A 59-year-old woman comes to her physician because she has been bothered by increasing swelling of her lower legs for the past 7 months. On examination her pulse is 80/min with blood pressure 140/85 mm Hg. Her lungs have a few fine basilar crackles on auscultation, and her heart rate is regular with no murmurs. She has 1+ pitting edema to her mid-calf bilaterally. A chest radiograph shows an enlarged heart with blunting of costophrenic angles. Laboratory studies show sodium 144 mmol/L, potassium 4.2 mmol/L, chloride 108 mmol/L, CO2 26 mmol/L, glucose 89 mg/dL, creatinine 1.0 mg/dL, and urea nitrogen 15 mg/dL. A fasting lipid profile shows total cholesterol 223 mg/dL, HDL cholesterol 28 mg/dL, and triglyceride 177 mg/dL.

Questions:

6.1 How do you interpret these findings?

She has evidence for mild right-sided and left-sided heart failure. She has hypercholesterolemia. Her enlarged heart could be due to a variety of findings, including atherosclerotic cardiovascular disease and elevated blood pressure.

6.2 What pharmacologic therapy is indicated?

Her blood pressure alone does not warrant drug therapy. However, the congestive heart failure could benefit from a diuretic such as a thiazide. An angiotensin-converting enzyme (ACE) inhibitor might also be beneficial in reducing or reversing the cardiac "remodeling" even if her blood pressure does not warrant it.

6.3 How does this therapy work? Explain the pathophysiology.

Thiazide diuretics such a hydrochlorothiazide inhibit the Na+ Cl- cotransporter in the proximal part of the distal tubule. This promotes sodium diuresis and volume depletion.

Additional history:

A year later she comes back to the physician. Though she had some relief from the ankle swelling, she now has orthopnea. On physical examination her pulse is 87/min and blood pressure 130/80 mm Hg. She has diffuse crackles in all lung fields. Laboratory studies show sodium 135 mg/dL, potassium 3.7 mg/dL, chloride 92 mg/dL, CO2 24 mg/dL, glucose 80 mg/dL, and creatinine 1.1 mg/dL.

6.4 What pharmacologic therapy may be useful now?

She is switched to the "loop" diuretic, furosemide, which is helpful in the setting of refractory heart failure and with hyponatremia, hypokalemia, and hypochloremia. The loops diuretics inhibit the Na+ K+ 2Cl- cotransporter in the thick ascending limb of the loop of Henle.