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Response to Nitroglycerin Does Not Predict an Ischemic Cause for Chest Pain

Chest pain relief with nitroglycerin is not useful for diagnosing coronary artery disease in the acute setting.

It is common wisdom that chest pain that improves with nitroglycerin is probably ischemic in origin. However, the diagnostic and prognostic value of response to nitroglycerin in patients with chest pain has not been properly assessed. In a prospective study of 459 patients presenting to an emergency department with chest pain, researchers assessed whether a decrease in pain after the administration of a single nitroglycerin dose indicates an ischemic cause of the pain.

The cause of chest pain was considered ischemic if the patient had active coronary artery disease (CAD), as defined by the presence of appropriate symptoms and any one of the following: elevated troponin T levels, 70% stenosis of a coronary artery found on angiography, positive exercise test, or final diagnosis of CAD in the absence of testing (as noted by the attending physician and confirmed by a cardiologist blinded to the nitroglycerin response). CAD status was unclear in 43 patients. Response to nitroglycerin was defined as at least a 50% reduction in self-reported pain within 5 minutes after administration of 0.4 mg. Nitroglycerin relieved pain in 35% of patients with active CAD (49 of 141) and 41% of patients without active CAD (113 of 275). Overall, the sensitivity of response to nitroglycerin for predicting the presence of CAD was 35%, and the specificity was 59%. At 4-month follow-up, outcomes, including death and myocardial infarction, did not differ between the two groups.

An editorialist comments that these results should not alter the utility of diagnosing ischemia in the nonacute setting by evaluating the response to nitroglycerin, because the pathophysiology of chronic stable angina (demand related) differs from that of acute coronary syndrome (plaque disruption). This difference could account for the low sensitivity found in this study, as plaque disruption would not respond to nitroglycerin. The low specificity could be attributed to the placebo effect and to the known low prevalence of actual cardiac causes of chest pain in ED patients.

Comment: Response to nitroglycerin joins response to the gastrointestinal cocktail in the realm of "not a good test." The use of traditional cardiac risk factors is also in that realm, along with the finding of "atypical pain." Perfect tests for CAD do not exist. Goldman and Kirtane note in an accompanying report that aside from a careful history, the electrocardiogram is the most important piece of diagnostic information, particularly if it shows recent abnormalities. Unfortunately, a normal ECG does not rule out ischemia, as 50% of mistakenly discharged patients with undiagnosed MIs have normal ECGs.

Two quotes from Goldman nd Kirtane should guide practice: "the decision to measure and assess a biomarker level at presentation implies that the patient's risk is high enough to require a repeated assessment 6 hours later if the first level is normal," and "without compelling evidence for a noncardiac cause, there is no absolutely fail-safe way to exclude myocardial ischemia or infarction at the time of a patient's initial presentation." If "it could be heart," then a rapid rule-out protocol is needed to keep the patients (and the careers of emergency physicians) safe.

— J. Stephen Bohan, MS, MD, FACP, FACEP

Published in Journal Watch Emergency Medicine February 3, 2004

Citation(s):

Henrikson CA et al. Chest pain relief by nitroglycerin does not predict active coronary artery disease. Ann Intern Med 2003 Dec 16; 139:979-86.

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• Medline abstract (Free)

Gibbons RJ. Nitroglycerin: Should we still ask? Ann Intern Med 2003 Dec 16; 139:1036-7.

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• Medline abstract (Free)

Goldman L and Kirtane AJ. Triage of patients with acute chest pain and possible cardiac ischemia: The elusive search for diagnostic perfection. Ann Intern Med 2003 Dec 16; 139:987-95.

• Original article (Subscription may be required)
• Medline abstract (Free)