Featured Case: Spontaneous Multivessel Coronary Vasospasm Leading to Cardiogenic Shock

J INVASIVE CARDIOL 2007;19:E85-E88 Coronary vasospasm is a well-known cause of exercise-induced angina pectoris, Prinzmetal’s unstable angina, and myocardial infarction.^1–6 In general, the prognosis of patients with isolated coronary vasospasm is good, although in the setting of myocardial infarction, mechanical complications such as free wall or interventricular septal rupture, malignant arrhythmias, and sudden death can occur.^7,8 We report an unusual case of spontaneous multivessel coronary vasospasm leading to cardiogenic shock.

Case Presentation. An 84-year-old female with a history of hypertension, dyslipidemia, hypothyroidism, and Alzheimer’s dementia presented to the emergency room after experiencing dizziness and presyncope. Her outpatient cardiac medications included extended-release diltiazem 120 mg daily, extended-release metoprolol 25 mg daily, simvastatin 20 mg daily, gemfibrozil 600 mg twice daily, and spironolactone 25 mg daily. She was also taking thyroxine 75 µg daily, conjugated estrogens 0.625 mg daily, alprazolam 0.25 mg three times daily as needed, donepezil (cholinesterase inhibitor which increases acetylcholine concentration in the brain) 5 mg twice daily, and memantine (blocks the N-methyl-D-aspartate receptor which decreases the effects of glutamate in the brain) 10 mg twice daily. In addition, in the last month, she was started on methylphenidate (Ritalin, which stimulates the brain in a manner that is similar, but milder, than amphetamines) 5 mg daily, due to fatigue and social withdrawal. On presentation, she had also complained of excessive diaphoresis and flushing for the past month. Electrocardiography on presentation showed alternating junctional and sinus bradycardia with a pulse rate of 42 beats per minute and nonspecific ST-T-wave changes. Creatine kinase-MB and troponin I levels were initially negative. The diltiazem and metoprolol were held due to bradycardia and she reverted back to normal sinus rhythm.
Over the next 24 hours she developed waxing and waning chest pain and shortness of breath accompanied by hypotension, cool extremities with persistent systolic blood pressure ~80 mmHg, 2 mm ST-segment elevation in the precordial leads, and pulmonary edema with diffuse rales on examination. Emergent coronary angiography revealed a patent left main coronary artery, severe diffuse subtotal stenosis of the entire left anterior descending (LAD) coronary artery (Figure 1A, arrow, and Figure 1B), an apparently small left circumflex (LCx) coronary artery, and a diffusely diseased right coronary artery (RCA) (Figures 1C and 1D). Both the LCx and RCA had Thrombolysis in Myocardial Infarction 3 flow (TIMI 3). There was no angiographic evidence of the presence of thrombus such as filling defect or dye staining. Due to the rapid hemodynamic and respiratory compromise, she was treated with mechanical ventilation, epinephrine bolus, dopamine infusion and intra-aortic balloon counterpulsation. Percutaneous coronary intervention was then performed and an angiogram with the guiding catheter in place showed no change in the LAD (Figure 2A). A Traverse wire (Guidant Corp., Indianapolis, Indiana) was successfully placed in the distal LAD (Figure 2B), and several balloon inflations were performed with a 2.0 x 15 mm Maverick balloon (Boston Scientific Corp., Natick, Massachusetts) from the distal to proximal LAD (Figure 2C). This established antegrade flow in the areas of the balloon inflations, but there was persistent diffuse vessel stenosis in the distal LAD (Figure 2D). Because the vessel lumen was poorly responsive to balloon inflations, a 2.0 x 28 mm Pixel stent (Guidant) was deployed in the mid LAD at 12 atm (Figure 2E, arrowhead), establishing flow to the distal LAD. Several doses of intracoronary nitroglycerin, verapamil, and adenosine were then administered with ultimate restitution of TIMI 3 flow. There was no angiographic evidence of intracoronary thrombus or stenosis once normal flow was restored (Figure 2E). Interestingly, the LCx also responded to vasodilators, assuming a relatively normal caliber, particularly in the proximal segment (Figure 2E). Because of the high index of suspicion for diffuse multivessel vasospasm, it was decided to re-image the RCA, which revealed complete resolution of the diffuse stenoses with a normal angiographic appearance (Figure 2F).
Immediately following the intervention and after fairly rapid hemodynamic response, the pulmonary capillary wedge pressure was 23 mmHg and the cardiac index was 2.1 L/minute/m² using the assumed Fick method. The patient’s hemodynamic parameters improved very rapidly once the vasospasm resolved, and she was weaned off the dopamine while still in the cardiac catheterization laboratory. Her peak CPK was 1,953 IU/L, her CPK-MB was 486.1 ng/ml, and her troponin I was 58.7 ng/ml. An echocardiogram showed an ejection fraction of 37% with anterior and anteroseptal wall motion abnormalities. The balloon pump was removed within 24 hours and she was extubated. Pheochromocytoma and carcinoid syndrome were ruled out by laboratory tests, as well as chest and abdomen computed tomography. She was taken off the methylphenidate, conjugated estrogens, diltiazem and metoprolol and was treated with amlodipine and isosorbide mononitrate. At 24 months, the patient remained asymptomatic, her ejection fraction improved to 61% with a small anteroseptal wall motion abnormality, and a sestamibi scan showed a small, fixed anterior defect without any reversible perfusion abnormalities.

Discussion. This report describes a case of severe spontaneous multivessel coronary vasospasm complicated by cardiogenic shock that was successfully treated with hemodynamic support, stenting, and intracoronary vasodilators. Although a thrombotic occlusion of the ostial LAD due to atherosclerotic plaque rupture cannot be completely ruled out, it is unlikely, given the complete absence of angiographically-detectable thrombus or atherosclerotic disease once normal flow was reestablished. In addition, even though a stent was placed in the mid-distal LAD due to the appearance of diffuse vessel stenosis, the proximal site of occlusion was never stented and ultimately appeared quite normal. The patient had a remarkably rapid recovery following prompt institution of appropriate therapy and a good long-term clinical outcome. Although vasospasm is well appreciated clinically, it generally presents in a single coronary artery and has rarely been reported to be present in all three coronary arteries,⁹ or to present as cardiogenic shock. This case highlights the potential for diffuse, generalized vasospasm in susceptible patients and also underscores the importance of vascular tone in acute myocardial infarction.
This case is unusual given the severity of the clinical presentation and the occurrence of simultaneous multivessel vasospasm leading to severe narrowing of the LCx and RCA and complete occlusion of the LAD, with subsequent cardiogenic shock. Also, the withdrawal from calcium channel- and beta-blockers in the setting of methylphenidate use and medications for Alzheimer’s dementia may be implicated in the precipitation and severity of the vasospasm. There are currently no reports in the literature linking the use of methylphenidate, memantine, or donepezil to coronary vasospasm. However, it seems plausible that the combination of adrenergic and cholinergic actions of these drugs may disrupt the coronary autonomic balance in favor of coronary vasoconstriction, especially in the setting of withdrawal from calcium antagonists.
Coronary artery vasospasm is the cause of Prinzmetal’s angina and generally occurs at rest in the early morning hours, is usually transient, is accompanied by pronounced ST-segment elevation, and resolves promptly with the administration of nitrates.¹ Coronary artery vasospasm has also been suggested as a cause of exertion-induced angina pectoris, myocardial infarction with or without underlying coronary atherosclerosis, malignant arrhythmias, sudden death, and mechanical complications such as free-wall or interventricular septal rupture.^1–6 Vasospasm can lead to stunned myocardium, heart failure, and reversible left ventricular regional wall motion abnormalities.10 Germane to this case, coronary vasospasm has been previously attributed to withdrawal from beta-blockers and calcium channel antagonists.^11,12 Other factors have also been associated with coronary vasospasm, including cold weather, mental stress, vigorous exercise, all major coronary risk factors, and in particular, smoking, coronary ectasia, cocaine use, withdrawal from alcohol, and endothelial nitric oxide synthase (eNOS) gene polymorphisms.¹³ Multivessel coronary vasospasm has also been described following coronary bypass surgery,¹⁴ coronary stenting,¹⁵ or in association with thyrotoxicosis.^16,17
The diagnosis of coronary vasospasm is based upon the angiographic finding of epicardial coronary narrowing that is promptly reversed by vasodilators. If normal coronaries are found at angiography, the diagnosis usually becomes one of exclusion based on clinical and electrocardiographic criteria. However, many patients have luminal irregularities suggesting underlying atherosclerosis.¹⁸ Several provocation tests including intracoronary acetylcholine injections, hyperventilation, and intravenous ergonovine have been historically employed in the diagnosis of this condition.^18–20 However, due to low yield depending upon the population screened, false-positive findings due to diffuse vasospasm, small risk of myocardial infarction, and the possibility of empirical treatment with coronary vasodilators, provocation tests are less commonly employed in routine clinical practice. The prognosis of patients with coronary vasospasm without underlying coronary artery disease is generally good.^7,8 However, the prognosis of patients with vasospasm and underlying atherosclerotic coronary disease is largely dependent on the extent of atherosclerotic involvement and left ventricular function. The medical treatment of vasospasm consists of coronary vasodilators such as nitrates and calcium channel-blockers. There are few controlled trials assessing the efficacy of these therapies, in isolation or in combination, given the relatively low number of patients with isolated vasospasm.^21,22 In cases refractory to medical therapy, stenting and even more rarely, coronary bypass graft surgery, have been employed.²³ In cases of vasospasm complicating percutaneous coronary interventions, patients generally respond to intracoronary administration of vasodilators.²⁴ There have been reports of vasospasm refractory to injection of vasodilators through the guiding catheter, possibly due to the inability of the drug to reach the distal circulation in cases of markedly diminished coronary flow. These cases may respond to distal intracoronary drug delivery via a transit catheter or balloon.²⁵
In conclusion, this case highlights diffuse coronary vasospasm as an etiology of cardiogenic shock and the favorable intermediate-term prognosis with appropriate medical and interventional therapy. It underscores the importance of considering this condition in the differential diagnosis of acute myocardial infarction, and also illustrates the difficulty in identifying one specific precipitating factor of vasospasm in such patients who often have to be treated in an empiric fashion.

References

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