INTRODUCTION

MYOCARDIAL INFARCTION
Myocardial infarction, commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia. This usually results from an imbalance in oxygen supply and demand, which is most often caused by plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium.

CLASSIFICATION 1. Based on pathology:

Transmural: associated with atherosclerosis involving a major coronary artery. It can be subclassified into anterior, posterior, inferior, lateral or septal. Transmural infarcts extend through the whole thickness of the heart muscle and
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are usually a result of complete occlusion of the area's blood supply. In addition, on ECG, ST elevation and Q waves are seen. Subendocardial: involving a small area in the subendocardial wall of the left ventricle, ventricular septum, or papillary muscles. The subendocardial area is particularly susceptible to ischemia.In addition, ST depression is seen on ECG.

2 .Based on clinically ST elevation MI (STEMI) non-ST elevation MI (non-STEMI) A 2007 consensus document classifies myocardial infarction into five main types:

Type 1 Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring, or dissection Type 2 Myocardial infarction secondary to ischemia due to either increased oxygen demand or decreased supply, e.g. coronary artery spasm, coronary embolism, anaemia, arrhythmias, hypertension, or hypotension Type 3 Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischaemia, accompanied by new ST elevation, or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood Type 4 Associated with coronary angioplasty or stents: Type 4a Myocardial infarction associated with PCI Type 4b Myocardial infarction associated with stent thrombosis as documented by angiography or at autopsy Type 5 Myocardial infarction associated with CABG

SIGNS AND SYMPTOMS

Chest pain or pressure (usually in the center of the chest) that may radiate to the neck, jaw or one or both arms/shoulders. This may occur with exertion or at rest Shortness of breath
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Diaphoresis, or generalized sweating Nausea and vomiting Palpitations Weakness Anxiety, or a sense of impending doom or death Lightheadedness or loss of consciousness EPIDEMIOLOGY Myocardial infarction is a common presentation of ischemic heart disease/coronary artery disease. The World Health Organization estimated in 2004, that 12.2% of worldwide deaths were from ischemic heart disease with it being the leading cause of death in high or middle income countries and second only to lower respiratory infections in lower income countries. Worldwide more than 3 million people have STEMIs and 4 million have NSTEMIs a year.Rates of death from ischemic heart disease have slowed or declined in most high income countries, although cardiovascular disease still accounted for 1 in 3 of all deaths in the USA in 2008. In contrast, ischemic heart disease is becoming a more common cause of death in the developing world. For example in India, ischemic heart disease had become the leading cause of death by 2004 accounting for 1.46 million deaths (14% of total deaths) and deaths due to ischemic heart disease were expected to double during 19852015. Globally it is predicted that disability adjusted life years (DALYs) lost to ischemic heart disease will account for 5.5% of total DALYs in 2030, making it the second most important cause of disability (after unipolar depressive disorder), as well as the leading cause of death by this date. ETIOLOGY Atherosclerosis is the disease primarily responsible for most acute coronary syndrome (ACS) cases. Approximately 90% of myocardial infarctions result from an acute thrombus that obstructs an atherosclerotic coronary artery. Plaque rupture and erosion are considered to be the major triggers for coronary thrombosis. Following plaque erosion or rupture, platelet activation and aggregation, coagulation pathway activation, and endothelial vasoconstriction occur, leading to coronary thrombosis and occlusion.Within the coronary vasculature, flow dynamics and endothelial shear stress are implicated in the pathogenesis of vulnerable plaque formation. Evidence indicates that in numerous cases, culprit lesions are stenoses of less than 70% and are located proximally within the coronary tree. Coronary atherosclerosis is especially prominent near branching points of vessels. Culprit lesions that are particularly prone to rupture are
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atheromas containing abundant macrophages, a large lipid-rich core surrounded by a thinned fibrous cap. Non modifiable factors

Age Sex Family history of premature coronary heart disease Male-pattern baldness Modifiable factors

Smoking or other tobacco use Diabetes mellitus Hypertension Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders Dyslipidemia Obesity Sedentary lifestyle and/or lack of exercise

PATHOPHYSIOLOGY Heart attack, known in medicine as an acute myocardial infarction (AMI or MI), occurs when the blood supply to part of the heart is interrupted. This is most commonly due to occlusion (blockage) of a coronary artery following the rupture of a vulnerable atherosclerotic plaque, which is an unstable collection of lipids (like cholesterol) and white blood cells (especially macrophages) in the wall of an artery. The resulting ischemia (restriction in blood supply) and oxygen shortage, if left untreated for a sufficient period, can cause damage and/or death (infarction) of heart muscle tissue (myocardium).

COMPLICATIONS Sudden death : The risk of sudden death is highest at the onset of symptoms and declines progressively over a number of hours. Disturbance of rate, rhythm and conduction Dysrhythmias are experienced more frequently than any other MI complication, with the incidence of some type of disturbance at virtually 100 per cent.. Cardiogenic shock The term cardiogenic shock is used to describe a complex syndrome associated with inadequate perfusion of vital organs - most significantly the brain, kidneys and heart. of these.Cardiogenic shock is caused by massive irreversible damage to the myocardium, so early treatment of dysrhythmias may prevent its development.
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 Cardiac rupture After arrhythmias and cardiogenic shock, the commonest cause of death after acute MI is rupture. Cardiac rupture complicates 10 per cent of acute MIs and occurs in the healing stages at around five to nine days.. Attempts have been made to reduce the risk by early treatment with betablockers. The risk appears to be higher with hypertension or an extensive MI, and it is four times more common in women than men. The commonest site is through the left ventricular wall, manifesting as chest pain, hypotension and dyspnoea. Death is rapid due to haemopericardium and the resultant cardiac tamponade leading to a pulseless electrical activity cardiac arrest. Heart failure Heart failure is one of the more severe complications of MI and results from the heart's inability to provide an adequate cardiac output for the body's metabolic requirements . Heart failure complicates 25-50 per cent of acute MIs arising from the loss of contractility in the damaged myocardium as left ventricular remodelling occurs. It tends to develop insidiously during the first few days following MI. Angina pectoris Recurrent and persistent anginal symptoms may occur in the early post-infarction period and have been associated with an unfavourable prognosis. Anginal pain is due to the increased oxygen demand on the viable myocardium. Cardiac catheterisation and surgical revascularisation may be indicated in these patients. Pericarditis This is often acute and usually occurs 24-72 hours post-MI. It is seen in 20 per cent of patients following a Q-wave MI. It is usually transient, benign and self-limiting but symptoms may be distressing. Pain is typically felt in the region of the heart, is worse on inspiration and relieved by sitting up or leaning forward. Ventricular septal defect This structural complication occurs in two per cent of cases as a late complication around days three to five. A hole occurs in the intraventricular septum, resulting in a left to right shunt with subsequent cardiogenic shock, pulmonary circuit overload and severe pulmonary oedema. Chest pain may occur at the time of rupture. Treatment involves early intervention with surgery and the insertion of a Dacron graft over the hole.
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 Ventricular aneurysm Aneurysm formation results in 10-15 per cent of cases following extensive destruction of cardiac muscle, and its replacement by scar tissue. During ventricular systole the aneurysm bulges outwards and reduces the ejection fraction by absorbing the force of myocardial contraction. In effect it steals some of the left ventricular stroke volume. Ruptured papillary muscles This rare complication affects one per cent of patients, but 70 per cent of these die within the first 24 hours. Rupture of the papillary muscles occurs in the healing stages usually complicating an inferior or anteroseptal MI. There is a sudden onset of mitral insufficiency and heart failure. Treatment is surgical and involves an urgent valve replacement Dressler's syndrome It presents as pleuropericarditis occurring within the first 12 weeks following an acute MI. The pericarditis is secondary to the MI and is induced by an abnormal autoimmune mechanism. This syndrome is rarely serious but may be distressing and frightening to the patient still recovering from an acute MI. It is treated with anti-inflammatories in the first instance and steroids as a last resort.

Shoulder hand syndrome Left shoulder pain and stiffness is felt two to eight weeks after MI and there may be pain and swelling of the hand. With early mobilisation of the patient it has become a rare complication. It is treated with physiotherapy and is usually resolved after two years. Psychological problems and depression Up to one-third of MI patients may present with anxiety, depression and over-dependence. Early mobilisation and exercise programmes help prevent this. DIAGNOSIS Physical examination The general appearance of patients may vary according to the experienced symptoms; the patient may be comfortable, or restless and in severe
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distress with an increased respiratory rate. A cool and pale skin is common and points to vasoconstriction. Some patients have low-grade fever (3839 C). Blood pressure may be elevated or decreased, and the pulse can become irregular.[8][9] If heart failure ensues, elevated jugular venous pressure and hepatojugular reflux, or swelling of the legs due to peripheral edema may be found on inspection. Rarely, a cardiac bulge with a pace different from the pulse rhythm can be felt on precordial examination. Various abnormalities can be found on auscultation, such as a third and fourth heart sound, systolic murmurs, paradoxical splitting of the second heart sound, a pericardial friction rub and rales over the lung.[8][10] Electrocardio gram The primary purpose of the electrocardiogram is to detect ischemia or acute coronary injury in broad, symptomatic emergency department populations. A serial ECG may be used to follow rapid changes in time. The standard 12 lead ECG does not directly examine the right ventricle, and is relatively poor at examining the posterior basal and lateral walls of the left ventricle. In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG.[11] The use of additional ECG leads like right-sided leads V3R and V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. The 12 lead ECG is used to classify patients into one of three groups:[12] 1. those with ST segment elevation or new bundle branch block (suspicious for acute injury and a possible candidate for acute reperfusion therapy with thrombolytics or primary PCI), 2. those with ST segment depression or T wave inversion (suspicious for ischemia), and 3. those with a so-called non-diagnostic or normal ECG. A normal ECG does not rule out acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care.[13]

Cardiac markers

Cardiac markers or cardiac enzymes are proteins that leak out of injured myocardial cells through their damaged cell membranes into the bloodstream,, the enzymes SGOT andLDH were used to assess cardiac injury. Now, the markers most widely used in detection of MI are MB subtype of the enzyme creatine kinase and cardiac troponins T and I as they are more specific for myocardial
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injury. The cardiac troponins T and I which are released within 46 hours of an attack of MI and remain elevated for up to 2 weeks, have nearly complete tissue specificity and are now the preferred markers for asssessing myocardial damage. Heart-type fatty acid binding protein is another marker, used in some home test kits. Angiography In difficult cases or in situations where intervention to restore blood flow is appropriate, coronary angiography can be performed. A catheter is inserted into an artery (usually the femoral artery) and pushed to the vessels supplying the heart. A radio-opaque dye is administered through the catheter and a sequence of x-rays (fluoroscopy) is performed. Obstructed or narrowed arteries can be identified, and angioplasty applied as a therapeutic measure Exercise tolerance testing 24Exercise tolerance (stress) testing (ETT) is recommended for pa-tients with intermediate pretest probability of CAD based on age,gender, and symptoms, including those with complete right bundlebranch block or less than 1 mm of rest ST-segment depression .Although ETT is insensitive for predicting coronary artery anatomy, it does correlate well with outcome, such as the likelihood of progressing to angina, the occurrence of acute MI, and cardiovascular death. Ischemic STsegment depression that occurs during ETT is anindependent risk factor for cardiac events and cardiovascular mortal-ity. Thallium (201Tl) myocardial perfusion scintigraphy may be used in conjunction with ETT to detect reversible and irreversible defects in blood flow to the myocardium because it is more sensitive than ETT. Histopathology Histopathological examination of the heart may reveal infarction at autopsy. Under the microscope, myocardial infarction presents as a circumscribed area of ischemic, coagulative necrosis (cell death). On gross examination, the infarct is not identifiable within the first 12 hours. Although earlier changes can be discerned using electron microscopy the myocyte cytoplasm becomes more eosinophilic (pink) and the cells lose their transversal striations, with typical changes and eventually loss of the cell nucleus.[20] The interstitium at the margin of the infarcted area is initially infiltrated with neutrophils, then with lymphocytesand macrophages,
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who phagocytose ("eat") the myocyte debris. The necrotic area is surrounded and progressively invaded by granulation tissue, which will replace the infarct with a fibrous (collagenous) scar (which are typical steps in wound healing). The interstitial space (the space between cells outside of blood vessels) may be infiltrated with red blood cells.[18] These features can be recognized in cases where the perfusion was not restored; reperfused infarcts can have other hallmarks, such as contraction band necrosis.

TREATMENT NON-PHARMACOLOGICAL TREATMENT

Compliancegive careful advice about disease, treatment, and self help strategies Dietensure adequate general nutrition and, in obese patients, weight reduction Saltadvise patients to avoid high salt content foods and not to add salt (particularly in severe cases of congestive heart failure) Fluidurge overloaded patients and those with severe congestive heart failure to restrict their fluid intake Alcoholadvise moderate alcohol consumption (abstinence in alcohol related cardiomyopathy) Smokingavoid smoking (adverse effects on coronary disease, adverse haemodynamic effects) Exerciseregular exercise should be encouraged Vaccinationpatients should consider influenza and pneumococcal vaccinations

Non-pharmacological measures for the management of heart failure

Compliancegive careful advice about disease, treatment, and self help strategies Dietensure adequate general nutrition and, in obese patients, weight reduction Saltadvise patients to avoid high salt content foods and not to add salt (particularly in severe cases of congestive heart failure) Fluidurge overloaded patients and those with severe congestive heart failure to restrict their fluid intake

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Alcoholadvise moderate alcohol consumption (abstinence in alcohol related cardiomyopathy) Smokingavoid smoking (adverse effects on coronary disease, adverse haemodynamic effects) Exerciseregular exercise should be encouraged Vaccinationpatients should consider influenza and pneumococcal vaccinations

PHARMACOLOGICAL TREATMENT Oxygen Oxygen is indicated in the presence of hypoxemia. In uncomplicated cases, its use should probably be limited to the first 24 hours. Oxygen, via nasal prongs, at 2 - 4 litres/min is usually adequate. One should aim to maintain the oxygen saturation above 95%. Antiplatelet Agents A) Aspirin Aspirin is indicated in all patients at diagnosis and should be continued indefinitely unless contraindicated. The initial dose of 100- 300mg should be followed by a maintenance dose of 75 - 150mg daily. B) Clopidogrel

Clopidogrel, when given together with aspirin and fibrinolytic therapy in STEMI, has been shown to reduce the odds of an occluded infarct related artery, death or reinfarction without increasing the risk of bleeding or cerebrovascular accidents. 10,11A loading dose of 300 mg should be given followed by a maintenance dose of 75 mg daily. We recommend treatment for at least 1 month after fibrinolytic therapy. Following PCI, a longer period of dual antiplatelet therapy (up to 12 months) is necessary particularly when drug-eluting stents are used.

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REVIEW OF LITERATURE Long-Term Safety and Efficacy of Pitavastatin in Patients With Acute Myocardial Infarction.

1. Soon Yong Suh et al conducted prospective, open, observational, multicenter study to evaluate the long term Safety and Efficacy of Pitavastatinin in Patients WithAcute Myocardial Infarction. This study consisted of 1,039 consecutive patients with AMI (74.0%men, mean age 61.412.6 years) who presented in 10 major percutaneous coronary intervention centers in Korea from February 2007 through September 2009. Pitavastatin 2mg/day was routinely administered in patients with AMI from time of presentation. They investigated changes of lipid profiles, biochemical markers, adverse events, and clinical outcomes up to 12 months. During the study 318 events overall occurred in 220 patients(21.2%) who reported >1 treatment emergent adverse
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event, although 20 events in 14patients (1.4%) were treatment-related adverse events. Low-density lipoprotein (LDL)cholesterol percent change was25.6% and LDL cholesterol target attainment was 70.5%at 12-month follow-up. Levels of creatinine phosphokinase, serum glutamic oxaloacetictransaminase, glutamic pyruvic transaminase, and high-sensitivity C-reactive protein decreased significantly during the first 1 month of pitavastatin treatment and were sustained to 12-month follow-up. Major adverse cardiac events occurred in 66 patients (7.3%).All-cause deaths occurred in 32 patients (3.5%) including 19 (2.1%) cardiac deaths and recurrent MIs occurred in 14 (1.6%) and target lesion revascularizations in 42 (4.7%).The study resulted that administration of pitavastatin 2 mg/day in patients with AMI showed 70.5% LDL cholesterol target attainment with good tolerance and was associated with favorable clinical outcomes up to 12 months.

Beneficial Effects of Statin Therapy on Survival in Hypertensive Patients With Acute Myocardial Infarction

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