Refractory Vasospasm Presenting as Acute Myocardial Infarction

Abstract

Refractory coronary artery spasm is a challenging condition with many complications, including acute myocardial infarction. We present the case of an elderly woman who developed refractory coronary artery vasospasm requiring extensive hemodynamic support. She had an abnormal electrocardiogram. She was diagnosed with severe coronary artery vasospasm that initially responded to intracoronary nitroglycerin. However, the course was complicated by arrhythmias and cardiogenic shock following an additional episode of vasospasm that required higher concentrations of nitroglycerin. Notably, this case is relatively less documented in women and within the South Bronx population. Refractory coronary artery spasm is a critical condition that can lead to life-threatening outcomes. Prompt and effective treatment is essential, especially for high-risk patients, to prevent cardiac ischemia. Given the significant dangers of delayed or insufficient treatment, it is crucial to manage coronary artery spasms proactively to enhance patient outcomes and avoid severe complications. In addition, this diagnosis should be strongly considered in women, with an emphasis on following guidelines for managing cases of acute myocardial infarction.

Background

About 20% of patients presenting with chest pain are usually found to have normal coronaries on angiograms when evaluated for obstructive coronary artery disease.^1,2 Coronary artery vasospasm (CVS) induced chest pain, causing complete or near-complete occlusion of the vessels, can present similarly to acute myocardial infarction (AMI). This is the case of a 78-year-old woman presenting with acute chest pain and abnormal electrocardiogram (ECG), diagnosed with severe vasoconstriction of the coronary arteries with complications including cardiogenic shock in the setting of stunned myocardium requiring multiple intracoronary nitroglycerin doses. This case is relatively less documented in women and in the South Bronx population.

Case Presentation

This is a 78-year-old woman with past medical history of hypertension, hyperlipidemia, Prinzmetal angina (on isosorbide mononitrate and nifedipine), invasive ductal carcinoma (refused treatment) who presented with acute onset of retrosternal chest pain that began suddenly while sleeping. The patient had no history of smoking. Her ECG was concerning for inferior wall ST elevation MI. She underwent urgent left heart catheterization that revealed focal spasm of mid and distal right coronary artery (RCA) as well as mid left anterior descending artery (LAD) (Figure 1). Intracoronary nitroglycerin was given with resolution of spasm and good TIMI 3 flow in all coronaries. She had no chest pain post-procedure and was admitted for monitoring. However, the patient became hypotensive after left cardiac catheterization and developed new-onset atrial fibrillation with highly variable heart rates (40-140 beats per minute). Transthoracic 2-dimensional echocardiogram demonstrated reduced ejection fraction of 29% and regional wall motion abnormalities in the LAD and RCA distribution. The hospital course further deteriorated with the development of cardiogenic shock requiring vasopressors and acute hypoxic respiratory failure requiring mechanical ventilation secondary to pulmonary edema. She underwent urgent right heart catheterization, showing severely reduced cardiac output and cardiac Index with pulmonary capillary wedge pressure of 15 mm Hg, requiring intra-aortic balloon pump (IABP) placement and inotropic support for hemodynamic stability. On day 3, the patient developed new ischemic ECG changes as well as several episodes of unstable ventricular tachycardia requiring direct cardioversion. A third urgent angiogram now showed severe, diffuse coronary vasospasm involving LAD, left circumflex (LCx) and RCA, which was worse than prior vasospasm from 2 days ago (Figure 2), requiring multiple intracoronary nitroglycerin pushes (total 700 µg administered) to completely resolve the coronary vasospasm and restore TIMI III flow in all coronaries. Over the subsequent days, the patient was able to be weaned off IABP and vasopressors. Nitrate and calcium channel blockers were resumed after achieving hemodynamic stability. A follow-up echocardiogram was also performed, revealing improvement in left ventricular ejection fraction and resolution of wall motion abnormalities. She remained stable throughout the rest of her stay and was discharged home.

Figure 1.

Focal spasm of mid and distal right coronary artery (RCA) as well as mid left anterior descending artery (A and C). Intracoronary nitroglycerin was given with resolution of spasm and good TIMI 3 flow in all coronaries (B and D).

Figure 2.

A third angiogram with severe, diffuse coronary vasospasm involving LAD, left circumflex (LCx), and RCA, which was worse than prior vasospasm from 2 days ago (A, B, and C). multiple intracoronary nitroglycerin pushes to completely resolve the coronary vasospasm and restore TIMI III flow in all coronaries (D and E).

Discussion

A transient and reversible vasoconstriction of the major epicardial coronary artery can lead to vasospasm resulting in AMI.^1,2 While ischemic diseases are more common, female patients presenting with vasospasm were found to be younger, less likely to have smoking history and more likely to need extensive provocation testing for diagnosis. ³ There is a heterogeneity in the distribution of the disease overall, but it is expected to be common in Asian patients. ⁴ Data regarding other races are also increasing. ⁴

Coronary artery vasospasm results from localized coronary artery abnormality and a vasoconstrictor stimulus. ⁵ Endothelial dysfunction is thought to play a role by impairing vasodilation, making arteries more susceptible to spasm. ⁵ Numerous preclinical studies have demonstrated that smoking and nicotine contribute to oxidative stress, leading to impaired endothelial function and decreased nitric oxide availability. Importantly, this damage is at least partially reversible, as quitting smoking has been shown to reduce coronary vasoconstriction. ⁶ Primary vascular smooth muscle cell hyperreactivity is also responsible. ⁵ Other mechanisms, such as passive mechanical collapse, have also been proposed, but coronary artery spasm frequently occurs in normal arteries, suggesting other contributing factors. ⁵ In addition, serotonin levels can act as inciting stimulus for large coronary arteries causing contractions because these contractions are mediated by serotonin receptors. ⁷

Estrogen protects against atherosclerosis by stimulating the endothelial production and release of nitric oxide and prostacyclin, scavenging superoxide, and reducing endothelin-1 activity. ⁸ Although coronary spasm is more common in postmenopausal women, it has also been reported in a few premenopausal women. Tezuka et al ⁸ found that the frequency of spasm in premenopausal women is highest during the late luteal and menstrual phases when estradiol levels are lowest. The exact mechanism is unclear, but estrogen receptors may have abnormalities, even though blood estrogen levels are normal. ⁸ Estrogen supplementation has been shown to improve endothelium-dependent dilation by increasing nitric oxide production in postmenopausal women with coronary artery spasm, its effectiveness in premenopausal women remains uncertain. ⁸ A postulated mechanism in this patient is regarding the use of vasopressors which has been discussed in literature earlier with use of norepinephrine, epinephrine, and vasopressin. Epinephrine, due to its alpha-adrenergic effect at higher doses and in large boluses as used for anaphylactic shock, can cause contractions in the large coronary arteries and lead to ischemia as a result. ⁹ Similarly, vasopressin has been shown to cause myocardial ischemia. Although vasopressin is usually maintained at low infusion rates, stress states such as shock lead to high secretion of vasopressin that can have a cumulative impact, leading to vasospasm and ischemia. ¹⁰ Similarly, norepinephrine dose increase has been associated with vasospasm and stress cardiomyopathy.^11,12 The development of worsened vasospasm and subsequent improvement in ejection fraction after nitroglycerin supports this hypothesis.^13,14

Patients often present with classic chest pain, which may be accompanied by transient ST segment elevations or, occasionally, ST segment depressions and T wave inversions. These symptoms tend to resolve spontaneously or after the administration of nitrates. ¹⁵ The diagnosis of coronary vasospasm is established if there are spontaneous episodes with ECG changes that are reversed by nitroglycerin, or if chest pain, ECG changes, or angiographic evidence of epicardial coronary vasospasm occur upon provocation. ¹⁵ Since coronary vasospasm is a transient functional abnormality, provocation testing is essential for diagnosis. ¹³ This testing can be conducted through exercise, hyperventilation, or pharmacologic methods under controlled conditions in a catheterization laboratory. Acetylcholine provocation testing is the gold standard for demonstrating reversible coronary obstruction and the demand-supply mismatch in coronary blood flow. ¹⁵ The limitation of this diagnostic modality is not being readily available in most of the cath labs, as well as the tedious titration of acetylcholine administration.

Coronary artery spasm can lead to severe complications like ventricular arrhythmias, syncope, sudden death, and AMI due to prolonged spasms. ¹⁶ Since many spasm-induced myocardial ischemia cases are silent, treatment should address both angina and silent ischemia, particularly in high-risk patients. ¹⁶ Long-term vasodilator therapy is recommended, especially for high-risk patients, to prevent spasm recurrence, which could lead to serious complications. Management usually involves nitrates like nitroglycerin, though intravenous nitrates or calcium channel blockers may be needed in rare cases. ¹⁶ Nitrates, while effective for acute angina relief, are less reliable for long-term prevention due to tolerance and potential adverse effects. Some studies have reported increased cardiovascular risks with long-term nitrate use, making them a second-line treatment alongside calcium channel blockers when necessary. ¹⁶ Nicorandil, another vasodilator, has shown promise in small studies for CVS refractory to therapy but lacks strong evidence for long-term efficacy. ¹⁶ Lifestyle changes, notably quitting smoking and reducing alcohol intake, are recommended. ¹⁶

Refractory cases may require higher doses or combinations of calcium channel blockers and nitrates. Clevidipine is an intravenous calcium channel blocker of the dihydropyridine class, characterized by rapid onset and a short half-life, and is approved for managing hypertension. ¹⁷ It does not directly affect myocardial contractility and, unlike nitroglycerine, does not alter preload. ¹⁷ Clevidipine has been effectively used during cardiac surgery to prevent vasospasm of the internal mammary and radial arteries. ¹⁷ It has also shown to be effective in cases where suboptimal response to nitroglycerin was observed. ¹⁷ In cases with plaques identified by intracoronary imaging, stenting offers optimal management. ¹⁸ In addition, it has also been discussed as an acceptable mode of treatment in patients with multiple vessel disease refractory to medical management. ¹⁹

Managing refractory cases is challenging and may involve aggressive therapy to prevent life-threatening complications. ¹⁶ In addition, guidelines have to be streamlined to the cohort of patients presenting with AMI secondary to refractory vasospasm. ¹⁶

Conclusions

Refractory coronary artery spasm is a severe condition with potentially life-threatening consequences. Immediate and effective treatment is crucial, particularly in high-risk patients, to prevent both symptomatic and silent myocardial ischemia. Given the potential risks associated with delayed or inadequate treatment, a proactive approach to CVS management is vital to improving patient outcomes and preventing severe complications. In addition, this diagnosis should be considered strongly in women with a focus on guidelines to discuss management in cases with AMI.