CONTENTS

• Rapid Reference 🚀
• Limitations of this chapter
• Nomenclature & types of MI
• Diagnosis
  • DDx of MI
• EKG findings in MI
  • Anterior OMI
  • Inferior OMI
  • RV OMI (RVMI, including management)
  • Posterior OMI
  • High lateral OMI
  • OMI in LBBB or RV-pacing
  • OMI vs aneurysm
  • Hyperacute T-waves & de Winter pattern
  • Wellens patterns
  • Subendocardial ischemia patterns
• Risk stratification
• Management
  • General supportive care
  • Nitroglycerine
  • Beta-blocker
  • ACE inhibitor
  • PCI
  • Anticoagulation
    • Aspirin
    • P2Y12 inhibitors
      • Clopidogrel
      • Ticagrelor
    • Anticoagulation if no immediate PCI
• Approach to decompensation post-MI ➡️
• Podcast
• Questions & discussion
• Pitfalls

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rapid reference

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basics

• Aspirin load (4 x 81 mg non-enteric coated aspirin), then 81 mg enteric coated aspirin daily.
• Electrolytes: Target K>3.5 mM, Mg >2 mEq/L.
• Transfusion target: Hemoglobin >8 mg/dL.
• Atorvastatin 80 mg/day.
• Complete echocardiogram (STAT, if diagnosis is unclear or post-MI complications are a possibility).

indications for PCI 📖

• Indications for emergent PCI:
  • Occlusive MI (OMI).
  • Hemodynamic instability (shock or new/worsening heart failure).
  • Electrical instability (ventricular arrhythmia).
  • Recurrent or persistent chest pain refractory to medical therapy.
• ☎️ Consult cardiology if doubt exists regarding need/timing of PCI. Timing and selection of P2Y12 agents will be determined by cardiology.

anticoagulation 📖

• If going urgently for PCI: Heparin infusion.
• If future PCI is probable, but no definite plan for PCI:
  • 1st line = Fondaparinux 2.5 mg sq daily (unless GFR <20 ml/min).
  • 2nd line = Enoxaparin 1 mg/kg q12hr (unless GFR <30 ml/min or elevated risk of bleeding).
  • 3rd line = Heparin infusion.
• If there is no plan to pursue PCI, anticoagulation is not indicated.

P2Y12 inhibitor for non-PCI patients 📖

• Indications:
  • P2Y12 inhibitor is generally indicated.
  • Ticagrelor is preferred over clopidogrel (180 mg loading dose, then 90 mg BID).
• Contraindications:
  • Oral anticoagulation.
  • High risk for bleeding.
  • At risk for bradycardia (Clopidogrel can be substituted for ticagrelor if there is concern for bradycardia).

nitroglycerine 📖

• Indications:
  • Chest pain.
  • Hypertension.
  • Pulmonary edema.
• Contraindications:
  • Hypotension.
  • RV myocardial infarction.
  • Recent use of phosphodiesterase-5 inhibitors (e.g., sildenafil).

beta-blockers 📖

• Indications:
  • Early IV beta-blockers may be indicated for:
    • Hypertension.
    • Persistent chest pain.
    • Ventricular tachyarrhythmias.
  • Gradual initiation of oral beta-blockers are indicated within <24 hours if possible.
• Contraindications:
  • Bradycardia (heart rate <60 b/m).
  • Cardiogenic pulmonary edema.
  • Heart block:
    • PR interval >240 ms.
    • 2nd/3rd degree heart block.
  • Cardiogenic shock, or risk factors for developing shock, for example:
    • Heart rate >110 b/m.
    • SBP <120 mm.
    • Shock index (HR/SBP) >~0.8

ACE inhibitors / ARBs 📖

• Indications:
  • OMI patients with anterior MI, heart failure, or EF <40%.
  • Any MI with hypertension, heart failure, or EF <40%.
• Contraindications:
  • Renal dysfunction.
  • Hypotension.
  • Hyperkalemia.
• Generally initiate orally within 24 hours, followed by gradual uptitration.

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limitations of this chapter

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This chapter is intended as a guide to myocardial infarction for the general intensivist.  It is assumed that cardiology will be consulted in patients with more severe myocardial infarction (e.g., occlusive MI and more severe nonocclusive MI).  It is likewise assumed that cardiothoracic surgery will be consulted regarding patients who are potential candidates for CABG surgery.

Some information is provided regarding which patients may be candidates for cardiac catheterization and/or CABG surgery.  However, this is not a focus of the chapter, since in reality these decisions will be driven by cardiology and/or cardiothoracic surgery.  This chapter is not intended as a guide to determine who requires these therapies – when doubt exists, appropriate consultation should be immediately obtained.

Likewise, this chapter omits the use of thrombolysis for management of MI.  Although thrombolysis is appropriate in some contexts, this is rarely a treatment modality utilized in the ICU.  Furthermore, decisions regarding thrombolysis will be driven by cardiologists (rather than intensivists).

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nomenclature

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diagnosis of MI

• For general clinical purposes, an MI is defined as the following:(22923432)
  • (1) A dynamic rise and fall in troponin (with at least one value above the 99th percentile of normal).
  • (2) Ischemic symptoms <OR> ischemic EKG changes <OR> new wall-motion abnormality on echocardiography.
• Most troponin elevation in the ICU does not represent an MI. 📖
  • Troponin levels should not routinely be measured in all critically ill patients, as this will primarily generate false-positive results. 📖
• Patients with elevated troponin that isn't due to MI should not be treated with therapies for MI.

type-1 MI vs. type-2 MI

• Type-1 MI refers to acute plaque rupture in a coronary artery leading to myocardial ischemia. Nearly all available research and therapies for MI are based on patients presenting to the hospital with Type-1 MI.
• Type-2 MI refers to patients with stable coronary artery stenosis who develop myocardial ischemia due to diminished myocardial perfusion (e.g., anemia, hypotension) and/or increased myocardial demand (e.g., tachycardia, hypertension).(31815570) The key therapy for Type-2 MI is to treat the underlying cause, rather than use any therapy directed at the coronary arteries (although aspirin might be reasonable).📖
• Differentiating type-1 MI vs type-2 MI usually involves a subjective judgement that compares the amount of physiologic stress versus the amount of myocardial ischemia (table below, discussed further here 📖).

STEMI-NSTEMI, OMI-NOMI

• Traditionally, Type-I MI has been divided into patients with ST elevation (STEMI) vs. patients without ST elevation (NSTEMI). The number of mm of ST elevation was used to determine which patients had coronary artery occlusion. However, this is a gross oversimplification of how EKGs should be interpreted to diagnose coronary occlusion. For example, it has long been recognized that many EKG patterns without ST elevation also reflected coronary artery occlusion (these patterns were termed “STEMI-equivalents”).
• More recently, a new nomenclature system has been proposed that encourages clinicians to be more thoughtful about various EKG patterns that reflect coronary artery occlusion:
  • Occlusive MI (OMI): STEMI plus STEMI-equivalent patterns.
  • NonOcclusive MI (NOMI): Other EKG patterns (usually reflective of subendocardial ischemia).
• These categorization schemes are useful, but not perfect. For example, as coronary artery thrombosis propagates and then recedes over time, patients may transition between OMI and NOMI patterns. Likewise, the presence or absence of physiologic stress may greatly affect EKGs (e.g., cardiac arrest or epinephrine may cause ischemic changes which subsequently resolve). Ultimately, patient management should be based on a thoughtful assessment of all clinical data.

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diagnosis of MI

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usual components of diagnosis

• Clinical history. Concerning features may include:
  • Pain radiating to the shoulders, both arms, right arm/shoulder, neck, or jaw.(31855327)
  • Pain worse with exertion.
  • Associated emesis or diaphoresis.
  • ⚠️ Unusual presentations (e.g., MI without chest pain) are more likely in women, elderly, and/or diabetic patients. Presentations can vary broadly (e.g., nausea/vomiting, dyspnea, syncope, fatigue, jaw pain, epigastric pain).
• EKGs (including baseline EKGs, EKGs obtained by paramedics in the field, and additional serial EKGs).
• Echocardiography.
• Troponin level (may be normal initially).
• Potassium level (hyperkalemia may generate pseudo-MI patterns on EKG).
• Chest X-ray, mostly to exclude alternative diagnoses (although pulmonary congestion may be seen in severe MI).

echocardiography

• Focal wall-motion abnormalities support the diagnosis of MI. A complete study (e.g., formal echocardiography with contrast) has excellent sensitivity for occlusive myocardial infarction. However, the presence of wall-motion abnormalities has a low specificity (since this may reflect a remote myocardial infarction, myocarditis, or Takotsubo cardiomyopathy). Combining echocardiography with EKG can improve specificity (more on this below).
• Echocardiography is also essential to evaluate for alternative diagnoses:
  • RV dilation should always prompt consideration of pulmonary embolism (although other possibilities include right ventricular MI or chronic pulmonary hypertension).
  • Aortic dilation and/or aortic valve regurgitation suggests aortic dissection.
  • Pericardial tamponade.
• Echocardiography allows for hemodynamic assessment of patient and risk stratification. 📖
• Echocardiography will occasionally reveal a complication of MI (e.g., flail mitral valve, ventricular septal defect).

synergistic combination of echocardiography plus EKG

• Echocardiography and EKG are often taught separately. However, synergistic use of these two modalities is the most powerful.
• To maximize efficiency, it's often useful to start with EKG interpretation and then use echocardiography to sort out different possibilities. For example:
  • (1) A patient presents with diffuse ST elevation, concerning for either a very large occlusive myocardial infarction or pericarditis. Echocardiography can readily differentiate these possibilities.
  • (2) A patient presents with right precordial T-wave inversion that is concerning for either Wellens pattern or a submassive PE. Echocardiography can rapidly evaluate the right ventricle, to assess the likelihood of a submassive PE.

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differential diagnosis of MI

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The differential diagnosis of chest discomfort is broad. The following entities are most notable, especially among critically ill patients.

type-I MI

• Subjective:
  • Chest pain (often pressure, may radiate to arms/jaw).
  • Associations include vomiting, diaphoresis, dyspnea.
• EKG: Findings of occlusive or nonocclusive MI (see above).
• Exam: POCUS may show wall-motion abnormality.
• Other tests: Troponin elevation, cardiac catheterization.

type-2 MI 📖

• Subjective: Patient usually presents with noncardiac problems (e.g., pneumonia, sepsis, DKA, gastroenteritis).
• EKG: Usually will show features of NOMI.
• Exam: POCUS may be reassuring (e.g., hyperkinetic heart without wall-motion abnormality).
• Other tests: Troponin elevation (but usually less than with type-I MI).

PE causing pleural infarct with chest pain

• Subjective: Sharp, pleuritic chest pain.
• EKG: Often unchanged.
• Exam: POCUS may show pleural effusion, small area of lung consolidation, and possibly DVT.
• Other tests: D-dimer elevation; focal opacity may be seen on chest X-ray; CT angiography is diagnostic.

PE causing RV strain with myocardial ischemia

• Subjective: May cause ischemic-quality anginal chest pain due to hypoperfusion of the right ventricular free wall. Patients often present with (pre)syncope or dyspnea.
• EKG may show:
  • T-wave inversion involving the interior leads and/or right precordial leads.
  • Right axis deviation (RAD).
  • Complete or partial right bundle branch block (RBBB).
  • SI-QIII-TIII pattern.
  • ST elevation rarely seen (aVR).
  • Tachycardia.
• Exam: POCUS should show RV dilation and RV systolic dysfunction. DVT study may be positive.
• Other tests: CT angiography should be diagnostic.
• 💡 (Sub)massive PE causing ischemia of the right ventricular free wall can closely mimic MI (e.g., with anginal-type chest pain, positive troponin, and dynamic EKG changes).

aortic dissection

• Subjective: Chest pain (sharp, tearing/ripping, rapid acceleration to maximal pain, radiation to shoulders, migratory). May be associated with a variety of symptoms beyond the chest (e.g., neurologic, abdominal pain).
• EKG: Usually nonspecific. Aortic dissection may rarely cause occlusion of a coronary artery, producing an OMI-pattern EKG.
• Exam: Findings vary based on location of dissection, potentially including:
  • Bp differential between limbs.
  • POCUS: Aortic root dilation, aortic regurgitation, pericardial effusion. Ultrasound of abdominal aorta, carotids, or femoral arteries may show a dissection flap.
• Other tests: Chest X-ray may show widening of mediastinum. Dissection protocol CT angiography should be diagnostic.

pericarditis

• Subjective: Chest pain is often positional (worse lying flat), pleuritic, and may be sharp. Pain may be associated with fever and flu-like symptoms.
• EKG: May see diffuse ST elevation or T-wave changes.
• Exam: Pericardial friction rub may be heard. Echo may show pericardial effusion.

pneumothorax

• Subjective: Sharp pleuritic pain, dyspnea.
• Exam: Subcutaneous emphysema may occur. Lung ultrasonography should be diagnostic.
• Other tests: Chest X-ray or chest CT scan in more complex cases.

pneumonia

• Subjective: Pleuritic pain (sharp). Associated with dyspnea, productive cough, and fever.
• EKG: Relatively unchanged.
• Exam: POCUS should show focal B-lines, consolidation, and/or pleural effusion.
• Other tests: Chest X-ray +/- CT scan should show pulmonary infiltrates.

takotsubo cardiomyopathy

• Subjective: May cause anginal chest pain, dyspnea, arrhythmia, or cardiogenic shock. Often preceded by emotional or physical stress.
• EKG: STE is generally the first finding (usually greatest V3-V6). TWI may follow.
• Exam: POCUS typically shows apical hypokinesis. However, some patients may display a pattern of circumferential mid- or basal hypokinesis.
• Other tests:
  • Troponin elevation (albeit lower than would be seen with occlusive MI).
  • Cardiac catheterization often needed to exclude MI.

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EKG findings in MI

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Diagnosis of MI is unfortunately vastly more complex than simply counting the number of millimeters of ST elevation in various leads (thereby invalidating the traditional STEMI/NSTEMI dichotomy). This is evolving into the NOMI/OMI conceptualization, which emphasizes more holistic EKG interpretation to detect a variety of patterns suggestive of coronary occlusion.

Below are several EKG patterns associated with MI. These don't represent every possible EKG manifestation of ischemia, but rather a foundational set of patterns that practitioners should be able to quickly recognize.

The sections below focus on EKG features. However, context is king. Therefore, in clinical practice the following information will often be invaluable:

• Clinical context, for example:
  • Routine screening EKG vs. suspected MI.
  • Correlation with STAT echocardiography.
• Comparison to baseline EKG (if available).
• Evolution of serial EKGs over time.
• Proportionality of abnormalities compared to the overall EKG (e.g., 0.5 mm STE may be significant if the QRS complex is tiny).

Finally, it should be borne in mind that the purpose of EKG interpretation is not to secure a diagnosis with 100% certainty. Rather, the goal of EKG interpretation is merely to get a fairly reasonable concept of the diagnosis – to get pretty close. When interpreting an EKG, one should not feel pressured to render a final diagnosis, but rather should feel comfortable expressing uncertainty between a few differential possibilities. Definitive diagnosis will often require additional EKGs, echocardiography, and/or cardiac catheterization.

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anterior OMI

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features that support anterior OMI diagnosis

• (1) Anterior STE
  • Most often in V2.
  • STE >5 mm favors OMI.
  • Convex (“coved”) STE favors ischemia if seen (but anterior OMI can also cause concave STE).
• (2) T-wave changes
  • Hyperacute T-waves may be seen.
  • Terminal QRS distortion in V2-V3 may occur (results from broad, malignant T-waves that invade the QRS complex and obliterate any S- or J-waves; figure below).
• (3) Q-waves may emerge rapidly (these aren't a contraindication to revascularization).
• (4) Loss of R-waves:
  • Areas with reversed R-wave progression (e.g., RV4 > RV3).
  • Loss of R-wave amplitude compared to prior EKG.
• (5) STE in aVL supports the diagnosis, if seen.
• (6) Reciprocal ST depression or ST flattening supports the diagnosis (but is often absent).
  • STD anywhere other than in aVR or V1 favors OMI.

anterior OMI vs. benign early repolarization

• In the presence of anterior STE of at least >1 mm, the following approach may help differentiate OMI versus benign early repolarization.
• If present, any of the following features suggest anterior OMI:
  • STE >5 mm.
  • Any convex STE in V2-V6.
  • Inferior reciprocal changes.
  • Anterior ST depression.
  • Any Q-wave in V2-V4.
  • Any TWI in V2-V6.
  • Terminal QRS distortion in V2 or V3 (distortion is defined as lack of either an S-wave or a J-wave in that lead; figure below).
• If none of the above features is present, Smith's formula can be used to differentiate OMI versus benign early repolarization.🧮
  • Caution: This formula is designed only to sort out OMI vs. benign early repolarization. It will not differentiate OMI from other MI mimics (e.g., LVH or pericarditis).

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inferior OMI

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core features of inferior OMI

• (1) STE in inferior leads (can be subtle).
  • Should generally see STE in two inferior leads.
• (2) STD in aVL (+/- Lead I).
  • If no STD in aVL, the diagnosis should be questioned. STD in aVL may theoretically be obscured by simultaneous lateral ischemia (with STE in V5 or V6). However, evidence shows that STD occurs in 99% of inferior OMI.(26542793)
  • TWI in aVL may also support the diagnosis (this is the mirror image of hyperacute T-waves in the inferior leads).

additional features that can be seen in inferior OMI

• Right precordium:
  • RV MI may cause STE in V1.
  • Manifestations of posterior ischemia (~V2-V4).
    • ST depression or flattening.
    • T-wave abnormalities.
• STE in V5, V6 may occur in left circumflex occlusions.
• 💡 In inferior MI, always systematically evaluate for possible RV myocardial infarction, as discussed further below. 📖

EKG mimics of IMI

• LVH.
  • Can be very difficult to sort out.
  • Features that may support inferior MI:
    • STE disproportionately large compared to preceding S-waves.
    • Ischemic features in other territories (e.g., right precordial STD).
• PE can cause STE in inferior leads and V1, with reciprocal changes in aVL.
  • Diffuse and prominent TWI in the inferior and anterior leads may help suggest PE.
• Old inferior MI (aka, inferior aneurysm) – more on this distinction below. 📖
• Benign early repolarization. Clues that suggest benign early repolarization:
  • Benign early repolarization may also be present in precordial leads.
  • Benign-appearing morphology (e.g., concave STE, J-waves).
  • Absence of STD in aVL.

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right ventricular MI (RVMI)

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introduction

• Right ventricular MI (RVMI) refers to transmural infarction of the free wall of the right ventricle.
• Isolated RVMI is rare. However, RVMI is seen in about a third of patients with inferior OMI. Within the context of an inferior OMI, RVMI is nearly always due to occlusion of the right coronary artery.
• RVMI is important to recognize, because:
  • (1) It has specific implications for hemodynamic management.
  • (2) RVMI is one form of occlusive MI, requiring immediate revascularization.
  • (3) Patients with RVMI have a higher risk of mortality and major complications.

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clinical findings in RVMI 

• Features of myocardial infarction (e.g., chest pain, nausea, vomiting).
• Patients may develop severe hypotension following nitroglycerine or morphine.
• The traditional triad of findings seen in RVMI is hypotension, clear lung fields, and jugular venous distention. However, in practice this has very low sensitivity.
• Refractory hypoxemia can occur, due to shunting of deoxygenated blood through a patent foramen ovale.

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EKG diagnosis of RVMI 

RVMI in the context of inferior MI

• RVMI almost always occurs in the context of inferior MI due to a proximal RCA occlusion.
• This may be diagnosed as follows:
• Step #1) Diagnose an inferior MI (as described above).
• Step #2) Look for signs of an RCA culprit lesion (table below).
• Step #3) Look for evidence of RV ischemia:
  • STE of at least 0.5 mm in V1 suggests RVMI (STE may extend a bit into the precordial leads, but it should be maximal in V1-V2).
  • If there is STD in V2 due to a posterior MI, this may obscure RVMI. In the presence of STD in V2, an isoelectric ST segment in V1 might suggest the possibility of RV MI.
  • Right-sided EKG showing >0.5-1 mm STE in V4R may be the most accurate EKG finding.(24294033) Note, however, that STE in V4R may also occur with anteroseptal MI, prior anterior MI with aneurysm, LV hypertrophy, or pulmonary embolism – so taken in isolation this finding is not diagnostic of RVMI.(29902098)
  • (When in doubt, POCUS may be the fastest way to evaluate right ventricular function.)

isolated RVMI or “predominant” RVMI

• RVMI can rarely occur alone, or it may be the most obvious finding on the EKG. This may occur in two situations: 🌊
  • (1) Isolated RV marginal branch occlusion.
  • (2) Old inferior MI with a new proximal occlusion of the right coronary artery (the inferior wall is already scarred, so only the RV MI causes ST elevation).
• The main finding here is STE in V1-V3 (which will tend to be misdiagnosed as anterior MI).
• Features that favor RVMI rather than anterior MI:
  • STE greatest in V1-V3 favors RVMI, whereas STE greatest in V2-V4 favors anterior MI.
  • STE in V1 > STE in V4 favors RVMI.
  • Subtle findings of inferior OMI or an old Q-wave inferior MI may support the possibility of RVMI.

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echocardiographic findings in RVMI 

• (1) RV dilation & dysfunction, which may also include:
  • McConnell's sign can be seen (focal hypokinesis of the right ventricular free wall – this is classically associated with PE, but isn't specific for PE).
  • Tricuspid regurgitation may occur.
• (2) Inferior vena cava dilation can occur.
• (3) Inferior wall-motion abnormality may be seen, if there is a simultaneous inferior infarction.
• (4) Classically in RVMI, left-sided filling pressures are low or normal, because the RV is not pumping sufficient blood across to the left side of the heart. Consequently, lung ultrasonography should show a normal, A-line pattern (dry lungs).

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differential diagnosis of RVMI 

• {RVMI plus inferior MI} vs. isolated inferior MI
  • Many RVMIs may be overlooked, and patient diagnosed with inferior OMI.
  • This isn't a terrible mistake, but may lead to hemodynamic errors.
• RVMI vs. PE
  • Most RVMI can be sorted out from PE on the basis of simultaneous inferior OMI. However, ~2% of RVMIs occur in isolation, which is much harder to differentiate from PE.

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management of RVMI 

revascularization

• Emergent revascularization is needed. Subgroup analysis of the SHOCK trial suggested substantial mortality benefits from revascularization among patients with RVMI and shock (similar to other patients with MI that causes shock).(12706920)

hemodynamic optimization

• Generally avoid:
  • Any agents that may reduce preload (e.g., nitrates, morphine, diuretics, ACE-i/ARBs).
  • Excessive PEEP, hypoxemia (increase pulmonary vascular resistance).
• Volume management:
  • Some fluid administration may often be beneficial (the dilated RV is preload-dependent).
  • Excessive fluid will distend the right ventricle, worsening its function and compressing the left ventricle.
  • If a central line is in place, targeting a central venous pressure of ~10-14 mm may be reasonable.(24222834, 29902098)
• Inhaled pulmonary vasodilators:
  • Inhaled nitric oxide has been shown to increase cardiac output among patients with RVMI, without causing hypotension.(15312861) Case reports likewise describe patients with refractory cardiogenic shock who have responded well to inhaled pulmonary vasodilators.(28298620, 20674235)
  • Inhaled pulmonary vasodilators are generally safe, with the main drawback being cost (particularly with nitric oxide). Theoretically, increased RV function could cause overload of the left ventricle and pulmonary congestion – but this doesn't seem to occur clinically.(15312861)
  • Compared to inotropes, pulmonary vasodilators have the advantage that they reduce myocardial workload and thereby lessen RV ischemia.
• Vasopressors & inotropes:
  • Alpha-adrenergic stimulation may increase pulmonary vasoconstriction, exacerbating RV failure. Alternatively, beta-agonist stimulation may cause pulmonary vasodilation.
  • For patients with reasonable blood pressure and low cardiac output, dobutamine may be useful (both to improve inotropy and reduce pulmonary vascular resistance).
  • For hypotensive patients, low-dose epinephrine may be considered (with similar benefits compared to dobutamine, but with a slight amount of vasoconstriction to avoid hypotension).
  • Pure alpha-agonists (e.g., phenylephrine) should be avoided.

treatment of hypoxemia

• Some patients with RVMI may develop shunting of deoxygenated blood through a patent foramen ovale. This will manifest as hypoxemia refractory to supplemental oxygen.
• Patients with severe hypoxemia should undergo bedside echocardiography with injection of agitated saline, to evaluate for an intracardiac shunt.
• Patients with a right-to-left shunt may benefit from inhaled pulmonary vasodilators (either nitric oxide or epoprostenol) and/or diuresis (if hemodynamically feasible).

arrhythmia management

• Atrial fibrillation may cause significant hemodynamic deterioration. If this occurs, an aggressive rhythm-control strategy may be required (e.g., emergent cardioversion +/- amiodarone).📖
• Bradycardia may occur, which is often not tolerated hemodynamically (as patients often have a fixed stroke volume). Aggressive management of bradycardia may be needed, including placement of a temporary transvenous pacemaker.📖

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posterior OMI

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general properties of posterior OMI

• Posterior OMI can occur alone, but this isn't common (perhaps ~5% of OMIs).
• Posterior OMI is usually associated with inferior OMI and/or lateral OMI.

key diagnostic findings in posterior MI

• (1) Precordial STD >1 mm that is maximal in V1-V4.
  • Normally there is slight STE in V2-V3, so any STD is worrisome.
  • This differentiates posterior OMI from subendocardial ischemia (wherein STD is usually maximal ~V4-V6).
• (2) Tall R-waves in the right precordial leads.
  • This represents a Q-wave equivalent.
  • It is not invariably present, nor is it necessarily an early finding.
• (3) Abnormal T-waves in the right precordium.
  • TWI may occur as a mirror-image of hyperacute posterior T-waves.
  • Prominent upright T-waves can occur as a mirror-image of posterior TWI (due to reperfusion).
• (4) Ischemic morphology using the mirror test.
  • The mirror test inverts the precordial EKG, to mimic what you would see using posterior leads. This is probably about as good as getting an EKG with posterior leads (V7-V9), and it's much faster.
  • Using paper: flip the EKG over and look through it.
  • Using a smartphone: Take a picture of the precordial leads, then flip horizontally and rotate 90 degrees twice. This is exactly the same as a traditional mirror test, but can be used if the EKG is available only on a computer display (figure below).
• (5) Ischemia in the inferior or lateral leads.
  • Posterior ischemia often occurs together with inferior or lateral ischemia.

differential diagnosis of posterior OMI

• (1) RV hypertrophy may cause a tall R-wave in the right precordial leads and a strain pattern in V1-V3 with STD.
  • Other features of RV hypertrophy may suggest this diagnosis (e.g., terminal S-wave in lead I, TWI in lead III).
• (2) Digoxin or hypokalemia may cause scooped STD in the right precordial leads. Clues to suggest digoxin or hypokalemia:
  • (a) STD is diffusely present throughout the EKG (including the inferior leads).
  • (b) Other features:
    • Hypokalemia: Prominent U-wave.
    • Digoxin: short QTc, unusual rhythms.
• (3) Subendocardial ischemia (NOMI):
  • Maximal STD in ~V2-V4 favors posterior OMI, whereas maximal STD in ~V4-V6 favors subendocardial ischemia.
  • If seen, posterior OMI is suggested by:
    • Tall R-waves in the right precordium.
    • Upright T-waves in the right precordium (however, TWI in the right precordium can be consistent with either posterior OMI or subendocardial ischemia).
• (4) anterior de Winter T-wave pattern
  • Suggested by lack of a tall R-wave and broad/hyperacute T-waves.

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high lateral OMI

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cornerstone findings of lateral OMI

• STE in aVL +/- Lead I.
  • STE is often <1 mm (especially with low QRS voltages).
• Inferior reciprocal changes.
  • STD in lead III (+/- STD in II and aVF) – may be the most obvious abnormality.
  • TWI may occur as a reciprocal of hyperacute T-waves in lateral leads (more worrisome if this occurs in leads with a positive QRS complex).

mimics of lateral OMI

• Anterior aneurysm involving the lateral wall.
• Atrial flutter (flutter waves can obscure the ST segments).
• Pericarditis (suggested by more diffuse STE and lack of reciprocal STD).
• Benign early repolarization (suggested by large complexes with proportionally unimpressive ST deviation, lack of hyperacute T-waves, benign early repolarization morphology in anterior leads).
• Right ventricular hypertrophy (suggested by tall R-wave in V1, terminal S-wave in lead I).

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OMI in context of LBBB or RV-paced rhythm

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A new LBBB in the context of acute MI implies a large infarction, which is potentially an indication for catheterization. However, in practice, many patients present with a chronic LBBB – so the finding of LBBB alone is nonspecific. For patients with either LBBB or an RV-paced rhythm, ischemia may be diagnosed using the Smith-modified Sgarbossa criteria as listed below.

Smith-Modified Sgarbossa Criteria (OMI is revealed if ANY criteria is met, even in just a single lead):

1. Concordant STE of at least 1 mm in any lead.
2. Concordant STD of at least 1 mm in V1-V3.
3. Excessive discordant STE or discordant STD in any lead that is >1 mm and also >25% of the depth of the preceding R-wave or S-wave, respectively (figure below). However, this doesn't apply in extreme tachycardia, pulmonary edema, hyperkalemia, or hypertension (if these conditions are present, then treat them and repeat the EKG).(22939607)

other features that may support the presence of ischemia:

• Marked convexity of the ST segment (especially in the precordial leads).
• T-wave inversion in leads with a negative QRS (concordant TWI).
• Substantial qualitative changes compared to the baseline EKG.

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OMI versus LV aneurysm

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The features below may help sort out acute anterior OMI versus chronic aneurysm. For patients presenting late in the course of MI (e.g., >6 hours after chest pain onset), this distinction will become blurred.

typical findings in anterior aneurysm

• Deep Q-waves in V1-V4 (usually with at least one QS wave in these leads).
• Coved STE in V1-V4.
• Often causes some TWI, which is typically shallow.

features that suggest acute anterior MI (rather than solely an aneurysm)

• (1) Any tall upright T-wave in V1-V4, with T-wave >36% the size of the QRS complex.(29407007)
• (3) Other ischemic findings on the EKG, for example:
  • STE in leads without deep Q-waves (especially aVL).
  • Reciprocal STD.

inferior aneurysm vs. ischemia

• Typical findings in inferior aneurysm:
  • Deep, well-developed inferior Q-waves.
  • STE in inferior leads, with reciprocal STD in aVL.
  • Shallow TWI can occur.
• Sorting out aneurysm vs. active MI is extremely difficult, but some clues may be:
  • (1) Inferior T-waves:
    • Upright T-waves suggest hyperacute ischemia (especially if changed from baseline).
    • TWI suggests no current artery occlusion (but this doesn't differentiate recent vs. remote IMI).
  • (2) More pronounced STE supports ischemia.
  • (3) Inferior MI tends to develop Q-waves more slowly than anterior MI. Thus, well-formed Q-waves argue against a very acute MI.

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hyperacute T-waves & de Winter pattern

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significance of hyperacute T-waves

• Hyperacute T-waves suggest ischemia which is either transmural or nearly transmural.
• Isolated hyperacute T-waves (without ST deviation) are often a harbinger of impending ST elevation. However, isolated hyperacute T-waves may also be seen following spontaneous thrombus lysis that has recently led to resolution of ST elevation.

characteristics of hyperacute T-waves

• Broad-based, with a relatively blunt peak.
  • T-waves may obliterate the ST segment and even encroach on the QRS complex (leading to QRS distortion as discussed above). 📖
• Straightened upslope (they should not be deeply concave).
• Relatively symmetric.
• Tall in comparison to the R-wave.
• Involving multiple leads in an anatomic pattern:
  • Hyperacute T-waves typically involve several contiguous leads.
  • If only one lead looks hyperacute, this may be an anomaly.
  • If all of the EKG leads look similar, this argues against hyperacute T-waves (suggesting hyperkalemia or benign early repolarization).
• May be associated with other ischemia features, for example:
  • STE or STD (de Winter pattern; see below).
  • Loss of R-wave progression.
• Changed compared to baseline EKG.

differential diagnosis of hyperacute T-waves

• Prominent T-waves as a reciprocal change to TWI:
  • Reperfused posterior MI may cause prominent right precordial T-waves.
  • Reperfused high-lateral MI may cause large inferior T-waves.
  • Reperfused inferior MI may cause large T-waves in aVL.
• Benign early repolarization:
  • T-waves are tall and asymmetric.
  • R-waves are also tall.
• Hyperkalemia:
  • T-waves are narrow-based, pointy, symmetric, and tall.
  • T-waves are most marked in V2-V3, but the overall pattern is one of diffuse T-wave abnormality.
  • May see other features of hyperkalemia (e.g., diminished P-waves, QRS widening).
• Left ventricular hypertrophy.

de Winter T-wave complex

• Classically defined as a combination of the following:
  • (1) Tall, hyperacute T-waves in the precordial leads.
  • (2) Up-sloping STD >1 mm in the precordial leads.
  • (3) Absence of STE in the precordial leads.
  • (4) Normal QRS duration.
  • (5) Often, mild STE is seen in aVR.(31455501)
• Abnormalities are often maximal around V3.(31455501)
• This pattern reflects nearly complete LAD occlusion and should be treated as an occlusive MI (e.g., with cath lab activation). However, a de Winter pattern can also occur in the inferior or lateral territories, with similar implications.

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Wellens patterns

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Wellens patterns reflect transient occlusion of the left anterior descending coronary artery (LAD) with spontaneous reperfusion. Clinically, this is often associated with a history of chest pain which has currently resolved. Wellens Pattern A refers to biphasic T-waves, suggestive of very recent occlusion (figure below). Over time, Wellens Pattern A will evolve into deep, symmetric T-wave inversion (Pattern B). Wellens Pattern B is less immediately worrisome, because it implies that the vessel has managed to remain open for a bit longer, without re-occluding. Wellens patterns do not indicate an active occlusive MI, but they imply the presence of a high-grade proximal LAD lesion that needs to be taken very seriously. One series found that most patients with Wellens syndrome who didn't undergo revascularization went on to develop an anterior OMI within a few weeks. Patients with Wellens pattern should not undergo stress testing, as this may trigger an acute MI.(31455501)

EKG criteria for Wellens pattern

• TWI in V2-V3 (and possibly extending out as far as V5).
• Preservation of the R-wave (if the R-wave is replaced by deep Q-waves, this suggests anterior aneurysm).
• Evolution over time (in particular, Wellens A is never a static pattern).

differential diagnosis of Wellens pattern

• Pulmonary embolism
  • TWI in lead III is found in 88% of PE patients compared to 15% of MI patients, so inferior TWI favors a diagnosis of PE.(17350373)
  • TWI deepest in V1-V2 favors PE, whereas TWI deepest in V3-V4 favors Wellens.
  • Other features that may suggest PE include right axis deviation, retained S-waves in the left precordial leads, SI-QIII-TIII, or partial RBBB.
• Left ventricular hypertrophy (LVH)
  • LVH can very closely mimic Wellens (creating a “pseudo-Wellens” pattern).
  • LVH tends to cause TWI in a more lateral distribution (V3-V6) than Wellens (V2-V4).
  • LVH creates a more static EKG pattern over time, whereas Wellens A should always evolve.
• Benign T-wave inversion
  • Often occurs in the context of benign early repolarization.
  • Leads with TWI often have distinct J-waves with some STE, tall R-waves, and small S-waves.

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subendocardial ischemia pattern

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EKG features of subendocardial ischemia

• (1) Diffuse STD, which is maximal in V4-V6 and lead II.
• (2) No evidence of focal OMI (e.g., no STE in leads other than aVR and V1).
• (3) If very severe, this may be accompanied by STE in aVR (and sometimes V1 as well).

common differential diagnostic considerations:

• Hypokalemia or digoxin can cause diffuse STD with STE in aVR.
  • These are suggested by down-sloping STD followed by prominent U-waves.
• Posterior MI may cause STD with STE in aVR.
  • Posterior MI: STD is more localized to the right precordial leads (greatest in ~V2-V4).
  • Diffuse subendocardial ischemia: STD greatest in ~V4-V6.
• Anteroseptal MI: LAD occlusion proximal to the septal perforator may cause STE in V1-V2 or V1-V3 with STD in inferior leads and V5-V6. Clues to anteroseptal MI:
  • STE in V1 may be greater and extend out to V2-V3.
  • May see hyperacute T-waves in the right precordial leads.
  • Less pronounced STD in limb leads.
• De Winter's pattern: If there are superimposed hyperacute T-waves in the context of ST depression, this may reveal an impending occlusive MI.(more here 📖)
• Massive or submassive PE: This may be suggested by terminal right axis deviation (causing a terminal S-wave in V1 and a terminal R-wave in lead III).
• Left ventricular hypertrophy (may also cause STE in aVR).

clinical significance of severe subendocardial ischemia with STE in aVR

• This pattern reveals diffuse, severe subendocardial ischemia of the entire myocardium. It is often due to stenosis of the left main coronary, or stenosis of multiple coronary arteries.
• This pattern doesn't indicate active coronary vessel occlusion.
• Diffuse ischemia may be caused in various ways:
  • (1) It can reflect acute plaque rupture (Type I MI) with partial occlusion of the vessel. This is a very scary scenario, because there is a lot of myocardium in jeopardy if the stenosis progresses to an acute occlusion.
  • (2) It can reflect stable coronary stenoses plus acute physiological stress (Type-2 MI).
• Management depends on clinical context:
  • If context suggests a Type I MI (e.g., patient presenting with chest pain) – treat medically for MI and pursue prompt catheterization. However, be cognizant that patients will often have severe coronary artery disease that cannot be treated by percutaneous coronary intervention. Therefore, consider holding P2Y12 inhibitors, since CABG may be needed.
  • If context suggests a Type-2 MI (e.g., patient presenting with gastrointestinal hemorrhage) – treat the underlying cause of stress and follow the EKGs carefully to ensure resolution of ischemia.

clinical significance of milder subendocardial ischemia without STE in aVR

• Nonocclusive MI of any vessel causing subendocardial ischemia will tend to create this same EKG pattern. (For some reason, subendocardial ischemia doesn't localize on EKG.)
• This is perhaps the most classic EKG pattern associated with nonocclusive MI (NOMI).

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risk stratification in acute MI

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Risk stratification and hemodynamic status can be rapidly determined at the bedside as shown in the figure above. 📖 This may be very helpful regarding disposition and management. For example, the presence of severely reduced LV systolic function suggests that the patient may respond poorly to beta-blockers.

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general supportive measures

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general measures

• Discontinue NSAIDs (NSAIDs may impair renal function and myocardial remodeling, and mute the beneficial effect of aspirin).
• Target potassium >3.5 mEq/L 📖 and magnesium >2 mEq/L 📖 (avoids arrhythmia).
• Target hemoglobin >8 mg/dL. 🌊 (REALITY trial)
• Supplemental oxygen only for patients with hypoxemia, titrated to a target of normoxia (e.g., target saturation 92-97%).(AVOID trial)
• High-intensity statin (e.g., 80 mg atorvastatin daily).(11277825)

avoid opioids

• Reasons not to use opioid:
  • (1) Opioid runs the risk of masking ongoing ischemia without resolving it. Urgent catheterization is indicated for patients who can't be rendered pain-free with medical therapy (e.g., nitroglycerine and beta-blockade).
  • (2) Opioid administration may delay oral absorption of P2Y12 inhibitors.
• For patients who have already had catheterization, opioid can be helpful.

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nitroglycerine

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evidentiary basis

• Evidence supporting the use of nitroglycerine is not robust. Clinical trials have not found benefit from nitrates (GISSI-3, ISIS-4).(7910229, 7661937) Furthermore, relief of chest pain following nitroglycerine is not a useful diagnostic indicator of myocardial ischemia.(14678917)
• Nevertheless, nitroglycerine may be useful for symptom management (e.g., relief from anginal chest pain, management of hypertension, and treatment of pulmonary edema).

indications

• Anginal chest pain (or other anginal equivalent).
• Cardiogenic pulmonary edema.
• Possibly hypertension (although hypertension may be managed by other agents supported by more robust evidence, such as beta-blockers or ACE inhibitors).

contraindications

• Hypotension.
• Hypertrophic cardiomyopathy or severe aortic stenosis (relative contraindication).
• RV infarction.
• Recent use of phosphodiesterase inhibitors:
  • Sildenafil or vardenafil within 24 hours.
  • Tadalafil within 48 hours.

dosing

• Initially may be given as a sublingual tablet of 0.4 mg q5 minutes (up to three doses).💊
• If the patient responds favorably, may transition to a nitroglycerine infusion.💊

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beta-blocker

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evidentiary basis

• Beta-blockers reduce the risk of malignant arrhythmia, but they may also increase the risk of cardiogenic shock. The balance of these effects depends on the patient population, dose, and timing of initiation. For example, the COMMIT trial found that an aggressive regimen of metoprolol (up to 15 mg IV, followed by 200 mg/day) reduced death due to malignant arrhythmia, increased death due to cardiogenic shock – and ultimately had no net effect on the overall mortality.(16271643)
• The risk of harm from beta-blockers due to cardiogenic shock seems to occur early (during the first day), whereas benefits due to reduction in reinfarction and ventricular fibrillation emerge more gradually.(16271643) This implies that a gradual, cautious approach to beta-blocker initiation may be most beneficial.

indications

• Guidelines recommend initiation of beta-blockers within 24 hours among patients with either OMI and NOMI, in the absence of contraindications.(25260718, 23256914) For most patients, oral beta-blockers can be gradually introduced, with careful hemodynamic monitoring.
• Early use of IV beta-blockers may be considered in patients with hypertension, persistent anginal chest pain, or ventricular arrhythmia (in the absence of contraindications). The benefit of early IV beta-blockers might be greatest in patients with more robust hemodynamics and lower shock index.

contraindications

• Bradycardia (heart rate <60 b/m).
• Heart block (PR interval >240 ms, or second/third degree heart block).
• Heart failure (e.g., cardiogenic pulmonary edema).
• Cardiogenic shock, or risk factors for developing shock (e.g., heart rate >110 b/m, SBP < 120 mm, or shock index = HR/SBP above ~0.8).(21570515, 30285644)
  • Clinical and echocardiographic risk stratification may help predict which patients will tolerate beta-blockade.📖
  • ⚠️ Tachycardia is a relative contraindication to beta-blockade. That may be counterintuitive, but compensatory tachycardia may reflect underlying instability which indicates an inability to tolerate beta-blockade.

dosing

• IV beta-blockade is generally achieved with sequential 5-mg doses of metoprolol (up to a total of 15 mg, as tolerated/required).💊
• For most patients, starting an oral beta-blocker within 24 hours is adequate. Preferred agents are metoprolol or carvedilol.💊

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ACE-inhibitor

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evidentiary basis

• ACE inhibitors have been studied predominantly in STEMI patients, with numerous studies demonstrating mortality benefit in the context of more severe MI. One RCT suggests that benefit might extend to NSTEMI patients as well.(16923416)

indications

• For STEMI patients, ACE inhibitors are strongly recommended (Class I) within 24 hours of presentation in the presence of any of the following:(23256914)
  • Anterior MI.
  • Heart failure.
  • Ejection fraction <40%.
• ACE inhibitors may also be considered for:
  • Any patient with STEMI (Class IIA recommendation).(23256914)
  • Any patient with MI plus persistent hypertension, heart failure, diabetes, or ejection fraction <40%.(31815570)

contraindications

• Renal dysfunction (especially if plans are underway for cardiac catheterization).
• Hypotension.
• Hyperkalemia.

dosing

• ACE inhibitors don't usually need to be started immediately, but rather may be started within 24 hours.
• When in doubt about a patient's ability to tolerate therapy, oral captopril titration 💊 may be useful. Captopril is rapidly absorbed and short acting, allowing for greater titratability. Captopril may be started at 6.25 mg initially, followed by 12.5 mg q8hr. Typically this is increased to 25 mg q8hr over the next few days, with eventual up-titration to 50 mg q8hr (if tolerated). Captopril may be titrated against the mean arterial pressure (MAP), with a target MAP in the low-normal range (e.g., ~70-80 mm). Once the patient is stabilized, captopril may be converted to an equivalent dose of lisinopril using a ~5:1 conversion, as discussed below.
• Lisinopril 💊 is often useful for longer term administration, with more convenient once-daily dosing.
  • If beginning lisinopril de novo, start at 5 mg daily, gradually increase to 10 mg daily over 2-3 days (if tolerated).
  • If transitioning from captopril to lisinopril: The total daily captopril dose divided by five may approximate a roughly equivalent lisinopril dose. When in doubt, round down and begin with a more conservative lisinopril dose.(8773158) 🌊
• For patients unable to tolerate an ACE inhibitor (e.g., due to cough), an angiotensin receptor blocker (ARB) may be substituted. Valsartan 💊 is often preferred: Start at 20 mg PO BID, may increase to 40 mg PO BID within a week, with eventual up-titration to target 160 mg BID (if tolerated).

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PCI

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general indications for emergent PCI

• Occlusive MI (OMI).
• Hemodynamic instability (including shock, or new/worsening heart failure attributable to the acute MI).
• Electrical instability (ventricular tachycardia or ventricular fibrillation).
• Recurrent or persistent chest pain that is refractory to medical therapy.
• (If unsure about need for PCI: optimize medically, obtain serial EKGs & echocardiography.)

relative contraindications to PCI

• Severe renal failure.
• Patients at high risk of bleeding (after stenting, patient must remain on dual antiplatelet therapy).
• Patients who are unlikely to be compliant with dual antiplatelet therapy.
• Low life expectancy (e.g., severe dementia, advanced malignancy with poor oncologic prognosis, extremely elderly).
• Patients with a history of prior CABG may benefit less from PCI. 🌊

early invasive strategy vs. conservative strategy in NOMI

• Patients with NOMI without indications for emergent PCI (as listed above) may be treated either with an early invasive strategy (e.g., catheterization within 24 hours) or with a conservative strategy (including medical management followed by a stress test, with PCI performed only if there is recurrent spontaneous ischemia or a positive stress test).
• An early invasive strategy generally reduces the risk of recurrent myocardial ischemia or rehospitalization for acute coronary syndrome. However, meta-analysis involving 10,150 patients found no difference in the risk of mortality after one year (4.3% vs. 4.4%).(18594042) ESC 2020 guidelines likewise state that an early invasive strategy doesn't reduce all-cause mortality in the overall population of patients with NSTEMI.(32860058)
• When unclear, the decision to pursue PCI will be made in conjunction with cardiology consultation. This should take numerous factors into account (e.g., the specifics of EKG and echocardiography findings, renal function, indicators of risk due to myocardial ischemia, other active medical problems, and patient preferences).

anticoagulation for patients undergoing PCI

• This will be determined by cardiology.
• The typical regimen involves aspirin, ticagrelor, and an unfractionated heparin infusion. Following successful PCI, heparin is discontinued (leaving the patient on aspirin and ticagrelor). For patients on oral anticoagulation, clopidogrel may be favored over ticagrelor.
• For patients with EKGs suggestive of surgical coronary disease (e.g., diffuse ST depression with ST elevation in aVR 📖), it may be wise to initially hold dual antiplatelet therapy in anticipation of the possibility of CABG surgery. A potent P2Y12 inhibitor may be initiated in the catheterization laboratory, if coronary anatomy is amenable to PCI (either prasugrel or ticagrelor).

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aspirin

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evidentiary basis

• Aspirin has been robustly demonstrated to cause mortality benefit following MI. For example, ISIS-2 found that aspirin caused a 2.4% reduction in vascular mortality after 5 weeks.(2899772)
• Aspirin is the most important anticoagulating agent in the context of MI.🐐

indications

• Should be given immediately to any patient with definite or probable Type-I MI (unless contraindicated).

contraindications

• Active bleeding or very high risk of bleeding.
• Aspirin allergy (in which case ticagrelor or clopidogrel may be used instead; if clopidogrel is utilized then a 600-mg loading dose should be given to achieve therapeutic levels sooner).

dosing

• Loading dose: 325 mg of non-enteric-coated aspirin (e.g., four uncoated 81-mg tablets).
• Maintenance dose: 81 mg enteric-coated aspirin daily (higher doses are not more effective, but carry greater bleeding risk).(18819961, 20818903)

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P2Y12 inhibitors

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All patients undergoing PCI will require a P2Y12 inhibitor, as determined by the interventional cardiology team. The following discussion is focused on patients undergoing medical management.

role of P2Y12 inhibitors in medical management

• Adding a P2Y12 inhibitor has benefit even in patients who aren't undergoing PCI (in terms of fewer myocardial infarctions and potentially reduced mortality).(18359315, 24727884)
• Evidence supporting the use of P2Y12 inhibitors is more robust that evidence supporting the use of heparin anticoagulation (which is essentially nonexistent). If it is felt that an MI patient being medically managed needs something more powerful than aspirin, the logical next step is to add on a P2Y12 inhibitor (rather than heparin).
• Studies investigating P2Y12 inhibitors generally excluded patients at high bleeding risk or patients on oral anticoagulation. Thus, the benefit of P2Y12 inhibitors may not apply to such patients. The ESC2020 NSTEMI guidelines recommended considering P2Y12 inhibitors in patients who are not planned to undergo PCI and do not have a high bleeding risk (Class IIb).(32860058)
  • More on general risk factors for hemorrhage here.📖

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clopidogrel

evidence

• The benefit of clopidogrel is based on the CURE trial investigating the use of clopidogrel when added to aspirin within <24 hours after hospital admission among patients with NSTEMI and unstable angina.(11519503) The study found benefit from clopidogrel, which was driven primarily by a 1.5% reduction in the rate of myocardial reinfarction. However, this benefit was offset by a numerically similar 1% increase in the rate of major bleeding.
• Some exclusion criteria from the CURE trial were:
  • Contraindications to antithrombotic or antiplatelet therapy.
  • High risk of bleeding or severe heart failure.
  • Patients taking oral anticoagulants.

when to use clopidogrel?

• ESC 2020 NSTEMI guidelines recommend using clopidogrel only when ticagrelor is unavailable, contraindicated, or cannot be tolerated (Class IC recommendation).(32860058)
• NICE 2020 guidelines recommend considering clopidogrel rather than ticagrelor for patients with high bleeding risk.(33301270) However, if the bleeding risk is very high, then it might be safer to omit a P2Y12-inhibitor entirely. The difference in bleeding risk between placebo-vs-clopidogrel is considerably larger than the difference in bleeding risk between clopidogrel-vs-ticagrelor.(11519503, 24727884)

clopidogrel dose 💊

• Loading dose of 300 mg or 600 mg, followed by 75 mg daily.
• 600-mg loading dose takes effect more rapidly (2 hours), compared to 300 mg loading dose (~6 hours).
• 300-mg is often used for medical management. A 600-mg loading dose has been demonstrated to be superior to 300 mg prior to PCI.(19796737)

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ticagrelor 

evidence

• Pharmacologically, ticagrelor works more rapidly and consistently than clopidogrel (which may have slow absorption and erratic metabolism, depending on individual CYP2C19 activity).
• The PLATO trial:(24727884)
  • RCT comparing clopidogrel vs. ticagrelor among 18,000 patients with acute coronary syndrome.
  • Ticagrelor was superior to clopidogrel, including a 1.4% absolute reduction in all-cause mortality. 
  • Among patients with NSTEMI, ticagrelor did cause a 1% increase in non-CABG related major bleeding. However, this increase in bleeding risk was largely restricted to patients undergoing PCI. 📄
  • Notable exclusion criteria from PLATO trial:
    • Any contraindication to the use of clopidogrel.
    • Need for oral anticoagulation therapy.
    • Increased risk of bradycardia.
    • Concomitant therapy with a strong CYP3A inhibitor or inducer.

when to use ticagrelor?

• Ticagrelor should be considered for MI patients who aren't taking oral anticoagulation and aren't at high risk of bleeding (recommended by both ESC and NICE guidelines).(32860058, 33301270)
• Ticagrelor is contraindicated among patients at risk for bradycardia (and also contraindicated in patients taking a daily aspirin dose >100 mg/day – but there are very few reasons to use such a high aspirin dose).

dose 💊

• 180-mg loading dose, followed by 90 mg BID.

side effects of ticagrelor

• Ticagrelor may cause nonexertional dyspnea as a side effect. This may improve over time, with continued use of ticagrelor.(33877270) Aminophylline may be utilized to transiently reverse dyspnea or bradycardia due to ticagrelor.(27920235)

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anticoagulation for patients not immediately undergoing PCI

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(Anticoagulation for patients undergoing PCI is discussed above. 📖)

who should receive anticoagulation?

• Heparin anticoagulation causes a short-term reduction in reinfarction. However, after stopping heparin there is a rebound in events. Ultimately, there is no net difference in the total number of reinfarctions.(1976875) Thus, a rational use of heparin is as a temporary bridge to stabilize coronary stenoses prior to PCI.🌊
• There isn't evidence to support anticoagulation in patients who aren't planned to undergo catheterization.(31855327) However, short-term anticoagulation may be reasonable in patients who are evolving rapidly and might become candidates for catheterization.
• The traditional practice of providing heparin anticoagulation for 48 hours as “medical management” without subsequent PCI is not evidence-based and needs to be abandoned. It exposes patients to the hemorrhage risk of a heparin infusion, without gaining any sustained benefit.

1st-line anticoagulant: Fondaparinux 2.5 mg sq daily 💊

• Compared to enoxaparin, fondaparinux caused less bleeding and reduced mortality in the OASIS-5 trial.(16537663) A prespecified subgroup analysis of the OASIS-6 trial likewise found that fondaparinux was superior to heparin among patients with STEMI not receiving reperfusion treatment.(18084015)
• The ESC 2020 NSTEMI guidelines and NICE 2020 guidelines both recommend fondaparinux as the first-line anticoagulant for patients not undergoing immediate catheterization (i.e., patients being medically managed, or receiving delayed PCI).(32860058, 33301270)
• Fondaparinux is contraindicated in renal dysfunction (GFR <20 ml/min).
• If fondaparinux is used alone, this will lead to an increase in catheter-related thrombi among patients undergoing PCI. However, this problem may be avoided by the addition of a single heparin bolus during the PCI procedure.
• Note that fondaparinux 2.5 mg sq daily is the same dose that is utilized for venous thromboembolism prophylaxis. This explains why fondaparinux 2.5 mg sq daily was proven to be safer than therapeutic enoxaparin in the OASIS-5 trial. The real strength of fondaparinux 2.5 mg sq daily is that it is a safe prescription that is less likely to cause harm than therapeutic low molecular-weight heparin or therapeutic unfractionated heparin.

2nd line anticoagulant: Low molecular-weight heparin

• Low molecular-weight heparin is useful when full anticoagulation is required for another reason (e.g., atrial fibrillation or pulmonary embolism).
• Low molecular-weight heparin has more predictable pharmacology than unfractionated heparin, often making it safer and more effective. Indeed, meta-analyses have found that low molecular-weight heparin is superior to unfractionated heparin in myocardial infarction.(22306479, 15238596)
• The usual dose is enoxaparin 1 mg/kg sq q12hr (contraindicated if GFR <30 ml/min).

3rd line anticoagulant: Unfractionated heparin infusion

• Unfractionated heparin is the only available option for patients with GFR<20 ml/min (who cannot be treated with fondaparinux or enoxaparin).
• Unfractionated heparin infusions have the highest risk of bleeding complications (compared to either fondaparinux or low molecular-weight heparin).

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Utilization of heparin infusions for “medical management” in patients who aren't going for catheterization.
• Undertreatment of an occlusive MI, due to lack of sufficient ST elevation to meet traditional definitions of STEMI.
• Forgetting to give aspirin (aspirin is the least exciting therapy, so it doesn't attract much attention – but it's one of the most important treatments).
• Failure to properly distinguish between Type-1 vs. Type-2 MI among patients admitted to ICU for a noncardiac reason.
• Giving beta-blocker to a tachycardic patient with soft blood pressures, thereby pushing a patient into frank cardiogenic shock.
• Misdiagnosis of submassive PE as NOMI (routine use of echo should avoid this; there are also characteristic EKG patterns of PE).🌊

Guide to emoji hyperlinks

• = Link to online calculator.
• = Link to Medscape monograph about a drug.
• = Link to IBCC section about a drug.
• = Link to IBCC section covering that topic.
• = Link to FOAMed site with related information.
• 📄 = Link to open-access journal article.
• = Link to supplemental media.

Guidelines

• European Society of Cardiology (ESC) guidelines:*
  • 2017 ESC guidelines for STEMI.
  • 2020 ESC guidelines for NSTEMI.
• NICE guidelines from the UK:* 2020 MI guidelines.
• 2013 ACCF/AHA guideline for STEMI.
• 2014 AHA/ACC guidelines for NSTEMI.
• *This chapter was largely based on ESC & NICE guidelines.

Review of seminal studies

• CURE trial (2001) – Addition of clopidogrel to aspirin among patients with unstable angina or NSTEMI within <24 hours after admission reduced the rate of myocardial infarction (but increased the rate of major bleeding).🌊 (11519503)
• AVOID trial (2015) – Supplemental oxygen is potentially harmful in normoxic patients with STEMI.🌊 (26002889)
• REALITY trial (2021) – No difference found between hemoglobin target of >7 mg/dL vs. >10 mg/dL. This suggests that a restrictive transfusion is safe. 🌊 (33560322)