Article, Cardiology

Thrombolytic therapy-associated acute myocardial infarction in patients with acute ischemic stroke: A treatment dilemma

a b s t r a c t

Acute myocardial infarction (AMI) is uncommon in the acute phase of acute ischemic stroke and occurs in approximately 1% of the population. Here, we report a paradoxical case of AMI during tissue plasminogen activa- tor (t-PA) infusion for AIS. We review and analyze the previously reported cases. We found that only patients with AMI which occurred after thrombolytic therapy for AIS who received an adequate combination of anticoagulation plus percutaneous coronary intervention survived their events. Several mechanisms have been proposed for the development of AMI after thrombolytic therapy. These mechanisms include fragmented intra-cardiac thrombus, intensified Platelet aggregation that may lead to an increased potential for intra- cardiac thrombus formation, and a reduction in clot-associated plasminogen that may lead to a paradoxical hy- percoagulable state of the coronary arteries. Currently, there is no consensus regarding this specific scenario. We propose that the therapeutic benefit and the potential risk of hemorrhagic complications should be further investigated and individualized. In patients who receive thrombolytic therapy for AIS and who then develop post-thrombolytic AMI, we suggest that the maximum treatment for the subsequent AMI be instituted promptly to avoid short-term mortality.

(C) 2016

Case report

A 79-year-old right-handed man with a history of hypertension and transient ischemic attack presented to the emergency department with sudden onset right-sided weakness. An unenhanced cranial computed tomography revealed Brain edema involving the left middle cerebral ar- tery (MCA) territory (Fig. 1). Initial Electrocardiography revealed normal sinus rhythm with no evidence of ischemia (Fig. 2A). The patient was diagnosed with a left MCA infarction syndrome (National Institute of Health Stroke Scale, NIHSS: 12) and received intravenous recombi- nant tissue plasminogen activator (t-PA) within 1 h after symptoms onset. Fifteen minutes following the initiation of t-PA infusion, the pa- tient developed cold sweating and chest pain. At that time, his blood pressure was 72/40 mm Hg, with a heart rate of 45 beats per minute. Re- peated ECG showed junctional rhythm with ST-segment elevation in the inferior leads (Fig. 2B). Simultaneous Right-sided ECG revealed ST- segment elevation in lead V4. A diagnosis of inferior wall acute

* Corresponding author at: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Number 325, Section 2, Cheng-Kung Road, Neihu, 114 Taipei, Taiwan.

E-mail address: [email protected] (S.-H. Tsai).

myocardial infarction (AMI) with right ventricular involvement was made. The serum levels of cardiac troponin-T rose to 77 ug/L. A bedside Transthoracic echocardiography showed significant inferior Wall motion abnormality without evidence of vegetation, intra-cardiac thrombus, pericardial effusion, or aortic root dilation. Dual antiplatelet therapy with aspirin and clopidogrel and heparinization were initiated. Immediate coronary angiography showed a complete occlusion of the right coronary artery. The patient underwent primary coronary angio- plasty and stenting to the proximal right coronary artery. The patient became hemodynamically stable after the procedure and was trans- ferred to the intensive care unit for further monitoring. The NIHSS im- proved to 8 24-hours after the event. The patient was discharged under a stable condition with a Modified Rankin scale of 2 on the four- teen hospital day. He actively participated the rehabilitation program at the outpatient department.

Discussion

Acute myocardial infarction (AMI) in the acute phase of ischemic stroke (AIS) is uncommon, accounting for approximately 1% of the AIS patients [1]. Current standard of care, intravenous thrombolytic therapy is the mainstay of treatment for eligible patients with AIS [2]. AMI after

http://dx.doi.org/10.1016/j.ajem.2016.11.044

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804.e2 C.-J. Yang et al. / American Journal of Emergency Medicine 35 (2017) 804.e1804.e3

Fig. 1. Unenhanced cranial computed tomography shows edema involving the left middle cerebral arterial territory.

systemic thrombolytic therapy for AIS is very rare. Here, we report a paradoxical case of AMI during administration of intravenous t-PA for AIS. As shown in Table 1, we analyzed the present case as well as those of another eight patients who sustained AMI after intravenous thrombo- lytic treatment for AIS by reviewing the medical literature over the past 10 years. Among all those nine cases (including the present case), the pa- tient age ranged from 58 to 88 years (mean age 72.5 years), the Patient sex ratio indicated a nearly equal number of men and women, and the stroke territory mostly involved large vessels. The onset time of develop- ing AMI after the initiation of intravenous t-PA infusion was relatively short (from during infusion to 3 h after infusion). The major presenting symptoms of patients with post-systemic thrombolytic therapy AMI were sudden onset hypotension (88.9%), bradycardia (55.6%) and chest pain (44.4%). Inferior wall AMI was the most frequently involved infarc- tion territory (66.7%). Although most of the patients were evaluated through TTE, intra-cardiac thrombus was detected in only one patient. The prognosis of these patients was generally poor despite various treat- ments: only three patients were treated successfully.

There are several postulated mechanisms for myocardial injury fol- lowing intravenous IV t-PA for AIS. One of the plausible mechanisms for post systemic thrombolytic therapy AMI is that systemic thrombol- ysis could result in fragmentation and subsequent coronary emboliza- tion of an existing intra-cardiac thrombus [3-6]. Though an intra- cardiac thrombus could not be identified in most cases, it is worth not- ing that abnormal transesophageal echocardiography findings may de- cisively affect the selection of an appropriate therapeutic strategy in approximately 1 of 7 patients with embolic strokes of undetermined source [7]. Coronary artery disease is highly prevalent in patients with a transient ischemic event and AIS. It has been reported that up to one-third of AIS patients with no cardiac history had more than 50% coronary stenosis, and 3% of them developed AMI within a year [8,9]. A previous study in patients with unstable angina/non-ST elevation myocardial infarction had shown that thrombolytic therapy could result in the deterioration of myocardial perfusion and recurrent ischemia [10, 11]. Those paradoxically Ischemic events could be attributed to several mechanisms. These mechanisms include fragmented intra-cardiac thrombus, intensified platelet aggregation that may lead to an increased potential for intra-cardiac thrombus formation, and a reduction in clot- associated plasminogen that may lead to a paradoxical Hypercoagulable state of the coronary arteries [12,13]. In addition, emergency medicine (ED) physicians should still promptly search for other possible etiolo- gies that could result in concurrent AIS and AMI, such as aortic dissec- tion, large vessel arteritis, endocarditis, cardiac tumors, Myocardial stunning, and illicit drug use.

Although the Optimal treatment for AMI after t-PA for AIS remains unclear, systemic thrombolytic therapy for simultaneous AMI and AIS had been suggested [14]. Nevertheless, antiplatelet drug administration is not recommended within 24 h after intravenous IV t-PA administra- tion for AIS. Clinical studies also show that the use of anti-coagulant/ anti-platelet therapy could cause substantially higher bleeding rates without Mortality benefit in AIS patients who had received intravenous thrombolytic therapy, whereas adjunctive medical therapy could signif- icantly improve the outcomes of AMI [15,16]. In reviewing those cases, we found that patients who lacked adequate therapy with antiplatelet drugs (aspirin and clopidogrel), an anticoagulant drug (heparin), and Primary percutaneous coronary intervention failed to survive; whereas 3 patients receiving a combination of anticoagulant and prima- ry PCI survived. Given that the treating ED physicians might hesitate to use adjunctive medical therapy because of concerns of an increased risk of intracranial hemorrhage, we emphasize that the beneficial effects of post-thrombolytic adjunctive anticoagulant/antiplatelet therapy should be weighed against the risk of hemorrhagic complications.

Fig. 2. Twelve-lead electrocardiogram taken on admission shows normal sinus rhythm without ischemic change (A). Electrocardiogram during IV t-PA administration shows junctional rhythm with ST segment elevation in leads II, III, and aVF with reciprocal change in leads aVL and V2-6 (B).

C.-J. Yang et al. / American Journal of Emergency Medicine 35 (2017) 804.e1804.e3 804.e3

Table 1

Summary of 9 patients with AMI after intravenous t-PA for AIS.

Age/sex

Stroke territory

Onset time after t-PA

Presentation

MI territory

Treatment

Thrombus

Outcome

References

62/F

Right MCA

120 min

Hypotension

Anterior wall

PCI

Yes

Heart failure -> dead

[3]

88/F

Possible right MCA

10 min

Chest pain

N/A

No

N/A

Heart failure -> dead

[4]

65/F

Right MCA

15 min

hypotension

Hypotension

Inferior wall

Aspirin

No

Multiple organ failure -> dead

[5]

81/F

Right MCA

10 min

bradycardia

Hypotension

Inferior wall

heparin

PCI

No

Multiple organ failure -> dead

[5]

78/M

Right MCA

120 min

bradycardia

Chest pain

Inferolateral wall

Aspirin

N/A

Ventricular fibrillation -> dead

[6]

58/M

Left MCA

120 min

hypotension

Hypotension

Anterior and lateral wall

Atropine

No

Probable heart failure -> dead

[6]

70/M

Left ICA

180 min

bradycardia

Hypotension

Inferior wall

pacemaker

Aspirin

No

Survived

[17]

78/F

Right MCA

180 min

bradycardia

Chest pain

Inferior wall

clopidogrel heparin PCI

Heparin

No

Survived

[18]

79/M

Left MCA

During infusion

palpitation Chest pain hypotension bradycardia

Inferior wall

PCI

Aspirin clopidogrel heparin PCI

No

Survived

Present case

Abbreviations: ICA, Internal carotid artery; MCA, Middle cerebral artery; N/A, not available; PCI, percutaneous coronary intervention.

In conclusion, we propose that the therapeutic benefit and potential risk of complications should be further investigated and individualized. In patients who received thrombolytic therapy for AIS and then devel- oped post-thrombolytic AMI, we suggest that adequate treatment for AMI be promptly initiated to avoid short-term mortality.

References

  1. Gattringer T, et al. Myocardial infarction as a complication in acute stroke: results from the Austrian stroke unit registry. Cerebrovasc Dis 2014;37(2):147-52.
  2. Jauch EC, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Associa- tion/American Stroke Association. Stroke 2013;44(3):870-947.
  3. Meissner W, et al. Fatal embolic myocardial infarction after systemic thrombolysis for stroke. Cerebrovasc Dis 2006;22(2-3):213-4.
  4. Fitzek S, Fitzek C. A myocardial infarction during intravenous recombinant tissue plasminogen activator infusion for evolving ischemic stroke. Neurologist 2015; 20(3):46-7.
  5. Mehdiratta M, et al. Myocardial infarction following t-PA for acute stroke. Can J Neurol Sci 2007;34(4):417-20.
  6. Sweta A, et al. Acute myocardial infarction following intravenous tissue plasminogen activator for acute ischemic stroke: an unknown danger. Ann Indian Acad Neurol 2010;13(1):64-6.
  7. Katsanos AH, et al. The value of transesophageal echocardiography for embolic strokes of undetermined source. Neurology 2016;87(10):988-95.
  8. Calvet D, et al. Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study. Circulation 2010;121(14):1623-9.
  9. Gunnoo T, et al. Quantifying the risk of heart disease following acute ischaemic stroke: a meta-analysis of over 50 000 participants. BMJ Open 2016;6(1).
  10. Freeman MR, et al. Thrombolysis in unstable angina. Randomized double-blind trial of t-PA and placebo. Circulation 1992;85(1):150-7.
  11. Ellis SG, et al. Recurrent ischemia without warning. Analysis of risk factors for in- hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator. Circulation 1989;80(5):1159-65.
  12. Fitzgerald DJ, et al. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988;77(1):142-50.
  13. Owen J, et al. Thrombolytic therapy with tissue plasminogen activator or streptoki- nase induces transient thrombin activity. Blood 1988;72(2):616-20.
  14. Gonzalez-Pacheco H, et al. Reperfusion strategy for simultaneous ST-segment eleva- tion myocardial infarction and acute ischemic stroke within a time window. Am J Emerg Med 2014;32(9):1157, e1-4.
  15. Seet RC, et al. Subtherapeutic international normalized ratio in warfarin-treated pa- tients increases the risk for symptomatic intracerebral hemorrhage after intrave- nous thrombolysis. Stroke 2011;42(8):2333-5.
  16. Mehta SR, et al. Dose comparisons of clopidogrel and aspirin in acute coronary syn- dromes. N Engl J Med 2010;363(10):930-42.
  17. Wallace EL, Smyth SS. Spontaneous Coronary thrombosis following thrombolytic therapy for acute cardiovascular accident and stroke: a case study. J Thromb Throm- bolysis 2012;34(4):548-51.
  18. Almasi M, et al. Does intravenous administration of recombinant tissue plasminogen activator for ischemic stroke can cause Inferior myocardial infarction? Neurol Int 2016;8(2):6617.

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