Acute coronary syndrome (ACS) Causes, Symptoms and Management

Definition and overview

Acute coronary syndrome (ACS) is a term that describes a range of conditions related to sudden, reduced blood flow to the heart, that result in myocardial ischemia with or without infarction. 

What is Acute Coronary Syndrome (ACS)?

Acute coronary syndrome (ACS) is a clinical manifestation of rupture of atherosclerotic plaques and obstruction of a coronary artery, often causing severe chest pain or discomfort. It is a medical emergency that needs a diagnosis and care right away.

Term generally refers to unstable angina, NSTEMI, or STEMI

Causes of Acute Coronary Syndrome

1. Rupture of an atherosclerotic plaque (The prototypical and most common mechanism of ACS) 
2. Stent thrombosis (Consider this etiology in patients who recently underwent primary coronary intervention). Stent thrombosis is largely an early complication of bare metal stents (within 30 days); it tends to be a late complication of drug-eluting stents (after several years).
   
3. Coronary artery embolism. Atrial fibrillation is the most common risk factor for coronary artery embolism. 
   
4. Coronary artery vasospasm, including Prinzmetal’s (ie, variant) angina. Coronary artery vasospasm is more likely to result in myocardial infarction in patients with underlying CAD.
5. Coronary artery dissection (Consider this etiology in pregnant women who present with ACS) - The majority of coronary artery dissections occur in women. Among them, onethird of cases occur in the peripartum period. 

Clinical features of Acute coronary syndrome (ACS) 

• Acute coronary syndrome (ACS) pain is usually substernal chest pain/discomfort lasting longer than 15 minutes with little relief from nitroglycerin. 
• Sharp or stabbing pain lasting seconds located to the extreme sides of the chest (right or left) is less likely to be associated with an ACS.
•  In ACS the pain often radiates down the left arm and shoulder, neck, and jaw. And is usually associated with symptoms as N/V, Diaphoresis, Dizziness, Dyspnea, Palpitations.

Sensory nerves from the heart enter the spinal cord at levels C7–T4, causing diffuse referred pain/discomfort in the associated dermatomes.

Who are Most ssusceptible to have “Silent” Acute myocardial infarction? 

The combination of substernal chest pain persisting for longer than 30 minutes and diaphoresis strongly suggests acute MI.

“Silent” AMIs occur in ~15% of cases. Its most common Seen in: 

• Elderly, Diabetic neuropathy, Patient under anesthesia or coma, transplanted heart. 
• May also occur in people who have a high pain threshold.
  

Atypical symptoms are more likely in women, the elderly, and diabetic patients.

What is the Markers for ischemia/infarction on ECG?

1. Peaked T waves: Tall (hyperacute) in the first few minutes after vessel occlusion (the earliest change); Occur very early and may be missed.
2. ST-segment elevation: indicates transmural injury and can be diagnostic of an acute infarct 
3. Q waves (specific): pathological Q waves occur, representing significant myocardial necrosis & replacement by scar tissue; Q waves are usually seen late; typically not seen acutely (indicates old MI). 
4. T-wave inversion: representing sever ischemia (sensitive but not specific) 
5. ST-segment depression: Subendocardial injury

ST-segment elevation or diagnostic Q waves in contiguous leads are more specific than ST-segment depression in localizing the region of myocardial ischemia or infarction.

Unstable angina (UA) & Non–ST-elevation myocardial infarction (NSTEMI) 

Definition and overview

• UA and NSTEMI are subtypes of ACS, but can be differentiated based on the degree of mycoardial injury, reflected by the presence of serum biomarkers (eg, troponin).
• Unstable angina (UA) is considered an intermediate syndrome between stable angina & MI, that occurs when blood flow to the heart decreases. It takes place when the coronary artery is occluded > 90%.
• While Non–ST-elevation myocardial infarction (NSTEMI) is considered an ischemic necrosis limited to 1/3rd of ventricular wall, that caused by Near total Occlusion of the supplying vessel (Subendocardial infarction)
  
• UA/NSTEMI can be caused by a reduction in oxygen supply and/or by an increase in myocardial oxygen demand (tachycardia or severe anemia) superimposed on a coronary obstruction.
  
• Prognosis: 15% of patients with UA/ NSTEMI progress (STEMI or Death), & 1/3 will suffer recurrence of severe ischemic pain within next 6 months of event.
  

The Pathophysiologic processes of UA?

The most common mechanism leading to UA are plaque rupture or erosion with superimposed nonocclusive thrombus 

Other: 

1. Dynamic obstruction [coronary spasm, as in Prinzmetal’s variant angina).
2. Progressive mechanical obstruction (rapidly advancing coronary atherosclerosis or restenosis following percutaneous coronary intervention (PCI))
3. Secondary UA related to increased myocardial oxygen demand and/or decreased supply (anemia).

More than one of these processes may be involved in many patients.

How UA & NSTEMI is diagnosed?

Investigations

• ECG: The classic findings on include: ST segment depression & /or New T wave inversion. Both unstable angina and NSTEMI lack ST-segment elevations and pathologic Q waves.
• Stress testing only detects flow-limiting high-grade lesions. Thus, can still have MI despite negative stress test because mechanism of MI is acute plaque rupture onto a moderate lesion.

Patients with unstable angina have a higher risk of adverse events during stress testing. These patients should be stabilized with medical management before stress testing or should undergo cardiac catheterization initially.

• The distinction between unstable angina and NSTEMI is based entirely on cardiac enzymes. Unlike UA, NSTEMI is associated with elevated serum troponin.

In one third of the patients, angina may be associated with slightly elevation of troponin.

Diagnosis 

• The diagnosis of UA relies mostly upon the clinical history; electrocardiographic features of ischemia may or may not be present.
• The diagnosis of NSTEMI is established if a patient with the clinical features of UA develops evidence of myocardial necrosis, as reflected in elevated cardiac biomarkers.

Coronary artery spasm (Variant angina) Or  Prinzmetal's angina.

1. Definition: Episodes of angina occur at rest and are associated with ventricular arrhythmias, some of which may be life threatening. 
2. Features: It's Involves transient coronary vasospasm that usually is accompanied by a fixed atherosclerotic lesion but can also occur in normal coronary arteries.
   
3. C/F: The angina classically occurs at night.
   
4. ECG: Hallmark is transient ST-segment elevation (not depression) on ECG during chest pain, which represents transmural ischemia.
   
5. Diagnosis: Coronary angiography is a definitive test—displays coronary vasospasm when the patient is given IV ergonovine or acetylcholine (to provoke vasoconstriction).
   
6. Treatment: Long acting nitrates and calcium antagonists (Not b-blockers, may ↑ coronary spasm). 
   
7. Prognosis: Myocardial infarction and death may occur in 15% of cases/year 

ST-elevation myocardial infarction (STEMI)?

Definition and overview 

STEMI: It's an ischemic necrosis involves full thickness of ventricular wall (Transmural MI), that caused by total occlusion for > 30min of the supplying vessel

ECG change that occur in STEMI: 

• ST segment elevation; New Q waves develop in an ECG. 
• An early ECG manifestation of STEMI can be the presence of hyperacute (ie, broad-based, tall, symmetrical) T-waves in at least 2 contiguous leads.
  
• Transient Q waves may also be observed in acute myocardial ischemia.
  
• ECG May show evidence of previous Ml (Q waves are consistent with a prior MI)
  
• If there is repeat ST-segment elevation on ECG within the first 24 hours after infarction, suspect recurrent infarction or LV aneurysm

It is important to recognize that ST-segment elevation can occur as a result of conditions other than myocardial infarction (eg, acute pericarditis).

What is Cardiac enzymes that is Elevated in STEMI?

All cardiac enzyme Elevated in ST-elevation myocardial infarction (STEMI) includes:  

1) Troponin T and Troponin I: Obtain serum levels of either troponin T or troponin I on admission, and again every 6 hours for 18 to 24 hours.

• They are very specific for MI, Troponin I is more important than troponin T.
• Starts to rise at 4-6 hours, peaks at 12-24 hours and falls to normal within 7-10 days (Troponin I), 10 14 days (troponin T)
  
• These enzymes cannot be used for diagnosis of reinfarction because their levels remain elevated for along time from the first attack.
  

Troponin I can be falsely elevated in patients with renal failure; thus following trend of levels is important.

2) Creatine kinase (CK): Levels of total CK and CK-MB should be measured on admission and every 8 hours thereafter for 24 hours.

• When measured within 24 to 36 hours of onset of chest pain, has greater than 95% sensitivity and specificity.
• CK starts to rise at 4-6 hours, peaks at 12 hrs. and falls to normal within 2-3 days. 
  
• This is the enzyme of choice for diagnosing reinfarction. 
  

Any absence of elevation of CK-MB in the first-two days excludes the diagnosis of MI.

3) Myoglobin: It is the earliest enzyme to increase after MI, starts to rise at 1-2 hours, peaks at 6-8 hours and falls to normal within 1-2 days

4) LDH: Normally, serum LDH2 is greater than LDH1 but in MI, LDH1 is more than LDH2. This is called “flipping of LDH ratio”. Starts to rise at 24-48 hours, peaks at 72 hours and falls to normal within 8 – 10 days.

What is Complications of STEMI AMIs? 

1) Pump failure (CHF): It's the most common cause of in-hospital mortality, Usually occurs within the first 24 hours.

2) Stroke: Patients who suffer an acute MI have a high risk of stroke during the next 5 years.

3) Cardiogenic shock (Seen in ~7% of cases)

4) Acute pericarditis: This is particularly common on the second and third days following infarction. 

5) Arrhythmias: Nearly all patients with acute MI have some form of arrhythmia

• Ventricular fibrillation is the most common arrhythmia within one hour whereas supraventricular tachycardia is the most common arrhythmia after one hour of MI.
• Most common cause of death in the first few days after MI is ventricular arrhythmia (either VT or VFib).
• AV block: Occurs in 5% of inferior AMIs, Occurs in 3% of anterior AMIs

6) Sudden cardiac death (SCD): unexpected death from cardiac causes in persons without symptomatic heart disease or within 1 hour after the onset of symptoms 

• It is most commonly due to ventricular fibrillation.
• Most frequently occurs in the morning hours (8 am to 11 am) and late afternoon to evening hours (pm to 7 pm). 
• Approximately 70% of sudden natural deaths have a cardiac cause, and 80% of those are attributable to CIHD. 

7) Ventricular pseudoaneurysms tend to become a free wall rupture

8) Ventricular aneurysm: Associated with a high incidence of ventricular arrhythmias,  rarely rupture (in contrast to pseudoaneurysms)

9) Myocardial Rupture: It is most frequent 3 to 7 days after MI,  Usually leads to hemopericardium and cardiac tamponade

• Rupture of ventricular free wall is the most common cardiac rupture syndrome
• The anterolateral wall at the midventricular level is the most common site for postinfarction free wall rupture. 

10) Dressler syndrome: It is an autoimmune disorder that occurs weeks to months after the infarct. Which autoantibodies are directed against the damaged pericardial antigens 

• It's characterised by persistent fever, pericarditis and pleurisy. 
• Aspirin is the most effective therapy. Severe symptoms may require treatment with an NSAID or corticosteroids.

Treatment & Monitoring For Patient with ACS 

Cardiac Monitoring for a Patient With an Acute MI

1. BP and HR: HTN increases afterload and thus oxygen demand, whereas hypotension reduces coronary and tissue perfusion. Both nitrates and morphine can cause hypotension.
2. Rhythm strip with continuous cardiac monitor: Watch for dysrhythmias. Note that PVCs can lower stroke volume and coronary artery filling time. A high frequency of PVCs may predict VFib or VT. 
   
3. Auscultate the heart (third and fourth heart sounds, friction rub, and so on) and lungs (crackles may indicate LV failure, pulmonary edema). 
   
4. Hemodynamic monitoring (CVP, PCWP, SVR, cardiac index [CI]) with a pulmonary artery catheter is indicated if the patient is hemodynamically unstable. Monitoring is helpful in assessing the need for IV fluids and/or vasopressors.
   
5. Cardiac enzymes are drawn serially—once on admission and every 6 hours until three samples are obtained. The higher the peak and the longer enzyme levels remain elevated, the more severe the myocardial injury and the worse the prognosis.

Remember that patients can have a recurrent infarction on same hospital admission. CK-MB is the most helpful laboratory test to detect this if patient develops recurrent chest pain. 

Medical therapy for  pt. With ACS

All pts with suspected ACS should be placed on a monitor and begin immediate medical therapy with: 

1. Admit patient to a cardiac monitored floor (CCU) and establish IV access.
2. Oxygen inhalation: May limit ischemic myocardial injury in hypoxic patients. Does not improve mortality in patients with normal oxygen saturation. 
   
3. IV fluids: in a case of hypotension. 
   
4. Aspirin: is now considered an essential element (325 mg initial dose chewed, then 75 mg daily-oral) 
5. Antiplatelet agent reduces coronary reocclusion by inhibiting platelet aggregation on top of the thrombus Has been shown to reduce mortality and should be part of long-term maintenance therapy
6. P2Y12 inhibitors (clopidogrel, ticagrelor): Used in conjunction with aspirin; have been shown to reduce recurrent MI 
   
7. Subcutaneous Heparin: "Initiate in all patients with MI; prevents progression of thrombus
   
8. β-Blockers: Block stimulation of HR and contractility --> decrease myocardial O2 consumption, relive pain and limit infarct size, and decrease arrhythmias so it reduces mortality. 
   
9. Analgesics for pain (Morphine 5-10 mg IV)
   
10. Consider revascularization for pts who still have symptoms despite maximum medical therapy, in post-MI or unstable angina pts with evidence of ischemia despite symptom control
11. If CAD is severe (e.g., left main or three-vessel disease, or two-vessel disease with concurrent DM), refer patient for surgical revascularization (CABG).

Heparin is used for unstable angina and MI (both NSTEMI and STEMI). It is NOT used for stable angina.

After the acute treatment 

1) Continue aspirin (or other antiplatelet therapy), β-blockers (metoprolol), nitrates, and statin therapy

2) Reduce risk factors

1. Smoking cessation, weight loss 
2. Treat diabetes, HTN 
3. Treat hyperlipidemia—patients with any form of CAD should be started on an HMG-CoA reductase inhibitor regardless of LDL level. Clinical trials of statins have shown the efficacy of such therapy for secondary prevention in CAD (see Quick Hit on CARE trial)

The CARE trial: Patients with prior history of MI were randomized to treatment with statins or placebo. The statin group had a reduced risk of death (by 24%), a reduced risk of stroke (by 31%), and a reduction in need for CABG or coronary angioplasty (by 27%).

Medications commonly use in ACS 

1) β-Blockers (first-line agents): Metoprolol (25 to 400 mg daily [succinate] or divided BID [tartrate]) or carvedilol (3.125 to 25 mg BID).

• B-blocking drug should not be withdrawn sudden because this may have, A rebound effect and precipitate dangerous arrhythmias, worsening angina or MI.

2) Nitrates: Sublingual nitroglycerin (0.4 mg every 5 minutes for 2 to 3 doses) may be used for acute anginal episodes.

• Long-acting nitrates such as isosorbide mononitrate (30 to 240 mg daily [extended release]) can be used for angina prophylaxis.
• Nitrate tolerance develops --> If they are given throughout the 24 h, so a "nitrate free" period of 6-8 hours is needed.
  
• Nitrates have no effects on mortality in this disease, only on the symptoms. 
• NB: Contraindicated with concomitant PDE5 inhibitor use

3) CCBs (third-line agents): Similar effectiveness to β-blockers; may be used instead of, or in addition to βblockers.

• Only long-acting CCBs should be used: Nifedipine (30 to 90 mg/day), amlodipine (5 to 10 mg/day), or felodipine (2.5 to 10 mg/day) 
• Dihydropyridine calcium antagonists such as (nifedipine & nicardipine) because they can act on peripheral blood vessel in addition to their action on the heart they often cause a reflex tachycardia, so use these drugs in combination with a B-blocker. BUT (verapamil) and diltiazem are particularly suitable for patients who are not Receiving a B-blocker, because they act selectively on the heart.
  

CCBs is the first-line therapy in pts with Prinzmetal’s angina or coronary vasospasm.

4) Lipid-lowering agents: Atorvastatin (20 to 80 mg/day) and rosuvastatin (10 to 40 mg/day) are highintensity statins.

5) Antiplatelets: Aspirin (75 to 162 mg/day) decreases risk of first MI and reduces adverse cardiovascular events in those with stable angina. Clopidogrel (75 mg/day) may be used in patients with contraindications to aspirin.

6) ACEIs such as lisinopril (5 to 40 mg/day) and enalapril (2.5 to 20.0 mg BID) have been shown to reduce both cardiovascular death and MI in patients with CAD and left ventricular systolic dysfunction.

In MI, aspirin, ticagrelor, β-blockers, and ACE inhibitors are the only agents shown to reduce mortality.

Revascularization 

Revascularization options in ACS include: Thrombolysis, PCI, or CABG

• Benefit highest when performed early (within 90 minutes of hospital arrival for patients with STEMI or new LBBB). Should be considered in all patients.
• All patients initially treated conservatively (i.e., without revascularization) for UA/NSTEMI should have a stress test before leaving the hospital to determine the need for angiography (which in turn determines the need for angioplasty or CABG).

Thrombolytic Therapy (Streptokinase, Urokinase, Alteplase): Administer as soon as possible up to 24 hours after the onset of chest pain. outcome is best if given within the first 6 hours. 

• The main reason to initiate therapy with thrombolytics/angioplasty is whether there is ST segment elevation on ECG.
• It is useful for patients with a delayed presentation, and for those in whom PCI is contraindicated.
  

Absolute Contraindications to Thrombolytic Therapy 

1. Trauma: Recent head trauma or traumatic CPR 
2. Major surgery within past 2 weeks.
3. Previous stroke 
4. Recent cerebral hemorrhage within past 12 months.
   
5. Active bleeding or bleeding diathesis 
   
6. Sever hypertension. 
   
7. Diabetic retinopathy with recent bleed. 
   
8. Aortic dissection. 
   
9. Pericarditis.

Percutaneous coronary intervention (PCI): Consists of both coronary angioplasty with a balloon and stenting. 

• It’s the treatment of choice-if readily available, also indicated in patients in which thrombolytic therapy is contraindicated, or fails.
• Aspirin + potent antiplatelet as clapidogrel or glycoprotein (IIb/IIIa) receptor antagonists shown to improve the outcome of PCI
  
• Restenosis is a significant problem (up to 40% within first 6 months); however, if there is no evidence of restenosis at 6 months, it usually does not occur.
  
• If catheterization cannot be performed immediately, initiate thrombolytic therapy with streptokinase or tissue plasminogen activator.

Coronary artery bypass graft (CABG): Arterial graft (usually using internal-mammary artery) is superior to venous grafts (usually grater saphenous-vein).

• It remains the procedure of choice in patients with severe multivessel disease and complex coronary anatomy.
• Less often used than the other two in the acute setting. 
  
• It is almost never performed in the acute setting on a stable patient. 
  
• Urgent/emergent CABG is typically performed only in the setting of mechanical complications of an acute MI, (cardiogenic shock, life-threatening ventricular arrhythmias), or after failure of PCI.