Myocardial Infarction

Etiology

As stated above, myocardial infarction is closely associated with coronary artery disease. INTERHEART is an international multi-center case-control study which delineated the following modifiable risk factors for coronary artery disease:[5][6]

1. Smoking
2. Abnormal lipid profile/blood apolipoprotein (raised ApoB/ApoA1)
3. Hypertension
4. Diabetes mellitus
5. Abdominal obesity (waist/hip ratio) (greater than 0.90 for males and greater than 0.85 for females)
6. Psychosocial factors such as depression, loss of the locus of control, global stress, financial stress, and life events including marital separation, job loss, and family conflicts
7. Lack of daily consumption of fruits or vegetables
8. Lack of physical activity
9. Alcohol consumption (weaker association, protective)

The INTERHEART study showed that all the above risk factors were significantly associated with acute myocardial infarction except for alcohol consumption, which showed a weaker association. Smoking and abnormal apolipoprotein ratio showed the strongest association with acute myocardial infarction. The increased risk associated with diabetes and hypertension were found to be higher in women, and the protective effect of exercise and alcohol was also found to be higher in women.[5]

Other risk factors include a moderately high level of plasma homocysteine, which is an independent risk factor of MI. Elevated plasma homocysteine is potentially modifiable and can be treated with folic acid, vitamin B6, and vitamin B12.[7]

Some non-modifiable risk factors for myocardial infarction include advanced age, male gender (males tend to have myocardial infarction earlier in life), genetics (there is an increased risk of MI if a first-degree relative has a history of cardiovascular events before the age of 50).[6][8] The role of genetic loci that increase the risk for MI is under active investigation.[9][10]

Epidemiology

The most common cause of death and disability in the western world and worldwide is coronary artery disease.[11] Based on 2015 mortality data from the National Health Interview Survey (NHIS-CDC), MI mortality was 114,023, and MI any-mention mortality (i.e., MI is mentioned as a contributing factor in the death certificate) was 151,863.

As per the National Health and Nutrition Examination Survey (NHANES)-CDC data from 2011 to 2014, an estimated 16.5 million Americans older than 20 years of age have coronary artery disease, and the prevalence was higher in males than females for all ages. As per the NHANES 2011 through 2014, the overall prevalence of MI is 3.0% in US adults older than 20 years of age.

Prevalence of MI in the US Sub-populations

Non-Hispanic Whites

• 4.0% (Male)
• 2.4% (Female)

Non-Hispanic Blacks

• 3.3% (Male)
• 2.2% (Female)

Hispanics

• 2.9% (Male)
• 2.1% (Female)

Non-Hispanic Asians

• 2.6% (Male)
• 0.7% (Female)

Based on the Atherosclerosis Risk in Communities Study (ARIC) performed by National Heart, Lung, and Blood Institute (NHLBI) collected between 2005 and 2014, the estimated annual incidence is 605,000 new MIs and 200,000 recurrent MIs.[12]

The ARIC study also found that the average age at first MI is 65.6 years for males and 72.0 years for females. In the past decades, several studies have shown a declining incidence of MI in the United States.[12]

Pathophysiology

The acute occlusion of one or multiple large epicardial coronary arteries for more than 20 to 40 minutes can lead to acute myocardial infarction. The occlusion is usually thrombotic and due to the rupture of a plaque formed in the coronary arteries. The occlusion leads to a lack of oxygen in the myocardium, which results in sarcolemmal disruption and myofibril relaxation.[2] These changes are one of the first ultrastructural changes in the process of MI, which are followed by mitochondrial alterations. The prolonged ischemia ultimately results in liquefactive necrosis of myocardial tissue. The necrosis spreads from sub-endocardium to sub-epicardium. The subepicardium is believed to have increased collateral circulation, which delays its death.[2] Depending on the territory affected by the infarction, the cardiac function is compromised. Due to the negligible regeneration capacity of the myocardium, the infarcted area heals by scar formation, and often, the heart is remodeled characterized by dilation, segmental hypertrophy of remaining viable tissue, and cardiac dysfunction.[13]

History and Physical

The imbalance between oxygen supply and the demand leads to myocardial ischemia and can sometimes lead to myocardial infarction. The patient’s history, electrocardiographic findings, and elevated serum biomarkers help identify ischemic symptoms. Myocardial ischemia can present as chest pain, upper extremity pain, mandibular, or epigastric discomfort that occurs during exertion or at rest. Myocardial ischemia can also present as dyspnea or fatigue, which are known to be ischemic equivalents.[14] The chest pain is usually retrosternal and is sometimes described as the sensation of pressure or heaviness. The pain often radiates to the left shoulder, neck, or arms with no obvious precipitating factors, and it may be intermittent or persistent. The pain usually lasts for more than 20 minutes.[15] It is usually not affected by positional changes or active movement of the region. Additional symptoms, such as sweating, nausea, abdominal pain, dyspnea, and syncope, may also be present.[14][16][17] The MI can also present atypically with subtle findings such as palpitations, or more dramatic manifestations, such as cardiac arrest. The MI can sometimes present with no symptoms.[18]

Evaluation

The three components in the evaluation of the MI are clinical features, ECG findings, and cardiac biomarkers.

ECG

The resting 12 lead ECG is the first-line diagnostic tool for the diagnosis of acute coronary syndrome (ACS). It should be obtained within 10 minutes of the patient’s arrival in the emergency department.[17] Acute MI is often associated with dynamic changes in the ECG waveform. Serial ECG monitoring can provide important clues to the diagnosis if the initial EKG is non-diagnostic at initial presentation.[14] Serial or continuous ECG recordings may help determine reperfusion or re-occlusion status. A large and prompt reduction in ST-segment elevation is usually seen in reperfusion.[14]

ECG findings suggestive of ongoing coronary artery occlusion (in the absence of left ventricular hypertrophy and bundle branch block):[19]

ST-segment elevation in two contiguous lead (measured at J-point) of

1. Greater than 5 mm in men younger than 40 years, greater than 2 mm in men older than 40 years, or greater than 1.5 mm in women in leads V2-V3 and/or
2. Greater than 1 mm in all other leads

ST-segment depression and T-wave changes

1. New horizontal or down-sloping ST-segment depression greater than 5 mm in 2 contiguous leads and/or T inversion greater than 1 mm in two contiguous leads with prominent R waves or R/S ratio of greater than 1

The hyperacute T-wave amplitude, with prominent symmetrical T waves in two contiguous leads, maybe an early sign of acute MI that may precede the ST-segment elevation. Other ECG findings associated with myocardial ischemia include cardiac arrhythmias, intraventricular blocks, atrioventricular conduction delays, and loss of precordial R-wave amplitude (less specific finding).[14]

ECG findings alone are not sufficient to diagnose acute myocardial ischemia or acute MI as other conditions such as acute pericarditis, left ventricular hypertrophy (LVH), left bundle branch block (LBBB), Brugada syndrome, Takatsubo syndrome (TTS), and early repolarization patterns also present with ST deviation.

ECG changes associated with prior MI (in the absence of left ventricular hypertrophy and left bundle branch block):

1. Any Q wave in lead V2-V3 greater than 0.02 s or QS complex in leads V2-V3
2. Q wave > 03 s and greater than 1 mm deep or QS complex in leads I, II, aVL, aVF or V4-V6 in any two leads of contiguous lead grouping (I, aVL; V1-V6; II, III, aVF)

• R wave > 0.04 s in V1-V2 and R/S greater than 1 with a concordant positive T wave in the absence of conduction defect.

Biomarker Detection of MI

Cardiac troponins (I and T) are components of the contractile apparatus of myocardial cells and expressed almost exclusively in the heart. Elevated serum levels of cardiac troponin are not specific to the underlying mode of injury (ischemic vs. tension)[14] [20]. The rising and/or falling pattern of cardiac troponins (cTn) values with at least one value above the 99 percentile of upper reference limit (URL) associated with symptoms of myocardial ischemia would indicate an acute MI. Serial testing of cTn values at 0 hours, 3 hours, and 6 hours would give a better perspective on the severity and time course of the myocardial injury. Depending on the baseline cTn value, the rising/falling pattern is interpreted. If the cTn baseline value is markedly elevated, a minimum change of greater than 20% in follow up testing is significant for myocardial ischemia. Creatine kinase MB isoform can also be used in the diagnosis of MI, but it is less sensitive and specific than cTn level.[4][21]

Imaging

Different imaging techniques are used to assess myocardial perfusion, myocardial viability, myocardial thickness, thickening and motion, and the effect of myocyte loss on the kinetics of para-magnetic or radio-opaque contrast agents indicating myocardial fibrosis or scars.[14] Some imaging modalities that can be used are echocardiography, radionuclide imaging, and cardiac magnetic resonance imaging (cardiac MRI). Regional wall motion abnormalities induced by ischemia can be detected by echocardiography almost immediately after the onset of ischemia when greater than 20% transmural myocardial thickness is affected. Cardiac MRI provides an accurate assessment of myocardial structure and function.[14]

Treatment / Management

Acute Management

Reperfusion therapy is indicated in all patients with symptoms of ischemia of less than 12-hours duration and persistent ST-segment elevation. Primary percutaneous coronary intervention (PCI) is preferred to fibrinolysis if the procedure can be performed <120 minutes of ECG diagnosis. If there is no immediate option of PCI (>120 minutes), fibrinolysis should be started within 10 minutes of STEMI after ruling out contraindications. If transfer to a PCI center is possible in 60 to 90 minutes after a bolus of the fibrinolytic agent and patient meets reperfusion criteria, a routine PCI can be done, or a rescue PCI can be planned.[19][17] If fibrinolysis is planned, it should be carried out with fibrin-specific agents such as tenecteplase, alteplase, or reteplase (class I).[19]

Relief of pain, breathlessness, and anxiety: The chest pain due to myocardial infarction is associated with sympathetic arousal, which causes vasoconstriction and increased workload for the ischemic heart. Intravenous opioids (e.g., morphine) are the analgesics most commonly used for pain relief (Class IIa).[19] The results from CRUSADE quality improvement initiative have shown that the use of morphine may be associated with a higher risk of death and adverse clinical outcomes.[22] The study was done from the CIRCUS (Does Cyclosporine Improve outcome in STEMI patients) database, which showed no significant adverse events associated with morphine use in a case of anterior ST-segment elevation MI.[23] A mild anxiolytic (usually a benzodiazepine) may be considered in very anxious patients (class IIa). Supplemental oxygen is indicated in patients with hypoxemia (SaO2 <90% or PaO2 <60mm Hg) (Class I).[19](B2)

Nitrates: Intravenous nitrates are more effective than sublingual nitrates with regard to symptom relief and regression of ST depression (NSTEMI). The dose is titrated upward until symptoms are relieved, blood pressure is normalized in hypertensive patients, or side effects such as a headache and hypotension are noted.[17]

Beta-blockers: This group of drugs reduces myocardial oxygen consumption by lowering heart rate, blood pressure, and myocardial contractility. They block beta receptors in the body, including the heart, and reduce the effects of circulating catecholamines. Beta-blockers should not be used in suspected coronary vasospasm.

Platelet inhibition: Aspirin is recommended in both STEMI and NSTEMI in an oral loading dose of 150 to 300 mg (non-enteric coated formulation) and a maintenance dose of 75 to 100 mg per day long-term regardless of treatment strategy (class I).[17] Aspirin inhibits thromboxane A2 production throughout the lifespan of the platelet.[24]

Most P2Y12 inhibitors are inactive prodrugs (except for ticagrelor, which is an orally active drug that does not require activation) that require oxidation by hepatic cytochrome P450 system to generate an active metabolite which selectively inhibits P2Y12 receptors irreversibly. Inhibition of P2Y12 receptors leads to inhibition of ATP induced platelet aggregation. The commonly used P2Y12 inhibitors are clopidogrel, prasugrel, and ticagrelor.

The loading dose for clopidogrel is 300 to 600 mg loading dose followed by 75 mg per day.

Prasugrel, 60 mg loading dose, and 10 mg per day of a maintenance dose have a faster onset when compared to clopidogrel.[19]

Patients undergoing PCI should be treated with dual antiplatelet therapy (DAPT) with aspirin + P2Y12 inhibitor and a parenteral anticoagulant. In PCI, the use of prasugrel or ticagrelor is found to be superior to clopidogrel. Aspirin and clopidogrel are also found to decrease the number of ischemic events in NSTEMI and UA.[17]

The anticoagulants used during PCI are unfractionated heparin, enoxaparin, and bivalirudin. The bivalirudin is recommended during primary PCI if the patient has heparin-induced thrombocytopenia.[19]

Long-Term Management

Lipid-lowering treatment: It is recommended to start high-intensity statins that reduce low-density lipoproteins (LDLs) and stabilize atherosclerotic plaques. High-density lipoproteins are found to be protective.[19]

Antithrombotic therapy: Aspirin is recommended lifelong, and the addition of another agent depends on the therapeutic procedure done, such as PCI with stent placement.

ACE inhibitors are recommended in patients with systolic left ventricular dysfunction, or heart failure, hypertension, or diabetes.

Beta-blockers are recommended in patients with LVEF less than 40% if no other contraindications are present.

Antihypertensive therapy can maintain a blood pressure goal of less than 140/90 mm Hg.

Mineralocorticoid receptor antagonist therapy is recommended in a patient with left ventricular dysfunction (LVEF less than 40%).

Glucose lowering therapy in people with diabetes to achieve current blood sugar goals. [19]

Lifestyle Modifications

Smoking cessation is the most cost-effective secondary measure to prevent MI. Smoking has a pro-thrombotic effect, which has a strong association with atherosclerosis and myocardial infarction.[6](B2)

Diet, alcohol, and weight control: A diet low in saturated fat with a focus on whole grain products, vegetables, fruits, and the fish is considered cardioprotective. The target level for bodyweight is body mass index of 20 to 25 kg/m2  and waist circumference of <94 cm for the men and <80 cm for the female.[25]

Differential Diagnosis

1. Angina pectoris
2. Non-ST segment elevation myocardial infarction (NSTEMI)
3. ST-segment elevation myocardial infarction (STEMI)
4. Pulmonary embolism
5. Pneumothorax

Prognosis

Despite many advances in treatment, acute MI still carries a mortality rate of 5-30%; the majority of deaths occur prior to arrival to the hospital. In addition, within the first year after an MI, there is an additional mortality rate of 5% to 12%. The overall prognosis depends on the extent of heart muscle damage and ejection fraction. Patients with preserved left ventricular function tend to have good outcomes. Factors that worsen prognosis include:

• Diabetes
• Advanced age
• Delayed reperfusion
• Low ejection fraction
• Presence of congestive heart failure
• Elevations in C-reactive protein and B-type natriuretic peptide (BNP) levels
• Depression

Complications

Type and Manifestation

I: Ischemic

• Reinfarction
• Extension of infarction
• Angina

II: Arrhythmias

• Supraventricular or ventricular arrhythmia
• Sinus bradycardia and atrioventricular block

III: Mechanical

• Myocardial dysfunction
• Cardiac failure
• Cardiogenic shock
• Cardiac rupture (Free wall rupture, ventricular septal rupture, papillary muscle rupture)

IV: Embolic

• Left ventricular mural thrombus,
• Peripheral embolus

V: Inflammatory

• Pericarditis (infarct associated pericarditis, late pericarditis, or post-cardiac injury pericarditis)
• Pericardial effusion