The Question
A 58-year-old woman with a history of HER2-positive breast cancer, treated 5 years prior with a doxorubicin-based regimen followed by trastuzumab, presents with a three-month history of progressive dyspnea on exertion and lower extremity swelling. Her blood pressure is 128/76 mmHg and her heart rate is 105/min. Physical examination reveals jugular venous pressure elevated to 10 cm H2O, bibasilar crackles on lung auscultation, and 2+ pitting edema to the mid-shins. A transthoracic echocardiogram demonstrates a new global hypokinesis with a left ventricular ejection fraction of 35%; her pre-chemotherapy ejection fraction was 65%. She is currently taking lisinopril for hypertension. In addition to her current lisinopril, which of the following is the most appropriate long-term therapy for this patient's cardiac condition?
See the answer and explanation below:
Post-Call Recovery Reads
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A
Explanation
Clinical Pearl:
Patients who develop heart failure with reduced ejection fraction (HFrEF) from cardiotoxic chemotherapy, such as anthracyclines or trastuzumab, should be managed with standard guideline-directed medical therapy for HFrEF, prioritizing agents with proven mortality benefit.
Explanation:
This patient has developed symptomatic HFrEF (LVEF 35%) as a late complication of her cancer treatment, a classic example of chemotherapy-induced cardiotoxicity. Management follows the same principles as for other causes of HFrEF. The patient is already on an ACE inhibitor (lisinopril), a foundational therapy. The most appropriate next step is the addition of an evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), which is proven to improve survival in HFrEF. Sacubitril-valsartan is an excellent therapy for HFrEF, but it is an angiotensin receptor-neprilysin inhibitor (ARNI) and would be used to replace lisinopril, not added to it, due to an increased risk of angioedema. Furosemide, a loop diuretic, is appropriate for managing her volume overload and congestive symptoms but does not provide a mortality benefit. Spironolactone, a mineralocorticoid receptor antagonist, is another pillar of HFrEF therapy but is typically added once a patient is stable on an ACE inhibitor and a beta-blocker. Digoxin is a later-line agent used for symptom control in patients who remain symptomatic despite optimal therapy or for rate control in atrial fibrillation; it does not reduce mortality.
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