Methamphetamine-Associated Acute Myocardial Infarction and Cardiogenic Shock with Normal Coronary Arteries: Refractory Global Co

J INVASIVE CARDIOL 2007;19:E89-E92

Case Report. A 19-year-old male college student was admitted with 2 days of progressive, intermittent substernal chest pain. He had driven home from his out-of-state campus, where 2 days earlier he had abused large quantities ofmethamphetamine (MET) purchased from a new dealer. He was initially evaluated at a local hospital, but signed out against medical advice. His past medical and social history is significant for substance abuse including: methylphenidate (Ritalin), amphetamine/dextroamphetamine (Adderall), heroin, and tobacco. The patient had no prior history of cardiovascular disease. In the emergency room, his blood pressure was 86/54 mmHg, and his pulse was 113 beats per minute. Aside from lethargy, the physical examination was unremarkable. The electrocardiogram revealed prominent ST-segment elevations in the infero-lateral leads (Figure 1).
Emergency cardiac catheterization was performed and revealed no evidence of significant epicardial coronary stenoses. The flow in all 3 coronary systems, however, was markedly reduced, at Thrombolysis in Myocardial Infarction (TIMI) grade 1, with a myocardial blush grade of 0 (Figure 2). Left ventriculography revealed mild-to-moderate left ventricular dysfunction with infero-apical akinesis. Attempting to improve microvascular vasodilatation, we administered multiple doses of intracoronary nitroprusside and adenosine into all 3 distal coronary beds via an angioplasty balloon catheter central lumen. Despite these attempts, however, the angiographic “slow-reflow” persisted. Intravenous dopamine infusion and intra-aortic balloon counterpulsation were initiated for cardiogenic shock. The patient’s angina subsequently resolved; however, the ST-segments remained elevated. Two hours after transfer to the coronary care unit, his ST-elevations again increased dramatically, despite a lack of recurrent angina. Repeat emergency angiography, however, revealed normalization of all epicardial coronary TIMI grade flow and myocardial blush grade to 3.
The cardiac markers were only mildly elevated, with a peak creatine kinase level of 245 IU/L, a myoglobin-brain fraction of 12.1 ng/mL, and a troponin I level of 3.1 ng/mL. The patient’s hemodynamics continued to improve, and 3 days later the intra-aortic balloon pump and dopamine infusion were discontinued.
Electrocardiographically, the ST-segments normalized, with residual inferior T-wave inversions (Figure 3). Unfortunately, despite our best efforts, the patient refused any form of drug detoxification or rehabilitation program. On the sixth day, he was discharged on diltiazem and nitrates. The patient informed the author that he was truly grateful and had learned a valuable lesson. He stated remorsefully that he would never repeat this mistake again; in the future, he would only purchase his drugs from a known and reputable source. He has subsequently been lost to follow up.

Discussion. MET is among the fastest growing illicit drug problems in this country today.¹ Previously concentrated in Hawaii and the Philippines, the illegal MET market is now well established in the continental United States. The National Household Survey of Drug Abuse reported that over 8.8 million Americans abused this compound in 2000,² a figure that dramatically increased from 3.4 million in 1994.³ MET is a white, odorless, somewhat bitter crystal, which is water- and alcohol-soluble. The purified form is also called “ice” or “crystal”, and is easily synthesized in home laboratories. “Speed” or “crank”, the less pure version, derives its nicknames from its popularity amongst motorcycle gangs in the 1960s.⁴ Other street names include: “tweak”, “go fast”, “go”, and “glass”.⁵
This central nervous system stimulant, developed approximately 80 years ago,⁶ causes a generalized hypercatecholaminergic milieu by increasing the release and blocking the reuptake of dopamine and norepinephrine.^7,8 MET is synthesized by the N-Methyl substitution of the parent compound amphetamine, resulting in twice the potency.⁸ The “high” is similar to that experienced with cocaine, including euphoria, sexual arousal, heightened energy, as well as increased irritability and paranoia. Unlike cocaine, however, the effects are more prolonged, and administration via smoking achieves the same efficacy as the intravenous route. Additionally, its significantly lower cost further enhances its popularity, and thus its growing importance as a public health issue.⁹
When compared with cocaine, MET comprises only a minority of stimulant-induced acute coronary syndromes. This phenomenon may simply reflect the higher prevalence of cocaine use. However, there is animal evidence to suggest that MET may actually be less cardiotoxic. The drug causes production of heat shock proteins, which can protect and attenuate myocyte injury.¹⁰ Nonischemic cardiopulmonary complications of MET abuse include acute pulmonary edema,¹¹ dilated cardiomyopathy,¹² and pulmonary hypertension.¹³ Additionally, noncardiac chest pain can result from skeletal muscle necrosis.¹⁴
The syndrome of MET-induced acute myocardial infarction is well described.^15–18 In one postmortem series, Karch et al compared corpses with and without significant MET blood levels in the San Francisco medical examiner’s office between 1985–1997. For presumed MET-associated deaths, they found that there was a Caucasian and male predominance. Cardiac-wise, there were greater incidences of macroscopic epicardial coronary stenoses and cardiomegaly. In addition, higher rates of intracranial hemorrhage, as well as hepatic and pulmonary pathologies were also seen.¹⁹ Although no definitive mechanisms for MET-induced cardiac injury have been established, they are postulated to be similar to those seen with cocaine. These include: prothrombotic state, accelerated atherosclerosis due to endothelial injury, increased myocardial oxygen consumption, direct myocardial toxicity, and epicardial coronary vasospasm.^20–24
Turnipseed and colleagues reported a series of 33 patients with suspected MET-associated acute coronary syndromes. Of the 3 patients who underwent coronary angiography, all had significant epicardial coronary stenoses. Nine patients were ultimately diagnosed with acute coronary syndrome; however, 2 others who initially received thrombolytic therapy were later found not to have acute myocardial infarctions.⁴ In their series of 8 patients, Wijetunga and colleagues found that 5 of 6 patients who were catheterized had significant coronary stenoses. Epicardial coronary flow rates were normal in all of them, however.⁵
Potential mechanisms for MET-induced coronary atherosclerosis include accelerated hypertension, increased platelet aggregability, and heightened shear forces. While macrovascular epicardial coronary spasm has been attributed to both MET and cocaine,^24–26 microvascular spasm or thrombosis has not been previously reported. In our Medline literature search from 1995 to the present, we found no previous references to MET abuse associated with global coronary “slow-reflow” or “no-reflow”, as seen in our patient. This phenomenon describes attenuated flow into the distal vasculature despite a lack of significant epicardial luminal stenoses. The flow is described according to the TIMI grade as well as the corresponding myocardial blush grade of the distal vascular bed, both from 0–3.²⁷ The usual scenario for this abnormal flow pattern is after thrombolysis or percutaneous intervention in acute coronary syndromes, usually involving a thrombotic or friable plaque. Microvascular thromboemboli and spasm are implicated as the usual mechanisms. The microvascular spasm is likely mediated by platelet-derived vasoconstrictor substances. Several studies have clearly demonstrated an increase in major adverse cardiovascular events following “slow-reflow” or “no-reflow.”^28–30 Our patient, of course, had not undergone either thrombolytic therapy or percutaneous intervention.
Both mechanical and pharmacologic treatments are used with varying success in these situations. Aspiration devices, used alone or in combination with distal protection, have been shown to either decrease subsequent events or improve perfusion in both native coronary and saphenous vein graft interventions.^31–34 Since our patient had no visible lesions or thrombus, we saw no benefit to this approach.
Endothelium-independent intracoronary vasodilators such as nitroprusside, adenosine, and calcium channel-blockers have also been shown to improve flow in these settings. These agents are delivered into the distal bed, usually through the central wire lumen of a balloon catheter.^35–37 Alternatively, we have recently described the use of a dual-lumen catheter for the same purpose, allowing simultaneous maintenance of the guidewire position.³⁸ Although repeated administration of both adenosine and nitroprusside yielded no immediate benefit in our patient, it is possible that the therapy resulted in delayed flow improvement, as seen in the subsequent angiogram. Additionally, Rawitscher et al reported prompt resolution of “no-reflow” with abciximab;³⁹ however, again, since we saw no evidence of thrombus, this agent was not used in our patient.
Our case is unique in the finding of simultaneous “slow-reflow” in all 3 coronary systems. This observation essentially eliminates microvascular thrombi, which would likely be a local phenomenon, and favors a global vasospastic state as the pathophysiologic mechanism. Even so, local flow limitations were obviously not uniform, as evidenced by the regional infero-apical wall motion abnormality on the left ventriculogram. Although MET-induced vasospasm has previously been described in the epicardial coronary system, in this case, our patient’s microvasculature was affected.
Although global microvascular spasm is certainly consistent with our patient’s initial presentation, the second episode of ST-segment elevation in the setting of normalized flow is puzzling. One possibility is the occurrence of transient macrovascular spasm. The absence of visible coronary spasm, as well as the lack of angina, however, argue against this explanation. Postinfarct pericardial inflammation is likewise unlikely given the lack of symptomatology, as well as the transient time course. Alternatively, it may simply represent an unusual electrocardiographic manifestation of the drug’s cardiomyotoxic effects. As there have been no previous reports of this complication from MET, the true underlying mechanism of the ST-segment re-elevation in the setting of normalized flow remains unknown.
Given the global distribution of microvascular spasm, the relatively benign postinfarct course and mild cardiac enzyme elevation are somewhat surprising. This finding may be partially attributable to the previously discussed attenuation of myocardial necrosis by the “protective” properties of the MET-induced heat shock proteins. Moreover, intra-aortic balloon counterpulsation, initiated at the end of the initial procedure, may have subsequently facilitated microvascular delivery of the large boluses of intracoronary vasodilators, leading to a delayed but beneficial effect. In addition to these factors, the reduced, yet present, flow may have provided just sufficient perfusion to prevent extensive transmural damage, as reflected by the lack of pathological electrocardiographic Q-waves. Again, since no published data are available regarding MET-induced microvascular spasm, any explanation of these clinical events is purely speculative. Alternatively, the entire clinical scenario may have been self-limiting, and all the therapeutic measures simply acted to support the patient without altering the underlying pathophysiology.

Conclusion. In summary, to our knowledge, this is the first reported case of MET-associated slow-flow of the entire coronary vasculature in the absence of visible stenoses. The resistance or delayed response to repeated pharmacologic treatment likely reflects the tremendous “spasm burden” involving the entire coronary microvasculature. As “ice” continues to grow as a public health issue, physicians need to be vigilant of its high risk for acute coronary syndromes. This case illustrates yet another manifestation of the protean cardiac complications from this drug. Any unusual presentation of coronary ischemia, especially in a young patient, should prompt consideration of performing toxicology screening.

Acknowledgements. Special thanks to Mr. Allen Hsu and Mr. Scott Matthewson for their assistance.

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