Acute Cardiac Care, June 2014; 16(2): 83–87 Copyright © 2014 Informa UK, Ltd ISSN 1748-2941 print/ISSN 1748-295X online DOI: 10.3109/17482941.2014.902470


Thrombolytic-related complication in a case of misdiagnosed myocardial infarction Osereme Irivbogbe4, Brooks Mirrer1,2, Pablo Loarte3, Michael Gale4 & Ronny Cohen1,2 1Division

of Cardiology, Woodhull Medical Center, Brooklyn, New York, USA, 2NYU School of Medicine, New York, NY, USA, of Nephrology and Hypertension, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA, 4Department of Medicine, Woodhull Medical & Mental & Health Center, Brooklyn, NY, USA Acute Card Care Downloaded from by McMaster University on 12/17/14 For personal use only.


Case report

The importance of early thrombolysis in acute myocardial infarction has been highlighted in several large trials. The clinical decision is often taken by physicians who need to take a rapid action with the risk of misdiagnosing non-coronary events that mimic myocardial infarction. Here we describe a case of acute pericarditis in a 37-year-old man whom received thrombolysis and developed a sudden hemorrhagic pericardial effusion that evolved rapidly into a cardiac tamponade. These errors leading to lethal thrombolysis complications have been surprisingly rare; but a correct diagnosis of aortic dissection or hemorrhagic pericarditis needs to be stressed because even after obtaining the correct diagnosis, the prolonged disturbance of hemostasis prevents a rapid therapy being instigated.

A 37-year-old man with previous history of human immunodeficiency virus (HIV) infection, polysubstance abuse, and currently on maintenance methadone, arrived in the emergency department via ambulance, following episodes of chest pain for about three days, associated with syncopal episodes and seizure-like activity after using cocaine. The patient described the chest pain as very intense, sharp, non-radiating, and associated with dyspnea. The initial electrocardiogram (ECG) (Figure 1) was interpreted as an evolving acute myocardial infarction. Vital signs on presentation were blood pressure 116/81 mmHg, pulse rate of 94 bpm, temperature of 97.5°F and respiratory rate 16/min. The patient appeared diaphoretic and in moderate distress. An initial treatment with oral aspirin 162 mg and clopidogrel 600 mg was given. Heparin administration was deferred by the emergency team prior to the use of thrombolytics. The patient received two doses of intravenous alteplase 10 units given 30 min apart. A subsequent rhythm recording showed initial ECG findings but with a progressive decrease in voltage, and chest pain was relieved with the use of repeated doses of sublingual nitroglycerin. Approximately three hours after presentation, the patient became hemodynamically unstable with systolic blood pressure dropping to the 60s mmHg and diastolic to the 30s mmHg. He received large volumes of intravenous crystalloids, and was started on dopamine, and transferred to the coronary care unit. The patient remained tachycardic with no significant improvement in blood pressure. Subsequent electrocardiogram (Figure 2) revealed lower voltages and tachycardia. An immediate bedside echocardiogram (Figures 3 and 4) showed a large pericardial effusion with tamponade features and an estimated left ventricular ejection fraction of 25%.

Keywords: Myocardial infarction, thrombolysis, streptokinase

Introduction The use of thrombolytic therapy in properly selected patients with acute myocardial infarction (MI) has been proven to reduce mortality (1) and improve ventricular function (2). In hospitals without the availability of acute percutaneous intervention and without the possibility to transfer the patient in a predefined time period to catheterization, the use of thrombolytics remains the standard recommendation for treating acute ST-segment elevation myocardial infarction (STEMI). However, in instances where an initial diagnosis of MI is later determined to be incorrect, the use of acute thrombolysis carries a risk of fatal outcome and/or episodes of massive hemorrhage (3). This case report describes one terrible complication that if it remains unrecognized can carry a high mortality. We also summarize the literature on the complications of thrombolytic therapy in cases of misdiagnosed acute MI.

Correspondence: Ronny Cohen, Chief of Cardiology, Woodhull Medical Center/NYU School of Medicine, 760 Broadway, Suite 3B320, Brooklyn, NY 11206, USA. Fax: ⫹ 1 (718) 963 7881. E-mail: [email protected] (Received 16 December 2013; accepted 16 February 2014)


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O. Irivbogbe et al.

Figure 1. First ECG on arrival to the emergency department. 251 ⫻ 138 mm (72 ⫻ 72 DPI).

Emergency pericardiocentesis was conducted under echo-guidance with successful aspiration of 700 cc of hemorrhagic pericardial fluid with resultant improvement in blood pressure and clinical state. Left ventricle ejection fraction improved to about 50% and the patient was tapered off the vasopressor. An initial set of high-sensitive troponins were positive, but the remaining course was benign, and the patient received non-steroidal anti-inflammatory drugs with good response and resolution of his pericarditis. One year after the episode at follow-up, he remained asymptomatic and there was no recurrence of pericardial effusion.

Discussion The benefit of thrombolytic therapy was first demonstrated with streptokinase in GISSI-2 and ISIS-2 trials (4,5). The 2004 ACC/AHA Task Force on STEMI recommended that the door-to-needle time should be less than 30 min, but only about 50% of reported cases in trials meet this criterion. The short acceptable time interval for thrombolytic administration is crucial, but at the same time may contribute to inappropriate use of these agents. In a retrospective analysis of cases done by Khoury et al. from a group of 609 patients admitted for suspected MI, around 50% had transient ST-segment elevation and MI was subsequently ruled

Figure 2. ECG after thrombolytic administration. 279 ⫻ 215 mm (300 ⫻ 300 DPI). Acute Cardiac Care

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Thrombolytic-related complication

Figure 3. Echocardiogram with evidence of pericardial tamponade. 125 ⫻ 98 mm (72 ⫻ 72 DPI).

out by coronary angiography. The most common causes suggested for transient ST elevations were episodes of coronary spasm, transient coronary occlusion (‘aborted’ MI) or unstable angina. Fatal events related with the use of thrombolytics were reported in cases of acute aortic dissection and acute pericarditis (6). It is important to highlight that the GISSI-1 and GISSI-2 trials had the lowest prevalence of falsely suspected myocardial infarction with a 5.8% incidence of incorrect diagnosis of acute myocardial infarction. Meanwhile, in the ASSET trial, those patients treated with tissue plasminogen activator (TPA) without true MI had a 9.5% mortality rate as opposed to 1.2% in those treated with placebo (7). In view of the real risk of misdiagnosis, centers with no immediate access to invasive reperfusion strategy, appropriately adhere to the rigid diagnostic ECG criteria of acute STEMI (⬎ 1 mm of

ST-elevation in two contiguous leads) before considering a patient for thrombolysis. However, if doubt still exists, echocardiography performed promptly may help confirm a wall motion abnormality consistent with acute MI, or demonstrate pericardial effusion without ischemic features, and possibly show a suspicious aortic abnormality (4,7). In cases where the occult diagnosis of acute aortic syndromes is involved, the use of thrombolysis is associated with severe complications and mortality. Acute aortic syndromes comprise acute aortic dissection, intramural hematoma and penetrating ulcer of the aorta. In the study of Hansen et al. from a group of 66 patients with acute aortic syndrome (AAS), 39% of them were incorrectly diagnosed as acute coronary syndrome (ACS), and in around 12% of them, thrombolytic agents were used. The use of antithrombotic agents including heparin, aspirin and clopidrogrel was associated with hemorrhagic pericardial and pleural fluid and hemodynamic instability in this group as well as with a trend toward greater in-hospital mortality (8). In the retrospective analysis of 44 patients conducted by Davis et al., only 1 patient died after the use of thrombolytics administered in the emergency unit; however, 21% of patients presented with an ambiguous clinical picture and absence of classic changes in ECG and radiograph, making the diagnosis very challenging. At the end, the use of anticoagulation in this population carried a high rate of serious and life-threatening complications (9). Pericarditis and myopericarditis are other conditions that may mimic clinically and electrocardiographically a case of MI and can have fatal outcomes if thrombolytics are used. In cases of myopericarditis caused by viral infections, spontaneous hemorrhagic pericardial effusion may be observed and the proposed mechanism is an abnormal hemostatic function caused by the viral infection. In some reported cases, this pericardial effusion produced tamponade, which

Figure 4. Echocardiogram with evidence of pericardial tamponade. 101 ⫻ 78 mm (127 ⫻ 127 DPI). © 2014 Informa UK, Ltd.


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O. Irivbogbe et al.

was immediate and hemorrhagic or delayed and nonhemorrhagic. The existence of myopericarditis per se carries a high risk for hemorrhagic complications when thrombolytics are used; but not all of these patients developed this complication as documented by some reports. The development of hemorrhagic tamponade may be explained by the fibrinogen concentration levels and possibly the type of thrombolytic agent used. Although the association can be weak, some studies demonstrate an evident correlation, and the GUSTO trial showed that accelerated-dose TPA had a significant excess of hemorrhagic strokes as compared with streptokinase only, and it seems that accelerated-dose TPA is related with lower fibrinogen levels when used (10). Another confounding factor at the initial presentation of an acute aortic syndrome or pericarditis is the presence of elevated cardiac enzymes if these are available within 30 min. Table I summarizes other conditions in which falsely elevated cardiac troponins not due to MI can appear (11). ECG is decisive at the time of presentation for the patient with chest pain. However, several medical conditions may have electrocardiographic abnormalities mimicking those seen in acute MI. In general, approximately 1.3–1.4% of patients with initial presentation of acute chest pain and STsegment elevation will subsequently have acute myocardial infarction excluded. These conditions are summarized in Table II. Among all of them, pericarditis and myopericarditis remain the most frequently reported conditions that simulate STEMI (12). The ability to differentiate between an ischemic ST-segment elevation and a non-ischemic one is crucial, but can be difficult depending upon the reader's experience and the specificity and sensitivity conferred by the presence

Table I. Causes of increased cardiac troponins. Cardiovascular Acute aortic dissection Myocarditis Endocarditis Pericarditis Myocardial injury Cardioversion Apical ballooning syndrome Cardiac infiltrative disorders Heart failure Heart transplantation Pulmonary Acute pulmonary embolism ARDS Lung resection Blunt chest injury Critical illness Neurologic Ischemic stroke Intracranial hemorrhage Subarachnoid hemorrhage

Gastroenterological GI bleeding ERCP Infectious Sepsis Viral illness Others End stand renal disease (ESRD) Patients on dialysis Lithotripsy Rhabdomyolysis Kawasaki disease Thrombotic thrombocytopenic purpura False positives Heterophilic antibodies Rheumatoid factor Fibrin clots Analyzer malfunction

of coronary artery disease, based on underlying coronary risk (13). The use of automated ECG interpretive algorithms has been investigated but its sensitivity has proven to be low; also, in the aging population the prevalence of diagnostically challenging ECG abnormalities increases (14). Several studies, as noted previously have reported a significant percent of patients with acute chest pain and ST-segment

Table II. Conditions associated with ST-segment elevation different than acute myocardial infarction. Cardiovascular Normal-variant pattern Concave elevation of 1–3 mm more prominent in V2. Early repolarization Notching at J point with tall, upright T-wave and mostly seen in V4 and reciprocal ST depression in aVR. Left ventricular hypertrophy (LVH) Concave ST elevation commonly found in V1–V3. ST depression in lateral leads. If ST elevation is seen in aVR, can be confounded with left main territory ischemia. Left bundle-branch block Concave elevation. ST deviation discordant from the QRS. Acute pericarditis Diffuse ST-segment elevation and reciprocal ST depression in aVR and V1 are hallmark of Stage 1 pericarditis. Stage 2 Pericarditis may involve ST depressions. Hyperkalemia ‘Pseudo infarction’ pattern. The ST elevation is often downsloping. Brugada syndrome ST elevation in V1 and V2, typically downsloping. Cardioversion Striking ST-segment elevation, around 10 mm or above but lasting only minutes. Takotsubo syndrome ST elevation in precordial leads in up to 80% of patients. These patients have mildly positive cardiac biomarkers. Left ventricular aneurysm Following a myocardial infarction. Persistent ST elevation, which may be indistinguishable from acute STEMI. Wolf–Parkinson–White syndrome Intraventricular conduction delay Pulmonary Acute pulmonary embolism Changes that can be similar to acute MI seen often in both inferior and antero-septal leads. Acute Cardiac Care

Thrombolytic-related complication elevation eventually determined to have a diagnosis other than MI. These conditions can be initially misinterpreted as acute MI, resulting in misuse of thrombolytics (15).


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Conclusion According to the available medical literature, the rate of false STEMI is low, as is the rate of fatal complications in these misdiagnosed cases. However, when acute pericarditis and acute aortic syndromes are the underlying misdiagnosed conditions, the use of thrombolytics carries the risk of hemorrhagic fatal complications and the latter quoted low frequency of complications is misleading. The use of fibrinolytic therapy within 60 min from the onset of symptoms can reduce the mortality and morbidity. Due to the necessary short time to treatment, the primary diagnostic and therapeutic decisions depend on the ECG interpretative abilities and clinical judgment of the emergency physician. Additional testing via rapid portable echocardiogram may demonstrate wall motion abnormalities suggestive of MI, or alternatively demonstrate pericardial effusion, and to some extent suggest the presence of aortic dissection or pulmonary embolism. This is an original manuscript of original research and discussion presented for review and possible publication for advancement of medical education. It has not been submitted to any other journal. There are no financial interests tied to this original research, neither is there any other outside support. The authors listed originally prepared all materials. The authors listed have contributed to, read and approved the manuscript.










Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.




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Thrombolytic-related complication in a case of misdiagnosed myocardial infarction.

The importance of early thrombolysis in acute myocardial infarction has been highlighted in several large trials. The clinical decision is often taken...
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