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Three Part Question

In [patients with chest pain] does [responding to nitroglycerin] predict [cardiac chest pain]?

Clinical Scenario

A 47 year old man arrives to the emergency department with severe chest pain. His chest pain significantly improves with sublingual nitroglycerin. You wonder if the relief of patient’s chest pain with nitroglycerin has any prognostic value in the diagnosis of cardiac chest pain.

Search Strategy

MEDLINE 1996 to September Week 2 2010 using the OVID interface.
[(exp cardiac chest pain OR cardiac chest pain.mp. OR MI.mp OR exp myocardial ischemia OR myocardial ischemia.mp OR coronary artery disease.mp OR exp angina pectoris) AND (exp nitroglycerin OR nitroglycerin.mp)] LIMIT to human and English.

Search Outcome

23 articles of which 20 were irrelevant or of insufficient quality. The three remaining papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Henrikson CA et al 2003 USA	459 consecutive patients admitted from the ED for chest pain who received NTG	Single-center, prospective observational cohort study	Relief of CP in 39% of total patients	4 months clinical outcome were similar in patient with or without CP relief with NTG. Relief of chest pain after NTG does not predict active CAD and should not be used to guide diagnosis	Highly subjective self-reported pain using the scale of 0-10 which has many difficulties and interpretation and recall. Also there may be a work-up bias as physicians were aware of the CP response to NTG
			Relief of CP in 35% of patient with active CAD
			Relief of CP in 41% of patient without active CAD
Steele R et al 2006 USA	270 adult patients presenting to the ED with active chest pain who received NTG	Single-center, prospective cohort study	Relief of CP in 66% of total patients	NTG response had 72% sensitivity, 37% specificity, 34% PPV and 75% NPV for cardiac CP. Relief of CP with NTG does not distinguish between cardiac and non-cardiac CP.	Cannot eliminate selection bias based on exclusion criteria – excluding patients with lower likelihood of disease. While non-cardiac disease was defined as absence of objective findings, this does not completely rule out disease.
			Of those with relief – 34% had cardiac CP while 66% did not
			Of those with no relief – 25% had cardiac CP and 75% did not
Diercks D et al 2005 USA	664 consecutive chest pain patients in ED	Single center, prospective cohort study	Out of the total patients: 18% - cardiac related CP; 19% - no change; 31% - minimal reduction; 22% - moderate reduction; 28% - significant or complete reduction	No significant difference in overall response rates. The response of CP to NTG was not a reliable indicator of a cardiac etiology	Incomplete follow-up may have underestimated the predictive value of pain response to NTG. Assumptions that patient with a negative ECG and troponin I ruled out cardiac related CP though this may not completely rule out disease. The self-reporting numeric description pain scale is highly subjective.

Comment(s)

There are no randomised trials that address the question. The best evidence would appear to come from the above studies, which show that in patients from the general population presenting with chest pain, relief of pain with nitroglycerin is not a reliable diagnostic test and does not distinguish between cardiac and non- cardiac chest pain. Therefore, it should not be assumed that patients who do not have relief of chest pain with nitroglycerin are less likely to be suffering from a cardiac cause.

Clinical Bottom Line

Relief of chest pain with nitroglycerin does not predict cardiac etiology.

References

1. Henrikson CA, Howell EE, Bush DE, Miles JS, Meininger GR, Friedlander T, Bushnell AC, Chandra-Strobos N. Chest pain relief by nitroglycerin does not predict active coronary artery disease Ann Intern Med 2003 Dec 16;139(12):979
2. Steele R, McNaughton T, McConahy M, Lam J. Chest pain in emergency department patients: If the pain is relieved by nitroglycerin, is it more likely to be cardiac chest pain? CJEM 2006 May;8(3):164
3. Diercks DB, Boghos E, Guzman H, Amsterdam EA, Kirk JD Changes in the numeric descriptive scale for pain after sublingual nitroglycerin do not predict cardiac etiology of chest pain Ann Emerg Med 2005 Jun:45(6):581