Cardiology

Acute Coronary Syndromes Management: In-Hospital Treatment Considerations

I. Acute Coronary Syndrome: What every physician needs to know.

An acute coronary syndrome (ACS) is a constellation of symptoms and signs that result from obstruction of the coronary arteries. Common signs and symptoms include chest pain, dyspnea, and electrocardiographic abnormalities. The most common cause of acute coronary syndrome is blockage of the coronary artery from cholesterol rich plaque and thrombus.

In acute coronary syndrome, a previously quiescent plaque has ruptured, exposing the lipid core, inciting platelet activation and aggregation with subsequent thrombus formation. When the atherothrombotic material is totally occlusive with complete cessation of blood flow through the artery, the acute coronary syndrome is termed ST-Elevation myocardial infarction (STEMI).

If the occlusion is partially obstructive and there is no evidence of myocardial injury (e.g., elevated cardiac troponin), the ACS is termed unstable angina, but if cardiac injury is detected with a partial obstruction, then the term to describe the ACS is non-ST segment myocardial infarction (NSTEMI). ACS unrelated to plaque rupture can infrequently be seen from coronary vasospasm, embolization, or spontaneous coronary dissection.

II. Diagnostic Confirmation: Are you sure your patient has Acute Coronary Syndrome?

The diagnosis of ACS is based on finding a history compatible with active, obstructive coronary disease and supportive evidence based on ST segment deviation on ECG and evaluation of cardiac biomarkers (e.g., cardiac troponin, creatine kinase) suggestive of myocardial infarction.

A. History Part I: Pattern Recognition:

Typical patients with ACS will describe chest pain that is often located at the sternum and can be described as an ache or pressure. The textbook description is "an elephant sitting on my chest' with the patient's fist clenched over the sternum (classically referred to as the Levine's sign).

The chest symptoms classically last more than 20 minutes and may have increased in intensity, frequency, or duration recently. There may be radiation to the neck, jaw, back, or arms. There may be associated dyspnea, diaphoresis, and nausea.

If significant myocardial pump dysfunction is present, the patient may report orthopnea or paroxysmal nocturnal dyspnea. It should be noted that these "typical features" are helpful if present but the absence does not exclude ACS. The symptoms may be localized to the epigastrium or there may be no chest symptoms at all. In fact, some or all of these findings may be absent, especially among elderly patients, women, and those with psychiatric disorders.

The five most important factors from the initial history in the order of importance are (1) the nature of the anginal symptoms, (2) prior history of coronary artery disease (CAD), (3) sex, (4) age, and (5) the number of traditional risk factors present. For those with suspected ACS with prior history of heart disease, advanced age seems to be the most important risk factor (>55 years for males and >65 years for females).

B. History Part 2: Prevalence:

Acute coronary syndromes account for over 2.4 million discharges per year in the U.S. About 500,000 of these are for STEMI and the remainder are for NSTEMI or unstable angina.

The risk factors for coronary artery disease increase the risk for ACS. These include hypertension, hypercholesterolemia, diabetes, smoking, advanced age, and a family history of premature coronary artery disease.

These risk factors increase the risk for underlying atherosclerosis, the substrate for ACS. Several triggers for ACS have been implicated including: anxiety, emotional stress, strenuous exercise, influenza infection, and extreme physiologic stress due to concomitant medical or surgical illness.

C. History Part 3: Competing diagnoses that can mimic Acute Coronary Syndrome.

While the character of symptoms is often different from ACS, aortic dissection, pulmonary embolism, and pericarditis, with or without cardiac tamponade, should be considered. At times, pneumonia, pneumothorax, cholecystitis, peptic ulcer disease, and herpes zoster may be confused with ACS.

D. Physical Examination Findings.

The physical examination related to ACS is often nonspecific, but the complications associated with infarction and cardiac pump dysfunction may be manifest as tachycardia, bradycardia, hypotension, elevated jugular venous pressure, wheezes, crackles, or hepatomegaly. The heart examination may reveal right ventricular heave, sustained LV impulse, the presence of S3 and/or S4 as well as mitral regurgitation.

Aortic regurgitation may suggest an aortic dissection. Diminished heart sounds raise the possibility of a pericardial effusion and/or tamponade physiology. Pulses should be examined as they may be asymmetric or exhibit bruits if there is preexisting vascular disease or if there is an aortic dissection, or if pulses are either diminished and delayed as seen in some cases of severe aortic stenosis.

E. What diagnostic tests should be performed?

A 12-lead ECG should be obtained and interpreted within 10 minutes of hospital triage, if not obtained by emergency medical services (EMS). A chest x-ray should be obtained if pneumonia or aortic dissection is suspected. If STEMI has been diagnosed, chest x-ray and laboratory results should not delay implementation of reperfusion therapy.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Cardiac specific troponin is the preferred biomarker to diagnose myocardial injury; however, these may be initially negative in STEMI patients presenting early and some NSTEMI patients.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A 12-lead electrocardiogram should be obtained and interpreted within 10 minutes of presentation. While imaging studies, such as stress testing with echocardiographic or nuclear imaging and coronary angiography, are used to assess risk during ACS, these studies are not used to make a diagnosis of ACS.

III. Management.

Management of ACS is determined by the patient's risk. In the case of ACS, to complete coronary occlusion, STEMI, the goal is for immediate revascularization to salvage myocardium. For NSTEMI and unstable angina (UA), treatment is to mitigate the changes of recurrent infarction and/or to reduce the size of infarction.

Medical therapy is guided by the degree of patient risk for ischemic complications and balanced against the risk for bleeding or other complications from these treatments. If the patient is diagnosed with STEMI, the decision must be made as to whether fibrinolysis will be administered, primary percutaneous coronary intervention (PPCI) will be performed, or whether the patient will be transferred for primary PCI.

Determination of PPCI vs. fibrinolysis for STEMI

If PCI can be performed by skilled personnel in a timely fashion, door to balloon time <90 minutes, this is the preferable strategy for STEMI. If the patient is at a hospital where PCI is not performed, it is advisable to administer fibrinolysis if the delay related for transfer for PCI will exceed 60 minutes or if the total door to balloon time will exceed 120 minutes.

If transfer can be arranged rapidly and PCI can be performed within 120 minutes from initial presentation, the patient can be transferred to the PCI capable hospital. It is advisable to transfer the patient to a PCI capable hospital routinely after administration of fibrinolysis in case the medication does not work or if there is recurrent infarction.

A. Immediate management.

As mentioned previously, the management of STEMI is emergent revascularization with fibrinolysis or preferably PPCI. Aspirin and unfractionated heparin or bivalirudin should be administered. Clopidogrel, ticagrelor, or prasugrel can be administered in addition to aspirin for STEMI.

Early risk stratification is of paramount importance for patients presenting with NSTEMI/UA. Risk stratification tools, including the TIMI Risk Score for UA/NSTEMI and the GRACE risk score to help divide patients into low- or high-risk categories.

Immediate management involves administration of oxygen and placement of IV access. Aspirin (162 to 325 mg) is administered orally or rectally. Analgesia with morphine may be administered while blood pressure and oxygenation are monitored. If possible, the patient should chew the aspirin to enhance absorption.

An antithrombin should be selected for patients who are not low risk. Unfractionated heparin may be administered (50 units/kg up to maximum of 4000 units). Low molecular weight heparins (LMWH) have the advantage of fixed dosing that does not require monitoring, but should be avoided in patients who will be going on to coronary artery bypass grafting (CABG) surgery and in those with renal failure. Fondaparinux can be administered to patients who will be managed medically. Bivalirudin can be administered instead of UFH or LMWH.

Additional antiplatelet therapy should be administered to high-risk individuals with NSTEMI. A loading dose of clopidogrel or ticagrelor can be administered in the emergency department for NSTEMI. Prasugrel should be administered in the catheterization laboratory if the patient requires PCI and clopidogrel or ticagrelor have not already been administered.

Glycoprotein IIb/IIIa receptor antagonists are administered for high-risk individuals.

Oral beta-blocker therapy should be administered within 24 hours of presentation unless there are signs of heart failure, there is evidence of a low output state, increased risk for cardiogenic shock, or other contraindications to therapy.

An oral angiotensin converting-enzyme inhibitor (ACE-I) should be administered to those with left ventricular ejection fraction of ≤ 40%, without hypotension as defined by SBP <100 mm Hg or SBP >30 mm Hg below baseline, or shock, history of bilateral renal artery stenosis, or prior known allergy to ACEI. An angiotensin receptor blocker (ARB) may be used instead of an ACE-I if the patient is intolerant due to allergy or cough.

Invasive therapy, cardiac catheterization, should be performed in patients whose procedural risk is not prohibitive, if that patient's risk is not low. The angiogram allows for determination of whether medical therapy, CABG surgery, or PCI is the preferred management.

For patients initially selected for conservative therapy, recurrent symptoms, hemodynamic instability, or the development of heart failure, should prompt coronary angiography. Angiography is usually performed on an urgent basis (within 48 to 72 hours) but should be performed sooner for those with symptoms refractory to medical therapy or in those who develop hemodynamic instability.

Low-risk individuals should have a serial biomarker measurement. If these become elevated, an coronary angiography should be considered. For low-risk individuals whose biomarkers remain normal, further risk stratification can occur with stress testing.

Pharmacologic testing can be used for those who cannot exercise. Imaging (echocardiography or nuclear imaging) should be added to the exercise ECG testing if the 12-Lead ECG exhibits ST segment abnormality or left bundle branch block.

B. Physical Examination Tips to Guide Management.

The patient should be monitored for the development of mechanical complications of infarction. The development of signs of congestion (S3, crackles, elevated JVP) or a new murmur should prompt further work-up and aggressive therapy. Patients with signs of confusion and lethargy may be developing cardiac insufficiency and this should be considered even if narcotics for pain have been administered.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Complete blood count evaluating for anemia, leukocytosis, thrombocytosis, or thrombocytopenia should be obtained at baseline. Serum chemistries evaluating glucose, potassium, magnesium, bicarbonate, and renal function should be obtained at baseline for management of ACS.

A lipid profile should be obtained, and for those with elevated blood glucose, glycated hemoglobin should be measured. Stool guaiac is often obtained to screen for occult blood. Serum creatinine, platelet count, and hemoglobin are monitored to assess for contrast-induced nephropathy, or bleeding complications or thrombocytopenia associated with anticoagulant, antiplatelet therapy, or procedures.

D. Long-term management.

Long-term management includes use of medications shown to be beneficial in the secondary prevention of atherosclerotic disease and congestive heart failure. These include reduction of blood pressure with a goal of 130/80 mm Hg and cholesterol reduction with an LDL cholesterol goal of <70 mg/dl.

Patients should receive dual antiplatelet therapy with aspirin (75 mg to 100 mg QD) and either clopidogrel, ticagrelor, or prasugrel. The choice of the agent added to aspirin is somewhat dependent on the management strategy pursued in hospital and the optimal agent is a matter of debate.

The duration of dual antiplatelet therapy is suggested by societal guidelines to be 12 months regardless of whether the patient was managed with medical therapy alone or revascularization using PCI or CABG surgery for ACS. Beta-blockers and ACE inhibitors are used particularly in those patients who are hypertensive or whose ejection fraction is reduced. The goal for glycated hemoglobin for diabetic patients is <7.0%. Patients should receive smoking cessation counseling and referral to cardiac rehabilitation.

E. Common Pitfalls and Side-Effects of Management

Cardiac specific troponin elevation may occur in situations besides ACS. Elevated cardiac biomarkers can occur in the setting of profound demand ischemia during noncardiac illness, and ACS should be diagnosed, and anticoagulant and invasive therapies implemented with caution in these settings.

Nitrates should be avoided in those who have received phosphodiesterase III inhibitors for erectile dysfunction within 48 hours or those with SBP <90 mM Hg or >30 mm Hg below baseline and in those with a heart rate (HR) <50 beats/min or >100 beats/min in the absence of heart failure or right ventricular infarction.

Prasugrel should not be administered to patients with prior transient ischemic attack (TIA) or stroke, and a lower dose should be considered for those <60 Kg or >75 years of age. Prasugrel should be held for 7 days prior to CABG; ticagrelor and clopidogrel should be held for 5 days prior to CABG, if possible.

Abciximab should not be used for those who will not be undergoing PCI. Glycoprotein IIb/IIIa receptor antagonists can cause thrombocytopenia and unfractionated heparin can cause the heparin induced thrombocytopenic (HIT) syndrome. Eptifibatide, tirofiban, and enoxaparin should be dose adjusted for renal insufficiency.

Intravenous beta-blockers given during the first 24 hours of ACS may be associated with adverse outcomes and should be reserved for those who are hypertensive and with ongoing symptoms. NSAIDS apart from aspirin and steroids should be avoided in ACS.

Nitroglycerine 0.4 mg sublingually every 5 minutes up to 3 times. If chest pain persists, then 5 to 10 mcg/min titrating up 10 mcg/min every 10 minutes until chest pain free or SBP <100 mm Hg.

  • Morphine 1 to 5 mg IV, repeat as tolerated

  • Aspirin 162 to 325 mg orally or rectally initially, then 75 to 100 mg orally daily

  • Clopidogrel 300 to 600 mg orally once, then 75 mg daily; may consider 150 mg orally daily for first 7 days of ACS.

  • Prasugrel 60 mg orally once, then 10 mg orally daily; may use 5 mg orally daily for those <60 Kg or >75 years.

  • Ticagrelor 90 mg orally once, then 180 mg orally twice daily

  • Unfractionated heparin 50 U/kg IV up to 4,000 U, then 12 U/hr up to 1,000 U/hr IV

  • Fondaparinux 2.5 mg subcutaneously daily up to 8 days

Lovenox (UA/NSTEMI 1 mg/kg subcutaneously twice daily, dose adjust for GFR <30 cc/hr; STEMI 30 mg IV and 1 mg/kg subcutaneously twice daily if <75 years, if >=75 years, no bolus and 0.75 mg/kg subcutaneously twice daily if GFR <30 cc/min and <75 years then 30 mg IV and 1 mg/kg subcutaneously daily and if >=75 years no bolus and 1 mg/kg subcutaneously daily.

Bivalirudin 0.1 mg/kg IV bolus then 0.25 mg/kg/hr IV for NSTEMI/UA and for PCI 0.75 mg/kg IV bolus (0.5 mg/kg IV if already on therapy) then 1.75 mg/kg/hr for duration of procedure or 4 hours thereafter. Reduce infusion rate to 1 mg/kg/hr if GFR <30 cc/min.

  • Eptifibatide 180 mcg/kg IV twice followed by 2 mcg/kg/min IV; reduce to 1 mcg/kg/min if GFR is <50 cc/min

  • Tirofiban 0.4 mcg/kg/min for 30 minutes then 0.1 mcg/kg/min; 0.2 mcg/kg IV bolus and 0.05 mcg/kg/min for patients with GFR <30 cc/min

  • Abciximab 0.25 mg/kg IV bolus then 0.125 mcg/kg/min (up to 10 mg/min)

IV. Management with Co-Morbidities

Patients with impaired renal function, elderly patients, and women are at increased risk of bleeding complications from overdosing of medications and from invasive procedures. These patients should have close attention to dose adjustment, appropriate use of medications, and the appropriate use of invasive therapies.

Patients should also be counseled on the importance of dual antiplatelet therapy to prevent recurrent MI and to prevent stent thrombosis if a stent was implanted during PCI. Patients should be counseled regarding the the importance of lifestyle modification of risk factors as well as medical therapy for secondary prevention. In particular, patients with ACS should be counseled on smoking cessation and the importance of exercise in addition to compliance with diet and prescribed medical therapy to improve secondary prevention.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Patients with ACS are often started on multiple medications. Appropriate patient education regarding the utility of each of these medications, anticipated side effects, and dangers of discontinuation should be emphasized. Patients should be counseled regarding what types of symptoms require reevaluation and follow-up with a cardiologist. The patient should be referred for cardiac rehabilitation.

B. What's the Evidence for specific management and treatment recommendations?

"2011 ACCF/AHA Focused Update incorporated into the ACC/AHA 2007 guidelines for management of unstable angina/non-ST-elevation myocardial infarction". Circulation. vol. 123. 2011. pp. e426-e579.

"Primary and secondary prevention of cardiovascular disease: Antithrombotic therapy and management". Chest. vol. 41. 2012. pp. e637S-e668S.

Bavry, AA, Kumbhani, DJ, Rassi, AN. " Benefit of early invasive therapy in acute coronary syndromes: A meta-analysis of contemporary randomized clinical trials". J Am Coll Cardiol. vol. 48. 2006. pp. 1319-25.

C. DRG Codes and Expected Length of Stay.

DRG 303 Coronary Artery Disease with Unstable Angina

DRG 280 Acute MI discharged alive with major CC

DRG 281 Acute MI discharged alive with CC

DRG 282 Acute MI discharged alive without MCC/CC

DRG 283 Acute MI expired with major CC

DRG 284 Acute MI expired with CC

DRG 285 Acute MI expired without MCC/CC

Expected length of stay for uncomplicated ACS ranges from 1 day or longer depending upon the presence or absence of complications of therapy or the disorder.

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