UNIT 4 CORONARY ARTERY DISEASE AND ISCHAEMIC HEART DISEASE

Structure
4.0 4.1 4.2 4.3 4.4 4.5 4.6 Objectives Introduction Clinical Features Investigations General Management Acute Coronary Syndrome (ACS) Acute Myocardial Infarction (AMI)
4.6.1 4.6.2 4.6.3 4.6.4 Pathophysiology Clinical Presentation Investigations Management

4.7 4.8 4.9

Management of Complications of Acute Myocardial Infraction Let Us Sum Up Answers to Check Your Progress

4.0

OBJECTIVES
describe the clinical feature and management of ischaemic heart diseases; describe the clinical presentation of acute coronary syndrome; and describe the pathophysiology, clinical presentation and management of acute myocardial infarction.

After reading this unit, you should be able to:

4.1

INTRODUCTION

Ischaemia refers to a lack of oxygen due to inadequate perfusion of the myocardium, which is due to an imbalance between oxygen supply and demand. The spectrum of coronary artery disease ranges from stable coronary artery disease, asymptomatic coronary artery disease, unstable angina, acute myocardial infarction, ischaemic cardiomyopathy and sudden cardiac death. The causes are as follows: 1) Coronary blood flow to a region of the myocardium may be reduced by a mechanical obstruction that is due to: (The first two are the most frequent).


2)

Atheroma Thrombosis Spasm Embolus Coronary ostial stenosis Coronary arteritis (e.g. in SLE).

There can be a decrease in the flow of oxygenated blood to the myocardium that is due to:

3) 4)

Carboxyhaemoglobinaemia (rare) Hypotension causing decreased coronary perfusion pressure.

An increased demand for oxygen may occur owing to an increase in cardiac output (e.g. thyrotoxicosis) or myocardial hypertrophy (e.g. from aortic stenosis or hypertension). Congenitalcoronary anomalies.

4.2

CLINICAL FEATURES

Angina pectoris is a cardinal symptom. Typically described as heaviness, pressure, squeezing, smothering, choking or burning and rarely as frank pain. Angina usually crescendo-decrescendo, typically lasting 2-3 mins and can radiate to the left shoulder and to both arms, especially to 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. Angina is rarely localized below the umbilicus or above the mandible, even though headache can be a manifestation.
Table 4.1: Grading of Angina Pectoris According to CCS Classification
Class I Description of Stage Ordinary physical activity does not cause angina, such as walking or climbing stairs. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly; walking uphill; walking or stair climbing after meals; in cold, in wind, or under emotional stress; or only during the few hours after awakening. Angina occurs on walking >2 blocks on the level and climbing > 1 flight of ordinary stairs at a normal pace and under normal conditions. Marked limitations of ordinary physical activity. Angina occurs on walking 1 to 2 blocks on the level and climbing 1 flight of stairs under normal conditions and at a normal pace. Inability to carry on any physical activity without discomfort anginal symptoms may be present at rest.

II

III

IV

Physical Examination

This is often normal in patients with stable angina, but it may reveal evidence of atherosclerotic disease at other sites, such as an abdominal aortic aneurysm, carotid arterial bruits, and diminished arterial pulse in the lower extremities, or of risks factors for atherosclerosis, such as xanthelasma and xanthomas. Examination of the fundi may reveal increased light reflex and arteriovenous nicking as evidence of hypertension.

4.3

INVESTIGATIONS

Electrocardiogram A 12-lead ECG recorded at rest is normal in about half the patients with typical angina pectoris, but there may be signs of an old myocardial infarction. Although repolarization abnormalities, i.e., ST-segment and T-wave changes as well as left ventricular hypertrophy and intraventricular conduction disturbances, are suggestive of IHD, they are nonspecific. Typical ST-segment and Twave changes that accompany episodes of angina pectoris and disappear thereafter are more specific. Exercise ECG Exercise testing can be very useful both in confirming the diagnosis of angina and in giving some indication as to the severity of the CAD. ST-segment depression of 1 mm suggests myocardial ischaemia, particularly if typical chest pain occurs at the same time. The test has a specificity of 80 per cent and a sensitivity of about 70 per cent of CAD. A strongly positive test (within 6 minutes of starting the bruce protocol) suggests prognostic disease and helps to identify patients who should be offered coronary angiography. Exercise testing, however, can be misleading:

A normal test does not exclude CAD (so-called false-negative test) although these patients, as
a group, have a good prognosis.

Up to 20 per cent of patients with positive exercise tests are subsequently found to have no
evidence of coronary artery disease (so-called false-positive test). Cardiac Scintigraphy Myocardial perfusion scans both at rest and after stress (i.e. exercise or dobutamine) can be obtained using various radio nuclides (e.g. thallium or technetium MIBImethoxyisobutylisone). Redistribution of the contrast agent is a sensitive indicator of ischaemia and can be particularly useful in deciding if a stenosis seen at angiography is giving rise to ischaemia. A normal stress perfusion scan makes significant CAD unlikely. Echocardiography This can be used to assess ventricular wall involvement and ventricular function. Regional wall motion abnormalities at rest reflect previous ventricular damage, is useful especially in women with coronary artery disease. Stress echo reveals wall motion changes during ischaemia. Coronary Angiography This test is done to delineate the exact coronary anatomy. Indications for coronary angiography are: Angina refractory to medical therapy Strongly positive exercise test

Unstable angina Angina occurring after myocardial infarction Patients under 50 years with angina or myocardial infarction Where the diagnosis of angina is uncertain Severe left ventricular dysfunction after myocardial infarction Non Q-wave myocardial infarction Treatment of angina

4.4 GENERAL MANAGEMENT

Patients should be informed as to the nature of their condition and reassured that the prognosis is good (annual mortality less than two per cent). Underlying problems, such as anaemia or hyperthyroidism, should be treated. Management of coexistent conditions, such as diabetes and hypertension, should be optimized. Risk factors should be evaluated and steps made to correct them where possible; for example, smoking must be stopped, hypercholesterolaemia should be identified and treated, weight loss where appropriate and regular exercise should be encouraged. Choosing between medical therapy and revascularization (coronary artery bypass grafting and angioplasty) can be difficult and will depend on a number of factors including symptoms, angiographic anatomy and patient/physician preference. The various treatment options are not mutually exclusive and should be considered as complementary. Medical Treatment Progonostic Therapies 1) Aspirin reduces the risk of coronary events in patients with coronary artery disease. All patients with angina, therefore, should take aspirin (75 mg daily is probably adequate) unless contraindicated. Lipid-lowering therapy should be used in patients with total cholesterol above 4.8 mmol/l (190 mg per cent) (particularly if the LDL is > 3.3 mmol/l (> 130 mg per cent) and the HDL is < 1.0 mmol/l (<40 mg per cent)), despite a low fat diet.

2)

Symptomatic Treatment 1) Glyceryl trinitrate (GTN) used sublingually, either as a tablet or as a spray, gives prompt relief (in a few minutes) and can also be used prior to performing activities that the patient knows will provoke angina. Beta-blockers reduce the heart rate (negative chronotropic effect) and the force of ventricular contraction (negative inotropic effect), both of which reduce myocardial oxygen demand, especially on exertion. They are the drugs of choice in patients with previous myocardial infarction because of their proven benefit in secondary prevention. Atenolol, 50100 mg once/twice daily or Metoprolol 25-100 mg twice daily, is often used. Carvedilol is preferred in case of heart failure and LV dysfunction. Dose: 6.25 mg twice daily to 25 mg twice daily. (See under heart failure).

2)

3)

Long-acting nitrates (e.g. isosorbide mononitrate) are particularly useful in patients who gain relief from sublingual Glyceryl trinitrate(GTN). They reduce venous return and hence intracardiac diastolic pressures, reduce the impedance to the emptying of the left ventricle and relax the tone of the coronary arteries. Once-daily preparations are available which have a smooth pharmacokinetic profile and avoid the problem of tolerance. Calcium-channel blockers block calcium flux into the cell, relax coronary arteries, cause peripheral vasodilation and reduce the force of left ventricular contraction, thereby reducing the oxygen demand of the myocardium. The non-dihydropyridine calcium antagonists (e.g. diltiazem and verapamil) also reduce the heart rate and are particularly useful anti-anginal agents, but should be used with caution in combination with beta-blockers. Short-acting dihydropyridines (e.g. nifedipine) can cause reflex tachycardia when used alone and are avoided. Slow-release formulations and the third-generation agents (e.g. amlodipine) can be used once daily and have a smooth profile of action with no significant effect on the heart rate and no significant negative inotropic effect. Nicorandil is a potassium-channel activator with a nitrate component; it has both arterial and venous vasodilating properties. Whilst not used as a first-line drug, it is used when there are contraindications to the above agents and in refractory unstable angina. Other metabolic agents are aimed at facilitating metabolic efficancy of the heart by partially inhibiting fatty acid oxidation and reduce the frequency of angina. These metabolic agents do not produce any significant haemodynamic effects. Drugs belonging to the above class are Trimetazidine and Ranazoline.

4)

5)

6)

Coronary Revascularization While the basic management of patients with CAD is medical, as described above, many patients are improved by coronary revascularization procedures. These interventions should be employed in conjunction with but do not replace the continuing need to modify risk factors and medical therapy. Percutaneous Coronary Intervention (PCI) PCI, most commonly percutaneous transluminal coronary angioplasty with stenting, is widely used to achieve revascularization of the myocardium in patients with symptomatic IHD and suitable stenoses of epicardial coronary arteries. A number of different mechanisms have been postulated, including fracturing and compression of the plaque, and stretching of the artery. Endothelial denudation, local dissection and distal embolization also occur and may account for some of the complications of the procedure. Ongoing studies of drug coated stents and optimal antithrombotic therapies are being carried out. Risks When coronary stenoses are discrete and symmetric, two and even three vessels can be dilated in sequence. However, case selection is essential in order to avoid a prohibitive risk of complications, which are usually due to dissection or thrombosis with vessel occlusion, uncontrolled ischaemia, and ventricular failure. Oral aspirin, clopidogrel, and intravenous heparin are given to reduce coronary thrombus formation. In unstable angina and when intracoronary thrombus is seen, the use of specific platelet glycoprotein receptor (GpIIb/IIIa) antagonists further reduces thrombotic complications and increases success. In experienced hands, the overall mortality rate is < 0.5 per cent, the need for emergency coronary surgery < 1 per cent, and the occurrence of clinical myocardial infarction < 2 per cent. Minor complications occur in 5 to 10 per cent of patients and include occlusion of a branch of a coronary artery. Efficacy

Primary success, i.e., adequate dilation (an increase in luminal diameter > 20 per cent to a residual diameter obstruction < 50 per cent) with relief of angina, is achieved in > 95 per cent of cases. Recurrent stenosis of the dilated vessels occurs in ~20 per cent of cases within 6 months in 10 per cent of cases. Restenosis is more common in patients with diabetes mellitus, arteries with small caliber, incomplete dilation of the stenosis, occluded vessels, obstructed vein grafts, dilation of the left anterior descending coronary artery, and stenoses containing thrombi. In diseased vein grafts procedural success has been improved by the use of capture devices or filters that prevent embolization, ischaemia, and infraction. Moreover, the use of stents that locally deliver antiproliferative drugs such as rapamycin can significantly reduce restenosis within the stent and 3 to 7 per cent at the edges. These significant advances are extending the use of PCI. Successful PCI produces effective relief of angina in > 95 per cent of cases and has been shown to be more effective than medical therapy for up to 2 years. More than one-half of patients with symptomatic IHD who require revascularisation can be treated initially by PCI. PCI is less invasive and expensive than CABG, usually requires only 1 to 2 days in the hospital, and permits considerable savings in the initial cost of care (however drug eluting stents currently available are expensive). Coronary Artery Bypass Grafting (CABG) Anastomosis of one or both of the internal mammary arteries or a radial artery to the coronary artery distal to the obstructive lesion is carried out. For additional obstructions that cannot be bypassed by an artery, a section of a vein (usually the saphenous) is used to form a connection between the aorta and the coronary artery distal to the obstructive lesion. The operation is relatively safe, with mortality rates < 1 per cent in patients without serious comorbid disease and normal left ventricular function, and when the procedure is performed by an experienced surgical team. Intraoperative and postoperative mortality increase with the severity of ventricular dysfunction, comorbidities, age > 80 years, and lack of surgical experience. The effectiveness and risk of CABG vary widely depending on case selection and the skill and experience of the surgical team. Occlusion of venous grafts is observed in 10 to 20 per cent of patients during the first post operative year in approximately 2 per cent per year during 5 to 7 year follow-up and 4 per cent per year thereafter. Long-term patency rates are considerably higher for internal mammary and radial artery implantations than saphenous vein grafts. In patients with left anterior descending coronary artery obstruction, survival is better when coronary bypass involves the internal mammary artery rather than saphenous vein. Graft patency and outcomes are improved by meticulous treatment of risk factors, particularly dyslipidemia. Angina is abolished or greatly reduced in ~90 per cent of patients following complete revascularization.

4.5

ACUTE CORONARY SYNDROME (ACS)

ACS, is composed of patients with acute myocardial infarction (MI) with ST-segment elevation on their presenting electrocardiogram and those with unstable angina (UA) and non-ST-segment elevation MI. ACS is a medical emergency which, untreated, will progress to myocardial infarction in over 10 per cent of cases. Therapy reduces this rate to less than 5 per cent. However, death within 1 year still occurs in 5-15 per cent. Unstable Angina (UA) and Non-ST- Elevation (NSTEMI) UA is defined as angina pectoris or equivalent ischaemic 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 to 6 weeks), and/or (3) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously). The diagnosis of NSTEMI

is established if a patient with the clinical features of UA develops evidence of myocardial necrosis, as reflected in elevated cardiac biomarkers. Pathophysiology UA/Nstemi can be caused by a reduction in oxygen supply and/or by an increase in myocardial oxygen demand (e.g., by tachycardia or severe anemia) superimposed on a coronary obstruction. Four pathophysiology processes that may contributed to the development of UA have been identified: (1) plaque rupture or erosion with superimposed nonocculsive thrombus, believed to be the most common cause; (2) dynamic obstruction (e.g., coronary spasm, as in prinzmetals variant angina; (3) progressive mechanical obstruction (e.g., rapidly advancing coronary atherosclerosis or restenosis following percutaneous coronary intervention; and (4) secondary UA related to increased myocardial oxygen demand and/or decreased supply (e.g., anemia). More than one of these processes may be involved in many patients.

Clinical Presentation
History and Physical Examination The clinical hallmark of UA/NSTEMI is chest pain, typically located in the retrosternal region or sometimes in the epigastrium, that frequently radiates to the neck, left shoulder, and left arm. This discomfort is usually severe enough to be considered painful. Anginal equivalents such as dyspnea and epigastric discomfort may also occur. The examination resembles that in patients with stable angina and may be unremarkable.
Table 4.2: Braunwald Clinical Classification of Unstable Angina or NonST Elevation Myocardial Infarction
Class Severity Class I Definition Death or Myocardial Infarction 1 Year (%) 73

New onset of severe angina or accelerated Angina; no rest pain Angina at rest within past month but not within preceding 48 hr (angina at rest subacute) Angina at rest within 48 hr (angina at rest, subacute) Develops in the presence of extracardiac condition that intensifies myocardial ischaemia

Class II

10.3

Class III

10.8

Clinical circumstances A (secondary angina)

14.1

B (primary angina) C (postinfarction angina)

Develops in the absence of extracardiac condition Develops within 2 weeks after acute myocardial infarction Patients with unstable angina may also be divided into three groups depending on whether unstable angina occurs (1) in the absence of treatment for chronic stable angina, (2) during treatment for chronic stable angina or (3) espite maximal antiischemic drug therapy. The three groups may be designated by subscripts 1, 2 and 3, respectively. Patients with unstable angina may be further divided into those with or without transient ST-T wave changes during pain.

8.5 18.5

Intensity of treatment

Electrocardiographic changes

ECG in unstable angina shows, ST-segment depression, transient ST-segment elevation, and/or T-wave inversions which occur in 30-50 per cent of patients, depending on the severity of clinical presentation. T-wave changes are sensitive for ischaemia but are less specific, unless they are new, deep symmetrical T-wave inversions (>.3mv). Patients with ACS who have elevated biomarkers of necrosis, such as CK-MB and troponin are at increased risk for death or recurrent MI. Elevated levels of these markers distinguish patients with NSTEMI from those with UA. Patients require admission for bed rest, oxygen and morphine, plus aspirin and heparin as well as standard medical anti-anginal therapy (i.e. nitrates and beta-blockers). Aspirin decreases the incidence of both death and myocardial infarction. Oral clopidogrel, which inhibits the platelet ADP receptor, should also be given (CURE studly-clopidogrel in unstable angina to prevent recurrent events trial). Heparin, traditionally given intravenously, should be given for at least 3 days. There is increasing evidence that low-molecular-weight heparins (LWMH), such as delteparin or enoxaparin, are at least as effective as standard unfractionated heparin and have the advantage of being able to be given subcutaneously and of not requiring monitoring. Recent trials have shown that infusion of glycoprotein IIb/IIIa receptor inhibitors (e.g. tirofiban, eptifibatide) may have an additional advantage over heparin plus aspirin in reducing the mortality in high-risk patients. These receptors are activated in the final common pathway of platelet aggregation. In terms of the short-term risk of death or myocardial infarction, it is possible to risk-stratify patients with ACS into high risk, intermediate risk and low risk. Those at high risk should proceed promptly to angiography, with a view to proceeding to revascularization, where appropriate, during that admission. Those at low risk can be discharged and then assessed electively as outpatient. In between, there is much controversy regarding the optimal management of patients at intermediate risk, and in particular those who settle on initial medical therapy. Early intervention does not convincingly appear to influence the medium and long-term outcomes. Irrespective of the immediate success of treatment, early coronary angiography and, depending on the results, referral for revascularisation are usually advised. Thrombolytic therapy has not been shown to be of benefit in patients with ACS. Occasionally, intra-aortic balloon pumping can be helpful in stabilizing the patient, and to enable angiography ( PTCA) to be undertaken. Check Your Progress 1 1) What are the patho physiologic mechanisms for the development of unstable angina? ................................................................................................................................. ................................................................................................................................. 2) What are the definitions for unstable angina? ................................................................................................................................. ................................................................................................................................. 3) What are the ECG changes in unstable angina? ................................................................................................................................. .................................................................................................................................

4.6

ACUTE MYOCARDIAL INFARCTION (AMI)

Acute myocardial infarction continues to be a major public health problem and is one of the most common diagnosis occurring in hospitalized patients. Mortality with Acute Infarction is

approximately 30 per cent, with more than half of the deaths occurring before hospitalization. Although survival following hospitalization has improved over the last two decades, risk of excess mortality and recurrent non-fatal MI, still persists in patients who recover. Despite, the major health challenge presented by Coronary Heart Disease and Acute Myocardial Infarction, substantial progress has been made over the past 30 yrs. Mortality and morbidity due to coronary artery disease are on the decline. Improvements in primary prevention, therapy and secondary prevention are believed to have contributed to this decline. Progress has resulted from improved understanding of the pathophysiolgy in acute myocardial infarction. Drug therapy continues to be an integral part of the treatment of patients with acute myocardial infarction. But despite the gratifying success of all modalities of therapy for acute myocardial infarction, several observations indicate that considerable room for improvement exists.

4.6.1 Pathophysiology
Vast majority of myocardial infarctions result from occlusion of coronary artery due to thrombus propagating from a ruptured atheromatous plaque. Atheromatous plaques are of two types vulnerable and stable plaques. The vulnerable plaque typically has substantial lipid core and a thin fibrous cap. In contrast stable plaque has a relatively thick fibrous cap protecting the thin lipid core from contact with the blood. Clinical data suggest that stable plaques more often show luminal narrowing detectable by angiography than do vulnerable plaques. Mechanisms responsible for the conversion of Chronic Coronary Heart Disease to Acute Coronary Syndromes involves:

Endothelial injury usually at sites of atherosclerotic plaques or plaque fissuring or ulceration. This results in exposure of potent thrombogenic stimuli within the plaque and subendothelium of the vessel to be exposed to circulating platelets. Platelet adhesion, aggregation and fibrin formation takes place. Also activation of selected mediators occurs.
Pathophysiology

Mitogenic factors ADP 5-HT Tissue factor

Vaso constrictors Thrombin Thromboxane A2 5HT PAF

This results in mechanical obstruction of the narrowed artery. The relative absence of prostacyclin (PGI2), tissue plasminogen activator (TPA) and Endothelin derived relaxation factor (EDRF) (NO) at sites of endothelial injury contribute to the development of thrombosis, vasocontriction and neointimal proliferation. There is also evidence that in atherosclerotic plaques prone to rupture, there is increased rate of formation of melalloprotienase enzymes such as collagenase, gelatinase, stromelysins that degrade components of the protective matrix. These protienases may be elaborated by activated macrophages and mast cells which accumulate in high concentration at the site of atheroma. There are also T- lymphocytes in atheromatous plaque which secretes cytokine inerferone gamma (INF-) that inhibits the ability of vascular smooth muscles to form interstitial collagen.

A number of physiological parameters such as systolic BP, heart rate, blood viscosity, endogenous tissue plasminogen activator, plasminogen activation inhibitor I (PAI-I) levels, plasma cortisol levels and plasma epinephrine levels also influence the conversion of chronic stable coronary artery disease to ACS. Thus rupture of atheromatous plaque and platelet thrombus formation are the common pathophysiological substrate of ACS that range from UA through non- ST elevation and ST elevation AMI.
Plaque Rupture

Completely occlusive thrombus

Less obstructive thrombus

Transmural MI

Non-STEMI

UA

The thrombus is non-occlusive in 80 per cent of patients with UA and is composed primarily of platelets. The pathophysiology of non-Q wave MI is very similar to that of UA. It involves plaque fissuring with formation of mural intra luminal thrombus in most (75 per cent) patients. In the other 25 per cent of the subjects the thrombus is occlusive, but distal myocardium remains perfused by collaterals. The primary distinction between non-Q-wave MI and UA is the elevated level of cardiac enzymes associated with non-Q MI indicative of myocardial necrosis. Fixed and persistent blockage of a coronary artery by a combination of ruptured atherosclerotic plaque and superimposed intraluminal platelet rich thrombus leads to Acute Q-wave MI. The thrombus associated with Q-wave MI is occlusive in 80 per cent of patients and has a high content of trapped red blood cells. Diagnostic features of a Q-wave MI involves increased level of myocardial enzymes as well as ST-segment elevation and development of abnormal Q-waves. Ventricular Remodeling Ventricular remodeling is a descriptive term for the biologic adaptability of the cardiac chambers to adjust their size and configuration or remodel in response to long-term alteration in haemodynamic loading. The remodeling that occurs after AMI differs from the normal adaptive response, as well as the response to pathophysiologic loading conditions in that the initial inciting event in post MI remodeling is an abrupt loss of contractile tissue. This loss of myocytes leads to thinning and elongation of the infarct containing segment-infarct expansion. This creates abnormalities in wall stress that promote ventricular enlargement. Patients who exhibit infarct expansion early in their clinical course are at much greater risk for later complications such as heart failure and death. Post MI remodeling is a heterogenous and regional process. It is distinct from other conditions producing remodeling in that it is not a gradual response to supra-normal systemic workloads, but rather is an attempt to restore pump function of the actually damaged ventricle. Stunning Stunning is a acute reversible LV dysfunction following reperfusion of an occluded vessel or transient ischaemia due to any cause. It may occur following exercise induced ischaemia and coronary spasm. Myocardial stunning is an important feature of unstable angina. The severity of stunning is always greater in the subendocardial layers of the LV wall. The duration of ischaemia is a second important factor.

Hibernation Hibernation is a chronic reversible LV dysfunction due to chronic coronary artery disease. It recovers following revascularisation. Radionuclide imaging techniques, positron emission tonography and stress echocardiography are capable of assessing myocardial perfusion and viability and are helpful in determining whether myocardial dysfunction is due to necrosis or hibernation. It is important to diagnosis hibernation because successful restoration of flow will lead to improvement in LV function.

4.6.2 Clinical Presentation

Onset of MI may be at any time of the day or night, but a higher frequency of onset occurs in the morning within a few hours of awakening. Triggers such as physical exercise, emotional stress, medical and surgical illness can play a role in triggering an acute event. But in roughly one half of cases no precipitating factors appears to be present prior to MI. Pain is the most common presenting complaint in patients with myocardial Infarction.

Pain is usually retrosternal in location spreading to both sides of the anterior chest with prediliction for the left side. In about 30 per cent pain radiates down the ulnar aspect of the left wrist, hand and fingers. Pain is deep and visceral lasting more than 30 mts. It is typically described as constricting, oppressing or compressing. Often complaints of a sensation of heavy weight or squeezing in the chest. Less common sites of radiations include the epigastrium, back, lower jaw and neck. The pain in MI may radiate as high as the occipital area but not below the umbilicus. The pain is often associated with weakness, sweating, nausea, vomiting, giddiness and anxiety.

Unusual Presentation Although pain is the most common presenting complaint, 15-20 per cent of MI are painless. The incidence of painless infarcts are greater in women, diabetics and with increasing age. Other unusual presentations are in the form of pulmonary oedema, marked weakness, syncope, a confusional state, appearence of an arrhythmia, evidence of peripheral embolism or merely an unexplained drop in arterial pressure. Physical Examination Most patients are restless and in profound distress. They massage or clutch their chest and often describe their pain with a clenched fist held against the sternum (the Levine sign named after Dr. Samuel A. Levine). Pallor is common and is often associated with perspiration and coolness of the extremities. Heart rate may vary from marked bradycardia to a rapid regular or irregular tachycardia depending on the underlying rhythm. Patients in cardiogenic shock by definition have systolic BP below 90 mm of Hg and evidence of end organ hypoperfusion. JVP is normal in majority of patients with Anterior MI. The a wave may be prominent in patients with pulmonary hypertension secondary to LVF or reduced compliance. RV Infarction often results in marked Jugular venous distensions. JVP is elevated in patients with cardiogenic shock.

In 1967 killip proposed a prognostic classification based on the presence and severity of rales detected in patients presenting with AMI. Class I Patients are free of rales and third heart sound. Patients have rales but only to a mild to moderate degree (< 50 per cent of lung fields) and may or may not have S3. Patients have rales in more than half of each lung field and frequently have pulmonary oedma. Patients are in cardiogenic shock. Class II Class III Class IV

Precordial Examination Despite severe symptoms, findings on examination of the heart may be unremarkable. S4 is common. S3 occurs in the presence of LV systolic dysfunction. Dyskinetic segment may be palpable as an abnormal, paradoxic pulsation in the 3rd, 4th or 5th interspace to the left of sternum. Systolic murmurs transient or persistent are commonly audible in patients with AMI and generally result from mitral regurgitation secondary to dysfunction of mitral valve apparatus, rupture of interventricular septum or tricuspid regurgitation caused by right ventricular failure. Pericardial friction rub is audible in 6-30 per cent of all patients with AMI and is higher in patients with transmural infarction. Check Your Progress 2

1)

At what time is myocardial infarction most frequent?

....................................................................................................................... ....................................................................................................................... ........................................................................................................................

2) What are some of the triggers for myocardial infarction?

....................................................................................................................... ....................................................................................................................... ........................................................................................................................

3) What are some of the uncommon presentations of acute myocardial infarction?

....................................................................................................................... .......................................................................................................................
4) What is the Killip classification?

....................................................................................................................... ........................................................................................................................

4.6.3 Investigations
ECG is an important diagnostic tool in the diagnosis of Acute Myocardial infarction. Myocardial infarction results in myocardial necrosis, injury and ischaemia. Severe acute ischaemia lowers the

resting membrane potential and shortens the duration of action potential. Such changes cause a voltage gradient between normal and ischaemic zones. These so-called currents of injury are represented on the surface ECG by deviation of ST-segment. When acute ischaemia is transmural, ST-T vector is usually shifted in the direction of outer (epicardial) layers producing ST elevation and sometimes in the earliest stages of ishaemia tall, positive T-waves called hyperacute T-waves over the ischaemic zone. With ischaemia confined primarily to the subendocardium, ST vector typically shifts toward the subendocardium and ventricular cavity so that overlying (e.g. anterior precardial) leads show ST-segment depression (with ST elevation in lead a VR). Evolutionary changes in ECG are typical of myocardial ischaemia. Myocardial infarction evolves through four easily recognizable electrographic phases. 1) 2) 3) 4) Hyperacute Acute Subacute Chronic stabilized

In the hyperacute phase, the earliest manifestation of an acute infarction is straightening of the normal upward concavity of the ST-T-segment In acute phase ST-T-segment becomes elevated and ST-T-segment slopes upward. Also the amplitude of T-wave is usually increased. In subacute phase abnormal Q-waves representing myocardial necrosis appear. In the fully evolved phase the ST-T-segments begins to diminish in amplitude and become coved upwards and blends into the symmetrically inverted T-waves. During the chronic phase there is resolution of ST-T-waves with the only residual change being abnormal Q-waves. ECG leads are helpful in localizing the site of Q-wave infarction.

Fig. 4.1 (a): ECG wave with anterior Q wave infraction

Fig. 4.1 (b): ECG wave with inferior Q wave infraction

Fig. 4.1(c): Severe anterior wall ischaemia Site of Infarction 1) Anterior wall 2) Antero septal 3) Lateral or apical 4) Inferior RV Infarction Isolated RV infarction is a rarely recognized phenomenon. RV Myocardial infarction (RVMI) should be strongly suspected if in the clinical setting of Acute Inferior Wall MI (IWMI), there is ST segment elevations of 1mm or more in lead V1 and V4 R or any one of the extra right precordial leads (V4R-V6R). In most studies lead V4R was found to be the most sensititive of all-extra right precordial leads. ST-T-segment which is higher in lead V4R than in leads V1-V3 offers highest specificity in diagnosis. When there is ST-T segment elevation in lead V1 with ST-T-segment depression in lead V2-a discordant relationship, it also suggests the presence of RV infarction. A diagnosis of RV infarction should only be entertained if there is concomitant electrographic evidence of IWMI or Infero-Posterior myocardial Infarction. Posterior Wall MI Posterior myocardial infarction occurs in the posterior left ventricular wall. An isolated true posterior wall infarction is quite uncommon. It is usually associated with inferior or lateral infarction. ECG changes of a true posterior infarction are seen as mirror image representations in lead V1 to V3. Perloff described the criteria for a true posterior infarction as follows: R-waves of 40 ms in lead V1 and in contiguous right precordial leads with upright T-waves. In the acute phase STsegment depression and R/S Ratio equal to or greater than 1 in leads V1 and V2 are diagnostic. Usually there are associated changes in inferior and lateral leads. ECG Leads one or more of precordial leads (V1-V6), I, aVL V1-V3 V4-V6 II, III, avF

Atrial Infarction Usually reflected in PR-segment elevation or depression and P-wave abnormalities. It is frequently associated with supraventricular arrhythmias. Serum Enzymes Following MI large quantities of enzymes are released into the blood from necrotic heart muscle. The rate of liberation of specific enzymes are of diagnostic importance. Creatine Kinase (CK) CK is a 85-kDa enzyme found in all striated muscles. There are three isoenzymes of CK: CKMM is the predominant form in striated muscle. CK-MB, most common in the heart; and CK-BB, most common in brain but also found in gut and kidney. Sensitivity for acute MI is > 90 per cent by 6hrs. Total CK may be falsely elevated in many pathologic conditions like muscle diseases, alcohol intoxication, Diabetes Mellitus, skeletal muscle trauma, vigorous exercise, convulsions, intramusclar injection and pulmonary embolisms. Hence it is a relatively nonspecific marker. CK-MB In the bloodstream CK-MB exists predominantly in equilibrium between two forms, the tissue form (MB2) and the circulating seroconverted form (MB1). As cardiac muscle cells die, MB2 is converted to MB1 by carboxypeptidase enzyme. An absolute level of MB2 > 1U/L and MB2/MB1 ratio of > 1.5 are highly sensitive markers of myocardial necrosis. The ratio of CKMB mass of about 2.5 per cent CK activity is indicative of myocardial rather than skeletal source of the CK MB elevation. In addition to AMI secondary to coronary obstruction, other forms of injury to cardiac muscle such as those resulting from myocarditis, cardiac catheterization, shock and cardiac surgery may also produce elevated serum CK-MB levels. Normally, Baseline CK-MB activity is 2-4 IU/L. For a reliable diagnosis of MI, it should increase above 9-10 IU/L. Plasma CK-MB activity of reliable diagnostic sensitivity is reached with in 1216 hrs of onset of symptoms. Maximal levels are reached between 14-36hrs with a return to normal levels occurring after 48-72 hrs. Cardiac Specific Troponins Two new diagnostic cardiac markers have been introduced-Troponin T and Troponin I, which are part of the sarcomere complex. Troponin T has a molecular weight of 38,000 and Troponin I 23,000. Cardiac troponin I has 31 aminoacids which are not present in the skeletal forms. The recognition site of the antibody used in the assay is in the cardiac specific region, which makes the test very specific as a marker for myocardial injury. Cardiac Troponin I and Cardiac troponin T are not normally detected in the blood. Cardiac Troponin T has 11 aminoacids not present in the skeletal forms and hence it is also specific. It has similar sensitivity to troponin I but somewhat less specificity. Troponin I and Troponin T are released into the plasma so that a reliable diagnostic sensitivity is reached by 12-16 hrs and maximal activity is reached by 24-36 hrs. The levels return to normal within 10-12 days.

Myoblobin It is a low molecular weight heme protein found in cardiac and skeletal muscle. It is is not cardiac specific but released more rapidly from infarcted myocardium than CKMB. It is detected as early as 2 hrs after MI and remains increased for at least 7-12 hrs. Enzymatic Criteria for the Diagnosis of Myocardial Infarction Serial increase, then decrease of plasma MB-CK, with a change > 25 per cent between any two values. MB-CK >10-13 U/L or 75 per cent total CK activity. Increase in MB-CK activity > 50 per cent between any two samples, separated by at least 4 hrs. If only single is samples available MB-CK elevation > two fold. Beyond 75 hrs, an elevation of Troponin T or I or LDH-1 > LDH-2.

Serum Lipids Total cholesterol and HDL remain at or near baseline values during the 24-48 hrs after the acute event, but fall precipitously after that and later values are therefore, unreliable after the first 24 hours. Hematological Manifestations WBC count elevates within 2 hrs after chest pain and reaches a peak 2-4 days following infarction. It returns to normal within a week. ESR rises to a peak on the 4th-5th day of infarction. Chest X-ray Provides very important information in the assessment of myocardial infarction. Points to look into are (signs of left ventricular failure) cardiothoracic ratio to detect cardiomegaly, ventricular aneurysms, pericardial effusion, etc. Echocardiography It can be of importance in patients with acute MI. Abnormalities of wall motion are almost universally present. Estimation of left ventricular function is relatively accurate and can be useful prognostically. It may be particularly useful in the diagnosis of RV infarction, ventricular aneurysm, pericardial effusion and left ventricular thrombus. Additionally Doppler echocardiography is useful in the detection of a ventricular septal defect and mitral regurgitation. Check Your Progress 3 1) What are the phases in the evolution of ECG changes in acute myocardial infarction? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. How does the ECG help in localizing the site of infarction in the anterior, anteroseptal, lateral and inferior walls? ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

2)

3)

4)

How do you diagnose right ventricular infarction? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. How would you diagnose Posterior Wall MI? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. What is the level of CKMB suggestive of acute myocardial infarction? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. When is the troponin value elevated in acute myocardial infarction and when do the levels return to normal? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

5)

6)

4.6.4 Management
Pre-hospital Care Most deaths associated with AMI occur within first hour of its onset and are usually due to ventricular fibrillation. Hence the importance of immediate implementation of definitive resuscitative efforts and rapid transport of the patient to a hospital cannot be over emphasized. Establishment of a pre hospital fibrinolysis protocol is reasonable in: 1) 2) Settings in which physicians are present in the ambulance or In well organized Emergency Medical Services (EMS) systems with full time paramedics who have 12-lead ECG on line.

Randomized controlled trials of fibrinolytic therapy have demonstrated the benefit of initiating fibrinolytic therapy as early as possible after diagnosis of STEMI. Transport time to the hospital is variable from case to case, but the goal is to keep total ischaemic time within 120 minutes. Patients with STEMI who have cardiogenic shock and are < 75 yrs of age and patients who have contra indication (CI) for thrombolysis should be brought immediately or secondarily transferred to facilities capable of cardiac catheterisation and rapid revascularisation or CABG if it can be performed within 18 hrs of onset of shock. Management in the Emergency Department Hospitals should establish multidisciplinary teams (including primary health care physicians, emergency medicine physicians, cardiologist nurses and laboratorians) to develop a guideline based, institution specific written protocol for triaging and managing these patients. The goal for patients with STEMI should be to achieve a door to needle time (for thrombolysis) within 30 mts and a door to balloon time (for primary PCI) within 90 mts.

Routine Measures a) Oxygen Supplemental oxygen should be administered to patients with arterial oxygen desaturation (Sa O2 <90 per cent) (ClassI). It is reasonable to administer supplemental O2 to all patients with uncomplicated STEMI during the first 6 hrs. (Class II a). Dose: 2-4 l/mt of 100 per cent O2 by mask or nasal prongs for 6-12 hrs. b) Nitroglycerine NTG is indicated for ongoing chest discomfort, control of hypertension and management of pulmonary congestion. Dose: S/L NTG - 0.4 mg every 5 mts for a total 3 doses or IV NTG 5ug/mt infusion Contraindications BP < 90 mm of Hg > 30 mm of Hg below baseline BP Bradycardia < 50 bpm Tachycardia > 100 bpm Suspected RV infarction. c) Analgesia Most important initial objective is relief of pain. Morphine is an extremely effective analgesic. It also reduces sympathetically mediated arteriolar and venous contriction. Hypotension associated with venous pooling usually responds to elevation of legs. Morphine also has vagotonic effect and may cause bradycardia. This responds usually to IV atropine. Dose: Morphine sulphate 2-4 mg with increments of 2-8 mg IV repeated at 5-15 mts intervals. d) Aspirin Aspirin produces a rapid clinical antithrombotic effect caused by immediate and near total inhibition of thromboxane A2 production. It has become an integral part in the treatment of AMI. A 23 per cent reduction in mortality at 35 days in patients treated with aspirin during early stages of AMI was observed in ISIS-2 trial. Aspirin should be avoided in cases of true hypersensitivity. In the case of bleeding from peptic disease, rectal suppositories can be used. Ticlopidine can be used in cases were aspirin in contraindicated. Dose: 162-325 mg plain aspirin chewed preferably and not swallowed. e) Beta Blockers (BB) Analysis of pooled data from 28 trials revealed an average reduction of mortality of 28 per cent at 1st week and majority of the benefit was seen in the first 48 hrs. Immediate BB therapy appears to reduce the magnitude of infarction and limits infarct size. Other

commendable actions are it reduces ventricular ectopy, atrial fibrillation and non-fatal cardiac arrest. It reduces recurrent ischaemia and infarction during first 6 weeks after initial event. Oral beta blockers therapy should be administered promptly to all patients without a contrainidication. Other indications are the presence of tachyarrhythmia or hypertension. Dose: Betablocker of choice is Metoprolol. Beta blockers most often used are Atenolol and Metoprolol. These can be administered intravenously (Atenolol 5-10 mg IV bolus 2/Metaprolol 5 mg bolus 3 at 5 mts apart) followed by oral administration (Atenolol upto 100 mg daily/metoprolol 50 mg twice daily). Relative contraindications for the use of BB are: 1) Patients with heart failure (rales > 10 cm up from diaphragm) 2) Hypotension (SBP < 90 mm of Hg), 3) Bradycardia (HR< 60 bpm), or 4) Heart block (PR > 240 ms, 2nd and 3rd degree HB) f) Angiotension Converting Enzyme Inhibitors/Angiotension Receptor Blockers (ACEI/ARB) A large number of randomized clinical trials have assessed the role of ACEI early in the course of acute MI. All trials with oral ACE inhibitors have shown benefit from their early use. ACEI should be started within first 24 hrs. It should not be used if SBP is less than 100mmHg or less than 30mmHg below baseline or if there are other contraindication to ACEI. Some of the drugs dosages are as follows: Starting dose Captopril Enalapril Ramipril Indications 1) 2) 3) All patients with anterior wall MI. Pulmonary Congestion. LVEF < 40 per cent. Recommended Max 6.25 mg tds 2.5 mg bd 2.5 mg bd Dose 50 mg tds 10 mg bd 10 mg bd

ARB should be administered for those intolerant to ACEI. Valsartan and Candesartan have also established efficacy. g) Ca Channel Blockers Generally not used in the setting of acute MI. Only indication is in patients in whom betablockers are ineffective or contraindicated for relief of ongoing ischaemia or control of a rapid ventricular response with atrial fibrillation or flutter in the absence of CHF, LV dysfunction or atrioventricular block. Calcium channel blocker of choice is Verapamil or Diltiazem. Nifedipine (immediate release form) is contraindicated in STEMI.

h)

Thrombolytic Therapy Thrombolytic agents have been shown to limit infarct size, preserve ventricular function and improve infarct size. The impact of early treatment was first clearly shown in the initial GISSI trial and confirmed in ISIS-2. Trials have shown that benefits of thrombolytic therapy are directly related to achievement of early reperfusion. i) Mechanism of Action All of the so called thrombolytic agents are either direct or indirect activators of plasminogen, a circulating proenzyme. Plasminogen is converted by plasminogen activators or activator complexes to plasmin, the active fibrinolytic enzyme. Plasmin has relatively broad proteolytic properties, degrading fibrin, fibrinogen, prothrombin and factors V and V11. Plaminogen activators induced fibrinolysis may then act to disrupt thrombus. ii) Indications 1) To all STEMI patients with symptom onset within the prior 12 hrs and ST elevation greater than 1mm in at least 2 contiguous precordial leads or at least 2 adjacent limb leads, or new onset LBBB in the absence of contraindiations. To all STEMI patients with symptom onset within prior 12 hrs and new or presumably new LBBB, in the absence of contraindications. To STEMI patients with symptom onset within the prior 12 hrs and 12 lead ECG findings consistent with true and posterior MI, in the absence of contraindication. In the absence of contraindication, it is reasonable to administer fibrinolytic therapy to patients with symptoms of STEMI beginning within the prior 12-24 hrs who have continuing ischaemic symptoms and ST elevation. iii) Contraindications (CI) Absolute Contraindications 1) 2) 3) 4) 5) 6) 7) Any prior intra cranial hemorrhage. Known structural cerebral vascular lesions (AVM). Known malignant intracranial neoplasm. Ischaemic stroke within 3 months. Suspected aortic dissection. Active bleeding diathesis (excluding menstruation which is not a contraindication). Significant closed head or facial trauma within 3 months.

2) 3)

Relative Contraindications 1) 2) History of c/c severe, poorly controlled hypertension. Severe uncontrolled hypertension on presentation (SBP >180 mm of Hg or DBP > 110 mm of Hg).

3) 4) 5) 6) 7) 8) 9)

H/o prior ischaemic stroke > 3 months, dementia or known intracranial pathology not covered in contraindication. Traumatic or prolonged (>10 mts) CPR or major surgery (less than 3 weeks). Recent internal bleeding (2-4 wks). Non compressible vascular punctures. For streptokinase: prior exposure (more than 5 days ago) or prior allergic reactions to the agent. Pregnancy. Active peptic ulcer.

10) Current use of anticoagulants. The higher the INR, the higher the risk of bleeding. iv) Choice of Thrombolytic Agent Four thrombolytic agents have been approved for routine use. 1) 2) 3) 4) 1) Streptokinase (SK) rt- PA APSAC r-PA (reteplase) Streptokinase: This is a non-enzyme protein of mw (47,000-50,000) produced by several strains of hemolytic streptococci. Streptokinase activates plasminogen to plasmin indirectly. It is antigenic and has little fibrin specificity. A few days after administration of SK, antistreptokinase titer rises rapidly to 50100 times and remains high for 4-6 months during which period renewed treatment with SK is impracticable. Dose: 1.5million units IV over 30-60 mts. 2) t-PA: Native tissue-type plaminogen activator (t-PA) is a serine proteinase with a molecular weight of about 70,000. t-PA for clinical use is presently produced by recombinant DNA technology. The high affinity of t-PA for plasminogen in the presence of fibrin allows efficient activation on the fibrin clot, while no efficient plasminogen activation by t-PA occurs in plasma. Its half-life is about 5 mts. Dose: Initial bolus of 15 mg followed by an infusion of 50 mg or 0.75 mg/kg body weight over the next 30 mts and an infusion of 35 mg or 0.5 mg/kg body weight over the subsequent 60 mts, for a total of up to 100 mg over 90 mts. 3) APSAC: (Anisolylated plasminogenSK complex) Although APSAC is identical to SK as a thrombolytic agent, it can be given as a rapid infusion. Its therapeutic half-life is similar to that of SK, which is about 90 mts. Dose: 30 mg over 5-10 mts. 4) Reteplase (r-PA): This is a single chain non glycosylated deletion variant of r-PA consisting only of the kringle 2 and protenase domain of human t-PA. Both t-PA and r-PA have almost similar efficacy and safety. Retelplase has a longer half-life.

Dose: 2 doses of 10 units each 30 minutes apart to be given over 2 minutes. 5) Other Agents Urokinase: It has similar efficiency and safety to Streptokinase and is more approved for routine use, it was widely used as an intracoronary and intravenous agent. Prourokinase (saruplase): It is a naturally occurring glycoprotein that is rapidly converted into urokinase by plasmin. But not approved for routine use. TNK- t-PA: It has increased fibrin specificity and resistance to plasminogen activator inhibitor-1. Lanoteplase (n-PA): The half-life of n-PA is 23 mts. This is administered as a bolus. Staphylokinase: It has marked fibrin specificity and is administered in a dose of 20-30 mg in 30 mts. Repeat administration is not advisable due to immunogenecity. Chimeric Plasminogen Activators K1 K2 P4: This agent consists of bits of t-PA and SCU-PA to form a single compound with the help of recombinant technology. This results in marked enhancement of thrombolytic acitivity. FK 2 tu-PA and K 2 tu-PA are other chimeric agents. v) Selection of Reperfusion Strategy Several issues should be considered in selecting the type of Reperfusion therapy. Step I: Assess Time and Risk

Time since onset of symptoms. Risk of STEMI. Risk of fibrinolysis. Time required for transportation to a sterilized cardiac catheterisation lab.

Step II Determine whether fibrinolysis or invasive strategy is preferred. If presentation is < 3 hrs and there is the delay to an invasive strategy, there is no preference for either strategy. Fibrinolysis is generally preferred.

Early presentation (3 hrs or less from symptom onset and delay to invasive strategy). Invasive strategy is not an OPTION Catheterisation laboratory occupied or not available. Vascular access difficulties. Lack of access to a skilled PCI lab.

Delay to invasive strategy. Prolonged transport. (Door-to-Balloon)-(Door-to-Needle) time is greater than 1 hr. Medical contact-to-balloon or door-to-balloon time is greater than 90 minutes An invasive strategy is generally preferred if:

Skilled PCI laboratory available with surgical backup. Medical contact-to-balloon or door-to-balloon time less than 90 minutes.

High risk from STEMI. Cardiogenic shock Killip class greater than or equal to 3.

Contraindications to fibrinolysis, including increased risk of bleeding and ICH. Late presentation. Symptom onset was more than 3 hrs ago.

Diagnosis of STEMI is in doubt. With delayed PCI, the mortality benefit decreases, compared with a fibrinspecific lytic agent. A PCI strategy may not reduce mortality when a delay greater than 60 mts is anticipated versus immediate administration of lytic agent.

vi) Indications of Successful Reperfusion 1) 2) 3) Rescue PCI Rescue PCI refers to PCI within 12 hrs after failed fibrinolysis for patients with continuing or recurrent myocardial ischaemia. Indications for Rescue PCI 1) 2) In patients less than 75 yrs old who develop shock within 36 hrs of MI and are suitable for revascularisation that can be performed within 18 hrs of shock. In patients with severe CHF or pulmonary oedema (Killip class 111) and onset of symptoms within 12 hrs. Relief of symptoms. Maintainence of haemodynamic and or electrical stability. A reduction of at least 50 per cent of the initial ST-Segment elevation at 60-90 mts.

Facilitated PCI

Facilitated PCI refers to a strategy of planned immediate PCI after an initial pharmacological regimen such as full-dose fibrinolysis, half-dose fibrinolysis, a GP IIb/IIIa inhibitor or a combination of reduced-dose fibrinolytic therapy and a GP I1b/IIIa inhibitor. A strategy of facilitated PCI holds promise in higher-risk patients when PCI is not immediately available. Potential complications are: 1) 2) 1) 2) 3) 1) 2) 3) Increased bleeding complications. Added cost. Failed PCI with on going ischaemia or haemodynamic instability. In patients who are not candidates for fibrinolytic therapy or PCI and who have persistent ischaemia refractory to medical therapy, with a significant area of myocardium at risk. At the time of surgical repair of post infarction VSD or mitral valve insufficiency. In all patients undergoing PCI or surgical revascularisation. In patients undergoing reperfusion therapy using fibrin selective agents. In patients treated with non-selective fibrinolytic agents, UFH is indicated if they are at high risk for systemic embolisation (large anterior MI, atrial fibrillation, previous embolism, known LV thrombus). Dose: 60u/kg (4000 u maximum) followed by initial infusion of 12u/kg/hr (max 1000u/hr) Maintain APTT at 1.5-2 times control. Indications of Low Molecular Weight Heparin (LMWH) in AMI It may be considered as an acceptable alternative to UFH. It is not recommended in patients over 75 yrs who are receiving fibrinolytic therapy or in presence of renal dysfunction. Indications for Invasive Cardiac Monitoring in AMI 1) 2) 3) 4) Indications for Pulmonary artery (PA) catheter. Progressive hypotension, when unresponsive to fluid administration or when fluid administration may be contraindicated. Suspected mechanical complications of STEMI. Indications for intra-arterial pressure measurement a) c) Patients with severe hypotension (SBP < 80 mmHg). Cardiogenic shock. b) Patients receiving vasopressor/inotropic agents. A preshock state of hypoperfusion with normal blood pressure may develop before circulatory collapse. This is manifested by cold extremities, cyanosis, oliguria or decreased mentation. Hospital mortality is high; so these patients should be aggressively diagnosed and treated as though they are in cardiogenic shock.

Indication for Emergency or Urgent Coronary Artery Bypass Grafting (CABG) in AMI

Indication for Unfractionated Heparin (UFH) in AMI

Check Your Progress 4

1)

How do thrombolytic agents act? ................................................................................................................................. .................................................................................................................................

2)

Mention the absolute contraindications for thrombolytic therapy. ................................................................................................................................. .................................................................................................................................

3)

How is streptokinase administered? ................................................................................................................................. .................................................................................................................................

4)

Indication for Unfractionated heparin (UFH) in AMI. ................................................................................................................................. .................................................................................................................................

5)

What are the features of cardiogenic shock? ................................................................................................................................. .................................................................................................................................

4.7

MANAGEMENT OF COMPLICATIONS OF ACUTE MYOCARDIAL INFRACTION

Rapid volume loading with an IV infusion should be administered to patients without clinical evidence for volume overload. According to the haemocrit values saline/colloid solutions or blood to optimum LV filling pressures. (as high as 18 mm of Hg in cases of acute MI) can be used.

Hypotension

a)

Rhythm disturbances or conduction abnormalities causing hypotension should be corrected (see arrhythmias). Intra aortic balloon pulsation (IABP) should be inserted in patients who do not respond to other interventions. This helps in reducing afterload, and improve coronary perfusion. Ionotropic agents like dopamine, dobutamine should be started as indicated. Always rule out drug induced and mechanical complications. Left Ventricular Failure The immediate goals include adequate oxygenation, sedation and preload reduction to relieve pulmonary congestion. If LVF is associated with elevated blood pressure, medications to lower blood pressure should be started judiciously. Shortacting ACE inhibitors like captopril and IV nitrates can be started. If LVF is not associated with elevation systemic blood pressure, impending cardiogenic shock must be suspected and treated aggressively.

b)

Cardiogenic Shock

Early and prompt recognition of this clinical situation may save lives. Mortality is as high as 60-80 per cent. Features of cardiogenic shock: 1) Clinical evidence of hypoperfusion like cold extremities, perspiration low urine output. 2) Systolic blood pressure < 80-90 mm of Hg 3) LVEDP eH18 mm of Hg 4) PCWP eH 18 mm of Hg 5) Cardiac Index dH 1.8 L/mt/m Recognition of this clinical situation warrants invasive monitoring. Intervention should be performed as soon as possible. Early revasculariation, either PCI or CABG is recommended for patients less than 75 yrs old. Fibrinolytic therapy should be administered in patients not suitable for interventions stabilization of the patient with cardiogenic shock using mechanical circulatory arrest devices, such as intraaortic balloon pump is recommended. Therapeutic objective, is to establish and maintain systemic blood pressure. Judicious use of morphine and maintenance of adequate oxygenation using mechanical ventilation if necessary. The cornerstone of therapy are inotropic and vasopressor agents. Dopamine is the drug of choice. If high doses of dopamine are necessary to maintain adequate perfusion, a change to norepinephrine infusion may be considered. Dobutamine is preferred if systolic blood pressure is 90mmHg or more. Dopamine starting dose 3 g/kg/mt upto 20 g/kg/ mt. Dobutamine 2.5 g/kg/mt upto 30 g/kg/mt. Norepineprrine 2-10 g/minute as infusion. Right Ventricular Infarction Right ventricular infarction should be considered in all cases of acute inferior myocardial infarction, especially in the setting of low cardiac output. A typical presentation would include Inferior myocardial infarction. Clear lung field. Jugular venous distension which increases on inspiration (Kussmauls sign). tachycardia and

Treatment The major objectives in treating RV infarction are to: 1) 2) 3) 4) 5) 6) Maintain RV preload (IV normal saline 1-2 litres). Provide inotropic support. Reduce RV afterload. (Judicious use of vasodilators). Achieve early reperfusion by early thrombolysis or PCI. Maintain AV synchromy in case of high-grade AV block. Concomitant LV dysfunction should be treated:

 Avoid venodilators such as nitrates. Diuretic should be used with extreme caution. Arrhythmias Both bradyarrhythmias and tachyarrhythmias pose significant problems during early phases of AMI. Arrhythmia

Bradyarrhythmia 1) 2) 3) Sinus Bradycardia AV blocks Intraventricular blocks

Tacharrhythmia 1) VPBs 2) Ventricular tachycardia 3) Ventricular fibrillation 4) AVIR 5) Supraventricular tachycardia 6) Atrial fibrillation 7) Atrial flutter

Bradyarrhythmias 1) Sinus Bradycardia Treatment is indicated if there is haemodynamic compromise. Atropine IV 0.3-0.6 mg every 3-10 mts with a total dose not exceeding 2 mg. If bradycardia persists despite atropine, electrical pacing is indicated. Isoproterenol should be avoided. 2) Atrioventricular (AV) Blocks a) First degree AV Block Incidence of 1st degree AV block in acute myocardial infarction MI is less than 15 per cent. Location of block is usually above his bundle. Associated bifascicular block may indicate infrahisian block. Aviod drugs like Beta-blockers, Calcium antagonist and Digoxin if PR interval is > 240 ms or if there is associated haemodymanic compromise or high degree block. b) Second Degree AV Block First and type I second degree AV blocks do not appear to affect survival. They are most commonly associated with occlusion of right coronary artery and are caused by ischaemia of the AV node. i) Mobitz type 1 AV block Occurs in upto 10 per cent of patients with acute myocardial infarction (AMI). Site of block generally occurs within the AV mode. It is usually transient and does not require specific therapy.

ii)

Mobitz type II AV block It is rare. Incidence is < 1 per cent. It is usually infrahisian. More common with anterior myocardial infarction and reflects trifascicular block. It has worse prognosis because of its potential for progression to complete heart block. Hence it is an indication for temporary transvenous or external pacemaker.

c)

Complete AV Block Occurs in about 5 per cent of patients with AMI and can occur in patients with either anterior or more commonly with inferior infarction. Prognosis depends on the anatomical location of the block. CHB in patients with inferior wall infarction usually results from intranodal or supranodal lesion and develops gradually. The escape rhythm is usually stable, with a rate exceeding 40 beats/mt, and a narrow QRS in 70 per cent of cases. Temporary pacing should be done if haemodynamically unstable. This is often transient and resolves within a few days. If it does not resolve, rarely it may require permanent pacing (PPI), as per physicians discretion. The mortality may approach 15 per cent, but associated Right Ventricular MI (RVMI) doubles the mortality. In patients with anterior infarction CHB often occurs suddenly, 12-24 hrs after the onset of infarction. Such patients have unstable escape rhythms with wide QRS complexes and rates less than 40 beats/mt. Mortality is extremely high and approximately 70-80 per cent. Hence ventricular or AV sequential pacing is indicated in essentially all patients with Anterior Myocardial Infarction with Complete Heart Block.

3) Intraventricular Conduction Disturbances (IVCD) The development of BBB or fascicular block during AMI usually signifies an extensive infarct. Presence of BBB identifies patients who are more likely to develop congestive heart failure, high-grade heart block or an episode of ventricular fibrillation. So mortality is high. a) Isolated left anterior fascicular block This occurs in 3-5 per cent of patients with AMI. This is unlikely to progress into CHB.

b) Left posterior fascicular block This occurs in 1-2 per cent of patients. The posterior fascicle is larger than the anterior fascicle, and a larger infarct is required to block it. So mortality is markedly increased.

c)

RBBB This defect alone occurs in approximately 2 per cent of patients and frequently leads to AV block. This is associated with increased mortality. This has high incidence of ventricular fibrillation later and also CHF.

d) Bifascicular block

 e)

This is associated with high mortality because of the occurrence of extensive myocardial necrosis.

Asystole This has been reported to occur in 1-14 per cent of patients. In case of documented asystole immediate transvenous pacing is indicated. Because of the predominance of ventricular fibrillation as the cause of cardiac arrest in this setting, initial therapy include electrical cardioversion.

Indications for Permanent Pacing for Bradyarrhythmias in AMI 1) 2) 3) Persistent seconddegree AV block in the His-Purknije system with bilateral bundle branch block or third degree AV block within or below the His-Purknije system. Transient advanced second or third degree infra nodal AV block and associated bundle branch block. Persistent and symptomatic second or third degree AV block.

Pacing for persistent second or third degree AV block at AV node level. All patients who have an indication for permanent pacing after STEMI should be evaluated for implantable cardioverter defrillator which is found to be of benefit in patients who have VT or haemodynamically unstable VT and patients with associated LV dysfunction. Tachyarrhythmias Ventricular Premature Beats Treatment of isolated VPBs, Couplets and non-sustained VT is not recommended unless they lead to haemodynamic compromise. Accelerated Idioventricular Rhythm (AIVR) Commonly defined as ventricular rhythm with a rate of 60-125 beats/min frequently called as slow ventricular tachycardia. This occurs in 20 per cent of patients. It is often observed shortly after reperfusion. Antiarrhythmic therapy is not indicated for this situation. In rare circumstances where treatment is neccesary Ca or Na channel blocking agents can be used. Ventricular Tachycardia Episodes of sustained ventricular tachycardia during first 48 hrs following AMI are often polymorphic and are associated with a hospital mortality of about 20 per cent. Cardioversion is always indicated for episodes of sustained haemodynamically compromising VT. Initially treated with unsynchronized electric shock with 200 joules, if unsuccessful, a second shock of 200-300 J should be given and if necessary a third shock of 360 joules. Other Measures 1) 2) 3) Aggressive attempts to reduce myocardial ischaemia. Beta-blockers IV Metoprolol/Atenolol followed by oral maintenance as 3. mentioned earlier. IABP if necessary.

4) 5)

Emergency revascularisation. Normalization of S Potassium to > 4.5 mg/l and magnesium > 2 mg/l.

Episodes of sustained monomorphic VT associated with angina, pulmonary oedema, hypotension should be treated with synchronized electric shock of 100 J. Increasing energies may be used if not successful. Sustained monomorphic VT not associated with angina, pulmonary oedema or hypotension should be treated with: i) Amiodarone 150 mg infused over 10 minutes (or 5 mg/kg); repeat 150 mg every 10-15 mts as needed. Or 360 mg over 6 hrs (1mg/mt), then 540 mg over next 18 hrs (0.5 mg/mt). ii) Synchronized electrical cardioversion starting at 50 joules.

Ventricular Fibrillation This is the most important cause of sudden cardiac death following AMI. Primary ventricular fibrillation occurs within 12 hrs of AMI. Its incidence is now much lower than it was several decades ago (< 5 per cent). Secondary ventricular fibrillation is often the final event of a progressive downhill course with left ventricular failure and cardiogenic shock. It has poor prognosis with in hospital mortality rates of 40-60 per cent. Late ventricular fibrillation develops more than 48 hrs following AMI. It usually occurs in patients with large infarcts and ventricular dysfunction. Management Unsynchronized electric shock with an initial monophasic shock energy of 200 J, if unsuccessful, a second shock of 200-300 J should be given and then if necessary, a third shock of 360 J. Successful interruption of ventricular fibrillation or prevention of recurrent episodes may also be facilitated by administration of amiodarone. Electrolyte imbalance should be corrected (K to be kept > 4 mg/L and magnesium > 2 mg/dl).

PSVT

This arrhythmia occurs in < 10 per cent patients with AMI. Needs aggressive management because of its rapid rate. Management 1) 2) 3) 4) Carotid sinus massage. IV adenosine (6 mg IV over 1-2 secs, if no response, 12 mg IV after 1-2 mts may be given, repeat 12 mg if needed). IV metoprolol (2.5 mg-5 mg every 2-5mts to a total of 15 mg over 10-15mts). IV diltiazem (20 mg [0.25 mg/kg] over 2 mts followed by an infusion of mg/hr). 10

5)

IV Digoxin.

Atrial Flutter and Fibrillation Atrial flutter is the least common arrhythmia in AMI. Occurrence is < 5 per cent. Atrial fibrillation is more common occurring in 10-15 per cent of patients with AMI. It is usually observed in patients with left ventricular failure. Other causes are pericarditis, atrial infarction or right ventricular infarction. Atrial fibrillation during AMI is associated with increased mortality and stroke particularly in patients with anterior wall infarction. Management
Sustained atrial fibrillation and flutter

With haemodynamic compromise

Without haemodynamic compromise a) Betablockers

a) Synchronized cardioversion with 200 J for atrial fibrillation or 50 J for atrial flutter.

b) IV amiodarone (if unresponsive to above b) IV Diltiazem or measure or for recurrence). Verapamil c) IV Digoxin (in case of severe LV dysfunction). c) DC Cardioversion

Indication of Implantable Cardiocurter Defibrillator in AMI Patients 1) Patients with AMI who had VF or haemodynamically unstable VT more than 2 days after STEMI, provided the arrhythmia is not due to transient or reversible ischaemia or reinfarction. An ICD is also indicated in patients in whom a spontaneous VT or VF occurs atleast a month after AMI and who have an LVEF of 30 40 per cent. A nonsustained VT or inducible VF on electrophysiological testing are additional pointers for ICD implantation.

2)

Mechanical Complications Papillary Muscle Rupture Rupture of papillary muscle occurs in approximately 1 per cent of MI and usually occurs 2-7 days after the infarction. Patients presents with sudden onset of pulmonary oedema. Examination reveals a mid to holosystolic murmur. Although murmur is generally loud, a thrill is rarely present. Diagnosis can be confirmed by echocardiogram. The postreomedial papillary muscle is involved 6-12 times more frequently than antero lateral papillary muscles. So papillary muscle rupture with an acute anterior MI is uncommon. Prognosis is poor, so immediate recognition and surgical treatment should be considered. Ventricular Septal Rupture Rupture of IVS is estimated to occur in 1-3 per cent of AMI. Ventricular septal rupture occurs with an approximately equal frequency in anterior and inferior infarctions. Majority occur in the

first week 20-30 per cent may develop as early as 24 hrs after infarction. Patient presents with sudden clinical deterioration. Clinical evaluation reveal new systolic murmur along the left sternal border often associated with a thrill, features of pulmonary and systemic venous congestion. Signs of systemic venous congestion will be out of proportion to those of pulmonary venous congestive due to RV volume overload due to the shunt. The diagnosis can be established by echocardiography. Right heart catherisation is useful in confirming the situation. Cardiac Rupture Occurs in up to 24 per cent of fatal AMIs. After cardiogenic shock and arrhythmias, it is the most common cause of death. The free wall of the ventricle is the most common site of rupture. It generally occurs in the 1st 2nd week of infarction. Free wall rupture is more likely to occur with the initial myocardial infarction, in women, in the 6th decade of life or later and in patients with hypertension particularly if there is no hypertrophy. Presents as sudden unanticipated cardiac death. Secondary Prevention Secondary prevention therapies are an essential part of the management of all patients with ischaemic heart disease. 1) Patient Education Before Discharge Before hospital discharge, all patients should be educated about life style changes and drug therapies that are important for the secondary prevention. Strict control of blood pressure and diabetic status is a must. 2) Weight Management Desirable body mass index is 185-24.9 kg/m. A waist circumference greater than 40 inches in men and 35 inches in women needs in evaluation for metabolic syndrome and implimentation of weight reduction strategies. 3) Smoking Smoking has multiple cardiovascular effects that can promote AMI, including enhanced platelet aggregation, coronary vasospasm, and vascular inflammation. Complete abstinence from smoking is an essential goal after AMI. 4) 5) Physical Activity Encourage minimum of 30-60 mts of activity, preferably daily or at least 3-4 times weekly. Lipid Management a) Diet: Diet low in saturated fat and cholesterol (less than 7 per cent of total calories as saturated fat and less than 200gm/d cholesterol) should be started after recovery from AMI.

b) Drug therapy: The target LDL-C level post MI should be substantially less than 100 mg/dl. Additional drug therapy should be instituted according to the following guide. LDL-C substantially less than 100 mg/dl (baseline or on treatment) Continue therapy.

LDL-C greater than or equal to 100 mg/dl (baseline or on treatment) Intensify LDL-C lowering therapy with drug treatment, giving preference to statins. If TG is 200 mg/dl or greater. Non HDL-C should be substantially lower than 130 mg/dl.

If TG is e150 mg/d or HDL-C is < 40 mg/dl. Emphasize weight management and physical activity, after LDL-C lowering therapy. Consider adding fibrate or niacin.

If TG is e 500 mmg/dl. Consider fibrate or niacin before LDL-C lowering. Consider omega 3 fatty acids as adjunct for high TG.

6)

Antiplatelets Aspirin should be continued indefinitely 75-162 mg/dl if not contraindicated. Consider clopidogrel 75 mg or warfarin if aspirin is contraindicated.

7)

Betablockers The benefits of Beta-blockers therapy for secondary prevention are well established. It should be started as early as possible post MI and continued indefinitely.

8)

Renin-Angiotension-Aldosterone System Blockers ACE inhibitors are started in all post STEMI patients, start early in stable high-risk patients (anterior MI, previous MI, Killip class > II, LVEF < 0.40) ARBs are indicated in patients who are intolerant of ACE inhibitors and who have either clinical or radiological signs of HF or LVEF < 0.40. Aldosterone blockage is indicated in post MI patients with LVEF d 0.40 and have either diabetes or heart failure. It is contraindicated in patients with significant renal dysfunction or hyperkalernia (K > 5.0).

Check Your Progress 5 1) Describe the features of complete heart block in acute myocardial infarction. ................................................................................................................................. ................................................................................................................................. 2) What are the clinical features of ventricular septal rupture during acute myocardial infarction? ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

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4.8 LET US SUM UP

The future of treatment of Coronary Artery disease and its sequelae remains wide open. Though angioplasty and CABG are only palliative procedures, they should be considered complementary. The ultimate goal of each are identical: to revascularize the ischaemic myocardium, reduce the pain of angina and prolong life. The problem of restenosis is still unsettled, even after lot of advances in stent implantation. Thrombolytic agents can promptly restore blood flow to the myocardium and are increasingly used alone and in combination with PTCA and surgery in acute cases. In the new era, the future for patients with CAD is certainly bright.

4.9
1) i)

ANSWERS TO CHECK YOUR PROGRESS

plaque rupture or erosion with superimposed non-occulsive thrombus, believed to be the most common cause.

Check Your Progress 1

ii) dynamic obstruction. iii) progressive mechanical obstruction. iv) secondary UA related to increased myocardial oxygen demand and/or decreased supply. 2) i) it occurs at rest (or with minimal exertion) usually lasting > 10 min, ii) it is severe and of new onset (i.e., within the prior 4 to 6 weeks), and/or iii) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously). ECG in unstable angina may show ST-segment depression, transient ST-segment elevation, and/or T-wave inversions which occur in 30-50 per cent of patients. Check Your Progress 2 1) 2) 3) Onset of MI may be at any time of the day or night, but a higher frequency of onset occurs in the morning within a few hours of waking up. Some of the triggers are physical exercise, emotional stress, medical and surgical illness. But in roughly one half of cases no precipitating factors appears to be present prior to MI. Unusual presentations are in the form of pulmonary oedema, marked weakness, syncope, a confusional state, appearence of an arrhythmia, evidence of peripheral embolism or merely an unexplained drop in arterial pressure. Class I Patients are free of rales and third heart sound. Class II Patients have rales but only to a mild to moderate degree (<50 per cent of lung fields)and may or may not have S3. Class III Class IV 1) Patients have rales in more than half of each lung field and frequently have pulmonary oedma. Patients are in cardiogenic shock.

4)

Check Your Progress 3 Myocardial infarction evolves through four easily recognizable electrographic phases.

1) Hyperacute 2) Acute 3) Subacute 4) Chronic stabilized 2) Site of infarction 1) 2) 3) 4) 3) Anterior wall Antero Septal Lateral or apical Inferior ECG Leads one or more of precordial leads (V1-V6), I, aVL V1-V3 V4-V6 II, III, avF

Should be strongly suspected if in the clinical setting of Acute Inferior Wall MI (IWMI), there is ST-segment elevations of 1mm or more in lead V1 and V4 R or any one of the extra right precordial leads (V4R-V6R). ECG changes of a true posterior infarction are seen as mirror image representations in lead V1 to V3. R-waves of 40ms in lead V1 and in contiguous right precordial leads with upright T-waves. In the acute phase ST-segment depression and R/S Ratio equal to or greater than 1 in leads V1 and V2 are diagnostic. Usually there are associated changes in inferior and lateral leads.

4)

5)

Normally, Baseline CK-MB activity is 2-4 IU/L. For a reliable diagnosis of MI, it should increase above 9-10 IU/L. Plasma CK-MB activity of reliable diagnostic sensitivity is reached within 12-16 hrs of onset of symptoms. Maximal levels are reached between 14-36 hrs with a return to normal levels occurring after 48-72hrs. Troponin I and Troponin T are released into the plasma so that a reliable diagnostic sensitivity is reached by 12-16 hrs and maximal activity is reached by 24-36 hrs. The levels return to normal within 10-12 days. All of the so called thrombolytic agents are either direct or indirect activators of plasminogen, a circulating proenzyme. Plasminogen is converted by plasminogen activators or activator complexes to plasmin,the active fibrinolytic enzyme. Plasmin has relatively broad proteolytic properties, degrading fibrin, fibrinogen, prothrombin and factors V and V11.Plaminogen activators induced fibrinolysis may then act to disrupt thrombus. i) Any prior intra cranial hemorrhage. ii) Known structural cerebral vascular lesions (AVM). iii) Known malignant intracranial neoplasm. iv) Ischaemic stroke within 3 months. v) Suspected aortic dissection. vi) Active bleeding diathesis (excluding menstruation which is not a contraindication). vii) Significant closed head or facial trauma within 3 months.

6)

Check Your Progress 4 1)

2)

3)

Dose: 1.5 million units IV over 30-60 mts.

A few days after administration of SK, antistreptokinase titer rises rapidly to 50-100 times and remains high for 4-6 months during which period renewed treatment with SK is impracticable. What are the indications for heparin in acute myocardial infarction? What is the dose used. 4) i) In all patients undergoing PCI or surgical revascularisation.

ii) In patients undergoing reperfusion therapy using fibrin selective agents. iii) In patients treated with non-selective fibrinolytic agents, UFH is indicated if they are at high risk for systemic embolisation (large anterior MI, atrial fibrillation, previous embolism, known LV thrombus). Dose: 60 u/kg (4000 u maximum) followed by initial infusion of 12 u/kg/hr (max 1000 u/hr) Maintain APTT at 1.5-2 times control. 5) Features of cardiogenic shock: i) Clinical evidence of hypoperfusion like cold extremities, perspiration tachycardia and low urine output.

ii) Systolic blood pressure < 80-90 mm of Hg. iii) LVEDP >18 mm of Hg. iv) PCWP > 18 mm of Hg. v) Cardiac Index < 1.8 L/mt/m. Check Your Question 5 1) Complete AV block occurs in about 5 per cent of patients with AMI and can occur in patients with either anterior or more commonly with inferior infarction. Prognosis depends on the anatomical location of the block. CHB in patients with inferior wall infarction usually results from intranodal or supranodal lesion and develops gradually. The escape rhythm is usually stable, with a rate exceeding 40 beats/mt, and a narrow QRS in 70 per cent of cases. Temporary pacing should be done if haemodynamically unstable. This is often transient and resolves within a few days. If it does not resolve, rarely it may require permanent pacing (PPI), as per physicians discretion. The mortality may approach 15 per cent, but associated Right Ventricular MI (RVMI) doubles the mortality. In patients with anterior infarction CHB often occurs suddenly, 12-24 hrs after the onset of infarction. Such patients have unstable escape rhythms with wide QRS complexes and rates less than 40 beats/mt. Mortality is extremely high and approximately 70-80 per cent. Hence ventricular or AV sequential pacing is indicated in essentially all patients with Anterior Myocardial Infarction with Complete Heart Block. 2) Rupture of IVS is estimated to occur in 1-3 per cent of AMI. Ventricular septal rupture occurs with an approximately equal frequency in anterior and inferior infarctions. Majority occur in the first week. 20-30 per cent may develop as early as 24hrs after infarction. Patient presents with sudden clinical deterioration. Clinical evaluation reveal new systolic murmur along the left sternal border often associated with a thrill, features of pulmonary and systemic venous

congestion. Signs of systemic venous congestion will be out of proportion to those of pulmonary venous congestive due to RV volume overload due to the shunt. The diagnosis can be established by echocardiography. Right heart catherisation is useful in confirming the situation.