Internet Book of Critical Care (IBCC)

CONTENTS

diagnosis & risk stratification

• Nomenclature & types of MI
• Diagnosis
  • Differential diagnosis
  • ECG findings ➡️
• Risk stratification

general MI management

• General supportive care
  • Laboratory studies
  • Electrolytes
  • Hemoglobin & anemia
  • Analgesia
  • Oxygen
• PCI
• Aspirin
• Antithrombotic treatment for patients not undergoing prompt PCI:
  • P2Y12 inhibitors
  • Anticoagulation
• Beta-blocker
• Nitroglycerin
• ACE inhibitor or ARB
• Spirinolactone
• Lipid management
  • Statin pharmacology
• Shock management:
  • RVMI (right ventricular MI)
  • Cardiogenic shock ➡️
  • Impella ➡️

specific post/peri-MI complications

• Approach to the deteriorating post-MI patient
• Retroperitoneal hematoma
• Re-infarction
• Post-MI pericarditis
• Mechanical complications
  • Mitral valve chordae tendinae rupture
  • Ventricular septal defect (VSD)
  • Ventricular free wall rupture
  • LV pseudoaneurysm formation
  • LV aneurysm & thrombus
  • Dynamic LV outflow tract obstruction ➡️
• Tachyarrhythmia
  • Atrial fibrillation or atrial flutter
  • Ventricular arrhythmias
    • PVCs
    • Nonsustained VT
    • Sustained monomorphic VT
    • Polymorphic VT
    • AIVR (accelerated idioventricular rhythm)
  • Sinus tachycardia
• Bradyarrhythmia
  • Sinus bradycardia
  • Heart block
• LV thrombus

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 ECG 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 ECGs should be interpreted to diagnose coronary occlusion. For example, it has long been recognized that many ECG 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 ECG patterns that reflect coronary artery occlusion:
  • Occlusive MI (OMI): STEMI plus STEMI-equivalent patterns.
  • NonOcclusive MI (NOMI): Other ECG 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 ECGs (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.

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).
• ECGs (including baseline ECGs, ECGs obtained by paramedics in the field, and additional serial ECGs).
• Echocardiography.
• Troponin level (may be normal initially).
• Potassium level (hyperkalemia may generate pseudo-MI patterns on ECG).

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 ECG 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 ECG

• Echocardiography and ECG 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 ECG 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.

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.
• ECG: 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).
• ECG: 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.
• ECG: 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.
• ECG 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 ECG 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).
• ECG: Usually nonspecific. Aortic dissection may rarely cause occlusion of a coronary artery, producing an OMI-pattern ECG.
• 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.
• ECG: 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.
• ECG: 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.
• ECG: 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.

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

lab panel

• Electrolytes including Mg and Phos.
• Complete blood count.
• Liver function tests.
• Troponin levels.
• BNP.
• Lactate (if any concern for cardiogenic shock).
• Coagulation studies (tailored to any anticoagulants the patient may be receiving).
• Iron studies (if iron deficiency is suspected).
• Lipid profile (recommended as soon as possible after presentation, because LDL-C levels decrease modestly beginning 24 hours from symptom onset). (40014670)

electrolytes

• Target potassium >3.5 mEq/L. ?
• Target magnesium >2 mEq/L. ? (avoids arrhythmia).

hemoglobin & anemia

[1] hemoglobin transfusion target

• Summary:
  • A reasonable target hemoglobin level may be within the range of >8-10 mg/dL. The optimal hemoglobin level should be tailored to individual patient specifics. Studies comparing hemoglobin targets within this range have found essentially neutral results.
  • ACC 2025: Transfusion to ≧10 g/dL may be reasonable to reduce cardiovascular events. (Class IIb; 40014670)
• REALITY trial (2021) - No difference found between hemoglobin target of >7 mg/dL vs. >10 mg/dL. ? (33560322)
• MINT trial (2023)
  • Subjects: 3504 patients with OMI or NOMI and hemoglobin <10 mg/dL. Most patients had type-2 MI (56%) rather than type-1 MI (42%).
  • Randomization: Target >7-8 mg/dL or >10 mg/dL.
  • The study endpoint was neutral (including the composite endpoint, mortality, and reinfarction), but there were positive trends. (37952133)

[2] consider the source of bleeding

• [a] If there is possible GI bleeding, consider empiric proton pump therapy.
• [b] Retroperitoneal bleeding can occur after femoral PCI. ⚡️

[3] consider the need for IV iron

• Myocardial iron deficiency may impair the ability to recover from MI. (37722377)
• IV iron repletion should be considered for patients with iron-deficiency anemia, especially for patients with reduced ejection fraction.
• Additional information:
  • Iron-deficiency anemia: ?
  • IV iron for HFrEF: ?

analgesia

preferred approaches to the treatment of ischemic chest pain

• [1] Nitroglycerin. ⚡️
• [2] Beta-blockers (given selectively, if hemodynamically safe). ⚡️
• [3] Acetaminophen is reasonable. (39450757)

absolutely avoid NSAIDs for several reasons

• [1] Increased gastrointestinal bleeding.
• [2] Impaired renal function.
• [3] Impaired myocardial remodeling.
• [4] May mute the beneficial effect of aspirin.
• [5] Increased adverse cardiac events.

avoid opioids if possible

• Reasons to avoid opioids:
  • [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., nitroglycerin and beta-blockade).
  • [2] Opioid administration may delay oral absorption of P2Y12 inhibitors.
• For patients who have already had catheterization, opioids can be helpful (especially if complete revascularization was impossible, leading to ongoing ischemia).

oxygen

guideline recommendations

• If oxygen saturation is <90%, supplemental oxygen to increase saturation to ≧90% is recommended. (ACC 2025 Class I; 40014670)
• If oxygen saturation is ≧90%, routine administration of supplemental oxygen isn't recommended because it doesn't increase cardiovascular outcomes. (ACC 2025 Class III; 40014670)

evidentiary support

• AVOID trial: ?
  • Evaluated use of 8 liters nasal cannula for STEMI patients with saturation ≧94%.
  • Oxygen administration didn't help. It may have increased infarct size. (26002889)
• DETO2X-AMI: ?
  • Evaluated use of 6 liters nasal cannula among 6629 patients with suspected MI and oxygen saturation ≧90%.
  • Supplemental oxygen didn't affect mortality or hospitalization.

general indications for PCI

• ECG features:
  • OMI.
  • Recurrent dynamic ECG changes suggestive of ischemia (especially intermittent ST elevation).
  • NOMI with high risk of ischemic events (urgent PCI within 24 hours).
    • GRACE Risk score 2.0 ? may be preferred (with >140 suggesting PCI).
• Myocardial dysfunction:
  • Cardiogenic shock.
  • New/worsening heart failure attributable to acute MI (e.g., pump failure, ischemic mitral regurgitation).
• Electrical instability (VT/VF).
• Recurrent or persistent chest pain that is refractory to medical therapy. (ESC 2023, 37622654)

relative contraindications to PCI

• [1] Severe renal failure.
• [2] Patients at high risk of bleeding
  • After stenting, patient must remain on dual antiplatelet therapy.
  • Bleeding risk with antiplatelet therapy is discussed further below: ⚡️
• [3] Patients who are unlikely to be compliant with dual antiplatelet therapy.
• [4] Low life expectancy (e.g., severe dementia, advanced malignancy with poor oncologic prognosis, extremely elderly).
• [5] Patients with a history of prior CABG may benefit less from PCI. ?
• [6] Known coronary anatomy that precludes intervention.

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%) or readmission for heart failure. (18594042)
• When unclear, the decision to pursue PCI will be made with cardiology consultation. This should consider numerous factors (e.g., the specifics of ECG and echocardiography findings, renal function, indicators of risk due to myocardial ischemia, other active medical problems, and patient preferences).
  • Coronary CT angiography may help determine which patients will benefit from catheterization.

anticoagulation for patients undergoing PCI

• This will be determined by cardiology.
• The typical regimen involves aspirin and unfractionated heparin infusion before cardiac catheterization. Following successful PCI, ticagrelor is initiated and heparin is discontinued (leaving the patient on aspirin and ticagrelor).

indication

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

evidentiary basis

• Aspirin has been robustly demonstrated to cause a 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 critical anticoagulating agent in the context of MI.

further discussion of aspirin: ?

P2Y12 treatment before cardiac catheterization is usually not recommended, as this may delay CABG surgery. (35367005, 35166796) The challenging decision is whether to utilize P2Y12 inhibitors for patients who aren't undergoing an invasive treatment pathway.

[1] getting started: defining high bleeding risk

The Academic Research Consortium on High Bleeding Risk (ACR-HBR) may provide a helpful framework. High bleeding risk is defined as at least one major or two minor risk factors. (31116032)

major risk factors

• Anticipated use of long-term oral anticoagulation.
• Chronic kidney disease with GFR <30 ml/min.
• Hemoglobin <11 mg/dL.
• Spontaneous bleeding requiring hospitalization or transfusion within the past six months, or recurrent admissions.
• Platelet count <100 b/L.
• Chronic bleeding diathesis.
• Cirrhosis with portal hypertension.
• Active malignancy within the past year (excluding nonmelanoma skin cancer).
• Spontaneous intracranial hemorrhage at any time.
• Traumatic intracranial hemorrhage within the past year.
• Cerebral arteriovenous malformation.
• Moderate to severe ischemic stroke within the past six months (NIH stroke scale score >5).
• Nondeferrable major surgery on dual antiplatelet therapy.
• Major surgery or major trauma within a month.

minor risk factors

• Age >75 years.
• Moderate renal dysfunction (GFR 30-60 ml/min).
• Hemoglobin 11-13 g/dL (for men) or 11-12 g/dL (for women).
• Spontaneous bleeding requiring hospitalization or transfusion within the past 6-12 months.
• Long-term use of oral NSAIDs or steroids.
• Any ischemic stroke at any time not meeting the major criterion.

[2] indications for a P2Y12 inhibitor

• ESC guidelines recommend a P2Y12 inhibitor for patients who are not undergoing PCI and who don't have a high bleeding risk. (ESC2020 NSTEMI guidelines IIB; 32860058)
• ACC guidelines recommend a P2Y12 inhibitor for all patients with acute coronary syndrome. (Class IA, 40014670)

[3] choice of ticagrelor vs. clopidogrel

when to pick ticagrelor

• Indications for ticagrelor:
  • ESC and NICE guidelines: Ticagrelor should be considered for MI patients who aren't taking oral anticoagulation and aren't at high bleeding risk. (32860058, 33301270)
  • ACC guidelines: Ticagrelor is recommended to reduce MACE in patients with NSTE-ACS managed without planned invasive evaluation. (Class IB, 40014670) However, the supporting text acknowledges that clopidogrel could be helpful for patients at high bleeding risk.
• More on contraindications & dosing: ?

when to pick clopidogrel

• Indications for clopidogrel:
  • ESC 2023 guidelines recommend considering clopidogrel in patients >70 years old, especially if there is an increased bleeding risk. (Class IIb, LOE B) (37622654)
  • ACC guidelines: Clopidogrel is recommended if ticagrelor can't be tolerated or is contraindicated. (Class IB, 40014670)
• Contraindications to clopidogrel:
  • ⚠️ If the bleeding risk is very high, then P2Y12-inhibitors should be omitted 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)
  • ⚠️ For example, clopidogrel is not recommended in cancer patients with a platelet count <30,000 /uL. (ESC 2023, 37622654)
• More on contraindications & dosing: ?

evidentiary basis

Options include clopidogrel or ticagrelor. Pharmacologically, ticagrelor works more rapidly and consistently than clopidogrel (which may have slow absorption and erratic metabolism, depending on individual CYP2C19 activity). However, ticagrelor may carry an increased risk of bleeding.

CURE trial: aspirin plus {clopidogrel-vs-placebo}

• 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) Most patients didn't undergo angiography. 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.
• Notable 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.

PLATO trial: aspirin plus {ticagrelor-vs-clopidogrel}

• The PLATO trial was an RCT comparing clopidogrel vs. ticagrelor among 18,000 patients with acute coronary syndrome. (24727884)
• 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. ? There was no increase in life-threatening bleeding, ICH, or fatal bleeding.
• 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.

anticoagulation overview

• If going urgently for PCI: Heparin infusion.
• If future PCI is possible, 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 definitely no plan to pursue PCI, anticoagulation is not indicated.

1st-line anticoagulant if future PCI is possible: Fondaparinux 2.5 mg sq daily ?

• Evidence:
  • OASIS-5 trial: compared to enoxaparin, fondaparinux caused less bleeding and reduced mortality. (16537663)
  • OASIS-6 trial: A prespecified subgroup analysis of found that fondaparinux was superior to heparin among patients with STEMI not receiving reperfusion treatment. (18084015)
• Guidelines:
  • The ESC 2020 NSTEMI guidelines, NICE 2020 guideline, and ESC 2023 guideline all 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, 37622654)
  • ESC 2023 guidelines recommend fondaparinux for patients in whom PCI within 24 hours is not anticipated (Class IB recommendation). (37622654)
  • ACC 2025 guidelines recommend either enoxaparin or fondaparinux as an alternative to unfractionated heparin. for patients in whom an early invasive approach isn't anticipated. (40014670)
• Contraindications: Fondaparinux is contraindicated in renal dysfunction with GFR <20 ml/min.
• Risks: 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 heparin bolus during the PCI procedure.
• Dose & duration:
  • 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 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.
  • The OASIS-5 and OASIS-6 trials utilized fondaparinux for eight days or hospital discharge (whichever occurred first).

2nd line anticoagulant if future PCI is possible: 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 if future PCI is possible: 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).

evidentiary background: 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 before 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 risk of hemorrhage associated with a heparin infusion, without providing any sustained benefit.

contraindications to beta-blockers

• ⚠️ Bradycardia (HR <60).
• ⚠️ Heart block:
  • PR interval >240 ms.
  • Second/third-degree heart block.
• ⚠️ Cardiogenic pulmonary edema.
• ⚠️ Cardiogenic shock, or at-risk for developing shock: (21570515, 30285644)
  • Heart rate >110 b/m.
  • SBP <120 mm.
  • Shock index (HR/SBP) >~0.8
  • Severely reduced ejection fraction or RV failure.

indications for early, IV beta-blockers

• Who benefits from early IV beta-blockers?
  • [1] NO contraindications (listed above).
  • [2] If EF is relatively preserved, this supports the use of beta-blockers.
  • [3] Indications for early IV beta-blockers:
    • Ventricular tachyarrhythmias (strongest indication).
    • Hypertension (excluding SCAPE, which should not be treated with a beta-blocker).
    • Persistent anginal chest pain.
• Guidance:
  • ESC guidelines recommend considering IV beta-blockers for patients undergoing primary PCI and with systolic Bp >120 mm, no signs of acute heart failure, and no other contraindications. (ESC 2023 IIa recommendation, 37622654)
  • ACC 2025 guidelines state that evidence doesn't support the routine use of IV beta-blockers prior to PCI because of inconsistent results regarding whether they have any favorable effect on infarct size or clinical outcomes. (40014670)
• Dosing: sequential 5-mg doses of metoprolol (up to 15 mg, as tolerated/required). ?

indication for oral beta-blockers within the first 24 hours

• Guidance:
  • [1] In patients with ACS without contraindications, early (<24 hours) initiation of oral beta-blocker therapy is recommended to reduce the risk of reinfarction and ventricular arrhythmias. (Class IA, ACC 2025) This is consistent with other guidelines as well. (25260718, 23256914)
  • [2] Beta-blockers are also indicated for patients with HFrEF following MI.
• Dosing and agent selection: ?
  • Metoprolol tartrate may be preferred for more tenuous patients, since it is more easily titrated. Eventually, it may be consolidated into daily metoprolol succinate (for improved adherence).
  • Carvedilol is another excellent option. RCTs comparing metoprolol and carvedilol have shown similar outcomes. (28882337)

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 ideal.

indications

• [1] Symptomatic relief of anginal chest pain (or other anginal equivalent).
• [2] Hemodynamic optimization:
  • Cardiogenic pulmonary edema (especially SCAPE = strong indication for nitroglycerine).
  • Hypertension (although it's often preferable to use drugs supported by more robust evidence, such as beta-blockers or ACE inhibitors).

contraindications

• [1] Recent use of phosphodiesterase inhibitors:
  • Sildenafil or vardenafil within 24 hours.
  • Tadalafil within 48 hours.
• [2] Hypotension or normotension (caution if SBP <110 mm).
• [3] Marked bradycardia or tachycardia. (ESC 2023, 37622654)
• [4] Preload-dependent states:
  • Hypertrophic cardiomyopathy.
  • RV infarction.

dosing

• [1] Sublingual tablet of 0.4 mg q5 minutes (up to three doses).
• [2] If the patient responds favorably, may transition to a nitroglycerin infusion.
  • Anginal chest pain: infusion dosing may start at 10-20 ug/min.
  • Acute cardiogenic pulmonary edema: much higher doses may be needed. ?

evidentiary basis

• Physiological rationale:
  • [a] May cause coronary artery vasodilation.
  • [b] Decrease in preload and afterload may reduce myocardial oxygen demands.
• Evidence supporting the use of nitroglycerin is not robust. Clinical trials have not found benefit from nitrates (GISSI-3, ISIS-4). (7910229, 7661937) Furthermore, relief of chest pain following nitroglycerin is not a useful diagnostic indicator of myocardial ischemia. (14678917) Nonetheless, nitroglycerine remains clinically useful for specific indications as listed above.

Further discussion of nitroglycerin: ?

? ACE-i or ARBs don't usually need to be started immediately, but rather may be started within 24 hours.

contraindication to either ACE/ARB

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

indications for ACE-inhibitor or ARB

• Class IA indications: (2025 ACC guidelines, 23256914, 31815570)
  • LVEF ≦40%.
  • Diabetes.
  • Anterior OMI.
  • Persistent hypertension (note that this is an indication for both beta-blockers and ACE-inhibitors, so clinical judgement will be required regarding the sequence of agent selection).
• For patients with ACS who aren't considered high risk, an oral ACEi/ARB is reasonable to reduce MACE. (IIA ACC guidelines)

choice of ACE-inhibitor versus ARB

• The benefit of either an ACE-i or ARB seem to be similar.
• Indications to use an ARB:
  • (1) Patients unable to tolerate an ACE inhibitor due to a non-angioedema side effect (e.g., cough).
  • (2) For patients with heart failure and ejection fraction <40%, the combination of sacubitril plus valsartan may be superior to an ACE inhibitor. (25176015) Valsartan-sacubitril combination therapy hasn't been shown to be beneficial in the acute management of MI. However, initiation of valsartan may facilitate transition to valsartan-sacubitril later on for chronic therapy of heart failure.

dosing of ACE inhibitors ?

• Oral captopril titration ? may be useful when there is doubt about the patient's ability to tolerate an ACE-i. 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) ?

dosing of ARBs ?

• 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). (14610160)

evidentiary basis

• ACE inhibitors have been studied predominantly in OMI patients, with numerous studies demonstrating mortality benefit in the context of more severe MI. One RCT suggests that benefit might extend to NOMI patients as well.(16923416)
• The VALIANT trial found that valsartan was non-inferior to captopril in patients with recent MI plus either heart failure or ejection fraction <40%. (14610160)

indications of spironolactone in MI & heart failure:

• Post-MI patients with EF <40% and either diabetes or symptomatic heart failure (Class IB, ACC 2025 guidelines).
• In heart failure patients with EF<35% and persistent heart failure symptoms (NYHA class II-IV).

cautions/contraindications

• ⚠️ Renal dysfunction (GFR <30 ml/min).
• ⚠️ Hyperkalemia (contraindicated if K >5 mEq/L).
• Spironolactone may cause gynecomastia (but this doesn't occur with eplerenone).

dose

• Spironolactone:
  • Dose in heart failure: start 25 mg/day; if tolerated, may increase to 50 mg/day.
  • However, a clear dose-response relationship is not directly shown. (36229988)
  • >50 mg doses may be utilized for occasional patients with persistent volume overload and/or hypertension. (More on the use of spironolactone as a diuretic: ?)
• Eplerenone: same dose as spironolactone.

comments

• It doesn't acutely or significantly lower blood pressure. (Irwin & Rippe, 9th ed.)
• The primary limitation is hyperkalemia (which may be alleviated by using SGLT2-i and ARNI).
• (Further discussion of mineralocorticoid inhibitors: ?)

[1] high-intensity statin (discussed further in the section below)

[2] ezetimibe

• Potential indications for ezetimibe:
  • The patient is already on maximally tolerated statin therapy and LDL is still >70 mg/dL (Class IA, ACC 2025) or 55-69 mg/dL (Class IIA, ACC 2025).
  • Statin-intolerant patients. (Class IB, ACC 2025).
  • For any patients with ACS, the combination of ezetimibe may be considered along with a maximally tolerated statin. (Class IIb, ACC 2025).

contraindications, drug interactions, side effects ?

contraindications (class-wide)

• Acute liver disease or unexplained persistent elevation of serum transaminases.
• Renal impairment: increased risk of myopathy (relative).
• Risk for myopathy:
  • Pre-existing myopathy.
  • Uncontrolled hypothyroidism.
  • High-risk medications (see drug-drug interactions below).
• Consider temporary discontinuation if:
  • Uncontrolled seizures.
  • Severe electrolyte imbalance.
  • Severe hypotension.
  • Severe infections or illness.
  • Major surgical procedures.
  • Markedly elevated creatinine kinase.

drug-drug interactions with commonly used medications

• Class-wide interactions with all statins:
  • Myotoxins in general
    • Colchicine.
    • Daptomycin (recommended to hold statins).
    • Fibrates (especially gemfibrozil).
    • Niacin.
  • Inhibition of hepatic uptake transporter OATP1B1 (inhibits statin targeting to the liver, increases systemic side-effects).
    • Gemfibrozil.
    • Cyclosporine (also inhibits CYP3A4 and P-glycoprotein, which is especially problematic for atorvastatin).
    • Macrolide antibiotics (some also inhibit CYP3A4 and P-glycoprotein - greater interaction with atorvastatin).
  • Warfarin: Statins can potentiate the effects, causing an increase in INR.
• Pravastatin:
  • (No CYP interactions - only subject to the class-wide interactions listed above).
• Atorvastatin:
  • Inhibition of P-glycoprotein increases atorvastatin exposure.
  • Inhibition or induction of CYP3A4.
    • Dual inhibitors of CYP3A4 and P-glycoprotein may be especially problematic (e.g., amiodarone, diltiazem, ranolazine, ticagrelor, cyclosporine, and azole antifungals).
    • Ticagrelor may increase atorvastatin levels by 1.4-fold.
• Rosuvastatin:
  • Reduced absorption may result from the use of aluminum- and magnesium-containing antacids.

side effects

• Muscle issues:
  • Statin-associated muscle symptoms (SAMS) - May include muscle cramps and myalgia.
  • Myopathy (symptoms with CK elevation).
  • Rhabdomyolysis (marked CK elevation).
  • Immune-mediated necrotizing myopathy.
• Hepatitis (including rare cases of hepatic failure).
• Glycemic control: Increased serum glucose; may precipitate a new diabetes diagnosis.
• GI side effects: Constipation, nausea, diarrhea, abdominal pain.
• Differences between various agents:
  • Pravastatin is least likely to cause muscle or hepatic side effects.
  • Atorvastatin may be most likely to cause hepatic dysfunction or myopathy.
  • Rosuvastatin can cause transient, dose-related proteinuria and hematuria (which doesn't seem to relate to renal dysfunction and appears benign).

indications, advantages ?

• Acute Type I MI:
  • High-intensity statin therapy is recommended for patients with ACS to reduce the risk of MACE. (Class IA recommendation ACC 2025)
  • The benefit of high-intensity statin seems to be independent of baseline LDL-C concentration. (ACC 2025)
• Ischemic stroke.

dosing

• High-intensity (expected LDL reduction >50%):
  • Atorvastatin 40-80 mg (80 mg/day is often utilized). (11277825, 19958964)
  • Rosuvastatin 20-40 mg.
• Moderate-intensity (expected LDL reduction 30-50%):
  • Atorvastatin 10-20 mg.
  • Rosuvastatin 5-10 mg.
  • Simvastatin 20-40 mg.
  • Pravastatin 40-80 mg.
  • Lovastatin 40 mg.
  • Fluvastatin XL 80 mg.
  • Fluvastatin 40 mg BID.
  • Pitavastatin 1-4 mg.
• Low-intensity (expected LDL reduction <30%):
  • Simvastatin 10 mg.
  • Pravastatin 10-20 mg.
  • Lovastatin 20 mg.
  • Fluvastatin 20-40 mg.
• Renal failure:
  • Renal failure is a risk factor for myopathy and rhabdomyolysis.
  • Atorvastatin: No dose adjustment (drug levels unaffected).

pharmacology

• Chemical properties:
  • Pravastatin: Weight of 447 g/mol, LogP 0f 0.6
  • Atorvastatin: Weight 1209 g/mol, LogP 4.1
  • Rosuvastatin: Weight 481 g/mol, LogP 0.1
• Absorption:
  • Pravastatin:
    • Low oral bioavailability (20-30%). Absorption occurs via proton-coupled carrier-mediated transport (rather than passive diffusion). This contributes to low and variable bioavailability. Food reduces bioavailability.
    • There is extensive first-pass metabolism (extraction ratio 0.66).
  • Atorvastatin:
    • Atorvastatin is highly absorbed from the GI tract but has a low oral bioavailability (14%) due to extensive first-pass metabolism in the gut wall and liver.
    • Atorvastatin is a substrate for multiple transporters, including OATP-C, P-glycoprotein, and H+-monocarboxylic acid cotransporter. OATP-C genetic polymorphisms may affect the risk of statin-associated myopathy.
  • Rosuvastatin:
    • Absolute bioavailability is ~20%.
• Distribution:
  • Pravastatin:
    • Protein binding is 50%.
    • Vd is ~0.5 L/kg.
    • Limited tissue penetration: The hydrophilic nature of pravastatin helps target it to the liver. Hepatoselectivity is enhanced by selective hepatic uptake through a sodium-independent bile acid transporter (OATP1B1). Liver targeting may help reduce muscle and CNS adverse events as compared to more lipophilic statins.
  • Atorvastatin:
    • Protein binding is >98%.
    • Vd is high (381 L).
    • Hepatic uptake is facilitated by OATP1B1 and OATP1B3 transporters, allowing for hepatoselectivity (with minimal passive diffusion into nonhepatic tissues).
  • Rosuvastatin:
    • Protein binding is 88%.
    • The Vd is ~134 liters.
    • Limited tissue penetration: The hydrophilic nature helps maintain hepatoselectivity.
• Metabolism & elimination:
  • Pravastatin:
    • Unlike other statins, pravastatin isn't metabolized by CYP enzymes.
    • Major metabolites are formed by enzymatic ring hydroxylation in the liver.
    • Elimination is predominantly in the bile (~70%) with some secretion in the urine (~20%).
    • The half-life is ~2 hours, although the metabolites persist for a longer period.
  • Atorvastatin:
    • Metabolism is primarily by CYP3A4 to active ortho- and parahydroxylated derivatives and various beta-oxidation products. About 70% of circulating HMG-CoA reductase inhibitory activity is attributable to these metabolites. Inhibition of CYP3A4 increases atorvastatin exposure and the risk of adverse events.
    • Elimination is mostly in the bile.
    • The plasma half-life is ~14 hours, but the HMG-CoA reductase activity has a half-life of 20-30 hours due to the presence of active metabolites.
  • Rosuvastatin:
    • Minimal metabolism, primarily via CYP2C9.
    • >90% of the active plasma HMG-CoA reductase inhibitory activity is the parent drug.
    • Elimination is primarily (90%) via the bile. The half-life is ~20 hours.

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 requires immediate revascularization.
  • (3) Patients with RVMI have a higher risk of mortality and major complications.

clinical findings in RVMI

• Features of myocardial infarction (e.g., chest pain, nausea, vomiting).
  • VAgotonic manifestations may be prominent (nausea, vomiting, diaphoresis). (38692829)
• Patients may develop severe hypotension following nitroglycerin or morphine.
• The traditional triad of findings seen in RVMI is listed below. However, in practice, this has poor performance:
  • [i] Hypotension.
  • [ii] Clear lung fields.
  • [iii] Jugular venous distension.
• Refractory hypoxemia can occur due to the shunting of deoxygenated blood through a patent foramen ovale.

ECG diagnosis of RVMI

• Two specific ECG patterns are associated with RVMI:
  • [1] RVMI in the context of IMI ?
  • [2] Isolated RVMI (pseudo-anteroseptal MI) ?

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.
  • Reduced TAPSE (tricuspid annular plane systolic excursion). (34957766)
• [2] IVC 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).

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 it may lead to hemodynamic errors.
• RVMI vs. PE:
  • Most RVMI can be sorted out from PE based on simultaneous inferior OMI. However, ~2% of RVMIs occur in isolation, which is much harder to differentiate from PE.

management of RVMI

blueprint for RV failure management ?

mechanical support

• Options include ECMO with a Protek Duo catheter or Impella RP.

differential diagnosis for deterioration s/p MI

• Reinfarction (e.g., in-stent thrombosis).?
• Rupture:
  • Ventricular free wall rupture.?
  • Ventricular septal defect (VSD).?
  • Mitral valve chordae tendinae rupture.?
• Post-MI Pericarditis (Post-cardiac injury syndrome).?
• Hemorrhage (e.g., retroperitoneal hemorrhage ?).
• Medication effect (e.g., beta-blockers, ACE-inhibitors, diuretics).
• Arrhythmia.
  • Atrial fibrillation/flutter. ?
  • Ventricular tachycardia (VT).?
  • Heart block.?
• Other complications:
  • Pneumothorax.
  • Aortic dissection.
  • Pulmonary embolism.
  • Infection (e.g., ventilator-associated pneumonia, line infection).
  • Dynamic LV outflow tract obstruction (LVOTO).

investigation of delayed deterioration

• Review any recent interventions (e.g., medications, procedures).
• ECG (new ischemia?).
• Auscultation:
  • ? New murmur (mitral regurgitation, VSD).
  • ? Pericardial friction rub.
• Echocardiogram:
  • ? Pericardial effusion (pericarditis, ventricular wall rupture).
  • ? New mitral regurgitation.
  • ? New aortic regurgitation (may suggest aortic dissection).
  • ? Fall in ejection fraction or new wall motion abnormality (reinfarction, excess beta-blockers).
  • ? Evidence of VSD (color doppler shows flow across septum).
  • ? Hypovolemia (hemorrhage, over-diuresis).
  • ? RV dilation (RV infarction, PE, VSD).

epidemiology

• One of the most common complications (~1/200 procedures).
• Only occurs with femoral access (#RadialFirst).
• Usually occurs very early following catheterization.

presentation

• Severe hemorrhage manifests with hypotension and/or shock.
• Pain may occur in the abdomen, back, or flank. Tenderness or fullness may be noted.
• Less severe hematoma may present in a delayed fashion, with falling hemoglobin and hematoma tracking over abdomen/flank.
• Can present as jaundice and abnormal liver function tests (elevated lactate dehydrogenase, AST, and unconjugated bilirubin)

differential diagnosis

• Bleeding elsewhere (e.g., gastrointestinal bleed due to anticoagulation).
• Vasovagal reaction.
• Other causes of shock. ?

diagnostic tests

• CT angiogram - the study should be specifically protocoled to evaluate for active extravasation.
  • Performing a non-angiogram CT scan has little or no value. Merely identifying the hemorrhage isn't helpful, as this doesn't guide the next step in management. (28707444)

treatment

• (1) Supportive measures should be instituted without delay:
  • PRBC transfusion (type & cross-match, stay 2-4 units ahead).
  • Interruption of anticoagulation (e.g., if patient on a heparin infusion). For hemorrhagic shock, anticoagulation reversal may be considered (although this must be weighed against the risk of coronary stent thrombosis).
• (2) Interventional management:
  • Definitive control can generally be achieved by interventional radiology or interventional cardiology. Techniques will vary depending on the nature of the bleed, but may include coil embolization or placement of a covered stent.
  • Perhaps the most important indication for intervention is ongoing extravasation of blood seen on CT scan.
  • Most patients don't require interventional therapy. Rather, with conservative management most bleeds will tamponade eventually.
• (3) Vascular surgery?
  • Theoretically this is a third-line treatment, if all else fails.

presentation

• Recurrent ischemic symptoms (e.g., anginal chest pain).
• In-stent thrombosis may cause severe transmural infarction.

differential diagnosis

• Type-II MI due to another aggravating factor (e.g., anemia, hemorrhage).
• Pericarditis.
• Pulmonary embolism.

diagnostic tests

• EKG may show new ischemic changes.
• Troponin may re-elevate, but this is often difficult to discern in the context of previously elevated troponin values.
• Echocardiography may reveal a new wall motion abnormality.
• The key is comparison to the last EKG and echocardiogram obtained:
  • Some patients with poor reperfusion following their initial MI will have have persistent ST elevation (which may eventually evolve into an LV-aneurysm pattern on the EKG). This pattern of persistent ST elevation doesn't represent represent re-infarction.

treatment

• (a) In-stent thrombosis requires immediate repeat PCI.
• (b) Type-II MI may be treated in the usual fashion (e.g., beta-blocker to reduce myocardial oxygen demand, possibly nitroglycerine).

early infarct-related pericarditis

pathophysiology

• Occurs within the first 4 days after MI (due to transmural necrosis that directly causes pericardial inflammation).

diagnosis

• This occurs within ~1-4 days after a transmural MI.
• Diagnostic criteria are the same as for delayed pericarditis (as discussed below).

treatment

• This is generally self-limiting, so the intensity of treatment is unclear. It may be reasonable to individualize therapy based on the individual patient disease severity and risks of high-dose aspirin.
• ESC 2023 guidelines state:
  • Treatment includes aspirin 500 mg q8-12 hours, according to the clinical case.
  • Prolonged treatment beyond 5-7 days usually isn't required.
• ACC 2025 guidelines state:
  • Acetaminophen can be given for symptomatic relief.
  • High-dose aspirin may be used if symptoms persist over time. (40014670)

late pericarditis, aka post-cardiac injury (Dressler) syndrome

basics

• This is a delayed inflammatory reaction, which is more significant and requires more active therapy.
• This may solely include pericarditis, or it may involve a combination of pericarditis plus pleural effusions (pleuropericarditis).

epidemiology

• This is rare in the modern era of early reperfusion therapy (0.1-0.5%). (40014670)
• Occurs between one week to three months after MI (most frequently after 1-2 weeks). (ESC 2023, 37622654)

presentation

• Chest pain is typically pleuritic (different in quality from original ischemic pain).
  • Radiation to trapezius ridge supports pericarditis.
  • May improve with leaning forward.
• Fever is often seen.
• Tamponade is rare.

diagnostic tests

• Auscultation may reveal pericardial friction rub.
• EKG may reveal diffuse ST elevation.
• Echocardiogram may reveal pericardial effusions (although these may also occur in the absence of pericarditis).
• CXR may reveal pleural effusion and pneumonitis.
• Lab evaluation may show leukocytosis (which is neither sensitive nor specific).

diagnostic criteria for pericarditis

• Two of the following support the diagnosis of pericarditis: (ESC 2023, 37622654)
  • Pleuritic chest pain (>80%).
  • Pericardial friction rub (>60%).
  • Suggestive EKG changes.
  • New or worsening pericardial effusion (>70%).

differential diagnosis

• Re-infarction.
• Ventricular free wall rupture (may be suggested by pericardial effusion >1 cm).
• Pulmonary embolism.

treatment

• First line therapy is high-dose aspirin:
  • 500-1000 mg every 6-8 hours, until symptomatic improvement.
  • Then taper by 250-500 mg every two weeks. (ESC 2023, 37622654)
  • A proton pump inhibitor should be given to prevent gastric ulceration.
• Colchicine:
  • Colchicine is often recommended for patients without contraindications (e.g., renal insufficiency). (30987913)
  • Adjunctive colchicine may be used for three months (0.5 mg PO twice daily). (ESC 2023, 37622654)
• Pericardial effusion isn't a contraindication to using antithrombotics and/or anticoagulants if these are otherwise indicated. (ESC 2023, 37622654)

epidemiology

• Rare, usually occurs within a week of MI.
• Typically occurs with inferior or posterior MI, affecting the posteromedial valve leaflet (figure above).
• Can occur with relatively small infarctions in about half of cases.
• Rupture accounts for more than half of acute, severe mitral regurgitation that occurs after MI. (33295949)

presentation

• Dyspnea, respiratory failure due to pulmonary edema.
• Hypotension/shock.
• The initial MI may be mild, so patients may present initially with ruptured papillary muscle.
  • In this presentation, the initial findings are often those of acute heart failure.
  • ? Whenever a patient with heart failure is encountered with normal ejection fraction, be sure to investigate valvular function with color doppler.

diagnostic tests

• Lung ultrasound and/or chest radiograph shows cardiogenic pulmonary edema. Dysfunction of the posterior mitral valve leaflet may cause asymmetric pulmonary edema, which predominantly involves the right upper lobe.
• Echocardiography
  • Generally shows mitral regurgitation with a flail leaflet. However, this can be missed if there is a narrow and eccentric regurgitant jet. Transthoracic echocardiography only has a sensitivity of ~80%, so transesophageal echocardiography may be needed.(30987913)
  • Ejection fraction is often normal or elevated (due to unloading effect of mitral regurgitation). (Griffin 2022)
• ECG may be relatively benign. Shock which is disproportionate to ECG changes suggests acute mitral regurgitation. (Griffin 2022)
• (On auscultation, the murmur may be unimpressive or absent, due to rapid pressure equalization between the left ventricle and left atrium.)

differential diagnosis

• Ventricular septal defect can present in a similar fashion.
• Causes of acute mitral regurgitation after MI:
  • (1) Rupture of chordae tendineae.
  • (2) Papillary muscle dysfunction is common following MI (usually due to inferior MI).
  • (3) Mitral valve annulus dilation, due to dilation of the left ventricle.
  • (4) Anterior MI with dynamic LV outflow tract obstruction (LVOTO) and systolic anterior motion of the mitral valve.

treatment

• Temporary stabilization:
  • Afterload reduction reduces regurgitation. However, in patients with profound hypotension, norepinephrine may be required to maintain a minimal blood pressure consistent with life.
  • Inotrope may be required.
  • Intra-aortic balloon pump may be considered (but shouldn't delay surgery).
  • Noninvasive ventilation or intubation may be required for management of pulmonary edema. (33295949)
• Operative intervention is required:
  • (1) Generally this consists of emergent surgery.
    • If the patient hasn't been revascularized, this surgery should ideally be a combined CABG plus mitral valve repair/replacement.
  • (2) Transcatheter mitral valve repair may be another option. (33295949)

epidemiology

• Rare (~0.3%), typically within the first week post-MI. There may be a bimodal incidence, with the first peak within <24 hours and the second after 3-5 days. (33295949, Griffin 2022)
• Often follows a large anterior infarct, but the rate may be similar among either anterior or inferior MIs.

presentation

• Dyspnea that may be accompanied by cardiogenic pulmonary edema.
• Sudden hemodynamic deterioration.
• Recurrent anginal chest pain (due to myocardial strain).

diagnostic tests

• Auscultation: Loud, holosystolic, harsh murmur might be heard.
• Echocardiogram:
  • RV volume overload (dilation).
  • Doppler echo may show flow across ventricle.
  • Inferior or lateral infarction may cause basal VSDs that can be missed on routine transthoracic echocardiography. (33295949)
  • Best views:
    • Basal VSD: parasternal long-axis with medial angulation; apical long-axis, subcostal four-chamber view, parasternal short-axis.
    • Apical VSD: apical 4-chamber. (Griffin 2022)

differential diagnosis

• Presentation most similar to papillary muscle rupture.
• Hemodynamic deterioration with RV dilation may mimic PE.

treatment

• Stabilization:
  • Afterload reduction with a systemic vasodilator may favor blood flow from the left ventricle to the aorta (instead of refluxing into the right ventricle) - if the systemic blood pressure is high enough to tolerate this. Alternatively, for patients with profound hypotension, norepinephrine may be required to achieve a blood pressure compatible with life.
  • Inotropic support is often needed.
  • Intra-aortic balloon pump may be considered, but shouldn't delay surgery.
  • Cardiogenic pulmonary edema may be stabilized temporarily with noninvasive ventilation. Caution is required with intubation, as this may precipitate cardiovascular collapse.
• Repair:
  • Even small VSDs should be repaired (they may suddenly enlarge). Historical series suggest a mortality of ~95% without surgery. (10618300)
  • Surgery is generally preferred, but transcatheter closure is another option. In some cases, transcatheter closure may be used to stabilize the patient as a bridge to definitive surgical repair. Complications of percutaneous VSD closure may include persistent shunting, arrhythmias, tamponade, bleeding, device embolization, hemolysis, and tricuspid leaflet chordal rupture. (33295949)

epidemiology

• Rare.
• Typically occurs in the context of a large anterior MI with an occluded LAD (although LCX causes 40% of ruptures and RCA occlusion causes 18%).(30987913)
• Generally occurs within the first 1-2 weeks.
• Risk factors include:
  • Single-vessel transmural infarction.
  • Late or incomplete reperfusion.
  • Female gender.
  • No prior MI or angina.
  • Age >70 years. (Griffin 2022)

presentation

• Two types of presentation are described in the surgical literature as “blowout” or “oozing” presentations. (33295949) Overall, the presentation tends to mimic pericardial tamponade.
• Sudden rupture: Acute tamponade, cardiac arrest due to pulseless electrical activity.
• Subacute rupture: Chest pain, dyspnea, vomiting, fluctuating hemodynamic instability.

ECG

• May see variety of findings:
  • Persistent STE is often seen (due to failure to re-perfuse).
  • Recurrent STE or STD may occur.
  • New Q-waves may be seen.
• Overall, this may be misleading (potentially pointing towards re-infarction or pericarditis).

echocardiography

• Pericardial effusion:
  • Sensitive, but nonspecific in the context of MI.
  • The presence of internal echoes or echogenic masses (clot) within pericardial effusion increases specificity.
• Contrast echocardiography may show extravasation of contrast material into the pericardium.
• Additional diagnostic features are similar to other causes of tamponade. ?

differential diagnosis

• Post-MI pericarditis may cause a pericardial effusion.
• Aortic dissection may cause hemorrhagic tamponade.

treatment

• In tamponade, pericardiocentesis may be used as bridge to surgery. However, there is also a risk that pericardiocentesis could increase blood pressure and the pressure gradient across the myocardium, causing the wall rupture to extend further.(30987913) If echocardiography shows that the pericardium contains predominantly clotted blood, then pericardiocentesis is likely to fail. (33295949)
• Hemodynamic optimization (e.g., fluid, inotropes). However, avoid hypertension as that could theoretically aggravate bleeding from the left ventricle.
• Emergent surgical repair is generally required. Mortality with medical management is quoted at ~90%. (33295949)

• This is essentially a contained rupture of the LV (clot and pericardium seal off the rupture).
• Clinical presentation:
  • May include dyspnea or chest pain.
  • Thrombus formation with embolization may lead to systemic infarction(s).
  • Ventricular arrhythmias may occur. (Griffin 2022)
• ECG:
  • May show persistent ST elevation.
  • May show regional pericarditis.
  • Most often, ECG is nonspecific. (Griffin 2022)
• Diagnosis is often based on echocardiography (compared to a true aneurysm, the neck is generally narrower). In some cases, cardiac CT scan or cardiac MRI may help clarify the anatomy. (33295949)
• Don't be misled by the “aneurysm” verbiage - this is extremely dangerous.
• Treatment: overall, similar to the management of a subacute myocardial rupture. Stabilize the patient and consult cardiothoracic surgery.

These two pathologies are very closely linked, with LV thrombus usually complicating the presence of an LV aneurysm.

epidemiology

• LV aneurysm and thrombus both have an incidence of roughly ~10%.
• These tend to occur following transmural, anterior wall MI.
• The incidence of LV thrombus increases over the first two weeks following MI. (ESC 2023, 37622654)

symptoms

• LV aneurysm may lead to additional symptoms:
  • Heart failure (due to abnormal ventricular geometry, for example functional mitral regurgitation).
  • Recurrent ventricular arrhythmias. (Griffin 2022)
• LV thrombus may manifest with distal embolization (e.g., stroke).

diagnosis

• ECG in LV aneurysm often reveals persistent STE with shallow TWI.
• Echocardiography is the front-line screening test. However, echocardiography may be equivocal for thrombus formation.
• Cardiac MRI is the definitive gold-standard test. Cardiac MRI should be utilized if echocardiography yields unclear results. (ESC 2023, 37622654)

treatment

• LV aneurysm:
  • Treatment involves standard post-MI therapies (e.g., ACE-inhibitor or ARB may be especially useful to avoid aneurysm expansion).
  • It's controversial whether to anticoagulate patients for LV aneurysm without an identified thrombus, especially in the context of a patient who is already on dual antiplatelet therapy. (Griffin 2022)
• LV thrombus:
  • Anticoagulation is indicated (e.g., heparin infusion initially, with transition to chronic oral anticoagulation).
  • The duration of therapy may typically range from 3-6 months. Repeat imaging is important to ensure resolution. (ESC 2023, 37622654)

epidemiology

• AF may represent the recurrence of pre-existing paroxysmal AF or new-onset AF.
• Risk factors include:
  • History of atrial fibrillation.
  • Congestive heart failure, LV dysfunction.

treatment

• A rhythm-control strategy may be preferred for:
  • [1] AF that causes hemodynamic instability or ischemia (which may worsen the MI).
  • [2] New-onset AF in the context of MI.
• If a rate-control strategy is pursued:
  • Beta-blockade is preferred over diltiazem (if the patient is hemodynamically stable enough to tolerate it).
• (Further discussion of atrial fibrillation in general: ?)

PVCs (premature ventricular contractions)

background

• >10 PVCs per hour predict higher long-term mortality.
• The CAST trials demonstrated that arrhythmia suppression using class IC antiarrhythmics increased mortality (encainide, flecainide, and moricizine). Elevated mortality could be explainable by the proarrhythmic properties of IC agents.
• The CAMIAT trial (Canadian Amiodarone Myocardial Infarction Arrhythmia Trial) evaluated the role of amiodarone in patients with frequent PVCs or one run of VT. Amiodarone reduced the risk of resuscitated ventricular fibrillation or arrhythmic death from 7% to 4.5% (p = 0.016). (9078198) However, this result required long term therapy with amiodarone. A meta-analysis of 13 trials of amiodarone among patients with heart failure or following MI found a reduction in mortality. (9371164)

management of frequent PVCs and/or NSVT

• Repeat an ECG to evaluate for any acute ischemic changes.
• Electrolytes should be monitored and repleted (target Mg >2 mg/dL, K >3.5 mEq/L).
• Beta-blockade may be the optimal therapy if the patient is hemodynamically stable enough to tolerate.
  • Discussion on the role of beta-blockade s/p MI: ?.
• Amiodarone could be considered in selected situations:
  • Ectopy is causing symptoms or hemodynamic compromise. (Hurst 15e)
  • Escalating pattern of ventricular ectopy, long runs of NSVT that almost meet criteria for sustained VT). (37009192)

NSVT (nonsustained ventricular tachycardia)

• NSVT is defined as wide-complex tachycardia lasting <30 seconds, terminating spontaneously, and not causing hemodynamic collapse.
• Early NSVT (<48 hours after MI) may not be associated with a risk of sudden cardiac death, since this reflects transient elevated automaticity or triggered activity in the ischemic myocardium. NSVT after 48 hours is more likely to reflect scar formation, which may associate with an elevated long-term risk of sudden cardiac death. (37009192)
• Management of NSVT is similar to the management of PVCs as discussed in the section above. ☝️

sustained monomorphic VT

definition

• Sustained monomorphic VT is defined as ventricular tachycardia which lasts >30 seconds or causes hemodynamic collapse.
• Note that if the rate is low (<~110 b/m) this may represent accelerated idioventricular rhythm (AIVR ?) - which is typically a benign arrhythmia associated with reperfusion.

diagnosis

• Following MI, any monomorphic, wide-complex tachycardia is exceedingly likely to be VT and should generally be treated as such.
• (Further discussion of the approach to wide-complex tachycardia: ?.)

treatment: initial considerations

• Initial management is based on ACLS algorithms (DC Cardioversion for unstable patients versus amiodarone for hemodynamically stable patients). Following conversion to sinus rhythm, patients will often be treated with an amiodarone infusion to prevent recurrence. Lidocaine ? may be used as a second-line anti-arrhythmic (with typical dosing including a bolus of ~100 mg followed by 1-4 mg/min infusion).
• Ischemia should be considered as a potential underlying cause, and treated if appropriate (e.g., with percutaneous coronary intervention).
• Electrolyte abnormalities should be corrected (e.g. target Mg >2 mg/dL and K >3.5 mM).
• Avoid beta-agonists wherever possible (e.g., dobutamine, epinephrine). Beta-blockers should be considered if hemodynamics will tolerate them (noting that beta-blockers are supported by the most robust evidence to reduce post-MI ventricular arrhythmias). ?
• Treat conditions which may be increasing sympathetic tone (e.g., pain or anxiety). This is an especially important consideration among patients who are intubated and may be unable to report these symptoms.
• For recurrent arrhythmias refractory to therapy, see the section on VT storm. ?

treatment: longer term considerations

• Early VT (<48 hours post MI) may not require ongoing antiarrhythmic therapy, especially if the patient can be successfully revascularized.
• Sustained VT or VF >48 hours post MI generally implies the presence of myocardial scar with an ongoing risk of malignant arrhythmia:
  • [1] These patients may benefit from more extended periods of beta blockers and/or antiarrhythmic therapy (usually amiodarone). The risk of sudden cardiac death is highest in the first month post-MI. (40014670)
  • [2] 2025 AHA/ACC guidelines state that ICD implantation is reasonable for patients with clinically relevant ventricular arrhythmias >48 hours and within 40 days post MI to improve survival (Class IIa recommendation). (40014670)
• Additional indications for AICD insertion are listed below. (40014670) The decision to insert an AICD is generally delayed for at least a month after MI, to determine if the LVEF will improve over time:
  • EF ≦30% with NYHA class I, II, or III.
  • EF 31-35% with NYHA class II or III.
  • EF ≦40% with inducible VT.

polymorphic VT due to active ischemia

• Basics: Polymorphic VT often reflects active myocardial ischemia. It may be most common early in the course of a myocardial infarction (e.g., <48 hours after MI).
• Differential diagnosis: If the QTc is significantly prolonged, the differential diagnosis includes torsade de pointes. However, this can get confusing, because myocardial ischemia itself may prolong the QT interval somewhat. Torsade isn't particularly common among patients with acute MI, but it may be caused by various QT-prolonging medications (e.g., sotalol or dofetilide).
• Treatment:
  • Optimal treatment may be reperfusion (electrical instability is an indication for PCI).
  • Anti-arrhythmic therapies may be similar to monomorphic VT (see above).
  • If there is a concern regarding possible torsade de pointes, administration of IV magnesium is safe and reasonable. (Management of torsade is discussed here: ?)

• The key aspect of sinus tachycardia is evaluation and treatment of the underlying cause of the sinus tachycardia. In the context of MI, common causes of tachycardia could include:
  • Anxiety and/or pain.
  • Systolic heart failure with compensatory tachycardia.
  • Beta-adrenergic medications.
  • Anemia related to post-PCI bleeding; hypovolemia.
  • Pericardial tamponade.
  • Hypoglycemia.
  • (Further discussion of the causes of sinus tachycardia is here: ?)
• Evaluation should include bedside echocardiography.
• Beta-blockers should generally be reserved until a complete evaluation of the potential causes of sinus tachycardia has been performed. Cautious beta-blockade may be considered once the following factors have been established:
  • Absence of any other treatable cause of sinus tachycardia, especially:
    • Reasonable ejection fraction.
    • Absence of hypovolemia or acute hemorrhage.
  • Robust blood pressure with reassuring shock index (e.g., HR/SBP < ~0.8).

basics

• Sinus bradycardia is usually associated with inferior MI, typically due to proximal occlusion of the right coronary artery.
• Bradycardia may result from ischemic injury to the SA node, or increased vagal tone due to stimulation of nerves adjacent to the AV node (Bezold-Jarisch phenomenon). (34957766)
• Bradycardia is usually responsive to medical therapies and resolves within 24 hours. (34957766)

investigation

• Consider alternative causes of sinus bradycardia as discussed here (especially medications including ticagrelor): ?

management: acute

• ⚠️ Prompt management is warranted for HR <50 b/m, even without hypotension. (38692829) Especially in patients with RVMI, bradycardia may initiate a chain of events leading to RV failure and cardiogenic shock.
• Infusion of an inotrope is often adequate for initial therapy:
  • Epinephrine infusion may be suitable for patients with hypotension.
  • Dobutamine may be reasonable for patients with preserved blood pressure yet impaired perfusion.
• Atropine or glycopyrrolate may be effective for patients with bradycardia due to excessive vagal tone (as a component of the Bezold-Jarisch phenomenon due to stimulation of nerves adjacent to the AV node). (34957766)
• (Further general discussion of the management of bradycardia: ?).

management: chronic

• Indications for insertion of permanent pacemaker may include: (40014670)
  • [i] Substantial infranodal conduction system disease:
    • Mobitz II.
    • High-grade atrioventricular block.
    • Alternating bundle-branch block.
    • Infranodal 3rd degree AV block.
  • [ii] Persistent 3rd-degree AV block (e.g., perhaps >72 hours). (37009192)

heart block due to inferior MI

• Pathophysiology:
  • Generally due to ischemia involving the AV node and/or elevated vagal tone.
  • The AV node has dual circulation, so generally it is resistant to true infarction and will eventually recover. (Sadhu 2023)
• Clinical presentation:
  • Patients often have a junctional escape rhythm (narrow-complex, with heart rate 40-60 b/m).
  • Heart block is usually transient (resolving within a week).
• Treatment:
  • (Immediate management: see the chapter on bradycardia. ?)
  • Bradycardia may respond to atropine, especially if occurring early in course of MI. Alternative or additional therapies may include an epinephrine or dobutamine infusion.
  • This can generally be managed conservatively (without transvenous wire insertion). Recovery usually occurs relatively quickly, especially following revascularization.
  • Rarely, heart block may persist for 1-2 weeks. This may be responsive to theophylline or aminophylline. (Sadhu 2023)

heart block due to anterior MI

• Pathophysiology:
  • Generally reflects septal myocardial necrosis resulting from a very proximal LAD occlusion.
  • The block is located below the AV node.
• Clinical presentation:
  • May develop abruptly, or can be preceded with RBBB with either LAFB or LPFB (bifascicular block).
  • Often causes instability (or associated with instability).
• Treatment:
  • (Immediate management: see the chapter on bradycardia. ?)
  • ⚠️ Block below the AV node can be exacerbated by atropine, so this should be avoided. (37009192, Griffin 2022)
  • Indications to consider transvenous pacing may include:
    • (a) Mobitz II or higher grade block.
    • (b) New bundle-branch block (especially LBBB).
    • (c) Bifascicular block (RBBB plus either LAHB or LPFB, or alternating RBBB and LBBB).

clinical presentation

• [1] Thromboembolic complications.
• [2] Asymptomatic imaging finding.

risk factors

• Anterior OMI with apical hypokinesis.
• EF <30% (especially with an LV aneurysm).

diagnosis

• Transthoracic echocardiogram is the initial study.
• If TTE is unclear, CMRI is the preferred definitive imaging modality.

management

• Anticoagulation is generally warranted (either warfarin, heparin, or a DOAC).
• After three months, repeat imaging may be performed to determine if the thrombus is persistent.

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 essential 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 ECG patterns of PE). ?
• For suspected retroperitoneal hemorrhage, obtain a stat CT angiogram (make sure the study is protocoled as an angiogram).
• For decompensation after myocardial infarction, echocardiogram is critical to evaluate for a diverse range of complications.
• Some patients may present to the hospital with heart failure due to a ruptured chordae tendineae (following a silent or mildly symptomatic myocardial infarction). For patients with heart failure and a normal appearing ventricle, look carefully for a small eccentric regurgitant jet from the mitral valve.

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.

MI guidelines

• European Society of Cardiology (ESC) guidelines:
  • 2017 ESC guidelines for STEMI.
  • 2020 ESC guidelines for NSTEMI.
  • 2023 ESC unified guidelines for STEMI & NSTEMI.
• NICE guidelines from the UK:* 2020 MI guidelines.
• American guidelines:
  • 2025 unified guidelines for acute coronary syndrome.