Myocardial Infarction

WHO definition for Acute Myocardial Infarction

• Clinical history of ischemic type discomfort
• Rise and fall in serum cardiac markers
• Changes on serially obtained ECG's

Characteristic history of pain of Acute MI is:

• Chest pain usually retrosternal described as tightness, pressure squeezing
• Pain may radiate to the jaw, arms, neck, back and epigastrium.
• Dyspnea may accompany chest pain due to poor ventricular compliance
• Nausea, Vomiting and abdominal pain
• Anxiety
• Diaphoresis

The total leukocyte count is slightly elevated with a neutrophilia. This non-specific change is compatible with necrosis of the myocardium. The remaining lab data is normal.

The classic patterns enzymes may not be elevated very early in the course of the AMI. Therefore, you should not depend on one set of enzyme determinations but must order a sequence of test over several days.  The initial enzyme determination in the ER may be normal.

The total CK will begin to rise 4-6 hours after the onset of the infarct and reach a peak levels within 24 hours. 

The CK-MB level rises within the same time frame and disappears in about 72 hours and gradually disappear over 7-4 days post MI.

The levels of enzymes LDH-1 and LDH-2 "flip" or reverse in AMI. Normally, the LDH level is less than the LDH-2 level. AST(SGOT) levels rise within the first 24 hours and disappear in 3-4 days. 

AST and CK-MM, are not specific for myocardium. You should understand that the enzyme levels will vary depending on the amount of time between the onset of the infarct and when the test is performed.

 EKG changes of acute myocardial infarction 

Ischemia and infarction - 

• Generally ischemia results in ST segment depression and more severe injury results in ST segment elevation. However, elevation and depression can actually co-exist in the same EKG depending on the position of the recording lead. There is no easy or simple explanation for the EKG changes with either of these pathologies.

  •  It is believed that with more severe myocardial injury, intracellular potassium leaks out of damaged cells and makes the resting membrane potential more positive. As a result, current of injury flows from damaged cells to normal cells during the diastolic period (T-QRS segment). This shifts the baseline of the EKG down, giving the impression that the ST segment is elevated.

• New Q waves:  From the absence of depolarization current in the dead tissue and receding currents from opposite side of Heart.

• R wave progression: Alterations

High probability for infarction

• ST-segment elevation >1mm in 2 contiguous leads
• Q waves
  • Amplitude at least 25% of the R wave
  • Duration >.04 seconds

Normal or nonspecific ECG does not rule out acute MI. Only about half the patients will have diagnostic changes on their initial EKG.

 Correlation of the site of infarction to coronary circulation

Location of Infarction/ occlusion of branch of coronary artery

Evolution of EKG changes over time in Acute Myocardial Infarction

From this information you should understand the need for obtaining sequential cardiac enzymes and EKG and learn to interpret them based on the latency between onset of pain and the time of evaluation.

Conduction system defects with coronary circulation

Patho-physiology of atherosclerotic plaque leading to thrombosis.  

The evolution of a streak into a plaque occurs in the 2-4th decade of life with the number of plaques related to risk factors . The key element is the appearance of extracellular lipid. The lipid first appears in the extracellular matrix then as a lipid core. The lipid core is primarily acellular with loads of oxidized lipid and margins surrounded by numerous lipid-laden macrophages. These macrophages express Tissue Factor which makes the core area the most thrombogenic part of the plaque. The smooth muscle cells (SMC) produce collagen to encapsulate and limit the lipid core however activated Macrophages produce enzymes (e.g.…Metalloproteinases) capable of breaking down the connective tissue matrix. It's a war in there!

An atherosclrotic plaque ulcerates resulting in activation of the platelets and clotting cascade resulting in an occlusive thrombus.

The plaques that rupture most often are not the largest, most luminal impinging but most often are <75% diameter stenosis. They have a large core and thin fibrous cap.

Evolution of myocardial changes that occur following acute myocardial infarction. 

• Myocardial infarction represents coagulation necrosis of the myocardium, usually the left ventricle.
• There are two morphologic types of myocardial infarction: Transmural and subendocardial.
  • The transmural infarct involves the full thickness of the ventricular wall or septum.
  • Subendocardial infarct occupies a space within the inner third of the ventricular wall.
• If the patient survives , the infarct (coagulation necrosis) undergoes a sequence of macroscopic and microscopic changes which lead to healing. The infarct undergoes organization, i.e.; the soft, necrotic tissue is progressively replaced by granulation tissue which in turn is replaced by a firm scar.
• Complications may occur at any point during the healing process or following it.

Evolution of clot/thrombus over time.  

Thrombosis cab be defined as pathological transition of the state of blood from fluidity to non-fluidity. Initially a stationary thrombus is formed. The stationary clot (thrombus) may progress and eventually break into small pieces which when released into circulation are called emboli.  The fibrinolytic system is a network of enzymes that are responsible for the dissolution of a formed clot.

As clots age they are stabilized by factor XIIIa and there is cross-linking of fibrin and the beginning of collagen deposition. These are not lysable at this stage.

Clinical consequences of acute myocardial infarction

• Most often stable
• Ventricular dysfunction: Hypotension
• Ventricular dysfunction: Congestive Heart failure
• Irritable focus: Dysrhythmias
• Ischemia/necrosis of bundle of HIS: Heart block, Bundle branch blocks
• Elevated catecholamine release: Hypertension
• Papillary muscle ischenia/necrosis: Mitral regurgitation. Acute valvular dysfunction.
• Rupture of interventricular septum: Ventriculat septal defect
• Ventricular aneurysm

Mangement strategy when you suspect that the patient may have Myocardial infarction in the Emergency room 

• Oxygen by nasal cannula
• Sublingual Nitroglycerine
• Adequate analgesia
• Aspirin 160-325 mgm
• 12 lead EKG
• Draw baseline Cardiac Enzyme markers
• Limit activities 
• Use of Heparin, Beta blocker, ACE inhibitor
• Admit patient to ICU
• Abort the infarct
  • Decide on early reperfusion strategy with Cardiology consultation and do it.

The goals of therapeutic strategy for MI:

• To alter supply/demand of oxygen to Myocardium
• To prevent further progression of Thrombus/clot
• To re-establish perfusion
• To treat complications

With a normal arterial pO2, oxygen therapy probably has little effect on the supply/demand ratio of the myocardium. 

Morphine has venodilator effects which may cause a reduction in preload, ventricular wall stress and oxygen demand. Also the central effects of morphine to increase vagal tone and reduce the pain-mediated rise in sympathetic tone may also reduce myocardial oxygen demands

 Nitroglycerine and metropolol would both decrease oxygen demands in AMI as they do in stable and unstable angina. Although several clinical trials have shown that these agents may reduce the amount of muscles that become necrotic, the reduction in infarct size is minimal compared to what can be achieved by thrombolytic therapy. 

Since beta-blockers have been shown to reduce mortality for at least one year following a MI, it is advisable to initiate beta-blocker therapy prior to hospital discharge.

We should limit all activities for a period of time to limit the oxygen demand.

Role for aspirin and/or heparin

There is now extensive evidence that thrombosis occurs simultaneously with endogenous (spontaneous) and exogenous thrombolysis. Although aspirin and heparin will not lyse a coronary thrombus, these drugs are essential in preventing re-occlusion. Even during the administration of fibrinolytic agents, episodes of transient reperfusion followed by re-occlusion often precede sustained coronary reperfusion.

Options to re-establish coronary perfusion

The object of reperfusion is to prevent myocardial necrosis.

Early reperfusion improves LV function and survival in patients with

• ST elevation
• New or presumably new bundle branch block

Our job is to abort the infarct. Decide (with Cardiology consultation) on the method of reperfusion and "Just do it"

• Thrombolytic therapy
  • Removes thrombus not yet dissolved by endogenous fibrinolytic system
  • Maximum benefit when administered within 1-3 hours of symptoms onset
  • Restores patency, salvage myocardium and reduce morbidity and mortality
  • Risk of intracranial hemorrhage
• Percutaneous transluminal coronary angioplasty (PTCA).  
  • For patients failing thrombolytic therapy
  • As an alternative to thrombolysis
  • Requires experienced Physician and Lab
• Coronary artery bypass graft (CABG)

With experienced hands , PTCA may have slight advantage in mortality and complications over Thrombolytic therapy in the short run.

At this point PTCA is equal to not better than thrombolytics.

Thrombolytic therapy

Tissue plasminogen activator (t-PA) converts plasminogen to plasmin which acts to digest the fibrin clot that is occluding one of the major coronary arteries. A decrease in chest pain or reduction in the magnitude of ST-segment elevation in the ECG would suggest that reperfusion had been achieved. Unfortunately, these markers are rather imprecise and coronary angiography is the only definitive method for recognizing successful reperfusion. If a method was available for assessing reperfusion (after 90 minutes of IV thrombolytic therapy) could be transferred to the cardiac catheterization laboratory for rescue angioplasty.

How would the latency from the onset of symptoms to the start of t-PA therapy influence the effectiveness of therapy?

In order to salvage reversibly injured cardiac muscle, thrombolytic therapy should be initiated within the first six hours after the onset of symptoms. Beyond six hours cardiac myocytes are irreversibly injured and reperfusion probably does not reduce the ultimate amount of necrosis. There is evidence however, that reperfusion after six hours may help in the healing process with less thinning of the scar and less chance of aneurysm formation. The lack of any benefit after 12 hours may be due in part to the ineffectiveness of thrombolytics in lysing older thrombi. As clots age they are stabilize by factor XIIIa and there is cross-linking of fibrin and the beginning of collagen deposition.

Current thrombolytic agents

• Urokinase

• Streptokinase,

•  t-PA and

•  Anisoylated plasminogen streptokinase activator complex (APSAC). 

T-PA binds to fibrin with greater affinity than does urokinase or streptokinase and activated plasmin on the fibrin surface. In theory, this should lead to a more localized (clot specific) effect and less systemic fibrinolysis. T-PA also has no antigenicity. Although clinical trials have been conflicting, in general, streptokinase and t-PA are thought to produce similar results in terms of vessel patency and overall mortality. Since streptokinase costs only 1/5 to 1/10 as much as t-PA, it is used more often to treat acute myocardial infarction.

Major risk factors associated with the use of thrombolytic therapy

Intracrainal hemorrhage and bleeding are the main risk associated with thrombolytics. Lysis of a preformed thrombus at a site of recent stroke or surgery allow for bleeding. Thrombolytic agents should be avoided within 10 days of surgery and 6 weeks of a stroke. Extremely low fibrinogen levels can also result in bleeding as well as impaired platelet function due to lysis of the surface glycoproteins.

Complications of myocardial infarction and principles of management of each.