Differential Diagnosis in Myocardial Infarction: A Comprehensive Guide for Clinicians

Introduction

Acute myocardial infarction (AMI), a critical cardiovascular emergency, remains a leading cause of mortality worldwide. Characterized by myocardial necrosis due to abrupt reduction in coronary blood flow, AMI necessitates prompt recognition and intervention to minimize myocardial damage and improve patient outcomes. Effective management of AMI hinges not only on timely diagnosis and treatment but also on the ability to differentiate it from other conditions that present with similar symptoms. This article delves into the differential diagnosis of myocardial infarction, aiming to enhance the clinician’s competence in accurately distinguishing AMI from its mimics, thereby facilitating appropriate and timely patient care. Understanding the nuances of differential diagnosis is crucial for healthcare professionals to ensure optimal management and reduce morbidity and mortality associated with AMI and related conditions.

Etiology and Risk Factors of AMI

While the focus of this article is differential diagnosis, understanding the underlying causes and risk factors for AMI is essential for comprehensive patient assessment. Atherosclerotic plaque rupture with subsequent thrombus formation is the most common etiology of AMI, leading to acute coronary artery occlusion. However, other less frequent causes include coronary artery embolism, vasospasm, and coronary artery dissection.

Risk factors for AMI are broadly categorized into modifiable and nonmodifiable factors. Nonmodifiable risk factors include age, sex, family history, and even male pattern baldness. Modifiable risk factors, which contribute significantly to AMI incidence, encompass smoking, dyslipidemia, diabetes mellitus, hypertension, obesity, sedentary lifestyle, poor oral hygiene, peripheral vascular disease, and elevated homocysteine levels. Recognizing these factors helps in risk stratification and understanding the pretest probability of AMI in patients presenting with suggestive symptoms.

Clinical Presentation of AMI: Symptoms and Signs

The classic presentation of AMI involves chest pain, often described as a crushing or squeezing sensation, radiating to the left arm, jaw, or back. However, the clinical spectrum of AMI is broad, and presentations can vary significantly, particularly in women, the elderly, and patients with diabetes.

Typical AMI Symptoms:

• Chest pain or discomfort (angina)
• Shortness of breath
• Diaphoresis (sweating)
• Nausea and vomiting
• Lightheadedness or dizziness
• Palpitations
• Anxiety

Atypical AMI Symptoms:

• Abdominal pain
• Back pain
• Jaw pain
• Fatigue
• Indigestion-like symptoms
• Unexplained weakness

Physical examination findings in AMI can be variable and may not always be specific. Patients may exhibit signs of distress, diaphoresis, pallor, and altered vital signs. A thorough physical exam should assess heart rate and rhythm, blood pressure, pulses, respiratory rate and effort, and cardiac auscultation for murmurs, gallops, or rubs. Pulmonary auscultation should evaluate for signs of pulmonary edema, such as rales. However, it’s crucial to recognize that a normal physical exam does not rule out AMI.

Differential Diagnosis of AMI: Mimicking Conditions

The challenge in diagnosing AMI lies in its symptom overlap with numerous other conditions. Accurate differential diagnosis is paramount to avoid misdiagnosis, ensure timely intervention for AMI, and prevent unnecessary interventions for mimicking conditions. The differential diagnosis for AMI is broad and includes cardiac, pulmonary, gastrointestinal, musculoskeletal, and psychological conditions.

Cardiac Conditions Mimicking AMI

• Pericarditis: Inflammation of the pericardium often presents with sharp, pleuritic chest pain that may worsen with inspiration or lying down and improve with sitting up and leaning forward. ECG findings in pericarditis, such as diffuse ST-segment elevation and PR depression, can mimic early STEMI, but typically lack reciprocal ST depressions. A pericardial friction rub on auscultation is suggestive of pericarditis.

• Myocarditis: Inflammation of the myocardium can cause chest pain, shortness of breath, and fatigue, similar to AMI. Myocarditis can be caused by viral infections, autoimmune diseases, or toxins. ECG changes in myocarditis are non-specific but may include ST-segment elevation, T-wave inversions, and arrhythmias. Elevated cardiac biomarkers may also be present, making differentiation from NSTEMI challenging. Clinical history, risk factors, and other diagnostic modalities are crucial for differentiation.

• Hypertrophic Cardiomyopathy (HCM): HCM can cause angina due to myocardial ischemia from increased oxygen demand and microvascular dysfunction. Chest pain in HCM is often exertional and may be associated with shortness of breath and palpitations. ECG findings in HCM can include ST-segment and T-wave abnormalities, and even Q waves, potentially mimicking AMI. Echocardiography is essential for diagnosing HCM and differentiating it from AMI.

• Aortic Dissection: This life-threatening condition involves a tear in the aortic intima, leading to separation of the aortic layers. Aortic dissection typically presents with sudden onset of severe, tearing or ripping chest or back pain, often radiating between the shoulder blades. Unequal pulses, blood pressure differences between arms, and new aortic regurgitation murmur may be present. While ECG findings may be non-specific or show signs of ischemia, aortic dissection is a vascular emergency requiring immediate imaging with CT angiography or MRI for diagnosis.

• Pulmonary Embolism (PE): PE can cause acute chest pain, shortness of breath, and hemodynamic instability, mimicking AMI. Risk factors for PE, such as prolonged immobilization, surgery, malignancy, or hypercoagulable states, should be assessed. ECG findings in PE may include sinus tachycardia, S1Q3T3 pattern, or T-wave inversions, but are often non-specific. Elevated troponin levels can occur in PE due to right ventricular strain. CT angiography of the chest is the diagnostic modality of choice for PE.

Figure: ECG changes in Pulmonary Embolism mimicking Myocardial Infarction. Note the T-wave inversions which could be misinterpreted as ischemic changes.

Alt text: ECG showing T-wave inversions, a non-specific finding that can be seen in pulmonary embolism and may mimic ischemia on an electrocardiogram.

• Vasospastic Angina (Prinzmetal Angina): This type of angina is caused by coronary artery spasm, leading to transient myocardial ischemia. Chest pain in vasospastic angina typically occurs at rest, often at night or early morning, and is relieved by nitrates. ECG during an episode of vasospasm may show ST-segment elevation, which resolves spontaneously or with nitrates. Provocative testing with acetylcholine or ergonovine during angiography can confirm the diagnosis.

Non-Cardiac Conditions Mimicking AMI

• Esophageal Spasm and GERD: Esophageal spasm can cause severe chest pain that can mimic angina. Gastroesophageal reflux disease (GERD) can also cause chest pain, often described as burning or pressure, which may be confused with cardiac chest pain. A thorough history, including factors that provoke or relieve symptoms, and trials of acid-suppressing medications can help differentiate these conditions.

• Acute Gastritis and Peptic Ulcer Disease: Upper abdominal pain from gastritis or peptic ulcer disease can sometimes radiate to the chest and be mistaken for cardiac pain. Pain associated with gastritis or ulcers is often related to meals and may be relieved by antacids.

• Acute Cholecystitis: Inflammation of the gallbladder can cause right upper quadrant abdominal pain that may radiate to the chest and mimic cardiac symptoms, particularly inferior MI. Physical examination findings, including Murphy’s sign, and abdominal ultrasound can help diagnose cholecystitis.

• Musculoskeletal Chest Pain: Costochondritis, muscle strain, or rib fractures can cause chest pain that is often localized and reproducible with palpation. The pain is typically sharp or aching and may worsen with movement or breathing.

• Pleurisy and Pneumonia: Pleuritic chest pain, worsened by inspiration and coughing, can be associated with pleurisy or pneumonia. Respiratory symptoms, fever, and abnormal lung sounds on auscultation are suggestive of pulmonary pathology. Chest X-ray is useful for diagnosis.

• Pneumothorax: Spontaneous pneumothorax can cause sudden onset of sharp, unilateral chest pain and shortness of breath, which may mimic AMI. Decreased breath sounds and hyperresonance to percussion on the affected side, along with chest X-ray findings, confirm the diagnosis.

• Anxiety and Panic Disorder: Anxiety and panic attacks can manifest with chest pain, palpitations, shortness of breath, and dizziness, mimicking AMI symptoms. However, in panic disorder, the symptoms are often episodic, associated with psychological stress, and lack typical ECG or biomarker changes of AMI.

• Herpes Zoster (Shingles): Reactivation of varicella-zoster virus can cause chest pain preceding the characteristic vesicular rash of shingles. Pain is typically dermatomal and may be burning or lancinating.

Diagnostic Approach to Differential Diagnosis

The diagnostic approach to chest pain involves a systematic evaluation to differentiate AMI from its mimics. This includes:

1. History and Physical Examination: A detailed history focusing on the characteristics of chest pain (onset, location, radiation, quality, aggravating and relieving factors), associated symptoms, risk factors, and past medical history is crucial. Physical examination should assess vital signs, cardiac and pulmonary status, and look for signs of non-cardiac conditions.

2. Electrocardiogram (ECG): A 12-lead ECG is the cornerstone of initial AMI evaluation. ST-segment elevation is highly suggestive of STEMI. However, ECG changes can be non-specific or absent in NSTEMI and various mimicking conditions. Serial ECGs are often necessary to detect evolving changes.

Figure: ECG showing Pardee Waves indicative of Acute Myocardial Infarction. The ST-segment elevations in inferior leads are characteristic of STEMI.

Alt text: Electrocardiogram demonstrating ST-segment elevation in inferior leads II, III, and aVF, known as Pardee waves, indicative of acute ST-segment elevation myocardial infarction (STEMI).

3. Cardiac Biomarkers: Troponin is the preferred biomarker for detecting myocardial necrosis. Elevated troponin levels, in the appropriate clinical context, are diagnostic of myocardial injury, including AMI. However, troponin elevation can also occur in other conditions such as myocarditis, pericarditis, PE, sepsis, and renal failure. Serial troponin measurements are essential to assess for a rise and fall pattern suggestive of acute myocardial injury.

4. Chest X-ray: Chest X-ray is helpful in evaluating for pulmonary causes of chest pain such as pneumonia, pneumothorax, or pleural effusion. It can also provide information about cardiac size and pulmonary congestion.

5. Cardiac Imaging:

   • Echocardiography: Echocardiography can assess left ventricular function, regional wall motion abnormalities, valvular disease, and pericardial effusion. It is useful in evaluating for myocarditis, HCM, and aortic dissection, and can provide supportive evidence for AMI.
   • Coronary Computed Tomography Angiography (CCTA): CCTA is a non-invasive imaging modality to visualize coronary arteries and detect significant stenosis or occlusion. It is useful in patients with intermediate risk of coronary artery disease and can help rule out AMI or identify alternative diagnoses like PE or aortic dissection.
   • Cardiac Magnetic Resonance Imaging (CMR): CMR is highly sensitive for detecting myocardial edema, inflammation, and scar. It is valuable in diagnosing myocarditis, differentiating ischemic from non-ischemic cardiomyopathy, and assessing myocardial viability after AMI.

6. Other Investigations: Depending on the clinical suspicion, other investigations may be warranted, such as:

   • D-dimer: To rule out pulmonary embolism.
   • Upper endoscopy: To evaluate for esophageal or gastric causes of chest pain.
   • Pulmonary function tests: To assess for asthma or COPD exacerbation.
   • Arterial blood gas: To assess oxygenation and acid-base status, especially in suspected PE or respiratory conditions.

Management and Prognosis

Once AMI is diagnosed and differentiated from mimicking conditions, prompt management is critical. Treatment strategies for AMI include antiplatelet therapy, anticoagulation, reperfusion therapy (PCI or thrombolysis for STEMI), and guideline-directed medical therapy.

The prognosis of AMI depends on various factors, including the extent of myocardial damage, time to reperfusion, left ventricular function, and comorbidities. Early recognition, accurate differential diagnosis, and timely management are essential to improve patient outcomes and reduce mortality associated with AMI.

Conclusion

Differential diagnosis of acute myocardial infarction is a critical skill for clinicians managing patients with chest pain. A wide range of conditions can mimic AMI, requiring a systematic and thorough diagnostic approach. Integrating clinical history, physical examination, ECG findings, cardiac biomarkers, and appropriate imaging modalities is essential to accurately differentiate AMI from its mimics. By mastering the differential diagnosis of AMI, healthcare professionals can ensure timely and appropriate management, ultimately improving patient outcomes and reducing the burden of cardiovascular disease.

Figure: Gross specimen of Myocardial Infarction. The image visually represents the area of myocardial damage discussed in the article.

Alt text: Macroscopic view of a heart specimen exhibiting myocardial infarction, characterized by visible tissue damage in the left ventricle and interventricular septum, illustrating the pathological consequences of MI.

References

1. Nascimento BR, Brant LCC, Marino BCA, Passaglia LG, Ribeiro ALP. Implementing myocardial infarction systems of care in low/middle-income countries. Heart. 2019 Jan;105(1):20-26.
2. Barberi C, van den Hondel KE. The use of cardiac troponin T (cTnT) in the postmortem diagnosis of acute myocardial infarction and sudden cardiac death: A systematic review. Forensic Sci Int. 2018 Nov;292:27-38.
3. Alaour B, Liew F, Kaier TE. Cardiac Troponin – diagnostic problems and impact on cardiovascular disease. Ann Med. 2018 Dec;50(8):655-665.
4. Massberg S, Polzin A. [Update ESC-Guideline 2017: Dual Antiplatelet Therapy]. Dtsch Med Wochenschr. 2018 Aug;143(15):1090-1093.
5. Scheen AJ. [From atherosclerosis to atherothrombosis : from a silent chronic pathology to an acute critical event]. Rev Med Liege. 2018 May;73(5-6):224-228.
6. Berg DD, Wiviott SD, Braunwald E, Guo J, Im K, Kashani A, Gibson CM, Cannon CP, Morrow DA, Bhatt DL, Mega JL, O’Donoghue ML, Antman EM, Newby LK, Sabatine MS, Giugliano RP. Modes and timing of death in 66 252 patients with non-ST-segment elevation acute coronary syndromes enrolled in 14 TIMI trials. Eur Heart J. 2018 Nov 07;39(42):3810-3820.
7. Deng D, Liu L, Xu G, Gan J, Shen Y, Shi Y, Zhu R, Lin Y. Epidemiology and Serum Metabolic Characteristics of Acute Myocardial Infarction Patients in Chest Pain Centers. Iran J Public Health. 2018 Jul;47(7):1017-1029.
8. Haig C, Carrick D, Carberry J, Mangion K, Maznyczka A, Wetherall K, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Mordi I, Ahmed N, Teng Yue May V, Ford I, Radjenovic A, Welsh P, Sattar N, Oldroyd KG, Berry C. Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights. JACC Cardiovasc Imaging. 2019 Jun;12(6):993-1003.
9. Alquézar-Arbé A, Sanchís J, Guillén E, Bardají A, Miró Ò, Ordóñez-Llanos J. Cardiac troponin measurement and interpretation in the diagnosis of acute myocardial infarction in the emergency department: a consensus statement. Emergencias. 2018 Oct;30(5):336-349.
10. Perera M, Aggarwal L, Scott IA, Logan B. Received care compared to ADP-guided care of patients admitted to hospital with chest pain of possible cardiac origin. Int J Gen Med. 2018;11:345-351.
11. Riley RF, Miller CD, Russell GB, Soliman EZ, Hiestand BC, Herrington DM, Mahler SA. Usefulness of Serial 12-Lead Electrocardiograms in Predicting 30-Day Outcomes in Patients With Undifferentiated Chest Pain (the ASAP CATH Study). Am J Cardiol. 2018 Aug 01;122(3):374-380.
12. Jneid H, Addison D, Bhatt DL, Fonarow GC, Gokak S, Grady KL, Green LA, Heidenreich PA, Ho PM, Jurgens CY, King ML, Kumbhani DJ, Pancholy S. 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2017 Oct 17;70(16):2048-2090.
13. Larson EA, German DM, Shatzel J, DeLoughery TG. Anticoagulation in the cardiac patient: A concise review. Eur J Haematol. 2019 Jan;102(1):3-19.
14. Bath PM, Woodhouse LJ, Appleton JP, Beridze M, Christensen H, Dineen RA, Flaherty K, Duley L, England TJ, Havard D, Heptinstall S, James M, Kasonde C, Krishnan K, Markus HS, Montgomery AA, Pocock S, Randall M, Ranta A, Robinson TG, Scutt P, Venables GS, Sprigg N. Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT. Health Technol Assess. 2018 Aug;22(48):1-76.
15. Adamski P, Adamska U, Ostrowska M, Navarese EP, Kubica J. Evaluating current and emerging antithrombotic therapy currently available for the treatment of acute coronary syndrome in geriatric populations. Expert Opin Pharmacother. 2018 Sep;19(13):1415-1425.
16. Stone GW, Ellis SG, Gori T, Metzger DC, Stein B, Erickson M, Torzewski J, Williams J, Lawson W, Broderick TM, Kabour A, Piegari G, Cavendish J, Bertolet B, Choi JW, Marx SO, Généreux P, Kereiakes DJ., ABSORB IV Investigators. Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial. Lancet. 2018 Oct 27;392(10157):1530-1540.
17. Lopes RD, de Barros E Silva PGM, de Andrade Jesuíno I, Santucci EV, Barbosa LM, Damiani LP, Nakagawa Santos RH, Laranjeira LN, Dall Orto FTC, Beraldo de Andrade P, de Castro Bienert IR, Alexander JH, Granger CB, Berwanger O. Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the SECURE-PCI Randomized Clinical Trial. JAMA Cardiol. 2018 Nov 01;3(11):1113-1118.
18. Choi AR, Jeong MH, Hong YJ, Sohn SJ, Kook HY, Sim DS, Ahn YK, Lee KH, Cho JY, Kim YJ, Cho MC, Kim CJ., other Korea Acute Myocardial Infarction Registry Investigators. Clinical characteristics and outcomes in acute myocardial infarction patients with versus without any cardiovascular risk factors. Korean J Intern Med. 2019 Sep;34(5):1040-1049.
19. Piotrowicz R, Wolszakiewicz J. Cardiac rehabilitation following myocardial infarction. Cardiol J. 2008;15(5):481-7.
20. Ruano-Ravina A, Pena-Gil C, Abu-Assi E, Raposeiras S, van ‘t Hof A, Meindersma E, Bossano Prescott EI, González-Juanatey JR. Participation and adherence to cardiac rehabilitation programs. A systematic review. Int J Cardiol. 2016 Nov 15;223:436-443.
21. Contractor AS. Cardiac rehabilitation after myocardial infarction. J Assoc Physicians India. 2011 Dec;59 Suppl:51-5.
22. Sjölin I, Bäck M, Nilsson L, Schiopu A, Leosdottir M. Association between attending exercise-based cardiac rehabilitation and cardiovascular risk factors at one-year post myocardial infarction. PLoS One. 2020;15(5):e0232772.
23. Aeyels D, Seys D, Sinnaeve PR, Claeys MJ, Gevaert S, Schoors D, Sermeus W, Panella M, Bruyneel L, Vanhaecht K. Managing in-hospital quality improvement: An importance-performance analysis to set priorities for ST-elevation myocardial infarction care. Eur J Cardiovasc Nurs. 2018 Aug;17(6):535-542.
24. Schwaab B. [Cardiac Rehabilitation]. Rehabilitation (Stuttg). 2018 Apr;57(2):117-126.
25. El Hajj MS, Jaam MJ, Awaisu A. Effect of pharmacist care on medication adherence and cardiovascular outcomes among patients post-acute coronary syndrome: A systematic review. Res Social Adm Pharm. 2018 Jun;14(6):507-520.