Non–ST-Segment Elevation Myocardial Infarction

Etiology

The etiology of NSTEMI varies as there are several potential causes. These include tobacco abuse, lack of physical activity, high blood pressure, high cholesterol, diabetes, obesity, and family history.

Epidemiology

The median age at the time of presentation for ACS in the United States is 68 years. Males outnumber females by a 3:2 ratio. The incidence of ACS in the United States is over 780,000, and of those, approximately 70% will have NSTEMI.

Pathophysiology

ACS is simply a mismatch in the myocardial oxygen demand and myocardial oxygen consumption. While the cause of this mismatch in STEMI is nearly always coronary plaque rupture resulting in thrombosis formation occluding a coronary artery, there are several potential causes of this mismatch in NSTEMI. There may be a flow-limiting condition such as a stable plaque, vasospasm as in Prinzmetal angina, coronary embolism, or coronary arteritis. Non-coronary injury to the heart such as cardiac contusion, myocarditis, or presence of cardiotoxic substances can also produce NSTEMI. Finally, conditions relatively unrelated to the coronary arteries or myocardium itself such as hypotension, hypertension, tachycardia, aortic stenosis, and pulmonary embolism lead to NSTEMI because the increased oxygen demand cannot be met.[4][5]

History and Physical

The “typical” presentation of NSTEMI is a pressure-like substernal pain, occurring at rest or with minimal exertion. The pain generally lasts more than 10 minutes and may radiate to either arm, the neck, or the jaw.  The pain may be associated with dyspnea, nausea or vomiting, syncope, fatigue, or diaphoresis. Sudden onset of unexplained dyspnea with or without associated symptoms is also a common presentation. Risk factors for ACS include male sex, older age, family history of coronary artery disease, diabetes, personal history of coronary artery disease, and renal insufficiency. Atypical symptoms may include a stabbing or pleuritic pain, epigastric or abdominal pain, indigestion, and isolated dyspnea. While all patients presenting with ACS are more likely to present with typical symptoms than atypical symptoms, the likelihood of atypical presentations increases with age over 75, women and those with diabetes, renal insufficiency, and dementia.  

Physical Exam for ACS and NSTEMI is often nonspecific. Clues such as back pain with aortic dissection or pericardial friction rub with pericarditis may point to an alternative diagnosis for a patient’s chest pain, but no such exam finding exists that indicates ACS as the most likely diagnosis. Signs of heart failure should increase concern for ACS but are, again, nonspecific findings.[6][7][8]

Evaluation

History, ECG, and cardiac biomarkers are the mainstays in the evaluation. An ECG should be performed as soon as possible in patients presenting with chest pain or those with a concern for ACS. A normal ECG does not exclude ACS and NSTEMI. ST-elevation or anterior ST depression should be considered a STEMI until proven otherwise and treated as such. Findings suggestive of NSTEMI include transient ST elevation, ST depression, or new T wave inversions. ECG should be repeated at predetermined intervals or if symptoms return.

Cardiac troponin is the cardiac biomarker of choice. Troponin is more specific and more sensitive than other biomarkers and becomes elevated relatively early in the disease process. While contemporary cardiac troponin may not be elevated within the first 2 to 4 hours after symptom onset, newer high sensitivity troponin assays have detectable elevations much earlier. It is also true that the amount of troponin released, and therefore the time to elevation, is proportional with infarct size, so it is unlikely to have a negative initial troponin with larger infarcts. Regardless of infarct size, most patients with true ischemia will have elevations in troponin within 6 hours, and negative troponins at this point effectively rule out infarct in most patients.  Most assays use a cutoff value of greater than a 99th percentile as a positive test. In older, contemporary troponin assays, no detectable troponin is reported in most healthy individuals without the disease.  Newer high sensitivity troponin assays often will report a normal detectable range in healthy individuals without the disease. 

Several tools and scores have been developed to assist in the workup of ACS. These tools must be used with caution and in the appropriate context as none have been definitively shown to be superior to clinician judgment. Some common tools available are the TIMI (Thrombolysis In Myocardial Infarction) risk score, the GRACE (Global Registry of Acute Coronary Events) risk score, the Sanchis score, the Vancouver rule, HEART (History, ECG, Age, Risk Factors, and Troponin) score, HEARTS3 score, and Hess prediction rule. The HEART score was specifically developed for emergency department patients and has gained popularity in this setting. 

Diagnosis 

NSTEMI is diagnosed in patients determined to have symptoms consistent with ACS and troponin elevation but without ECG changes consistent with STEMI. Unstable angina and NSTEMI differ primarily in the presence or absence of detectable troponin leak. 

Treatment / Management

Initial management strategies aim to reduce cardiac ischemia and prevent death. Oxygen, aspirin, and nitrates are administered based on initial concern for ACS and prior to a definitive diagnosis. Subsequent treatment depends on confirmation of diagnosis or a high index of suspicion with or without a definitive diagnosis. [1][9][10][11][12](B2)

Oxygen was previously recommended for all patients presenting with concern for ACS, but newer data suggests this strategy may be harmful in patients who otherwise do not warrant supplemental oxygen. Supplemental oxygen is now recommended in patients with oxygen saturation less than 90%, those with respiratory distress, or when high-risk features of hypoxemia are present. 

Chewable, non-coated, aspirin 324 mg should be given to all patients who present with concern for ACS unless otherwise contraindicated.  Patients who cannot take aspirin may be given prasugrel 60 mg PO.

Patients with ongoing symptoms should receive 0.4 mg sublingual nitroglycerin every 5 minutes for up to three doses or until the pain is relieved, unless otherwise contraindicated. Contraindications include the recent use of phosphodiesterase inhibitors and hypotension. Nitrates should be used with extreme caution in patients with concerns for right-sided infarction. Continuous intravenous nitroglycerin should be considered in patients with persistent signs of heart failure or hypertension.

Many patients will present with concern for ACS but will not have positive findings of ischemic ECG changes or positive troponin on initial workup. These patients may be observed with serial ECG and troponin measurements every 3 to 6 hours. Patients also may undergo provocative testing such as the treadmill stress test or myocardial perfusion imaging prior to discharge or within 72 hours. Low-risk patients often may be discharged with a referral for further outpatient testing after initial ACS is ruled out.

In patients where NSTEMI has been definitively diagnosed or is highly likely, anticoagulation should be initiated. Protocols will vary by institution, so cardiology consultation should be obtained if readily available. This is especially true when there is the possibility of percutaneous intervention, as this may change anticoagulation strategies. Unfractionated heparin with bolus dosing and a continuous infusion is commonly used, with most institutions having protocols available. Other strategies may include the use of enoxaparin, bivalirudin, fondaparinux, and dual antiplatelet therapies. Fibrinolytic therapies should not be used in NSTEMI. 

When NSTEMI has been diagnosed, patients should be admitted to cardiac care units for further management. Beta-blocker therapy should be started within 24 hours after the presentation in patients who do not have a contraindication. Contraindications include signs of heart failure, hypotension, heart conduction block, or reactive airway disease. Unless otherwise contraindicated, ACE Inhibitors should be initiated in patients with an ejection fraction less than 40%, hypertension, diabetes, or chronic kidney disease. High-dose statins should be initiated for cholesterol management. Invasive and non-invasive testing strategies are employed. Both early intervention strategies with diagnostic angiography and intervention are applied as indicated, and conservative medical management strategies are employed. The rationale for choosing one strategy over the other is often patient and institution-specific and beyond the scope of this review.

Differential Diagnosis

Clinical conditions that can present with chest pain and have nonspecific ECG changes with an elevated troponin marker include:

• Myocarditis
• Pericarditis
• Pulmonary embolism
• Left ventricular aneurysm
• Prinzmetal angina
• Anxiety Disorder
• Aortic Stenosis
• Hypertensive emergency

Prognosis

Patients who present with NSTEMI have a lower 6-month mortality rate than those who present with unstable angina. Morbidity and mortality further depend on the degree of troponin elevation as well as comorbid conditions such as the severity of diabetes, presence of peripheral vascular disease, presence of renal dysfunction, and dementia.[13]

Complications

Complications of NSTEMI are secondary to the systemic effects of the disease rather than structural complications of STEMI. Cardiomyopathy with diffuse hypokinesis may be seen but left ventricular aneurysms or papillary muscle dysfunction is rare. Pulmonary edema due to poor cardiac output may be seen in severe cases. Other complications of poor cardiac output such as renal dysfunction may be seen as well.[14]