J INVASIVE CARDIOL 2008;20:E133-E135
The management of coronary disease in patients with spinal or intracranial disease may be challenging. In some cases, coronary lesions may require treatment before neurosurgery, while in others, myocardial ischemia or infarction may occur in the postoperative patient or simultaneously with stroke or intracranial hemorrhage. Patients with subarachnoid and intracranial hemorrhage have a high incidence of cardiovascular complications,1 and antiplatelet and anticoagulant medications normally used in coronary disease may further increase the risk of hemorrhage.2 Recent neurosurgery is widely considered to be a contraindication to the anticoagulation and antiplatelet therapy necessary for coronary revascularization, and there are no established guidelines for the management of these patients. We present 5 cases of coronary intervention in neurosurgical patients with a discussion of strategies to reduce procedure-related risk.
Case 1. A 44-year-old female presented with chest, neck and arm pain with elevated cardiac enzymes. She had history of subarachnoid hemorrhage one year prior to admission with prior clip of left anterior communicating artery aneurysm, and an unsecured left inferior cerebellar artery aneurysm planned for elective surgery. Computed tomography (CT) showed findings consistent with prior left frontotemporal craniotomy with aneurysm clips. An echocardiogram showed normal wall motion with an ejection fraction of 60% and normal pulmonary artery pressure. She underwent cardiac catheterization and was found to have 80% disease of the mid-left anterior descending artery (LAD) with local thrombus. Percutaneous intervention was performed using 2 bare-metal stents (BMS) to the anterior descending artery, and balloon angioplasty of the diagonal using a single bolus of 0.75 mg/kg of bivalirudin without infusion (Figure 1). Due to the presence of thrombus with transient slow-flow, bailout was performed using a double-bolus of 180 μg/kg of eptifibatide without infusion. Post procedure, the patient was treated with clodpidogrel (300 mg loading dose and 75 mg daily for for 2 weeks), and long term with aspirin 325 mg daily. The patient experienced no other complications and underwent successful clipping of her aneurysm 1 month later without incident.
Case 2. A 79-year-old male presented with syncope with nausea, vomiting, mental status changes and a large, spontaneous left frontal parenchymal hemorrhage with subarachnoid extension. Cerebral angiography showed no aneurysm or arteriovenous malformation. He had a prior history of insulin-dependent diabetes, hyperlipidemia, smoking with chronic obstructive pulmonary disease and myocardial infarction (MI) with coronary artery bypass graft surgery. He developed respiratory failure with acute pulmonary edema and elevated cardiac enzymes with a CK peak of 305, an elevated MB fraction of 9.6, and troponin I of 4.3. Echocardiography demonstrated moderate left ventricular dysfunction with inferior hypokinesis and an ejection fraction of 45%. Five days after admission at cardiac catheterization, the patient had a pulmonary artery pressure of 45/21 and a mean wedge pressure of 20 mmHg, with a cardiac index of 2.8 l/minute/m2. There was 80% disease of the mid-right coronary artery (RCA) and 70% disease of the circumflex. There were occluded vein grafts to the RCA and distal circumflex with a patent Y-graft between the two. The internal mammary graft was patent to the LAD, which was subtotally occluded proximally. Percutaneous coronary intervention (PCI) of the RCA was performed using a bare-metal stent (BMS) and bivalirudin (0.75 mg/kg bolus without infusion) without complication. Post procedure, he was treated with aspirin 325 mg daily. The patient was weaned from the respirator and discharged home 1 week later.
Case 3. A 55-year-old female with a posterior fossa cherry angioma in the fourth ventricle developed a non-ST-elevation MI. She signed out against medical advice, but returned 2 weeks later with severe chest pain at rest, again with elevated cardiac enzymes. Her past history was significant for coronary heart disease with prior stenting of the mid and distal RCA, non-insulindependent diabetes mellitus, hyperlipidemia, hypertension, cholelithiasis and bile duct stricture, Lyme disease, 1–2 pack per day smoking habit, with chronic obstructive pulmonary disease, bilateral arthroscopic knee surgery with deep venous thrombosis, and allergies to iodine and codeine. She returned with further angina and underwent catheterization, which showed patent stents in the RCA and 80% disease of the proximal circumflex, which was treated successfully with angioplasty and BMS implantation using bivalirudin (0.75 mg/kg bolus without infusion). Post procedure, she was treated with aspirin 325 mg daily. Six months later, she underwent successful resection of the tumor without incident.
Case 4. A 53-year-old male underwent bilateral suboccipital craniectomy and C1 and C2 laminectomy for Chiari malformation. He presented with hand numbness and poor balance. He developed angina postoperatively, and his symptoms were not well controlled on medical therapy. His past history was significant for hypertension, hyperlipidemia and coronary artery disease with prior PCI of the circumflex artery 7 years earlier. A nuclear stress test showed a fixed posterolateral defect with partial redistribution and an ejection fraction of 57%. Two months after surgery, he presented with crescendo angina. A diagnostic catheterization revealed 80% disease of the midleft anterior descending artery and 70% disease of the mid circumflex. The patient underwent angioplasty and stenting of the mid-LAD lesion with a 2.5 mm BMS, and the midcircumflex lesion with a 3.0 mm BMS using bivalirudin (0.75 mg/kg bolus without infusion). Post procedure, he was treated with aspirin 325 mg daily. He was free of angina 2 months post PCI.
Case 5. A 65-year-old female underwent cervical spine fusion at C6-7 and C7-T1 for pseudarthrosis. Postoperatively, she developed chest pain, pulmonary congestion and respiratory distress with anasarca, and the patient became respiratordependent. CT angiography of the chest was negative for pulmonary embolism, but did reveal bilateral pleural effusions and pulmonary edema. A bilateral lower-extremity Doppler examination was normal. Total CK was only 71, but the MB fraction and troponin I were elevated at 13.8 and 0.5, respectively. Echocardiography demonstrated mild global left ventricular dysfunction with a left ventricular ejection fraction of 45–50% and mild mitral regurgitation with moderate pulmonary hypertension. Cardiac catheterization performed 18 days postoperatively showed the following: RA 13/10/8, RV 45/1, PA 37/14, PCW 15/13/12, Ao 108/50, and CO 4.0/2.7. There was moderate 3-vessel disease with 70% stenosis of the ostial right coronary artery, 60% stenosis in the first diagonal and moderate mid-circumflex artery disease. A dobutamine stress echocardiogram showed inferior ischemia. One month post operation, PCI was performed in the ostial RCA lesion with successful placement of 2 BMS using bivalirudin (0.75 mg bolus without infusion) without complication. Post procedure, she was treated with aspirin 325 mg daily. The patient was successfully weaned from the respirator and discharged to a rehabilitation facility.
Discussion. In each of the cases presented here, care was taken to use short-acting anticoagulants (bivalirudin, integrilin) and BMS were used to avoid the need for prolonged used of clopidogrel. In spite of the use of anticoagulation and antiplatelet agents, there were no hemorrhagic events, and coronary intervention was accomplished without neurological complications. While the literature is very limited on this subject, evidence suggests that hemorrhagic complications may be associated with aggressive use of anticoagulant and antiplatelet agents.2
Remarkably, several investigators have published cases in which thrombolytic therapy was used in neurosurgical patients successfully and without hemorrhagic complications. Maggiolini et al reported 2 patients with a prior history of cerebral aneurysm who were given fibrinolytic therapy for MI without complication,3 and Rubinshtein et al also described a patient with a pituitary adenoma and 2 patients with meningioma treated successfully with thrombolytic therapy.4 The pituitary adenoma patient also underwent subsequent PCI successfully. However, meta-analyses of 23 randomized trials involving 7,739 patients (excluding neurosurgical patients) showed lower stroke rates with direct PCI compared to thrombolysis (1% versus 2%). The rate of hemorrhagic stroke was 0.05% for PCI and 1.14% for fibrinolysis.2 In the absence of any significant published data for neurosurgical patients, it seems reasonable to expect that hemorrhagic complications should be more commonly seen than in these trials, and PCI should be preferred to thrombolysis. Further evidence from clinical trials of thrombolytic therapy for MI has demonstrated that risk factors for intracranial hemorrhage include advanced age, female gender, low body weight, prior history of dementia or cerebrovascular disease or head or facial trauma, diastolic and systolic hypertension, especially with excess pulse pressure.2
There is very limited published experience of coronary intervention in patients with neurosurgical disease. Paolillo et al describe a case of direct stenting of the LAD for acute MI which occurred during craniotomy to evacuate an acute cerebellar hemorrhage.5 The operators used low-dose heparin (3,000 units) and abciximab (0.2 mg/kg bolus, followed by infusion of 0.125 ug/kg for 1 day and 0.0625 for 3 days), followed by 250 mg of intravenous aspirin daily for 6 days, and then 160 orally daily and ticlopidine 250 twice daily for 3 weeks, after which a ventricular cisternotomy was performed after stopping ticlopidine for 4 days. The patient returned for successful PCI of the RCA after 6 months. Almeda et al described a case of ST-elevation MI 6 hours after coiling of a basilar-tip aneurysm and placement of a right frontal external drain for subarachnoid hemorrhage with hydrocephalus.6 Bivalirudin 60.7 mg bolus followed by 1.75 mg/kg/hour infusion, aspirin and clopidogrel were used without a glycoprotein (GP) IIb/IIIa inhibitor, and the circumflex and RCA were treated with BMS. Since previous reports suggest that the use of GP IIb/IIIa antagonists during intervention may increase the risk of intracranial hemorrhage,7 it seems best to reserve their use for bailout situations, as in our first case, and a reversible agent such as eptifibatide or tirofiban may be preferred to abciximab, which has a longer-lasting and less easily reversed antiplatelet effect. We chose to use bivalirudin due to published data suggesting a lower bleeding complication rate compared to other agents,8,9 with provisional use of a GP IIb/IIIa antagonist. We also limited the use of bivalirudin to a bolus dose during the procedure without the usual postprocedure infusion, also to minimize risk of bleeding. We used BMS to limit the duration of antiplatelet therapy. In 1 case, a 2-week regimen of clopidogrel was given. In the others, only aspirin was used post procedure. Further experience will help us to arrive at optimal treatment strategies for these difficult patients.
1. Jain R, Develkis J, Thompson BG. Management of patients with stunned myocardium associated with subarachnoid hemorrhage. Am J Neuroradiol 2004;25:126–129.
2. Sloan MA. The continuing importance of prior stroke in STEMI patients. Am Heart J 2004;148:931–936.
3. Maggioni S, Cantu E, Lanterna AL, Valagussa F. Is a previous neurosurgical intervention a contraindication to fibrinolytic therapy? Description of two cases and review of the literature. Ital Heart J Suppl 2000;1:935–938.
4. Rubinshtein R, Jaffe R, Flugelman MY, et al. Thrombolysis in patients with a brain tumour. Heart 2004;90:1476.
5. Paolillo V, Gastaldo D, Ferrero B, et al. Successful treatment with primary angioplasty of acute myocardial infarction during cerebellar hemorrhage. J Invasive Cardiol 2002;14:562–564.
6. Almeda FQ, Lopes DK, Eybel CE. Management of a patient with ST segment elevation myocardial infarction immediately after successful coiling of a basilar tip aneurysm for a subarachnoid hemorrhage. J Invasive Cardiol 2004;16:166–167; Discussion 167–168.
7. Vahdat B, Canavy I, Fourcade L, et al. Fatal cerebral hemorrhage and severe thrombocytopenia during abciximab treatment. Catheter Cardiovasc Interv 2000;49:177–180.
8. Stone GW, McLaurin BT, Cox DA, et al; ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203–2216.
9. Carswell CI, Plosker GL. Bivalirudin: A review of its potential place in the management of acute coronary syndromes. Drugs 2002;62:841–870.