A 67-year-old man with known coronary artery disease complains of exertional chest pain that limits his daily activities. He has long-standing angina symptoms. The patient reports that over the last month his exercise tolerance has decreased significantly and he has chest pain after walking only half a block. He takes sublingual nitroglycerin 6-7 times a day. Seven years ago he had coronary artery bypass surgery due to severe multivessel coronary artery disease with 3 venous grafts and left internal mammary artery graft to the left anterior descending artery.
Since then, he has had 2 cardiac catheterizations; the last showed occlusion of venous grafts and progressive native coronary artery disease not amenable to revascularization. His last left ventricular ejection fraction was 45%. The patient's medications include aspirin, lisinopril, atorvastatin, amlodipine, metoprolol, and nitroglycerin as needed. Two months ago, he was started on isosorbide dinitrate that he currently takes 4 times daily.
His blood pressure is 122/70 mm Hg and pulse is 55/min. No murmurs are heard on cardiac auscultation. Peripheral pulses are 2+ bilaterally. The remainder of the examination is within normal limits.
Which of the following most likely contributes to this patient's current symptoms?

Question

A 67-year-old man with known coronary artery disease complains of exertional chest pain that limits his daily activities.  He has long-standing angina symptoms.  The patient reports that over the last month his exercise tolerance has decreased significantly and he has chest pain after walking only half a block.  He takes sublingual nitroglycerin 6-7 times a day.  Seven years ago he had coronary artery bypass surgery due to severe multivessel coronary artery disease with 3 venous grafts and left internal mammary artery graft to the left anterior descending artery.
Since then, he has had 2 cardiac catheterizations; the last showed occlusion of venous grafts and progressive native coronary artery disease not amenable to revascularization.  His last left ventricular ejection fraction was 45%.  The patient's medications include aspirin, lisinopril, atorvastatin, amlodipine, metoprolol, and nitroglycerin as needed.  Two months ago, he was started on isosorbide dinitrate that he currently takes 4 times daily.
His blood pressure is 122/70 mm Hg and pulse is 55/min.  No murmurs are heard on cardiac auscultation.  Peripheral pulses are 2+ bilaterally.  The remainder of the examination is within normal limits.
Which of the following most likely contributes to this patient's current symptoms?

Quizplus · Accepted Answer

This patient has the classic presentation of stable angina pectoris, with chest discomfort occurring predictably after a certain level of exertion and relieved with rest. The 3 main classes of drugs used in the management of patients with stable angina pectoris are nitrates, beta blockers, and calcium channel blockers. Chronic nitrate therapy is often used to prevent recurrent anginal episodes and improve overall exercise tolerance. However, patients may develop tolerance to antianginal effects of nitrates with chronic exposure. Tolerance in such patients should be managed by intermittent therapy with short periods of nitrate absence. One approach to prevent nitrate tolerance is to adjust the dosing schedule to allow for nitrate-free intervals. This patient is receiving isosorbide dinitrate 4 times a day. Changing the dosing schedule to 2 or 3 times daily restores the vascular responsiveness to nitrates, improves exercise tolerance, and allows for longer drug-free intervals. (Choice A) Ischemic conditioning is a process in which 1 or more brief episodes of ischemia and subsequent reperfusion "condition" or protect the myocardium from a potentially severe and sustained episode of ischemia. (Choice C) Rebound angina refers to the development of angina or an increase in angina episodes in patients with ischemic heart disease due to abrupt withdrawal of antianginal agents. (Choice D) Coronary steal phenomenon occurs in response to coronary vasodilation and refers to an absolute decrease in blood flow in the coronary bed distal to coronary stenosis compared to flow in areas without stenosis. During pharmacologic stress testing with coronary vasodilators (eg, adenosine, regadenoson, dipyridamole), coronary steal leads to ST-segment depression, angina, and perfusion defects on radionuclide imaging in patients with significant coronary artery stenosis. (Choice E) Variant angina (also known as Prinzmetal angina) is characterized by episodes of angina pectoris caused by coronary artery vasospasm. It generally occurs in the absence of high-grade coronary artery stenosis. These episodes usually occur at rest and cause transient ST-segment elevation. Educational objective: Development of tolerance to the effects of nitrate with chronic exposure is a major limitation to its use as an effective antianginal therapy. It can be prevented by adjusting the dosing schedule to provide an adequate number of drug-free intervals. __________ References: Effects of intervals between doses on the development of tolerance to isosorbide dinitrate. (http://www.ncbi.nlm.nih.gov/pubmed/3574424) Explaining the phenomenon of nitrate tolerance. (http://www.ncbi.nlm.nih.gov/pubmed/16195486)

A 67-Year-Old Man with Known Coronary Artery Disease Complains of Exertional