sarcoplasmic reticulum).
(c) Leak channel : Small amounts of Ca2+ leak into resting cell and are
pumped out by Ca2+

 Only the voltage sensitive L-type channels are blocked by the CCBs.
 The three groups of CCBs viz. phenylalkylamines (verapamil),
benzothiazepine (diltiazem) and dihydropyridines (nifedipine) bind to
their own specific binding sites on the α1, subunit; all restricting Ca 2+
entry, though characteristics of channel blockade differ.
 Further, different drugs may have differing affinities for various site
specific isoforms of the L-channels.
 This may account for the differences in action exhibited by various
CCBs. The vascular smooth muscle has a more depolarized mernbrane
(RMP about -40 mV) than heart.
 This may contribute to vascular selectivity of certain CCBs.

Pharmacokinetic characteristics of calcium channel blockers

Clinical uses of calcium channel blockers
 Arrhythmias (verapamil):
To slow ventricular rate in rapid atrial fibrillation.
To prevent recurrence of supraventricular tachycardia (SVT).
 Hypertension:
Usually a dihydropyridine drug (e.g. amlodipine or slow-release
nifedipine).
To prevent angina (e.g. dihydropyridine or diltiazem)

Clinical Application of hs-CRP for
Cardiovascular Risk Prediction
1 mg/L 3 mg/L 10 mg/L
Low
Risk
Moderate
Risk
High
Risk
>100 mg/L
Acute Phase Response
Ignore Value, Repeat Test in 3 weeks
Ridker PM. Circulation 2003;107:363-9

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