A 38-year-old woman comes to the office due to dyspnea on exertion for the past 6 months. She says, "I get out of breath even when I walk less than a block at my usual pace. I climb stairs very slowly." A year ago, the patient was able to walk 10-12 blocks without any limitations. She has no chest pain, palpitations, syncope, cough, or hemoptysis. She has no medical problems. The patient saw a doctor 2 years ago and had a routine physical that did not show any abnormalities. She does not use tobacco, alcohol, or illicit drugs. Her mother has a history of breast cancer and "blood clots" in her legs. Her father had a stroke. The patient takes no prescription or over-the-counter medications. She has no known drug allergies. On examination, she appears comfortable at rest. Temperature is 36.7 C (98 F), blood pressure is 143/91 mm Hg, pulse is 84/min, and respirations are 16/min. Pulse oximetry shows 94% saturation on room air. BMI is 34 kg/m². On cardiac auscultation there is a prominent S2 but no murmurs or additional sounds. The lungs are clear. Peripheral pulses are full and no finger or toe clubbing is present. There is no peripheral edema. Chest-x ray reveals prominent pulmonary arteries but no infiltrates. ECG reveals normal sinus rhythm with right axis deviation. Echocardiography demonstrates increased right-sided pressures, right ventricular dilation, and normal left ventricular size and function. Right heart catheterization reveals a mean pulmonary artery pressure of 40 mm Hg (normal:

Question

A 38-year-old woman comes to the office due to dyspnea on exertion for the past 6 months. She says, "I get out of breath even when I walk less than a block at my usual pace. I climb stairs very slowly." A year ago, the patient was able to walk 10-12 blocks without any limitations. She has no chest pain, palpitations, syncope, cough, or hemoptysis. She has no medical problems. The patient saw a doctor 2 years ago and had a routine physical that did not show any abnormalities. She does not use tobacco, alcohol, or illicit drugs. Her mother has a history of breast cancer and "blood clots" in her legs. Her father had a stroke. The patient takes no prescription or over-the-counter medications. She has no known drug allergies. On examination, she appears comfortable at rest. Temperature is 36.7 C (98 F), blood pressure is 143/91 mm Hg, pulse is 84/min, and respirations are 16/min. Pulse oximetry shows 94% saturation on room air. BMI is 34 kg/m². On cardiac auscultation there is a prominent S2 but no murmurs or additional sounds. The lungs are clear. Peripheral pulses are full and no finger or toe clubbing is present. There is no peripheral edema. Chest-x ray reveals prominent pulmonary arteries but no infiltrates. ECG reveals normal sinus rhythm with right axis deviation. Echocardiography demonstrates increased right-sided pressures, right ventricular dilation, and normal left ventricular size and function. Right heart catheterization reveals a mean pulmonary artery pressure of 40 mm Hg (normal: <20 mm Hg) and a pulmonary capillary wedge pressure of 10 mm Hg. Further studies, including pulmonary function test, ventilation/perfusion scan, and polysomnography, are unremarkable. This patient would benefit most from an antagonist of which of the following receptors?

Quizplus · Accepted Answer

Explanation: This patient's right heart catheterization confirms pulmonary hypertension (PH) (mean pulmonary arterial pressure >25 mm Hg). Pulmonary capillary wedge pressure <18 mm Hg rules out PH due to left heart failure, and unremarkable pulmonary function testing, ventilation/perfusion scan, and polysomnography rule out PH due to structural lung disease (eg, interstitial lung disease), chronic thromboembolic pulmonary disease, and sleep disorder, respectively. These findings are consistent with group 1 pulmonary hypertension, or idiopathic pulmonary arterial hypertension (PAH), a condition that typically affects young adults. group 1 pulmonary hypertension Because there is no specific therapy to target the underlying cause of idiopathic PAH, advanced therapy is used to dilate the pulmonary arteries. Endothelin is a potent vasoconstricting hormone that is produced by endothelial cells, and endothelin receptors are abundant in the pulmonary arteries of patients with idiopathic PAH. Endothelin receptor antagonists (eg, bosentan, ambrisentan) have demonstrated delayed progression of disease in symptomatic patients with idiopathic PAH. Other advanced therapies available for patients with idiopathic PAH include phosphodiesterase-5 inhibitors (eg, sildenafil, tadalafil) and prostacyclin pathway agonists (eg, epoprostenol, treprostinil, iloprost). For patients with a positive vasoreactive test during right heart catheterization, calcium channel blockers (eg, long-acting nifedipine) are another option. (Choice A) Adenosine receptor antagonists (eg, theophylline) are sometimes used in the management of asthma but have no role in the management of PAH. (Choice B) Alpha-1 adrenergic antagonists (eg, doxazosin, terazosin) are often used for the treatment of symptomatic benign prostate hyperplasia and are sometimes used for systemic hypertension. However, these drugs are not indicated in the management of PAH. (Choice C) Left ventricular systolic dysfunction leads to elevated left atrial pressures and is a common cause of secondary (group 2) PH. Angiotensin receptor blockers (eg, losartan, valsartan) are indicated in these patients to decrease afterload and minimize cardiac remodeling; however, these drugs have no role in the management of PAH. (Choice E) Muscarinic antagonists (eg, ipratropium, tiotropium) are useful in the management of patients with PH secondary to chronic obstructive pulmonary disease (group 3), but these drugs are not indicated for PAH. Educational objective: When possible, the treatment of pulmonary hypertension is directed at the underlying cause of the disease. As there is no available therapy to target the underlying cause of idiopathic pulmonary arterial hypertension (group 1 pulmonary hypertension), advanced therapy (eg, endothelin receptor antagonists) to dilate the pulmonary arteries is the treatment of choice in symptomatic patients. References: 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). (http://www.ncbi.nlm.nih.gov/pubmed/26320113)

A 38-Year-Old Woman Comes to the Office Due to Dyspnea