The following cases and commentary, which focus on heart failure, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 17), which released Part A on July 31 and Part B on Dec. 31, 2015.
Case 1: Continuing dyspnea after diuresis
A 57-year-old woman is evaluated in the hospital for chronic systolic heart failure. She was admitted with progressive dyspnea of 2 weeks' duration. After 3 days of aggressive diuretic therapy with weight loss of 5 kg (11 lb), she remained very dyspneic, and right heart catheterization was performed. Medications are lisinopril, digoxin, spironolactone, and intermittent furosemide intravenously.
On physical examination, blood pressure is 96/74 mm Hg, pulse rate is 118/min, and respiration rate is 20/min. The internal jugular vein is not visible when the patient is in an upright position. Lungs are clear. An S3 is heard on cardiac examination. There is bilateral edema to the knees. Her serum creatinine level is 1.7 mg/dL (150.3 µmol/L).
Hemodynamic measurements show right atrium pressure 4 mm Hg, pulmonary capillary wedge pressure 16 mm Hg, cardiac output 3.1 L/min (normal, 4.0-8.0 L/min), cardiac index 1.8 L/min/m2, and systemic vascular resistance 2050 dyne/s/cm2 (normal, 800-1200 dyne/s/cm2).
Which of the following is the most appropriate change in this patient's therapy?
A. Continuous intravenous furosemide
B. Dopamine infusion
C. Esmolol drip
Case 2: History of hypertension and volume overload
A 74-year-old man is evaluated in the emergency department for a 7-day history of progressive exertional dyspnea associated with a dry cough, increasing orthopnea (from 2 to 4 pillows), and inability to buckle his belt. He has a 20-year history of hypertension treated with diltiazem.
On physical examination, blood pressure is 162/86 mm Hg, pulse rate is irregularly irregular at 84/min, and respiration rate is 18/min. Estimated central venous pressure is 14 cm H2O. Cardiac examination reveals an irregularly irregular rhythm and an S4. Bibasilar crackles are heard on auscultation of the lungs. His liver is enlarged 2 cm below the costal margin. His extremity examination reveals bilateral pitting edema.
Serum electrolyte levels and kidney function tests are normal. Serum B-type natriuretic peptide level is 2,472 pg/mL (2,472 ng/L).
Electrocardiogram shows atrial fibrillation. Echocardiogram shows a left ventricular ejection fraction of 60%, septal wall thickness of 1.5 cm, and posterior wall thickness of 1.4 cm. Chest radiograph shows hazy bilateral infiltrates.
Which of the following is the most appropriate next step in management?
Case 3: Hypotension and confusion
A 56-year-old man with heart failure is admitted to the hospital with a 2-week history of increasing exertional dyspnea and fatigue. He also has type 2 diabetes mellitus. Medications are metformin, lisinopril, carvedilol, furosemide, metolazone, and digoxin.
On physical examination, blood pressure is 88/60 mm Hg, pulse rate is 95/min, and respiration rate is 20/min. He is somewhat confused and inattentive. Jugular venous distention is present to the angle of the jaw while sitting. Cardiac examination reveals an S3. There are bibasilar crackles on pulmonary examination. He has edema to the midthighs. Extremities appear mottled and are cool to the touch.
Serum creatinine level is 3.1 mg/dL (274 µmol/L); baseline value was 1.1 mg/dL (97.2 µmol/L). Serum sodium level is 133 mEq/L (133 mmol/L). Electrocardiogram shows no evidence of ischemia. Chest radiograph shows cardiomegaly and vascular congestion.
In addition to intravenous diuresis, which of the following is the most appropriate management?
B. Intra-aortic balloon pump
D. Right heart catheterization
Case 4: New-onset heart failure
A 48-year-old woman is evaluated for a 3-week history of progressive dyspnea, palpitations, and peripheral edema. She has loose stools and a recent 2.3-kg (5-lb) weight loss. Medical history is unremarkable, and she does not use injection drugs. She does not take any medications and has no known drug allergies.
On physical examination, temperature is 37.3 °C (99.2 °F), blood pressure is 92/60 mm Hg, pulse rate is 118/min, and respiration rate is 22/min. BMI is 23. Jugular venous distention extends to the jaw. The thyroid is palpable but without identifiable nodules. The precordium is hyperdynamic, and an S3 is heard on cardiac examination. She has severe bilateral lower extremity edema extending to the midcalf. Examination of the joints is normal, and there is no skin rash.
Leukocyte count is 6,000/µL (6.0 × 109/L) with a normal differential. Results of complete blood count are normal. Electrocardiogram shows sinus tachycardia, no Q waves or T-wave abnormalities, and no signs of left ventricular hypertrophy. Echocardiogram shows a left ventricular ejection fraction of 10% and no valvular regurgitation.
Which of the following is the most appropriate diagnostic test to perform next?
A. Antinuclear antibody level
B. Endomyocardial biopsy
C. Thyroid studies
D. Viral titers
Case 5: Progressive symptoms on treatment
A 72-year-old woman is evaluated for progressive heart failure symptoms. She has a 10-year history of nonischemic heart failure. She currently experiences exertional dyspnea with climbing 1 flight of stairs, which she was able to do without shortness of breath 3 months ago. Medical history is significant for hypertension, and her medications are lisinopril, carvedilol, furosemide, digoxin, and spironolactone. The patient is black.
On physical examination, blood pressure is 134/72 mm Hg and pulse rate is 66/min. BMI is 35. She has no jugular venous distention. Cardiac examination reveals a grade 1/6 holosystolic murmur but is otherwise normal. There is no lower extremity edema. The remainder of her examination is unremarkable.
Laboratory studies are significant for normal electrolyte levels and a serum creatinine level of 1.5 mg/dL (133 µmol/L).
Electrocardiogram shows normal sinus rhythm, a QRS duration of 110 ms, and nonspecific ST-T wave changes. Echocardiogram shows a left ventricular ejection fraction of 38% and trace mitral regurgitation.
Which of the following is the most appropriate treatment?
A. Add hydralazine and isosorbide dinitrate
B. Add losartan
C. Add warfarin
D. Cardiac resynchronization therapy
Answers and commentary
Correct answer: D. Nitroprusside.
The most appropriate additional treatment for this patient is nitroprusside. After several days of diuresis, this patient has a normal right atrial pressure (0-5 mm Hg) and pulmonary capillary wedge pressure above normal but within the acceptable range for patients with heart failure (<18 mm Hg) to provide optimal ventricular filling. These hemodynamic parameters suggest that the cardiac output is very low and is the major explanation for the patient's heart failure symptoms. Acute heart failure is typically marked by a combination of volume overload (manifested by an increased pulmonary capillary wedge pressure, usually ≥18 mm Hg) and reduced cardiac output. Part of the reason for reduced cardiac output is a very high systemic vascular resistance, as the systemic circulation increases afterload to maintain blood pressure in the setting of low stroke volume. With correction of the volume overload state, the next step in therapy is to reduce afterload with nitroprusside.
Nitroprusside is an intravenously administered vasodilator that lowers systemic vascular resistance and, therefore, increases cardiac output. This therapy should be used only in the setting of invasive monitoring, including a right heart catheter and possibly an arterial line to closely measure systemic pressure. Counterintuitive to what would be expected, the blood pressure usually rises with nitroprusside because of the improved cardiac performance. Nitroprusside is associated with possible rebound vasoconstriction following discontinuation and potential toxicity due to its metabolism to cyanide with longer term use; therefore, therapy is generally limited to no more than 24 to 48 hours in most patients. Patients with cardiogenic shock may also be treated with an inotropic agent such as dobutamine.
Changing to continuous intravenous furosemide is not indicated because the patient has normal filling pressures manifested by the pulmonary capillary wedge pressure of 16 mm Hg and right atrial pressure of 4 mm Hg. More aggressive diuresis will not impact the principal problem, which is low cardiac output and a high systemic vascular resistance. Studies have evaluated the efficacy of continuous versus intermittent boluses of intravenous diuretics in patients hospitalized with acute heart failure. There was no difference demonstrated in patients' symptoms, kidney function, or length of stay between the two strategies. High- versus low-dose diuretics also have been evaluated. Patients taking high dosages exhibited a trend toward more diuresis and slight worsening of kidney function. Diuresis should be performed using whatever strategy is necessary to remove the fluid.
Dopamine was recently compared with nesiritide and placebo in patients with acute heart failure and mild kidney dysfunction. No benefit was demonstrated with either dopamine or nesiritide compared with placebo for either urine output or protection of kidney function. In general, the results of studies evaluating the use of inotropic therapy for the treatment of patients hospitalized with acute heart failure have been negative. For the routine care of patients hospitalized with heart failure, dopamine, dobutamine, and milrinone have not been shown to be helpful and may be associated with adverse outcomes.
Esmolol is an intravenous beta-blocker. Like all beta-blockers, it has some negative inotropic activity, and use of this drug might worsen the patient's hemodynamic status, not improve it.
- In patients with low-output heart failure, nitroprusside can reduce afterload and increase cardiac output; nitroprusside should be used only in the setting of invasive cardiac monitoring.
Correct answer: C. Furosemide.
This patient should be admitted to the hospital and given intravenous furosemide. His presentation is characteristic for heart failure with preserved ejection fraction (HFpEF). He has volume overload manifested by increasing abdominal girth, increased exertional dyspnea, and progressive orthopnea. His left ventricular ejection fraction is normal, but he has mild left ventricular hypertrophy and a long history of hypertension. Additionally, he has a markedly elevated B-type natriuretic peptide level. The etiology of his acute exacerbation into heart failure is most likely acute atrial fibrillation, but because he is already on diltiazem and has a normal heart rate, he may have been in atrial fibrillation for some time and not noticed it.
In contrast to patients with a reduced ejection fraction, no drugs have been shown to reduce mortality rates in patients with HFpEF. Instead, guidelines emphasize controlling blood pressure and volume. Patients with HFpEF are often volume sensitive, and careful use of diuretics to maintain euvolemia is important. This patient is not already taking a diuretic, and starting with a low dose of furosemide is a reasonable approach. If the patient were already on an oral diuretic, giving at least the equivalent dose intravenously would be suggested. Patients with HFpEF should be encouraged to monitor their weight closely, as small differences in volume can quickly cause volume overload and subsequent hospital admissions.
Beta-blocker therapy is relatively contraindicated in this patient with acute decompensated heart failure as it may exacerbate his heart failure. Once his heart failure is successfully treated with diuretics, this patient may benefit from beta-blocker therapy to help manage his heart rate and blood pressure, but this should be avoided in the setting of acute volume overload, whenever possible.
Despite the fact that the patient is currently in atrial fibrillation, cardioversion at this point is incorrect. Because he is hemodynamically stable with good rate control, there is no indication for immediate cardioversion. In addition, because it is unclear how long he has been in atrial fibrillation, cardioversion without a transesophageal echocardiogram to rule out thrombus or initiation of prophylactic anticoagulation would place the patient at risk for embolization at the time of the procedure.
Several small trials have suggested that aldosterone antagonists may improve diastolic function in patients with HFpEF. However, a recent trial comparing spironolactone with placebo showed a reduction in heart failure hospitalizations but no difference in mortality rates or all-cause hospitalizations in patients with HFpEF, and spironolactone was associated with significant increases in serum creatinine and potassium levels. Given this minimal benefit but substantial increase in risk of adverse effects, the addition of spironolactone for his current symptoms is not appropriate in this patient with HFpEF.
- Patients with heart failure with preserved ejection fraction are often volume sensitive, and careful use of diuretics to maintain euvolemia is important.
Correct answer: A. Dobutamine.
This patient should be started on dobutamine for probable cardiogenic shock. Cardiogenic shock is present when there is systemic hypotension and evidence for end-organ hypoperfusion, primarily due to inadequate cardiac output. Cardiogenic shock usually requires treatment with intravenous vasoactive medications and, in severe cases, device-based hemodynamic support. Manifestations of end-organ hypoperfusion may include acute kidney failure, elevated serum aminotransferase levels or hyperbilirubinemia, cool extremities, and decreased mental status. In this patient, initiating inotropic therapy is reasonable. Both dobutamine and milrinone are used to increase cardiac output; however, in the setting of kidney dysfunction, dobutamine would be the appropriate choice because milrinone is metabolized by the kidneys. Also, milrinone is a vasodilator, which could exacerbate his hypotension.
Mechanical therapy for cardiogenic shock should be considered in patients with end-organ dysfunction that does not rapidly show signs of improvement (within the first 12-24 hours) with intravenous vasoactive medications and correction of volume overload. Options for mechanical therapy include placement of an intra-aortic balloon pump and percutaneous or surgically implanted ventricular assist devices (VADs). An intra-aortic balloon pump is timed to inflate during diastole, augmenting coronary and systemic perfusion, and deflate during systole, reducing left ventricular afterload. It is premature to consider mechanical therapy for this patient.
Right heart catheterization can be helpful to guide therapy if volume status or cardiac output is uncertain. However, it has not been shown to improve outcomes in patients hospitalized with heart failure. This patient has clinical evidence of volume overload, including jugular venous distention, pulmonary crackles, edema to the mid thighs, pulmonary edema on chest radiography, and an S3. Additionally, he has evidence of low cardiac output (narrow pulse pressure, hypotension, acute kidney injury, mottled and cool extremities). Placement of a right heart catheter is not necessary prior to initiating inotropic therapy.
- Cardiogenic shock usually requires treatment with intravenous vasoactive medications and, in severe cases, device-based hemodynamic support.
Correct answer: C. Thyroid studies.
The most appropriate diagnostic test to perform in this young patient with new-onset heart failure is to obtain thyroid studies. This patient exhibits signs and symptoms consistent with a diagnosis of hyperthyroidism, including tachycardia, a hyperdynamic precordium, palpitations, weight loss, and loose stools. Hyperthyroidism is a well-described, reversible cause of heart failure due to cardiac overstimulation by excess thyroid hormone that resembles sympathetic stimulation. Hyperthyroidism causes an increase in heart rate and myocardial contractility; systemic vascular resistance often decreases and may result in a widened pulse pressure. Hypothyroidism is also a known cause of heart failure, although it would be less likely in this patient with symptoms more consistent with excess thyroid hormone. Because thyroid function abnormalities are a potentially reversible cause of heart failure, assessment of thyroid function should be considered in patients with new-onset heart failure and clinical findings suggestive of thyroid dysfunction.
Evaluation of unusual causes of heart failure should not be performed routinely but should be pursued when there are suggestions of specific diseases by history or physical examination. The patient has no signs or symptoms suggesting a rheumatologic disorder, and routine screening with an antinuclear antibody level is not indicated. Similarly, this patient does not have a history of flu-like symptoms suggesting a viral etiology, making the potential yield of viral titers quite low. Furthermore, directed treatment options in the presence of positive viral titers are quite limited.
Endomyocardial biopsy is rarely indicated in the evaluation of acute heart failure as it is invasive and is unlikely to be helpful in identifying a reversible cause. It may be considered in patients whose heart failure is unresponsive to medical therapy or is associated with ventricular arrhythmias or conduction block in order to evaluate for giant cell myocarditis.
- Evaluation of unusual causes of heart failure should not be performed routinely but should be performed when there are suggestions of specific diseases by history or physical examination findings.
Correct answer: A. Add hydralazine and isosorbide dinitrate.
This patient should have hydralazine and isosorbide dinitrate added to her medication regimen for the treatment of her heart failure. She has New York Heart Association (NYHA) functional class III heart failure and is black. Hydralazine and isosorbide dinitrate have been demonstrated to improve symptoms and reduce mortality in patients who are black and who are already on maximal therapy with NYHA class III or IV heart failure symptoms. Adverse effects of this therapy include peripheral edema and headaches, but this regimen should be attempted in these patients.
Optimal therapy for patients with heart failure includes treatment with an ACE inhibitor, beta-blocker, and an aldosterone antagonist. The addition of an angiotensin receptor blocker, such as losartan, to this combination is generally not recommended, primarily because of concern for hyperkalemia. Additionally, no benefit to this treatment regimen has been documented. It would therefore not be appropriate in this patient.
In patients with heart failure, warfarin treatment is appropriate only in those with another indication, such as atrial fibrillation meeting CHA2DS2-VASc criteria, but not with heart failure alone. The routine treatment of patients with heart failure with warfarin is not indicated.
Cardiac resynchronization therapy (CRT) may be an effective therapy in patients with heart failure and a prolonged QRS duration indicating dyssynchrony. Indications include a left ventricular ejection fraction of 35% or less in patients in sinus rhythm, with a left bundle branch block, and with a QRS duration of 150 ms or greater in whom moderate to severe symptoms (NYHA class III or IV) are present despite optimal medical therapy. Because this patient does not have evidence of dyssynchrony or an ejection fraction of 35% or less, she is not a candidate for treatment.
- Hydralazine and isosorbide dinitrate improve symptoms and reduce mortality in patients with New York Heart Association class III or IV heart failure symptoms who are black and are already on maximal therapy.