Ischemic heart disease

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• Ischemic heart disease (IHD) or coronary

artery disease ( CAD) is defined as a lack

of oxygen and decreased or no blood flow

to the myocardium resulting from coronary

artery narrowing or obstruction ( i.e.,

insufficient supply of oxygen to

myocardium, so that oxygen demand

exceed oxygen supply).

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Etiology : The most common situation or process that produce IHD includes :

1)Decreased blood flow to the heart:

This means that a vascular supply to the heart is impeded by:

a) atheroma,

b)thrombosis

c) spasm of coronary arteries.

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a) Atheroma : ( atherosclerotic lesion ).

• It is the most common cause of IHD. The coronary arteries are narrowed by smooth muscle cell proliferation & the accumulation of lipid deposits along the inner lining of the arteries. This will be associated with a loss of endothelium which can serve as a stimulus for the formation of thrombus & result in more narrowing of vessels & a reduction in blood flow manifested as angina &MI.

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b) Thrombus embolic events:

• Also restricts the oxygen supply to the myocardium. In response to arterial vessel wall injury or traumatic injury (like for example atherosclerotic lesions), platelets will aggregate, vasoconstriction, & thrombus formation. This process leads to complete occlusion of the artery. That is why antiplatelet are used in treatment of IHD.

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c) Coronary artery spasm:

• Sustained constriction of one or more

coronary arteries either spontaneously or

induced by irritation ( ex: exposure to cold

or by ergot derivative drugs ), result in

spasm of this coronary artery & a

decrease in myocardial blood flow.

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2) Reduced blood oxygenation:

• Occur when O2 carrying capacity of the blood are reduced or impaired as in iron deficiency anemia.

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3) Increased oxygen demand:

• Myocardial ischemia can also arise if oxygen demand is abnormally increased, as in :

a) Severe ventricular hypertrophy due to hypertension .

b) thyrotoxicosis.

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Risk factors for IHD: 1-Hyperlipidemia: high total cholesterol, TG & elevated LDL\HDL ratio.

2-Hypertension.

3-Smoking .

4-Diabetes mellitus (Type I& II).

5-Obesity( over weight).

6-Family history of IHD.

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7-Chronic stress ( aggressive patient).

8-Male gender.

9 - Age

10- sedentary lifestyle

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Clinical manifestation: • Symptoms may include a sensation of pressure or

burning over the sternum i.e., sharp pain (tight in nature ) that occurs in the retrosternal region of the chest, may radiate to the left jaw, neck, back or left shoulder and arm.

• Chest tightness and shortness of breath may also occur.

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• The sensation usually lasts from 30 seconds to 30 minutes. Other signs are squeezing pressure, burning & indigestion like discomfort.

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Angina pectoris :

• It is a term applied to varying forms of transient chest discomfort that are attributed to myocardial oxygen insufficiency & is usually occurs when myocardial O2 demand exceed myocardial O2 supply.

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Type of angina:

1- Stable angina(classic or exertional angina)

• Usually precipitated by exertion, emotional stress or a heavy meal which lead to chest discomfort, that relieved by rest, Nitroglycerine or both.

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2- Unstable angina: • This type occurs at rest & has a decreased response

to rest or Nitroglycerin & characterized by increase in intensity, duration & frequency.

• Usually patient with unstable angina experience new onset angina or a change in their angina intensity, frequency or duration.

• Progressive unstable angina may lead to MI & should referred to physician as soon as possible. Increased symptom frequency, severity, or duration, and symptoms at rest suggest an unstable pattern that requires immediate medical evaluation.

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3- Prinzmetal angina ( variant angina or

vasospastic angina) :

• It is caused by coronary artery spasm.

• It is usually occurs at rest rather than with exertion or emotional stress ( often in morning hrs.).

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• ECG taken during attack reveals ST segment elevation . Patients with this type are usually younger than patient with stable angina.

• Smoking & alcohol are predisposing factors.

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4- Silent ischemia:

• Patient here doesn't experience chest pain at all but present with SOB or fatigue

• it is occur particularly in patients with diabetes.

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5- Syndrome X:

• Syndrome X can occur during exercise or at rest.

• Anatomically normal coronary arteries.

• Reduced capacity of vasodilation in microvasculature.

• B-blockers and ACE inhibitors are effective.

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DIAGNOSIS

• Clinical history includes the nature or quality of the chest pain, precipitating factors, duration, pain radiation, and the response to nitroglycerin or rest.

• The patient should be asked about existing personal risk factors for coronary heart disease (CHD).

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• A detailed family history should be obtained that includes information about hypertension, familial lipid disorders, and diabetes mellitus.

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Diagnostic procedure:

• Recommended laboratory tests include hemoglobin (to ensure adequate oxygen-carrying capacity), fasting glucose (to exclude diabetes), and fasting lipoprotein profile.

• Important risk factors in some patients may include C-reactive protein; homocysteine level, elevations of fibrinogen and plasminogen activator inhibitor.

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ECG:

• It is normal in 50-70% of patients at rest & who are asymptomatic. During chest pain, the ST segment will usually be depressed except in prinzmetal angina were the ST segment will elevated. So ECG during episode of pain is diagnostic.

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Exercise tolerance test or stress testing or

treadmill test :

• It aids diagnosis in patient who has normal resting ECG, An ST segment depression is an indication of vascular abnormality.

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• Alternatives diagnosis such as myocardial scintigraphy (isotope scanning)and stress echocardiography provide similar information.

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Cardiac catheterization and coronary angiography:

• Cardiac catheterization are specific & sensitive but are also invasive, expensive & have a slight risk (mortality rate 1-2 %) so rarely used in diagnosis of angina.

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• Catheterization is a procedure used to provide vascular access to the coronary arteries. By injection of radio contrast dye into the coronary arteries through the catheter that introduced from the femoral arteries , & through the vasculature until the coronary arteries are accessible , so that the location &extent of atherosclerosis can be determined.

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Treatment of stable angina

Treatment goal

1- improve prognosis by preventing myocardial infraction and death.

2- Relieve or prevent symptoms that limit exercise capability and impair quality of life.

Diabetes, hyperlipidemia and hypertension in Patients should be well controlled. Smoking cessation and weight loss should be attempted.

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Antithrombotic drugs

• One of the major complications arising from atheromatous plaque is thrombus formation.

• This causes an increase in plaque size and may result in myocardial infarction.

• Antiplatelet agents, in particular aspirin, are effective in preventing platelet activation and thus thrombus formation.

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Aspirin

• Aspirin acts via irreversible inhibition of platelet activation and thus thromboxane production, which is normally complete with chronic dosing of 75mg/day.

• Its action appears within 1 hr. of taking a dose of 300 mg.

• Maintenance dose is 75- 150 mg daily .Low doses are as effective as higher doses & have a lower risk of GI hemorrhage .

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Clopidogrel

• Clopidogrel inhibits ADP activation of platelets and is useful as an alternative to aspirin in patients who are allergic or cannot tolerate aspirin.

Statins

• In addition to cholesterol- lowering properties, statin has antithrombotic & antiproliferative properties.

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Angiotensin converting enzyme inhibitors :

• Recent information proves its role in treating patient with CHD by improving endothelial function.

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Symptom relief and prevention

β- adrenergic - blocker :

• It reduces myocardial oxygen demands both at rest and during exertion by decreasing catecholamine – mediated increase in heart rate, BP & to some extent myocardial contractility & decrease force of ejection in systole .

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• β- blockers are first line agents for angina treatment with the exception of Prinzmetals`angina.

• Ideal candidates for β-blockers include patients in whom physical activity is a prominent cause of attacks; those with coexisting hypertension, supraventricular arrhythmias, or postmyocardial infarction, angina; and those with anxiety associated with anginal episodes.

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Calcium channel blockers:

• Recently added to the family of drugs used to treat angina specially chronic stable angina that is not controlled by nitrate & β- blocker.

• Also used to treat prinzemetal angina (vasospastic angina ) alone or with nitrates .

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• Good candidates for calcium channel antagonists include patients with contraindications or intolerance to β-blockers, coexisting conduction system disease (excluding the use of verapamil and possibly diltiazem), Prinzmetal angina, peripheral vascular disease, and concurrent hypertension.

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• Nifedipine, Amlodipine & Nicardipene are example of CCB used in angina . They are effective peripheral dilators & improve coronary perfusion but also causing flushing, headaches, reflex tachycardia. This may be overcome by combination with a B-blockers.

• Verapamil & Diltiazem , if used in angina should be cautioned that the patients are not on β- blockers because of the additive effects on bradycardia & myodepressant . They must be used with caution in patients with preexisting conduction abnormalities or in patients taking other drugs with negative chronotropic properties.

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Nitrates:

• Nitrates decrease coronary vasoconstriction or spasm and increase perfusion of the myocardium by relaxing coronary arteries.

• Their potent vasodilator activity decrease myocardial oxygen demand by reducing venous return to the heart.

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• Tolerance is one of the main limitations to its use . This develops rapidly, and a nitrate free interval period of a few hours in each 24 hr. period is beneficial to maintain the effectiveness of treatment .

• This interval should scheduled with the period of lowest risk , usually at night time & not early morning which is a high risk period for angina.

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• During this nitrate –free interval , the patient may receive angina protection from β- blocker or CCBs.

• There are many nitrate preparation available, including intravenous infusion, slow release tablets and capsules ,transdermal patches, sublingual tablets and sprays and adhesive buccal tablets.

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• Three main nitrates are used 1- Glyceryl trinitrate (Angised). Available as sublingual tablet, buccal tablet, transdermal ointment ,transdermal patch & intravenous routes. 1)Sublingual tablet • Sublingual tablet used for prevention or relief of

acute attack of anginal pain . Also used as a prophylaxis 5-10 minutes before a patient undergoes heavy exertion.

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• A principle side effects of nitrate are dizziness , headache ,hypotension & fainting, which can be minimized by taking NTG, while a patient is in sitting position rather than standing. Sublingual tablet should not swallowed.

• Onset of action is within 1-2 minute & pain usually relieved within 3-5 minute .Patient can take a maximum of 3 tablets over 15 minute .If pain persists for more than 30 minute , then the patient should seek medical assistance because the patient may have MI. 44

• Sublingual tablets have a very short shelf life on exposure to air .They may degraded by heat ,moisture & light , so should stored in a brown container. Once a container is opened , the tablet should used for only a limited time (6 month).

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2)Transdermal patches :

• It provides protection with a once daily application . It maintains anti ischeamic effect for 12 hours after application .

• Usually start with a low dose & titrate upward as need.

• Contact dermatitis can be reported ,with its use . It is an expensive preparation.

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3) Transdermal ointment (paste):

• Applied 3t.d. beginning in early morning but should removed at evening , so that a nitrate free interval is maintained .

• Application sites should rotate to avoid skin irritation.

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4)Intravenous route :

• Used mostly for unstable angina .Also associated with nitrate tolerance if given as a sustained infusion .This can be prevented by infusing NTG for only 12 hr. followed by 12 hr. nitrate free interval.

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• Sublingual, buccal, or spray nitroglycerin products are preferred for alleviation of anginal attacks because of rapid absorption.

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2- Isosorbid dinitrate:

• The majority of angina patient controlled by oral Isosorbid dinitrate tablets which are cheap &can be administrated 3 times a day and which permit a nitrate free period at night.

• Oral nitrate has a first pass effect.

• Goal of therapy is to decrease the number ,severity &duration of attack .

• Onset of action 30 minute while duration 4-8 hr.

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• Isosorbid dinitrate also available as a sublingual tablet, its onset of action is delayed when compared with sublingual NTG.

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3- Isosorbid mononitrate:

• It is a primary metabolite of isosorbid dinitrate .It doesn’t undergo first pass metabolism. It should be used twice daily to minimize the development of nitrate tolerance.

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Adverse effects of Nitrates

postural hypotension with associated CNS symptoms, reflex tachycardia, headaches and flushing, and occasional nausea.

Noncardiovascular adverse effects include rash (especially with transdermal nitroglycerin) and methemoglobinemia with high doses given for extended periods.

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Nicorandil

• Nicorandil is a potassium channel openers causes activation of potassium channels, Nitric oxide release results dilation of the large coronary arteries.

• Used as prophylactic therapy .

• Adverse effect includes tachycardia, headache , flushing and dizziness.

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Ranolazine

• It is a Sodium Channel Blocker.

• It is decrease myocardial oxygen requirement; Increases coronary blood supply, decreasing frequency of angina and decreasing the use of GTN

• Side effects include dizziness, constipation and nausea.

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Ivabradine

• Ivabridine is similar in efficacy to atenolol and CCBs and may be of particular use in patients in whom β-blockers are contraindicated.

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