Variant angina is a distinct clinical entity first described by Prinzmetal and associates in 1959.1 The classic presentation is characterized by chest pain occurring at rest, and is more frequent in young women. Unlike true angina, the chest pain in variant angina is usually not triggered by physical exertion or emotional stress. Coronary spasm can occur in apparently normal vessels, but more frequently affects atherosclerosis- afflicted segments in the coronary tree.2,3 It frequently occurs in focal zones, and diffuse multivessel spasm is rarely reported. We report such a case of diffuse, unprovoked triple-vessel vasospasm misdiagnosed as atherosclerotic obstructive coronary artery disease resulting in coronary bypass graft surgery (CABG).
Case Report. A 50-year old African-American female with long-standing hypertension, diabetes, hypercholesterolemia and mildly impaired left ventricular systolic function was admitted with a history of severe chest pain at rest radiating to both upper extremities and both sides of her neck. Five years prior to this presentation, she reported admission to another hospital where she underwent triple-vessel CABG with a left internal mammary artery (LIMA) to the left anterior descending (LAD), and saphenous vein grafts (SVG) to both the posterior descending (PDA) and the first obtuse marginal arteries (OM1). Initial evaluation in the emergency department on this admission revealed negative cardiac biomarkers and a normal electrocardiogram (ECG). A urine drug screen revealed the presence of opiates and benzodiazepines, but no evidence of cocaine or its metabolites. A subsequent ECG during an episode of chest pain at rest showed significant ST depressions anterolaterally, which resulted in her being referred for coronary angiography. All three native coronary vessels demonstrated severe and diffuse spasm. There was total occlusion of the LAD in its mid portion, with severe ostial narrowing of the diagonal branch (Figure 1A) and severe mid-circumflex stenosis (Figure 1B), and obliteration of the right coronary artery beyond its mid-portion mimicking a nondominant vessel (Figure 1C). Selective cannulation of the saphenous vein grafts (SVGs) revealed total occlusion of the SVG to OM1 (Figure 2A) and a patent SVG to a diffusely small and diseased-looking PDA (Figure 2B). Following administration of intracoronary nitroglycerin (NTG), there was complete disappearance of all the lesions in the native vessels with widely patent and normal-appearing arteries (Figures 3A and B).
A selective LIMA injection at this stage revealed it to be widely patent and connected to a moderate-sized LAD (Figure 3C). We were unable to procure the angiograms performed prior to her CABG. We assume that the native anatomy was probably similar to that seen prior to the nitroglycerin injection on the current angiogram. The patient was discharged with complete relief of symptoms on a regimen of calcium channel-blockers and nitrates.
Discussion. Spontaneous coronary artery spasm is an important cause of morbidity both in patients with coronary artery disease and in those with Prinzmetal’s or variant angina. The pathophysiologic mechanism is an exaggerated contractile response of the vascular smooth muscle in large epicardial coronary arteries. The role of increased adrenergic stimuli in the pathogenesis of vasospasm in patients with susceptible genetic background has recently been addressed.4 The incidence of coronary vasospasm-related angina in the Japanese population is thought to be markedly higher than in Caucasians.3,5 Conversely, there is a lower prevalence of fixed atherosclerotic coronary artery stenoses and diffuse coronary hyperreactivity in Japanese patients. In a study of 596 consecutive patients in Japan (369 men, mean age 64.2 ± 10.3 years), Sueda et al3 reported an exceptionally high incidence (29%) of ergonovine-induced spasm, which is two to three times higher than in Caucasians. Spasm was predominantly seen in patients with underlying ischemic heart disease (43.3%), andwas relatively uncommon in patients without ischemic heart disease (3.7%). The prevalence and specific features of vasospasm in African-Americans has not been described.
Variant or Prinzmetal’s angina is an infrequently encountered clinical problem with most common manifestations result from myocardial ischemia.6,7 Clinical presentation mimicking acute coronary syndromes with nonobstructive coronary artery disease has been described.7,8 Life-threatening arrhythmias as well as mechanical complications of ongoing ischemia (i.e., papillary muscle dysfunction) have also been reported9,10 as has severe spasm presenting as sudden death.11 Most focal vasospasm tends to occur in the proximal third of the coronary arteries corresponding to the historical high-risk zones for acute coronary occlusion.12 More plaque burden also exists in the proximal third of the coronary arteries, and there is a general consensus that the locus for vasospasm is predominantly at atherosclerotic segments. Whether spasm initially contributed to arterial injury or is more likely to occur at sites of preexisting fixed atherosclerotic obstruction is unknown.
As evidenced by the clinical course of our patient, it is imperative to diagnose this condition correctly. Dynamic STsegment elevation on a surface ECG during chest pain is indicative of coronary spasm. In the emergency room, the ECG may be normal in the time between attacks of chest pain. Continuous monitoring may be more helpful in documenting the frequency and duration of attacks. Anecdotal evidence suggests that attacks of variant angina tend to be clustered between midnight and 8:00 am, and sometimes occur two or three times within 30 to 60 minutes.13 There are no specific laboratory parameters that indicate the presence of vasospasm. Unlike patients with obstructive coronary artery disease, those with variant angina may be less likely to have significant elevation in total cholesterol, triglycerides, or low-density lipoprotein.8 Coronary vasospasm should be suspected in patients with signs of coronary ischemia and angiographically insignificant disease. The role of provocation testing in the clinical diagnosis of coronary spasm is controversial. It appears to be a sensitive method to identify patient with variant angina but such patients can often be diagnosed clinically.14 In presence of spontaneous and persistent spasm, there are no specific features on coronary anatomy that could differentiate obstruction due to vasospasm from that of true atheroscleroticlesions. Routine utilization of intracoronary nitroglycerin during diagnostic coronary angiography is not practiced by most operators, hence the diagnosis in our case was missed. A similar case of multiple angiographic stenosis described before escaped placement of multiple stents due to intraprocedural relief of all the stenosis after administration of nitroglycerin.15
Conclusions. Occasionally, the presence of vasospasm can pose a serious therapeutic dilemma. It is particularly so when it occurs extensively, in multiple areas and in association with true obstructive coronary artery disease. Specific clinical features and characteristics of chest pain should raise the index of suspicion for vasospasm. In select situations, the use of nitroglycerin can relieve spasm and unmask the extent of true coronary artery disease. A thorough patient history and heightened suspicion with the appropriate use of nitroglycerin could prevent unnecessary high-risk interventions and aid in the optimal management of such cases.
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