(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

Stages of atherosclerosis

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.

TYPES OF ANGINA stable=unstable=varient=MI

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).

TYPES OF ANGINA stable=unstable=varient=MI

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.

TYPES OF ANGINA stable=unstable=varient=MI

Effects of myocardial ischaemia: This leads to cell death by one of two

pathways: Necrosis or apoptosis

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

Pathophysiology of myocardial ischemia

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

Released into the circulation from necrotic heart muscle

CK (creatine kinase) rises 4-8 hrs after onset of MIand normalize by 48-72 hrsnot specific for myocardial necrosis

MB isoenzyme of CK is more specific

Cardiac specific troponins: more sensitive and specific than CK and CKMB for identificationof myocardial necrosis

Myoglobin- first serum marker to rise after MI, but lacks specificity.

Serum cardiac markers

NEGATIVE

NEGATIVE

POSITIVE

NON DIAGNOSTIC

POSITIVE

NON DIAGNOSTIC

Diagnostic Decision Tree

for Coronary Artery Disease

~ 4.4 m

procedures/y

Stress ECG

Ultrasound

$ 400.-

rule out CAD

medication

Stress Perfusion Imaging

Nuclear Medicine rule out CAD

medication

~ 2.2 m

procedures/yX-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

RCARCA

RCA

RCA

LADLAD

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)

Time of OnsetTime of OnsetTime of Onset

ED Time Point 1:DOOR

ED Time Point 1:ED Time Point 1:DOORDOOR

ED Time Point 2:

DATA

ED Time Point 2:ED Time Point 2:

DATADATA

ED Time Point 3:

DECISION

ED Time Point 3:ED Time Point 3:

DECISIONDECISION

ED Time Point 4:

DRUG

ED Time Point 4:ED Time Point 4:

DRUGDRUG

Time Interval III

Decision to drug

Time Interval IIECG to decision to treat

Time Interval IDoor to ECG

NHAAP Recommendations. U.S. Department of Health NIH Publication: 1997:97-3787.

The Four DsThe Four DsThe Four Ds

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)

Cardiac catheterization Severe ischemia

Revascularization (PCI/CABG) Medical therapy

Stress test

yes

no

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

Fibrinolytic agents

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

Aortic dissection

History of cerebrovasculardisease

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)

بكفرالمركزةالعناية

سعدالفائدةمنكمولكمترجو

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

Aortic dissection

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

Differencial diagnosis of

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

Differencial diagnosis of

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

Differencial diagnosis of

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

Electrocardiogram

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

Electrocardiogram

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

Electrocardiogram

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

Electrocardiogram

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)

1 mg/L 3 mg/L 10 mg/L

Low

RiskModerate

RiskHigh

Risk

Acute Phase Response

Ignore Value, Repeat Test in 3 weeks

>100 mg/L

Ridker PM. Circulation 2003;107:363-9

Clinical Application of hs-CRP for

Cardiovascular Risk Prediction