MKSAP quiz on cardiac biomarkers

The following cases and commentary, which focus on use of cardiac biomarkers, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).

Case 1: Young cardiac inpatient

A 32-year-old woman is hospitalized for 2 days of malaise, fatigue, frequent chest pain without particular exacerbating or relieving factors, subjective fevers, and shortness of breath with exertion that is improved by rest. Her medical history is unremarkable, she does not smoke or use illicit drugs, and she is on no medications. She has no history of arthralgias, arthritis, photosensitivity, pleuritis, or pericarditis. Both of her parents are alive and well.

On physical examination, temperature is 38.1°C (100.6°F), blood pressure is 110/75 mm Hg, and pulse is 120/min. She is oriented and alert. There is mild jugular venous distention. Cardiac examination discloses a regular tachycardic rate and rhythm, a soft S1 and S2, and an S3. The lungs are clear. There is no hepatosplenomegaly, no rash, and no edema. Chest radiograph shows pulmonary congestion and cardiomegaly.

Laboratory studies show hemoglobin 14.0 g/dL (140 g/L), leukocyte count 8500/µL (8.5 × 109/L), platelet count 158,000/µL (158 × 109/L), creatinine 0.9 mg/dL (68.7 µmol/L), troponin 5 ng/mL (5 µg/L), liver chemistry tests normal, antinuclear antibody test negative and thyroid-stimulating hormone 3 µU/mL (3 mU/L).

Courtesy of American College of Physicians Medical Knowledge Self-Assessment Program
Courtesy of American College of Physicians Medical Knowledge Self-Assessment Program.

Electrocardiogram is shown. Echocardiogram shows an ejection fraction of 30%, global hypokinesis, and minimal pericardial effusion. There is no evidence of valvular heart disease.

Which of the following is the most appropriate treatment?

A. Amiodarone
B. Captopril and carvedilol
C. Methylprednisolone
D. Tissue plasminogen activator
E. Vancomycin and ceftriaxone

View correct answer for Case 1

Case 2: Anticoagulation for elderly woman

A 75-year-old woman is evaluated in the emergency department for chest pain that has been present for 1 hour. The pain is located in the mid-chest area, and she describes it as a heavy weight. She has not experienced any previous episodes. Medical history is notable for hypertension and chronic kidney disease. Current medications are lisinopril and furosemide.

Physical examination shows blood pressure of 150/70 mm Hg and heart rate of 65/min. Jugular venous pulsations are normal, and no murmurs, extra sounds, or rubs are heard on cardiac auscultation. The lungs are clear, there is no peripheral edema, and distal pulses are normal bilaterally.

Laboratory findings include serum troponin I, 2.0 ng/mL (2.0 µg/L); creatinine, 2.0 mg/dL (152.6 µmol/L); and potassium, 4.6 meq/L (4.6 mmol/L). Her estimated glomerular filtration rate is less than 30 mL/min/1.73 m2. Electrocardiogram shows T-wave inversions in leads V4 through V6.

Her chest pain resolves after one sublingual nitroglycerin tablet and supplemental oxygen.

Which of the following is the best anticoagulation management for this patient?

A. Low-dose unfractionated heparin
B. Full-dose unfractionated heparin
C. Low-dose low-molecular-weight heparin
D. Full-dose low-molecular-weight heparin

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Case 3: Choosing a scan for sudden chest discomfort

A 48-year-old man is evaluated in the emergency department for sudden onset of severe discomfort in the chest and between the shoulder blades. The pain was maximal in intensity at its onset 90 minutes ago and is unaffected by position or breathing. He has a history of hypertension, for which he takes hydrochlorothiazide, 25 mg/d; and lisinopril, 40 mg/d.

On physical examination, his temperature is normal, blood pressure is 200/120 mm Hg, pulse is 100/min, and respiration rate is 20/min. An S4 gallop is present. No cardiac murmur or pericardial rub is present. The lungs are clear to auscultation. Distal pulses are equal and symmetric. Results of a neurologic examination are normal. A urine toxicology screen is positive for cocaine. Serum creatinine level is 2.2 mg/dL (167.9 µmol/L). His creatinine level was 0.8 mg/dL (61.0 µmol/L) at the time of his last office evaluation. Oxygen saturation is 98% on ambient air. Serum cardiac troponin and myoglobin levels are normal. An electrocardiogram reveals left ventricular hypertrophy with a secondary repolarization abnormality and sinus tachycardia. Chest radiograph is normal.

In addition to emergently lowering the blood pressure and heart rate, which of the following diagnostic tests should be performed next?

A. CT scan of chest with intravenous contrast
B. Nuclear myocardial perfusion scan
C. Transesophageal echocardiogram
D. Ventilation-perfusion lung scan

View correct answer for Case 3

Case 4: Diagnosing dyspnea on exertion

A 48-year-old man is evaluated in the emergency department for dyspnea on exertion and paroxysmal nocturnal dyspnea for 3 days. He has a history of type 2 diabetes mellitus and hypertension but no other medical problems. He does not smoke cigarettes. He currently takes metformin, lisinopril, and low-dose aspirin.

On physical examination, he is afebrile. Blood pressure is 130/80 mm Hg, pulse is 100/min, and respiration rate is 20/min; BMI is 40. Jugular veins are distended. Cardiac examination reveals a normal S1 and S2, the presence of an S3, and a regular rate and rhythm with no murmurs. The point of maximal impulse is not displaced, and there are no heaves. Pulmonary auscultation discloses crackles at the bilateral lung bases. There is mild bilateral edema to the shins. Laboratory studies reveal a serum creatinine level of 1.0 mg/dL (76.3 µmol/L) and a B-type natriuretic peptide level of 100 pg/mL.

Courtesy of American College of Physicians Medical Knowledge Self-Assessment Program
Courtesy of American College of Physicians Medical Knowledge Self-Assessment Program.

Electrocardiogram is shown. Chest radiograph is pending.

Which of the following is the most likely diagnosis?

A. Acute heart failure
B. Acute pulmonary embolism
C. Cor pulmonale
D. Recent myocardial infarction

View correct answer for Case 4

Answers and commentary

Case 1

Correct answer: B. Captopril and carvedilol.

This patient has acute myocarditis, manifesting with flu-like systemic symptoms, chest pain, elevated troponin level, and reduced systolic function. The presentation of myocarditis is quite variable, ranging from asymptomatic to cardiogenic shock. Electrocardiographic findings may be variable as well, including findings mimicking acute coronary syndrome or myocardial infarction. Atrial or ventricular arrhythmias may be seen as well. Echocardiographic findings may show either global hypokinesis or regional wall motion abnormalities, the latter mimicking acute myocardial infarction. This patient's electrocardiogram demonstrates atrial tachycardia with 2:1 conduction. The initial laboratory screening for specific and treatable causes of myocarditis is negative. There is no specific treatment for idiopathic (also called lymphocytic) myocarditis other than supportive care and standard therapy for heart failure; thus, therapy with an angiotensin- converting enzyme (ACE) inhibitor such as captopril and a β-blocker such as carvedilol would be appropriate to start at this time.

Amiodarone is not indicated at this time because although an atrial tachyarrhythmia is present, it is not causing hemodynamic compromise and is well tolerated by the patient. The tachyarrhythmia is likely related to the acute illness and will likely resolve as the myocarditis resolves. If the tachyarrhythmia causes hemodynamic instability, cardioversion or rate- or rhythm-controlling medications should be considered.

There is no evidence for benefit of immunosuppression in acute myocarditis in recent randomized controlled trials, so methylprednisolone or other immunosuppressive agents would not be indicated.

It sometimes can be difficult distinguishing acute coronary syndrome from myocarditis. This patient's elevated cardiac enzymes indicate acute myocardial injury, which could be caused by myocardial infarction or myocarditis. Furthermore, in myocarditis, the electrocardiogram and echocardiogram can show focal abnormalities mimicking acute myocardial infarction. In this patient, however, the electrocardiogram shows only poor precordial R-wave progression without evidence for acute myocardial infarction, and the echocardiogram does not show focal wall motion abnormalities. Finally, the subacute appearance of flu-like symptoms and fever in a young person without risk factors for coronary artery disease is more compatible with myocarditis than coronary artery disease. Therefore, reperfusion therapy, including thrombolytic therapy with tissue plasminogen activator, is not correct.

Although various infections have been associated with myocarditis, there is little evidence to support bacterial infection in this patient. Sepsis can be associated with elevated cardiac biomarkers and systolic dysfunction that is reversible; however, this patient does not appear septic (she is not hypotensive, her leukocyte count is not significantly elevated, and her temperature is only slightly elevated). Therefore, treatment with antibiotics such as vancomycin and ceftriaxone is not indicated at this time. A potential cause of infectious cardiomyopathy is HIV infection. However, cardiomyopathy in this setting is typically asymptomatic or presents as chronic heart failure, rather than presenting acutely, as with this patient. If an infectious etiology were identified that would require specific treatment, standard treatment for heart failure would still be indicated.

Key Point

  • The primary treatment for acute myocarditis is supportive care and standard treatment for systolic heart failure, including therapy with angiotensin-converting enzyme inhibitors and β-blockers.

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Case 2

Correct answer: B. Full-dose unfractionated heparin.

This patient's electrocardiographic findings and elevated troponin levels indicate that she is having a non-ST-elevation myocardial infarction (NSTEMI). Medical management for NSTEMI includes aspirin, β-blockers, nitrates, and anticoagulants. Recent randomized trials have shown that full-dose low-molecular-weight heparin is more effective than full-dose unfractionated heparin without an increase in bleeding events. The advantages of low-molecular-weight heparin include ease of dosing (subcutaneous route) and achievement of predictable levels of anticoagulation without the need for monitoring. However, low-molecular-weight heparin is renally excreted, and if estimated glomerular filtration rate is below 30 mL/min/1.73 m2, the level of anti-factor Xa activity is increased, resulting in increased bleeding events. Full-dose unfractionated heparin is, therefore, preferable to full-dose low-molecular-weight heparin in patients with renal insufficiency.

Low-dose unfractionated heparin and low-dose low-molecular-weight heparin do not achieve sufficient systemic levels and therefore do not provide a benefit for patients with NSTEMI.

Key Point

  • Low-molecular-weight heparin is contraindicated in patients with renal insufficiency and estimated glomerular filtration rate below 30 mL/min/1.73 m2.

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Case 3

Correct answer: C. Transesophageal echocardiogram.

Clinical suspicion of aortic dissection is based upon presenting symptoms, physical findings, and radiographic tests. In this patient, the abrupt onset of chest discomfort of maximal intensity is consistent with an acute aortic syndrome. Physical examination findings typical of acute aortic dissection include severe aortic pain, blood pressure or pulse differential between the arms, and a widened mediastinum on chest radiograph. The positive likelihood ratio of aortic dissection in a patient with one of these findings is 0.5, with two of these findings, 5.3; and with all three of these findings, 66.

The recent use of cocaine increases the risks for aortic dissection acutely around the time of use. A transesophageal echocardiogram is the appropriate test at this time because it could be performed rapidly and would allow inspection of the ascending and descending thoracic aorta for dissection or other acute aortic pathology, as well as characterize the location and extent of such findings. Additionally, transesophageal echocardiography would allow evaluation of the pericardial space, competence of the aortic valve, and left ventricular function and regional wall motion analysis, elements that would be integral to treatment, especially if a proximal (type A) dissection is present.

A ventilation-perfusion lung scan would be useful for evaluation of pulmonary embolism. Although acute pulmonary embolism should be considered in a patient with chest pain, the lack of dyspnea, hypoxemia, or underlying risk factors for venous thrombosis and a reasonable alternative diagnosis make pulmonary embolism less likely.

Acute myocardial infarction is possible as a cause of chest pain, despite the lack of specific ST-T segment changes on the electrocardiogram and the initial normal cardiac troponin level. However, the normal myoglobin level measured 90 minutes after the onset of continuous symptoms makes this diagnosis less likely. Nuclear myocardial perfusion imaging is useful as part of the diagnosis of an acute coronary syndrome when the electrocardiogram is nonspecific, initial cardiac enzyme tests are negative, and clinical suspicion is high.

Transesophageal echocardiography (TEE), contrast-enhanced CT, and MRI (without contrast) have similar sensitivity and diagnostic accuracy for the detection of acute aortic dissection. TEE has the benefit of being a portable test that can be performed at bedside, and it yields additional information regarding ventricular and valvular function. Contrast-enhanced chest CT would normally be an acceptable test for further investigation of a suspected acute aortic syndrome. However, the patient's abnormal renal function makes this choice less attractive because of the risks of dye-induced nephropathy. Contrast is not necessary with MRI for definition of an acute aortic dissection, but it may be useful in the evaluation of chronic dissection for defining flow in the false lumen. However, gadolinium contrast should be avoided in this patient because of the risk of nephrogenic fibrosing dermopathy.

Key Point

  • When aortic dissection is suspected, transesophageal echocardiography can be performed quickly to assess the aorta, pericardium, aortic valve, and left ventricular function.

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Case 4

Correct answer: A. Acute heart failure.

This patient has acute heart failure, despite his relatively low B-type natriuretic peptide (BNP) level. Evidence for decompensated heart failure includes jugular venous distention, pulmonary crackles, an S3, and peripheral edema. Although the presence of jugular venous distention, abdominal jugular reflux, pulmonary crackles, S3, and lower extremity edema all increase the likelihood of heart failure, these findings often do not predict the hemodynamic impairment in chronic heart failure. For example, pulmonary crackles may reflect the rapidity of onset of heart failure, rather than the degree of volume overload. Two signs have prognostic value: elevated jugular venous pressure and an S3 are each independently associated with adverse outcomes, including progression of heart failure. BNP levels are affected by many factors and may be elevated with cardiovascular conditions other than heart failure, such as acute myocardial infarction and pulmonary embolism. Obesity is associated with lower BNP levels and, in this patient, the BNP level is relatively low due to his extreme obesity. The exact mechanisms that cause lower BNP levels in obese individuals have not been elucidated. BNP levels are higher in the settings of renal failure, older age, and female sex.

Although the patient has findings suggestive of acute pulmonary embolism, such as tachycardia and tachypnea, the presence of crackles and an S3 suggests left-sided heart failure, which would not be expected as a result of pulmonary embolism. If a pulmonary embolism were so significant as to cause the patient's right-sided heart failure symptoms (that is, acute cor pulmonale), hypotension would very likely be present, but is not.

Cor pulmonale would typically present with a chronic rather than acute course and generally occurs in the setting of established pulmonary disease, such as emphysema or interstitial lung disease. This patient does not have any documented history of pulmonary disease. As cor pulmonale is right-sided heart failure due to pulmonary hypertension of various causes, right-sided failure symptoms predominate. While this patient does demonstrate right-sided heart failure symptoms (jugular venous distention, peripheral edema), he also demonstrates left-sided failure symptoms (crackles) and absence of other supporting evidence for right-sided heart failure (tricuspid regurgitation murmur, right ventricular heave).

Although this patient does have risk factors for myocardial infarction, which can certainly present atypically in a patient with diabetes (such as with new-onset heart failure in the absence of typical chest pain), there is no evidence on the electrocardiogram to support recent myocardial infarction. The electrocardiogram shows only sinus tachycardia, without pathologic Q waves or suspicious ST changes.

Key Point

  • B-type natriuretic peptide levels are generally lower in obese persons, even those with acute heart failure.