A 48-year-old woman is evaluated during a new-patient visit. She reports no symptoms. She is fairly sedentary but is trying to become more active by joining the local health club. She has noticed that she is “out of shape” but can cycle on a stationary bike with moderate intensity to the end of her 30-minute workout. Medical history is otherwise unremarkable. She takes no medications.
On physical examination, vital signs are normal. The estimated central venous pressure is 6 cm H2O. The apical impulse is not palpable. Cardiac examination reveals a grade 2/6 midsystolic murmur localized to the left sternal border without radiation. The murmur does not change with respiration or handgrip but does diminish in intensity with standing. The S2 is physiologically split. There are no clicks. The lungs are clear to auscultation. Peripheral pulses are normal in volume and contour. No edema is present.
Which of the following is the most appropriate management?
A Cardiac magnetic resonance imaging
B Transesophageal echocardiography
C Transthoracic echocardiography
D Routine clinical follow-up without imaging
Answer & Critique Correct Answer: D
Educational Objective: Diagnose a benign heart murmur.
Key Point
Short, soft systolic murmurs (grade <3) that are well localized to the left sternal border and are not associated with symptoms often do not require further investigation.
The most appropriate management is routine clinical follow-up without imaging. Cardiac murmurs result from increased blood flow across a normal orifice (such as with anemia, thyrotoxicosis, pregnancy, or atrial septal defect), turbulent flow through a narrowed orifice (such as with aortic stenosis or mitral stenosis), or regurgitant flow through an incompetent valve (such as with aortic regurgitation or mitral regurgitation). Timing in the cardiac cycle, chest wall location, radiation, intensity, configuration, duration, and pitch all assist in the differential diagnosis.
Not all systolic murmurs are pathologic. Asymptomatic patients with short, soft systolic murmurs (grade <3) well localized to the left sternal border and associated with normal heart sounds do not usually require further investigation. Benign murmurs typically decrease in intensity with standing. The presence of any diastolic or continuous murmur, cardiac symptoms (chest pain, dyspnea, syncope), or abnormalities on examination (clicks, abnormal S2, abnormal pulses) requires evaluation by echocardiography.
Various interventions may alter the intensity of murmurs. The murmur of hypertrophic cardiomyopathy may increase with standing or Valsalva maneuver; both maneuvers decrease venous return, which decreases left ventricular chamber size and increases the degree of obstruction. The click and murmur of mitral valve prolapse may move earlier in systole and increase in intensity as left ventricular volume decreases (standing or Valsalva maneuver). Aortic outflow murmurs increase in intensity in the beat following a premature ventricular contraction due to increased left ventricular volume. Murmurs of mitral regurgitation, ventricular septal defect, and aortic regurgitation increase with handgrip because of increased cardiac output and peripheral resistance. Right-sided heart murmurs may increase during inspiration due to increased venous return.
Characteristics of the S2 may assist in determining the diagnosis or the severity of a valvular lesion. A fixed split of S2 (present during inspiration and expiration instead of only inspiration) results from a delay in right ventricular emptying and is strongly associated with atrial septal defect. A paradoxical split of S2 (present during expiration) indicates a delay in left ventricular emptying, such as with severe aortic stenosis. Presence of a physiologic split (present during inspiration) is helpful for excluding severe aortic stenosis.
Because this patient likely has a benign systolic heart murmur and is asymptomatic, imaging with echocardiography or cardiac magnetic resonance imaging is not necessary.
A 25-year-old woman is hospitalized with a 4-day history of fever and cough productive of brown sputum. She is at 14 weeks' gestation with her first pregnancy. Medical history is significant for mild persistent asthma. Medications are an albuterol inhaler, beclomethasone inhaler, and a prenatal vitamin.
On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is normal, pulse rate is 122/min, and respiration rate is 24/min. Oxygen saturation is 94% breathing ambient air. Crackles are heard at the left lung base on pulmonary auscultation.
Chest radiograph shows a left lower lobe infiltrate.
Which of the following is the most likely cause of pneumonia in this patient?
A Escherichia coli
B Klebsiella pneumonia
C Listeria monocytogenes
D Staphylococcus aureus
E Streptococcus pneumoniae
Answer & CritiqueCorrect Answer: E
Educational Objective: Evaluate community-acquired pneumonia in a pregnant patient.
Key Point:
The microbiology of community-acquired pneumonia in pregnancy is similar to that seen in the general population; among patients requiring hospitalization, the most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumonia.
Streptococcus pneumoniae is the most likely cause of this patient's community-acquired pneumonia (CAP). Pneumonia is the most common cause of fatal nonobstetric infection in pregnancy. The microbiology of CAP in pregnancy is similar to that seen in the general population. Among patients requiring hospitalization, the most common pathogens are S. pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Empiric treatment of pregnant patients is similar to that in nonpregnant adults, although quinolones and tetracyclines are relatively contraindicated because of the potential for teratogenic effects. In addition to these common bacterial causes of CAP, pregnant women are at increased risk for serious viral pneumonia from influenza virus and varicella-zoster virus, so it is recommended that pregnant women receive seasonal influenza vaccination.
Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter species, Escherichia coli, and Enterobacter species, are rarely implicated in CAP, including among pregnant women hospitalized for pneumonia. Most patients with CAP caused by gram-negative bacteria have a predisposing risk factor, such as bronchiectasis, cystic fibrosis, or COPD, and develop severe pneumonia necessitating admission and care in the ICU.
Pregnancy causes a decrease in T-cell function, and pregnant women are at increased risk for severe Listeria infections, including meningitis and sepsis. However, Listeria rarely causes pulmonary infection and would be an unlikely cause of infection in this patient.
Staphylococcus aureus is an increasingly recognized cause of CAP, with risk factors including antecedent viral infection or injection drug use. Maternal S. aureus infection can occur perinatally, related to delivery, surgery, or indwelling lines, but remains a rare cause of CAP in the prenatal period.
A 46-year-old man is evaluated for 6 months of exertional dyspnea, fatigue, and ankle edema. Recently he experienced near-syncope walking up two flights of stairs. He has no other medical problems and takes no medications.
On physical examination, blood pressure is 106/70 mm Hg, pulse rate is 94/min, and respiration rate is 18/min. Oxygen saturation is 90% breathing ambient air. On cardiac examination, a prominent jugular venous a wave is present along with widened splitting of S2. Lung examination is unremarkable.
A transthoracic echocardiogram demonstrates a normal size left ventricle with ejection fraction of 65% and right ventricular enlargement. The estimated pulmonary artery systolic pressure is 58 mm Hg. Spirometry, lung volumes, and ventilation-perfusion scan are unremarkable; DLCO is 42% of predicted. CT angiogram of the chest is negative for pulmonary embolism and interstitial lung disease. Right heart catheterization demonstrates a mean pulmonary arterial pressure of 36 mm Hg, with no change with inhaled nitric oxide. Pulmonary capillary wedge pressure is normal.
Which of the following is the most appropriate treatment?
A Bosentan
B Diltiazem
C Metoprolol
D Pirfenidone
Answer & CritiqueCorrect Answer: A
Educational Objective: Treat pulmonary arterial hypertension.
Key Point
Before administering advance therapy for patients with pulmonary arterial hypertension (PAH), particularly idiopathic PAH, vasoreactivity testing directs agent selection by identifying those who may respond to calcium channel blockers.
The most appropriate treatment is bosentan. This patient has pulmonary hypertension most consistent with Group 1 (pulmonary arterial hypertension [PAH]), based upon the right heart catheterization demonstrating high pulmonary arterial pressures in the absence of left-sided heart failure, lung disease, and venous thromboembolic disease. Before administering advanced therapy for patients with PAH, vasoreactivity testing with nitric oxide is performed to identify those who may respond to calcium channel blockers (CCBs). CCBs are desirable therapy because they are less expensive and have fewer side effects than other forms of advanced therapy. Failure to achieve a favorable hemodynamic response with nitric oxide predicts unresponsiveness to CCBs and the need for other advanced therapy. The endothelin receptor antagonist bosentan is one of many oral pulmonary vasoactive drugs that is indicated in PAH in patients with negative vasoreactivity testing, such as this patient, some of which have been shown to increase exercise capacity and improve echocardiographic parameters.
CCBs such as diltiazem may be used in the setting of PAH when a response to a vasodilator such as nitric oxide is demonstrated during right heart catheterization. When a response is not found, CCBs are not indicated.
β-Blockers such as metoprolol do not have a proved role specific to PAH, though they might be used as an adjunct agent for supraventricular tachyarrhythmias that are common in this population.
Pirfenidone is an antifibrotic agent indicated for the treatment of idiopathic pulmonary fibrosis. Pulmonary hypertension is frequently observed in patients with idiopathic pulmonary fibrosis, but pirfenidone would not be indicated for a patient with PAH without idiopathic pulmonary fibrosis.
A 35-year-old woman is evaluated after laboratory test results showed an elevated LDL cholesterol level during routine screening. Family history is remarkable for myocardial infarction in her father at age 45 years. She takes no medications.
On physical examination, vital signs are normal. BMI is 30. The remainder of the examination is unremarkable.
Laboratory studies:
Alanine aminotransferase 30 U/L
Thyroid-stimulating hormone Normal
Total cholesterol 294 mg/dL (7.61 mmol/L)
LDL cholesterol 195 mg/dL (5.05 mmol/L)
HDL cholesterol 55 mg/dL (1.42 mmol/L)
Triglycerides 220 mg/dL (2.49 mmol/L)
The patient is instructed in therapeutic lifestyle changes to lower her risk for atherosclerotic cardiovascular disease (ASCVD).
According to the American Heart Association/American College of Cardiology cholesterol treatment guideline, which of the following is the most appropriate additional treatment for primary prevention of ASCVD in this patient?
A Evolocumab
B High-intensity rosuvastatin
C Moderate-intensity atorvastatin
D No additional treatment is necessary
Answer & CritiqueCorrect Answer: B
Educational Objective: Treat a patient with an LDL cholesterol level higher than 190 mg/dL (4.92 mmol/L).
Key Point
The American Heart Association and American College of Cardiology recommend that patients aged 20 years or older with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher should receive high-intensity statin therapy for primary prevention of atherosclerotic cardiovascular disease.
The most appropriate treatment for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in this patient is high-intensity statin therapy with rosuvastatin or atorvastatin. According to the 2018 American Heart Association (AHA)/American College of Cardiology (ACC) Guideline on the Management of Blood Cholesterol, patients aged 20 years or older with severe LDL cholesterol elevation (≥190 mg/dL [4.92 mmol/L]) should receive the maximum tolerated statin therapy for primary prevention of ASCVD, regardless of 10-year risk for ASCVD. High-intensity statin therapy is recommended unless there are contraindications to its use. Sexually active women of childbearing age who are receiving statin therapy should be counseled to use a reliable form of contraception. Women who plan to become pregnant should stop taking statins 1 to 2 months before pregnancy is attempted. Those who become pregnant while on therapy should discontinue statins as soon as the pregnancy is discovered. It is reasonable to intensify statin therapy as tolerated to achieve an LDL cholesterol reduction of at least 50%. In contrast to the AHA/ACC recommendation, the U.S. Preventive Services Task Force recommends initiating low- to moderate-intensity statin therapy in adults aged 40 to 75 years without a history of ASCVD who have one or more traditional ASCVD risk factors (dyslipidemia, diabetes mellitus, hypertension, or smoking) and a calculated 10-year ASCVD event risk of 10% or higher. Similarly, the U.S. Department of Veterans Affairs/U.S. Department of Defense cholesterol guideline recommends moderate-intensity statin therapy for patients with a 10-year ASCVD risk of 12% or more, an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher, or diabetes.
In the absence of familial hypercholesterolemia or severe hypercholesterolemia despite maximally tolerated cholesterol-lowering therapy with a statin and ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, are not indicated in the primary prevention of ASCVD. Cost, treatment burden (injections), and absence of long-term safety data argue against their use in primary prevention. Such treatment might be considered if LDL cholesterol cannot be sufficiently reduced in the highest-risk patients.
In patients with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher, initial treatment with a moderate-intensity statin is less preferred according to the AHA/ACC guidelines; however, if the patient is unable to tolerate high-intensity therapy, down-titration to moderate-intensity therapy could be considered, especially if adequate LDL cholesterol reduction can be achieved.
An evaluation for secondary causes of hyperlipidemia is also indicated in patients with an LDL cholesterol level of 190 mg/dL (4.92 mmol/L) or higher. The most common secondary causes are obesity, hypothyroidism, biliary obstruction, and nephrotic syndrome. Medications can also increase LDL cholesterol level, and some of the most commonly implicated drugs include cyclosporine, HIV medications (such as protease inhibitors), glucocorticoids, and amiodarone. If a secondary cause is not identified, LDL cholesterol level elevation is considered primary, and family members should undergo screening because severe hypercholesterolemia is often genetically determined, as may be the case with this patient who has a first-degree relative with premature ASCVD.
A 29-year-old woman is evaluated during a new-patient appointment. She was diagnosed with hepatitis B virus (HBV) infection 10 years ago; her mother had HBV infection, and it was presumed that the patient acquired the infection at birth. She reports feeling well. Her medical history is otherwise unremarkable and she takes no medication.
On physical examination, vital signs are normal, as is the remainder of the examination.
Laboratory studies are positive for hepatitis B surface antigen and positive for hepatitis B e antigen. The serum HBV DNA level is 20,000,000 IU/mL. Alanine aminotransferase and aspartate aminotransferase levels are within normal limits.
Which of the following is the most appropriate next step in management?
A Entecavir
B Hepatic ultrasonography
C Pegylated interferon
D Repeat liver chemistry tests in 6 months
E Tenofovir
Answer & CritiqueCorrect Answer: D
Educational Objective: Manage the immune-tolerant phase of hepatitis B viral infection.
Key Point
Patients with hepatitis B infection in the immune-tolerant phase require serial monitoring of aminotransferase levels.
Repeat liver chemistry testing in 6 months is the most appropriate next step in the management of this patient. The patient has hepatitis B virus (HBV) infection in the immune-tolerant phase, which can be determined by the likely vertical transmission and the patient's young age, positive hepatitis B e antigen (HBeAg), high viral load, and normal aminotransferase levels. Therefore, the patient only requires serial monitoring of aminotransferase levels. There are four typical phases of HBV infection: (1) immune tolerant, (2) immune active, (3) immune control (inactive), and (4) reactivation. Not all patients go through each phase. Patients with infection in the immune-tolerant phase do not have significant hepatic inflammation and have no fibrosis, and, therefore, do not require treatment. However, infection can progress to the immune-active, HBeAg-positive phase, in which hepatic inflammation, elevated aminotransferase levels, and fibrosis develop, underscoring the need for surveillance of aminotransferase levels.
Patients with HBV infection in the immune-active, HBeAg-positive and reactivation, HBeAg-negative phases require treatment if the alanine aminotransferase level is elevated. Antiviral therapy is also required for patients who present with acute liver failure, all patients with cirrhosis, and patients undergoing treatment with certain immunosuppressive or chemotherapy regimens. None of these scenarios apply to this patient, so she does not require antiviral treatment such as tenofovir, entecavir, or pegylated interferon.
Patients with HBV infection are at increased risk for hepatocellular carcinoma, even in the absence of cirrhosis. Patients from Southeast Asia should undergo hepatocellular carcinoma surveillance with ultrasonography starting at age 40 years for men and at age 50 years for women, and patients from sub-Saharan Africa should begin at age 20 years. Other indications include persistent inflammatory activity (defined as an elevated alanine aminotransferase level and HBV DNA levels greater than 10,000 IU/mL for at least a few years) and a family history of hepatocellular carcinoma. The preferred surveillance strategy is liver ultrasonography with or without α-fetoprotein measurement. This patient is not yet old enough to warrant hepatocellular carcinoma surveillance, so hepatic ultrasonography is not indicated.
A 65-year-old woman is evaluated during a routine examination. She was diagnosed with a cardiac murmur in early adulthood. She is active, healthy, and without symptoms. She takes no medications.
On physical examination, vital signs are normal. A grade 3/6 holosystolic murmur preceded by multiple clicks is present at the apex. Physical findings are otherwise unremarkable.
An echocardiogram demonstrates a left ventricular ejection fraction of 50%. The left ventricle is moderately dilated with an end-systolic dimension of 42 mm. Myxomatous degeneration of the mitral valve is present with severe regurgitation due to posterior leaflet prolapse.
Which of the following is the most appropriate next step in management?
A Serial clinical and echocardiographic evaluations
B Surgical mitral valve repair
C Surgical mitral valve replacement
D Transcatheter mitral valve repair
Answer & CritiqueCorrect Answer: B
Educational Objective: Treat degenerative mitral regurgitation with surgical mitral valve repair.
Key Point
Mitral valve repair is strongly recommended for chronic severe primary mitral regurgitation in symptomatic patients with left ventricular ejection fraction greater than 30%, asymptomatic patients with left ventricular dysfunction, and patients undergoing another cardiac surgical procedure.
The most appropriate next step in management is surgical mitral valve repair. Myxomatous degeneration of the mitral valve is common, affecting 1% to 2% of the general population. In 10% of patients, the valvular lesion can progress, become life threatening, and require surgery. The only definitive therapy for severe mitral regurgitation is mitral valve surgery. Options are mitral valve repair, mitral valve replacement with preservation of part or all of the mitral apparatus, and mitral valve replacement with removal of the mitral apparatus. Mitral valve repair is generally preferred to valve replacement because it is associated with improved survival in retrospective studies. Mitral valve repair is strongly recommended for chronic severe primary mitral regurgitation in (1) symptomatic patients with left ventricular ejection fraction greater than 30%, (2) asymptomatic patients with left ventricular dysfunction (left ventricular ejection fraction of 30%-60% and/or left ventricular end-systolic diameter ≥40 mm), and (3) patients undergoing another cardiac surgical procedure. Additionally, mitral valve repair is reasonable in asymptomatic patients with chronic severe primary mitral regurgitation who have new-onset atrial fibrillation or pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg). Notably, a left ventricular ejection fraction of 60% or less is used in defining left ventricular systolic dysfunction in mitral regurgitation because ventricular emptying into the left atrium contributes to the relatively lower afterload conditions and higher ejection fraction despite impaired left ventricular performance.
Serial evaluations every 6 to 12 months are recommended for patients with severe mitral regurgitation who do not have indications for surgery. This patient meets the criteria for surgery; therefore, serial evaluations would not be appropriate at this time.
Many patients who could benefit from mitral valve repair are denied surgery because of high surgical risk, advanced age, or comorbid conditions. A catheter-based device can improve mitral valve function by delivering a clip percutaneously to approximate the valve leaflet edges and improve leaflet coaptation at the origin of the mitral regurgitation jet. The device is approved for patients with significant symptomatic degenerative mitral regurgitation for whom mitral valve surgery poses a prohibitive risk. This patient is healthy and does not have comorbid conditions that would significantly increase surgical risk; therefore, transcatheter repair is not indicated.
A 47-year-old woman is evaluated in the hospital for pyelonephritis not responding to antibiotic therapy. Five days ago she was evaluated in an urgent care center for abdominal and back pain, nausea, fever, and dysuria. She was started on oral ciprofloxacin for a urinary tract infection (UTI). Symptoms did not respond to this treatment, and two days ago, she was hospitalized. Acute pyelonephritis was diagnosed, and she was treated with intravenous fluids, vancomycin, and cefepime. Since hospitalization, her clinical condition has deteriorated, with continued fever and worsening flank pain. She also has stage 2 chronic kidney disease, recurrent UTIs, and a 6-year history of poorly controlled type 2 diabetes mellitus. Medications are amoxicillin, metformin, and insulin glargine.
On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 130/60 mm Hg, pulse rate is 106/min, and respiration rate is 22/min. Abdominal examination reveals diminished bowel sounds, bilateral costovertebral angle tenderness, and suprapubic pain. Other examination findings are unremarkable.
Laboratory studies:
Hemoglobin
11 g/dL (110 g/L)
Leukocyte count
21,000/µL (21 × 109/L) with 91% neutrophils and 9% lymphocytes
Platelet count
167,000/µL (167 × 109/L)
Creatinine
1.8 mg/mL (159 µmol/L)
Urinalysis
10 erythrocytes/hpf, leukocytes too numerous to count, many yeast forms, trace protein, and 4+ glucose.
Urine culture results show 10,000 colony-forming units of Candida glabrata. Blood culture results are negative.
A CT scan of the abdomen with contrast shows bilateral perinephric stranding, no masses, and no renal abscesses.
Which of the following is the most likely diagnosis?
A Acute diverticulitis
B Antibiotic-resistant bacterial pyelonephritis
C Candida pyelonephritis
D Renal infarction
Answer & CritiqueCorrect Answer: C
Educational Objective: Diagnose invasive candidiasis.
Key Point
In patients with invasive candidiasis, therapy with an oral azole (if the Candida species is susceptible) or amphotericin B should be initiated immediately; the total duration of therapy should be 10 to 14 days.
This patient has Candida pyelonephritis, a form of invasive candidiasis. She has several risk factors for candidiasis, such as recently taking broad-spectrum antibiotics, uncontrolled diabetes mellitus, and a history of recurrent urinary tract infections. These risk factors, in combination with the findings of yeast, leukocytes, and erythrocytes in the urine, is classic for this infection. Although the urine culture only grew 10,000 colony-forming units of Candida glabrata, the colony count may not correlate with active infection in Candida infections of the urinary tract. Thus, antifungal therapy with amphotericin B should be initiated immediately. After identification of the species, the antifungal agent may be de-escalated to an oral azole if the Candida species is susceptible to azoles. The total duration should be 10 to 14 days of antifungal therapy.
Acute diverticulitis may present with the same manifestations this patient had. However, the bilateral flank pain and the lack of abdominal pain make diverticulitis less likely. In addition, the urinalysis results showing leukocytes too numerous to count and the classic CT scan finding of perinephric stranding point to a kidney infection.
Antibiotic-resistant bacterial pyelonephritis is a possibility and could explain her progressive symptoms despite appropriate antibiotic therapy for pyelonephritis. However, this diagnosis is excluded by the patient's urine culture, which showed only Candida species.
Patients with acute kidney infarction typically present with acute flank pain or generalized abdominal pain, often associated with nausea and vomiting and, less commonly, with fever; hematuria is present in one-third of patients. Over half of kidney infarctions are cardioembolic, and atrial fibrillation is commonly found in patients with this diagnosis. A contrast-enhanced CT scan will show a wedge-shaped perfusion defect. This patient's normal abdominal contrast-enhanced CT scan and urinalysis argue against kidney infarction.
A 71-year-old man is evaluated during a follow-up visit for sleep-related breathing pauses observed by the hospital staff when he was admitted for implantation of a cardioverter-defibrillator for ischemic cardiomyopathy (left ventricular ejection fraction of 30%). He has recently experienced dyspnea, a few episodes of which have awakened him from sleep. He has no insomnia or daytime sleepiness. He has dyslipidemia, stable coronary artery disease, and hypertension. Current medications are aspirin, atorvastatin, valsartan, metoprolol, and nitroglycerin as needed.
On physical examination, vital signs are normal. Oxygen saturation is 93% breathing ambient air. BMI is 23. Lung examination reveals bibasilar crackles, faint end-expiratory wheezing, neck vein distention, and 1+ ankle edema.
Polysomnography demonstrates central sleep apnea with a Cheyne-Stokes breathing pattern.
Which of the following is the most appropriate treatment of the patient's central sleep apnea?
A Adaptive servo-ventilation
B Auto-adjusting positive airway pressure
C Furosemide
D Supplemental oxygen
Answer & CritiqueCorrect Answer: C
Educational Objective: Treat heart failure in a patient with a Cheyne-Stokes breathing pattern.
Key Point
Initial treatment of central sleep apnea should target modifiable risk factors; medical optimization of heart failure has been shown to improve central sleep apnea and Cheyne-Stokes breathing and should precede other therapies for sleep apnea.
Diuresis with furosemide is the most appropriate treatment option. This patient has central sleep apnea with Cheyne-Stokes breathing in the setting of decompensated heart failure, a state of ventilatory instability. Cheyne-Stokes breathing is an abnormal respiratory pattern characterized by cyclic crescendo-decrescendo respiratory effort during sleep (and sometimes during wakefulness), in the absence of upper airway obstruction. Apnea accompanying the decrescendo effort defines central sleep apnea. The degree of central sleep apnea tends to correlate with left ventricular dysfunction. This patient has evidence on examination of volume overload (crackles and wheezing on lung exam, jugular venous distention, peripheral edema). Optimizing medical management of heart failure and improving fluid balance should precede other therapies for sleep apnea.
Adaptive servo-ventilation is a form of positive airway pressure therapy initially designed as a treatment of Cheyne-Stokes breathing. However, a large multicenter trial unexpectedly showed increased mortality in a subset of patients with systolic heart failure (left ventricular ejection fraction less than 45%) and central sleep apnea treated with adaptive servo-ventilation.
Auto-adjusting positive airway pressure is not an initial treatment for central sleep apnea. It is used to treat obstructive sleep apnea, where proprietary algorithms deliver varying pressure sufficient to prevent upper airway closure.
Supplemental oxygen is sometimes used in advanced heart failure where impaired gas exchange results in hypoxemia. This patient has preserved oxyhemoglobin saturation. Small trials have studied the use of nocturnal supplemental oxygen in the setting of central sleep apnea, with variable results. Such treatment would be premature before optimization of fluid status.
An 84-year-old woman in hospice care is evaluated for “death rattle” that is disturbing to family members. She is in the active phases of dying, and her family is distressed by her noisy respiratory secretions; they are worried that she is choking. Medications are haloperidol, hydromorphone, lactulose, and acetaminophen.
On physical examination, respiration rate is 12/min. She is not responsive but does not appear uncomfortable. Extremities are cool. There are oropharyngeal secretions that produce a rattling and gurgling sound with inspiration.
Which of the following is the most appropriate initial management?
A Atropine ophthalmic drops given sublingually
B Glycopyrronium
C Scopolamine patch
D Suctioning by catheter
E Symptom explanation and reassurance
Answer & Critique Correct Answer: E
Educational Objective: Manage audible oropharyngeal secretions in a patient at the end of life.
Key Point
Audible posterior oropharyngeal secretions (“death rattle”) are common at the end of life and are best managed with family education and reassurance.
This patient has audible posterior oropharyngeal secretions, which are most appropriately managed with family education and reassurance. Although several studies suggest that respiratory distress is not typically associated with these secretions, caregivers are often concerned by what is commonly referred to as the “death rattle.” The first steps in management include caregiver education and anticipatory guidance. Additionally, repositioning often allows secretions to drain without pharmacologic intervention. Mouth hygiene with a sponge swab may also be helpful.
Current literature does not support the routine use of antimuscarinic drugs in the treatment of death rattle. A 2014 literature review acknowledged that death rattle leads to distress in both relatives and professional caregivers; however, its impact on patients is unclear, and medical therapy is unproven. Studies involving atropine, glycopyrronium, scopolamine, hyoscine butylbromide, and/or octreotide were reviewed, and only one study used a placebo group. There is currently no evidence that the use of any antimuscarinic drug is superior to no treatment. In addition, the use of anticholinergic agents in patients who are awake can lead to undesirable symptoms, such as dry mouth and urinary retention.
Suctioning by catheter should be avoided in managing end-of-life secretions unless the secretions are causing the patient obvious respiratory distress or cough. Suction catheters can cause local trauma.
A 26-year-old woman with Crohn disease is evaluated for a 2-week history of worsening abdominal pain in the right lower quadrant. She reports passage of one to two formed and nonbloody stools per day with no changes in bowel habits. The patient has required three courses of prednisone for disease flares over the past year. Her only medication is azathioprine.
On physical examination, temperature is 37.7 °C (99.9 °F) and pulse rate is 115/min; other vital signs are normal. Abdominal examination shows fullness and tenderness in the right lower quadrant with no distinct mass. The remainder of the examination is unremarkable.
Laboratory studies show a hemoglobin level of 10.5 g/dL (105 g/L) and a C-reactive protein level of 32 mg/dL (320 mg/L). Leukocyte count and liver chemistry tests are normal.
CT enterography shows asymmetric mural thickening and mucosal inflammation of a long segment of distal ileum without luminal narrowing.
Which of the following is the most appropriate treatment?
A Budesonide
B Infliximab
C Mesalamine
D Prednisone
Answer & CritiqueCorrect Answer: B
Educational Objective: Treat ileal Crohn disease.
Key Point
Anti–tumor necrosis factor agents such as infliximab are effective in inducing and maintaining remission in moderate to severe Crohn disease.
Infliximab is the most appropriate treatment for this patient. This patient has moderate to severe ileal Crohn disease that has required multiple courses of tapering prednisone for flares of disease over the last year, despite treatment with the immunomodulator azathioprine. Infliximab is an anti–tumor necrosis factor (TNF)-α antagonist effective in inducing and maintaining remission in moderate to severe Crohn disease. Other FDA-approved anti-TNF agents include adalimumab and certolizumab pegol. Evidence indicates that efficacy is better when an anti-TNF agent is used together with an immunomodulator. In addition, the risk for developing antibodies against the anti-TNF agent is lower with combination therapy. Patients whose disease does not respond to one anti-TNF agent are often switched to a second or third anti-TNF agent. Fibrostenosing Crohn disease in the absence of ongoing mucosal inflammation is unlikely to respond to any anti-TNF agent. Patients with no response to or intolerance of anti-TNF agents should be treated with either surgery or a leukocyte trafficking blocker (natalizumab or vedolizumab).
Budesonide is a potent glucocorticoid with high first-pass metabolism in the liver, which limits systemic side effects related to conventional glucocorticoids. Budesonide can be an effective therapy for treating mild flares of ileal Crohn disease, but it is unlikely to induce remission in more severe Crohn disease and cannot be used to maintain remission.
Mesalamine agents are mainly used to treat ulcerative colitis of mild to moderate severity. Mesalamine may have efficacy in treating mild to moderate Crohn colitis, but it is not efficacious in treating small-bowel Crohn disease.
Reinitiating prednisone may induce remission of the patient's current disease flare, but it would not be helpful for maintenance of remission. Because this patient has required three separate tapering doses of glucocorticoids over the last year, she requires a medication such as infliximab that can both induce remission and maintain Crohn disease in remission.
A 72-year-old woman is evaluated during a routine office visit. She has a 3-year history of heart failure with preserved ejection fraction and a long history of hypertension. She has exertional dyspnea with walking around the house, almost nightly paroxysmal nocturnal dyspnea, and peripheral edema. Cardiac catheterization performed 2 years ago revealed normal coronary arteries. Medications are hydrochlorothiazide and diltiazem.
On physical examination, the patient is afebrile, blood pressure is 136/82 mm Hg, pulse rate is 48/min, and respiration rate is 18/min. There is jugular venous distention. An S4 is present. Pulmonary examination reveals no wheezes or crackles. Peripheral edema is noted.
Laboratory studies are significant for a serum creatinine level of 1.2 mg/dL (106.1 µmol/L) and a serum sodium level of 139 mEq/L (139 mmol/L).
Which of the following is the most appropriate management?
A Add ivabradine.
B Add valsartan.
C Discontinue hydrochlorothiazide and diltiazem and start furosemide.
D Refer for pacemaker placement.
nswer & CritiqueCorrect Answer: C
Educational Objective: Treat heart failure with preserved ejection fraction.
Key Point:
The cornerstone of treatment for patients with heart failure with preserved ejection fraction is diuretic therapy to maintain euvolemia.
The most appropriate management is to discontinue hydrochlorothiazide and diltiazem and start furosemide. This elderly woman with heart failure with preserved ejection fraction (HFpEF) has signs and symptoms of volume overload in the setting of bradycardia. The cornerstone of treatment for patients with HFpEF is diuretic therapy to maintain euvolemia. Antihypertensive agents should also be used to maintain normal blood pressure in the setting of hypertension. Despite treatment with hydrochlorothiazide, this patient has evidence of volume overload, and she should be switched to furosemide for more efficacious diuresis. This patient is also taking diltiazem, which may be causing her bradycardia, and this agent should be discontinued. If the patient's heart rate fails to improve, she should be referred for pacemaker placement.
Ivabradine is a sinus node modulator that reduces heart failure–associated hospitalizations in select heart failure patients; however, it is indicated as therapy only in patients with a reduced left ventricular ejection fraction and heart rate higher than 70/min while receiving β-blocker therapy.
Although ACE inhibitors, angiotensin receptor blockers (such as valsartan), β-blockers, and aldosterone antagonists have been studied for the treatment of HFpEF, no drugs have been shown to reduce morbidity or mortality in these patients. Most recently, in the TOPCAT trial, there was no difference in the primary combined endpoint of death, aborted cardiac arrest, or heart failure hospitalization with spironolactone compared with placebo; however, spironolactone was associated with a reduction in heart failure hospitalizations. Notably, a retrospective analysis showed that spironolactone reduced the incidence of cardiovascular death and heart failure hospitalization in patients in the Americas compared with those in Eastern Europe, likely because of different patient demographic characteristics across regions.
Pacemaker placement would be indicated only for symptomatic bradycardia in the absence of a reversible cause; the response to diltiazem discontinuation should be assessed before pacemaker placement is considered in this patient.
A 42-year-old man is evaluated in the hospital for increased pain and drainage from a previously healed surgical wound over the left fibula. He underwent open reduction and internal fixation of a fracture 4 weeks ago. The patient has undergone incision and surgical debridement of the wound. A bone culture revealed methicillin-sensitive Staphylococcus aureus. Medical history is otherwise noncontributory, and his only medication is ibuprofen for pain.
On physical examination, vital signs are normal. A surgical wound over the left lateral leg is well approximated with no erythema or drainage.
A plain radiograph before debridement shows nonunion of the fracture with screws and K-wires in place.
Which of the following is the most appropriate treatment?
A Cefazolin
B Cefazolin and rifampin
C Ceftaroline
D Vancomycin and rifampin
Answer & CritiqueCorrect Answer: B
Educational Objective: Treat osteomyelitis associated with orthopedic hardware.
Key Point
Rifampin should be used in combination with another antistaphylococcal agent when managing Staphylococcus aureus osteomyelitis in the setting of orthopedic hardware if the hardware cannot be removed.
Cefazolin and rifampin are appropriate therapy for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis associated with orthopedic hardware. Identification of the causative pathogen, administration of adequate antimicrobials for a prolonged duration, surgical debridement (if warranted), and removal of orthopedic prosthetic devices (if feasible) influence the success of osteomyelitis treatment. Optimal management of this patient's infection includes hardware removal; however, this is not possible because the fracture has not yet healed. Hardware-associated infections caused by S. aureus are difficult to eradicate because of the biofilm that forms on the hardware. First-line treatment of MSSA osteomyelitis consists of a β-lactam agent such as cefazolin; a randomized controlled trial and systematic review of the literature have demonstrated that if infected hardware cannot be removed, the addition of rifampin increases the chances of therapeutic success compared with an antistaphylococcal agent alone.
Although cefazolin has activity against MSSA as well as good bone penetration, it would not be an appropriate therapeutic option for the treatment of hardware-associated osteomyelitis without the addition of rifampin.
Ceftaroline has coverage for MSSA, methicillin-resistant S. aureus, and Enterobacteriaceae, but it is unnecessarily broad coverage for the treatment of this patient's MSSA infection.
Vancomycin, a bacteriostatic agent, is less effective than β-lactam agents for the treatment of MSSA and is typically restricted to patients with drug intolerance or allergy.
A 36-year-old woman is evaluated for dry cough and progressive dyspnea that limits her ability to exercise. She initially presented 8 weeks ago with cough, fever, sputum production, and dyspnea. A chest radiograph at that time revealed left-lower-lobe opacities; she was diagnosed with pneumonia and treated with azithromycin but had little improvement in her symptoms. Her fever and sputum production have resolved. She is a nonsmoker.
On physical examination, vital signs are normal. Lungs are clear to auscultation.
Repeat chest radiograph reveals patchy opacities bilaterally and several nodular densities that are peripherally predominant in different locations than previous radiographs. High-resolution CT scan of the chest shows extensive ground-glass changes bilaterally with several areas of nodular consolidation that are peripherally predominant and along bronchovascular bundles.
Which of the following is the most likely diagnosis?
A Acute HIV infection
B Community-acquired pneumonia
C Cryptogenic organizing pneumonia
D Idiopathic pulmonary fibrosis
Answer & CritiqueCorrect Answer: C
Educational Objective: Diagnose cryptogenic organizing pneumonia.
Key Point
A typical presentation of cryptogenic organizing pneumonia includes cough, fever, and malaise for 6 to 8 weeks that does not respond to antibiotics; patchy opacities on chest radiograph; and ground-glass opacities on CT scan that are peripherally distributed; glucocorticoids are first-line therapy.
The most likely diagnosis is cryptogenic organizing pneumonia. This patient has a subacute history of progressive dyspnea and persistent cough after an initial history consistent with community-acquired pneumonia. Despite treatment with appropriate antibiotic therapy, she now has clear evidence of new opacities that are located in different areas, are peripherally predominant, and coalesce along broncho-vascular bundles. These findings are consistent with a diagnosis of organizing pneumonia, which involves proliferation of granulation tissue within alveolar ducts, alveolar spaces, and surrounding areas of chronic inflammation. There are many known causes of this pattern, including acute infections and autoimmune disorders like rheumatoid arthritis. The term cryptogenic organizing pneumonia is reserved for individuals who have this pattern but do not have a clear associated cause. Patients with cryptogenic organizing pneumonia will typically present with a 6-to-8-week history of symptoms that mimic community-acquired pneumonia. Typically, an initial empiric treatment of infection is given but fails; subsequently, noninfectious causes are considered. This patient has a subacute illness that began with viral symptoms, persistent and progressive cough and dyspnea that are not responsive to past antibiotics, and radiographic findings typical of cryptogenic organizing pneumonia. Patients with cryptogenic organizing pneumonia respond well to glucocorticoids. Glucocorticoids are slowly tapered during the subsequent 6 months.
Acute HIV is unlikely in this patient who initially presented with symptoms of community-acquired pneumonia and whose fever has resolved. Although acute HIV symptoms are not specific, the most common presentation includes persistence of symptoms including fever.
Recurrent community-acquired pneumonia is also unlikely in this patient who was appropriately treated with azithromycin and whose symptoms have partially improved with resolution of the fever and sputum production.
Idiopathic pulmonary fibrosis (IPF) is a disease that affects older patients (the mean age of presentation is in the mid- to late 60s) and presents with chronic (longer than 6 months) symptoms of dry cough and shortness of breath. This patient's presentation is not consistent with these criteria, making a diagnosis of IPF unlikely.
A 77-year-old woman is seen for a preoperative medical evaluation before resection of the sigmoid colon for recurrent diverticulitis scheduled 5 days from now. She has nonvalvular atrial fibrillation and is receiving long-term warfarin, without a history of bleeding complications. She has no history of stroke, transient ischemic attack, or intracardiac thrombus. History is also significant for hypertension. Medications are warfarin, chlorthalidone, and metoprolol.
The physical examination, including vital signs, is normal.
The INR measurement is 2.3. Calculated CHADS2 score is 2, and CHA2DS2-VASc score is 4.
In addition to withholding warfarin before surgery, which of the following is the most appropriate management of this patient's perioperative anticoagulation?
A Begin aspirin, 81 mg/d
B Begin enoxaparin when the INR drops below 2.0
C Begin unfractionated heparin when the INR drops below 2.0
D No additional interventions
Answer & CritiqueCorrect Answer: D
Educational Objective: Manage perioperative anticoagulation in a patient receiving warfarin.
Key Point
In patients on warfarin who are undergoing surgery, bridging anticoagulation is typically reserved for patients at highest risk for thromboembolism.
The most appropriate management of this patient's preoperative anticoagulation is to withhold warfarin without bridging anticoagulation. Anticoagulant therapy increases the risk for perioperative hemorrhage and should be discontinued in most patients before surgery. Bridging anticoagulation is the administration of therapeutic doses of short-acting parenteral therapy, usually heparin, when anticoagulant therapy is being withheld during the perioperative period in patients with elevated thrombotic risk. This patient is undergoing a procedure associated with elevated bleeding risk, and she has no history of stroke, transient ischemic attack (TIA), or intracardiac thrombus. Therefore, the risks of bridging anticoagulation outweigh the thrombotic risk, and the warfarin should be withheld without bridging anticoagulation.
There is no role for aspirin in bridging anticoagulation. In patients with normal kidney function who require bridging anticoagulation, low-molecular-weight heparin is the agent of choice.
In 2019, the American Heart Association/American College of Cardiology/Heart Rhythm Society updated their 2014 guideline on the management of atrial fibrillation. For patients with atrial fibrillation without a mechanical heart valve, the updated guideline recommends that decisions about bridging therapy should balance the risk for stroke with the risk for bleeding. Bridging is typically reserved for patients at highest risk for thromboembolism. The 2018 American College of Chest Physicians guideline on antithrombotic therapy for atrial fibrillation recommends forgoing bridging in patients with atrial fibrillation on warfarin who do not have a mechanical valve and are otherwise not at high risk for thromboembolism. This patient has no additional risk factors for thromboembolism other than chronic atrial fibrillation, and perioperative bridging is not required.
A 55-year-old man is evaluated for ascites. He recently went to the emergency department, where paracentesis was performed. He was then discharged for outpatient follow-up. He has a history of cirrhosis due to nonalcoholic steatohepatitis and also has hypertension. Endoscopy 3 months earlier showed small varices without stigmata, making prophylaxis for esophageal variceal bleeding unnecessary. His only medication is lisinopril.
On physical examination, vital signs are normal; BMI is 28. Abdominal examination shows abdominal distention without tenderness.
Laboratory studies of the ascitic fluid show a leukocyte count of 80/µL with 20% neutrophils and protein level of 1.6 g/dL (16 g/L). Serum studies show a creatinine level of 1.3 mg/dL (114.9 µmol/L) and sodium level of 134 mEq/L (134 mmol/L).
An abdominal ultrasound from the emergency department shows changes consistent with cirrhosis. The portal vein and hepatic veins are patent with normal flow direction. A moderate amount of free-flowing ascites is seen.
In addition to initiating a sodium-restricted diet, which of the following is the most appropriate next step in management?
A Discontinue lisinopril
B Initiate free-water restriction
C Initiate propranolol
D Insert an indwelling drain into the peritoneal cavity
Answer & CritiqueCorrect Answer: A
Educational Objective: Treat ascites caused by portal hypertension.
Key Point
Medications that decrease kidney perfusion, including NSAIDs, ACE inhibitors, and angiotensin receptor blockers, should be discontinued in patients with ascites.
Discontinuing lisinopril is the most appropriate next step in the management of this patient with ascites. Blood pressure falls with worsening cirrhosis, resulting in reduced renal blood flow and glomerular filtration. A compensatory upregulation of the renin-angiotensin system results in increased levels of vasoconstrictors, including vasopressin, angiotensin, and aldosterone, which support systemic blood pressure and kidney function. ACE inhibitors and angiotensin receptor blockers impair the compensatory response to cirrhosis-related hypotension and thereby impair the ability to excrete excess sodium and water and may also affect survival. Medications that decrease kidney perfusion, including NSAIDs, ACE inhibitors such as lisinopril, and angiotensin receptor blockers, should be discontinued because their use often worsens ascites due to portal hypertension. The mainstay of therapy of ascites is to initiate dietary changes, restricting sodium intake to less than 2000 mg (87 mEq) daily. If sodium restriction does not result in significant improvement of ascites, the initiation of diuretic therapy with spironolactone with or without furosemide can be effective in increasing urinary sodium excretion.
Free-water restriction can be useful for the management of dilutional hyponatremia that is sometimes seen in patients with advanced liver dysfunction. This patient has a normal serum sodium concentration, so free-water restriction is not indicated.
Propranolol and other nonselective β-blockers are often used prophylactically for the prevention of variceal hemorrhage, but they do not have a role in the management of ascites. Furthermore, in some patients with ascites that is refractory to medical management, β-blockers may worsen clinical outcomes, including survival.
Indwelling drains for ascites have been used for patients with malignant ascites, but in the setting of portal hypertensive ascites, such as seen in this patient, indwelling drains are associated with a high risk for infection and their use is contraindicated.