Handbook of Clinical Neurology, Vol. 119 (3rd series) Neurologic Aspects of Systemic Disease Part I Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 8

Neurologic complications of myocardial infarction MONEERA N. HAQUE AND ROBERT S. DIETER* Division of Cardiology, Department of Medicine, Loyola University Chicago, Stritch School of Medicine, Chicago, IL, USA

HISTORY Strokes are a devastating neurologic complication of acute myocardial infarction (Woods and Barnes, 1941; Vaitkus et al., 1992). Acute myocardial infarction (AMI) is characterized by the development of myocardial ischemia leading to myocardial injury or necrosis (Alpert et al., 2000; Thygesen et al., 2007). The term acute coronary syndrome (ACS) applies to patients in whom there is concern of acute myocardial ischemia. Three types of ACS are recognized: ST elevation MI (STEMI), non-ST elevation MI (NSTEMI), and unstable angina (UA). The first two are characterized by a typical rise and/or fall in biomarkers of myocyte injury (Anderson et al., 2007). Survivors of a myocardial infarction are at substantial risk for further complicating events, including the occurrence of mural thrombi contributing to embolic strokes. In 1856, Rudolf Virchow proposed three interrelated factors contributing to thrombosis: (1) injury of the blood vessel wall, (2) stasis of blood flow, and (3) generalized alterations in blood coagulation (Virchow, 1856). Furthermore, he reported brain arteries occluded by thrombi, seemingly originating in the heart; he termed this entity “embolism.” Gordinier suggested that sudden arterial plugging of the vessels of the brain, viscera, or extremities indicated involvement of a branch of the left coronary artery, whereas signs of pulmonary infarct suggested involvement of the right coronary artery or its branches (Gordinier, 1924). Blumer, recognizing the importance of embolism as a complication of cardiac infarction, stated that mural thrombi were frequent following cardiac infarction, and that remains may detach, generating embolic phenomena (Blumer, 1937).

EPIDEMIOLOGY The 2010 Heart Disease and Stroke Statistics update of the American Heart Association estimated that 17.6

million persons in the US have coronary heart disease (CHD), including 8.5 million with AMI (Lloyd-Jones et al., 2009). CHD is a major cause of death and disability in developed countries. Although CHD mortality rates have declined over the past four decades in the US, CHD accounts for about one-third of all deaths in individuals over age 35. Prevalence increases with age for both women and men (Rosamond et al., 2008). Atherosclerotic cardiovascular disease is a diffuse process. Stroke rate among patients with ACS can be extrapolated from the Framingham study. For those patients who had an initial MI, about 10% had previous intermittent claudication, and 5–8% had a stroke (Cupples et al., 1993). Among the cohort of 18 000 patients with non-ST elevation acute coronary syndrome enrolled in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) program, stroke was an infrequent but severe event, associated with considerable mortality. Overall, 238 patients (1.3%) had a stroke over a 6 month follow-up. A Cox multivariate regression analysis identified CABG surgery as the most important predictor of stroke (HR, 4.6), followed by history of stroke (HR, 2.3) (Cronin et al., 2001). Predicting stroke risk factors among hypertensive, clinically stable coronary artery disease patients was evaluated in the International VErapamil SR-trandolapril STudy (INVEST). African American ethnicity, US residency, circumstances associated with increased vascular disease severity, and arrhythmia predicted higher stroke risk; achieving a BP < 140/90 mmHg forecast a reduced stroke risk (Coca et al., 2008). Stroke remains the principal cause of neurologic death and a leading cause of disability among adults in the US. Ischemic stroke accounts for 85% of all strokes. Ischemic stroke subtypes include: (1) largeartery atherosclerosis, (2) cardioembolism, (3) smallvessel occlusion, (4) stroke of other determined

*Correspondence to: Robert S. Dieter, M.D., R.V.T., Associate Professor, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. Tel: þ1-708-216-4466, Fax: þ1-708-327-2770, E-mail: [email protected]

94 M.N. HAQUE AND R.S. DIETER etiology, and (5) stroke of undetermined etiology failure (HF) and/or left ventricular systolic dysfunction (Adams et al., 1993). (LVSD) following myocardial infarction (MI). Left venRisk of ischemic stroke among patients presenting tricular systolic dysfunction, diastolic blood pressure with AMI has declined from 2.4–3.5% to about >90 mmHg, prior stroke, and atrial fibrillation were 0.6–1.8%, probably reflecting a more aggressive the most influential predictors of stroke. Left ventricular approach to coronary revascularization as well as adminejection fraction and gender did not predict stroke risk in istration of thrombolytic or anticoagulant therapy in the this cohort (Sampson et al., 2007). In the Worcester acute phase (Komrad et al., 1984; Mahaffey et al., 1998; Heart Attack Study, a population-based investigation, Hurlen et al., 2002). However, despite the rare occuradvanced age, female gender, previous myocardial rence of ischemic strokes following AMI, their outcome infarction, and occurrence of atrial fibrillation during is often associated with high mortality (17%), and disabilhospitalization were associated with higher stroke risk. ity (80%) (Mahaffey et al., 1998). The association of Conversely, having a percutaneous coronary intervenischemic strokes and AMI is most likely multifactorial, tion during hospitalization was associated with a lower including older age, prior stroke, diabetes mellitus, risk of stroke (Saczynski et al., 2008). hypertension, and the presence of large akinetic segAmong the elderly, a large percentage of myocardial ments of myocardium with or without left ventricular infarctions remain unidentified and are often only thrombus (Vaitkus and Barnathan, 1993; Loh et al., recognized by electrocardiography. The relationship 1997; Hurlen et al., 2002). between unidentified “silent” myocardial infarction and stroke has been observed only among men. Most were cortical ischemic strokes. Thus, screening RISK FACTORS elderly patients for previously unidentified myocardial Risk factors for carotid artery atherosclerosis are similar infarction with electrocardiography may enhance the to those with coronary atherosclerosis. Patients with clinrecognition of a higher risk for stroke cohort (Ikram ically evident or silent myocardial ischemia frequently et al., 2006). have concurrent cerebrovascular disease. Conversely, Stroke is rare following non-ST-segment elevation many patients with cerebrovascular disease have differACS. Data from six trials of NSTE-ACS patients found ent stages of coronary artery disease. Moreover, cardiac older age, prior stroke, and elevated heart rate as the disturbances are common following strokes (Hachinski, strongest predictors of stroke within 30 days of the cor1993; Korpelainen et al., 1997). Among 111 023 Medicare onary event. Predictors were similar for nonhemorrhagic patients discharged with a principal diagnosis of AMI and hemorrhagic strokes. Interestingly, cigarette smokduring an 8-month period between 1994 and 1995, ing, previous myocardial infarction, diabetes, and hyper2.5% had an ischemic stroke within 6 months of hospital tension were not found to be independent predictors of discharge. Independent predictors of ischemic stroke stroke (Westerhout et al., 2006). included age  75 years, African American ethnicity, Delayed stroke following myocardial infarction is no aspirin at discharge, frailty, prior stroke, atrial fibrilunusual. A Swedish study of 3300 patients with a mean lation, diabetes, hypertension, and history of peripheral follow-up of 5 years (range 1.7–6.7 years) found that vascular disease (Lichtman et al., 2002). Among 15 904 approximately 6% (194) patients had a subsequent stroke stabilized patients with acute coronary syndrome, 113 (4.2% nonhemorrhagic, 0.5% hemorrhagic, and 1.3% (0.71%) had a stroke over a median follow-up of 90 days uncertain type). Risk factors included advanced age, his(Kassem-Moussa et al., 2004). Most strokes were ischetory of diabetes mellitus, prior stroke, arterial hypertenmic and occurred within 30 days of presentation. sion, and cigarette smoking (Herlitz et al., 2005). Patients with strokes were older and had more frequent An additional study evaluated the impact of stroke on comorbidities including arterial hypertension, diabetes, survival and the rate of stroke after myocardial infarcperipheral vascular disease, and atrial fibrillation. tion over time. A total of 2160 patients with myocardial Among the subset of stroke patients that had coronary infarction hospitalized between 1979 and 1998 were folrevascularization (percutaneous coronary intervention lowed for a median of 5.6 years (range 0–22.2 years). or coronary artery bypass grafting), strokes occurred The observed stroke rate was 22.6 per 1000 personprimarily following the procedure. Multivariate analyses months during the first 30 days following myocardial showed advanced age, heart failure, prior stroke, left infarction, representing a 44-fold increased risk for bundle branch block, and systolic blood pressure as prestroke. The risk for stroke remained threefold higher dictive of stroke occurrence. than expected during the first 3 years after myocardial The VALsartan In Acute myocardial iNfarcTion infarction. Diabetes, older age, and previous stroke mag(VALIANT) trial compared outcomes with captopril, nified the risk for stroke and did not dissipate over the valsartan, or both agents, among patients with heart study timeline. Strokes were also linked to a robust

NEUROLOGIC COMPLICATIONS OF MYOCARDIAL INFARCTION 95 increase in the risk of death following myocardial infarcof stroke due to thrombolytic therapy in selected patients tion (Witt et al., 2005). with acute myocardial infarction is relatively low comPatients at increased risk of embolic stroke, such as pared to the favorable risk–benefit assessment of this those with large anterior wall myocardial infarctions, therapy. The frequency of early cerebrovascular events may receive the greatest benefit from thrombolytic theramong unselected patients admitted to coronary care apy. However, the risk of intracerebral hemorrhage units in the prethrombolytic versus thrombolytic eras increases with advanced age, history of hypertension, continues to be alike in the overall profile, although morprior cerebrovascular disease or prior head trauma, high tality from acute myocardial infarction has decreased dose of thrombolytic therapy relative to bodyweight, considerably (Tanne et al., 1997). low bodyweight, female gender, African American In patients with ACS without persistent ST-segment ethnicity, high blood pressure upon presentation, and elevation, the occurrence of stroke is rather small. prolonged aPTT with heparin administration LifeA study involving 18 000 patients examining stroke occurthreatening ventricular arrhythmias and hypofibrinogenrence in relation to cardiac procedures among patients emia may also play a role in some cases (Sloan et al., with non-ST ACS, found those who had early coronary 1995). The higher than anticipated rate of intracranial artery bypass grafting surgery, but not early percutanehemorrhage among patients treated with heparin or hiruous coronary intervention, had a substantially increased din in conjunction with thrombolysis emphasizes the risk of stroke (Cronin et al., 2001). Dacey and colleagues risks associated with anticoagulation in combination studied the survival of 35 733 consecutive patients underwith thrombolysis. going isolated coronary artery bypass graft surgery Thrombolytic therapy decreases mortality following (Dacey et al., 2005). There were 147 931 person-years of acute myocardial infarction, but also has a small but follow-up and 5705 deaths. Survival for patients with noteworthy risk of severe bleeding complications, stroke at 1, 5, and 10 years was 83.0%, 58.7%, and including intracranial hemorrhage. Previous trials 26.9%, respectively. Patients who had strokes had more reported an overall incidence of stroke during hospitalcomorbidities. In patients undergoing coronary artery ization for acute myocardial infarction of 0.9–1.6%. bypass graft surgery, the independent predictors for Intracranial hemorrhage accounted for 0.2–0.9% of stroke, in order of risk, were: age older than 70 years, strokes, depending on the type and dose of thrombolytic poor preoperative neurologic status, and previous caragent used (ISIS-3 Collaborative Group, 1992; Maggioni diac surgery (Woods et al., 2004). The use of a stroke risk et al., 1992). Since recording and evaluation of strokes index to predict neurologic complications following corwere not standardized, and variable numbers of strokes onary revascularization on cardiopulmonary bypass was were not codified, the interpretation of these reports retrospectively among 6846 patients. A total of 217 must be approached cautiously. Moreover, in the thrompatients (3.2%), mean age of 65.9  11.7 years, had bolytic trials, high-risk patients (advanced age, prior hisadverse neurologic events following surgery. High-risk tory of stroke, or uncontrolled hypertension) were often variables included cardiac surgery, myocardial infarcexcluded, and as such, the reported rates may underestion, left ventricular ejection fraction < 30%, and timate the degree of this serious complication. Certainly, absence of sinus rhythm (Elahi et al., 2005). in clinical practice, more elderly patients with acute Cardiac catheterization-related stroke has been myocardial infarction have had adverse sequelae of reported in 0.03–0.3% of cases (Brown and Topol, intracranial hemorrhage (Gurwitz et al., 1998; Brass 1993; Lazar et al., 1995; Segal et al., 2001), and in et al., 2000). A registry of acute coronary syndromes 0.3–0.4% of percutaneous coronary interventions involving 111 Canadian hospitals evaluated 12 739 patients (PCI) (Fuchs et al., 2002; Dukkipati et al., 2004). The utiwho received fibrinolytic therapy for acute myocardial lization of guidewires and catheters may possibly cause infarction from 1998 to 2000. Of these, 146 patients fragmentation of atherosclerotic plaques with conse(1.15%) had strokes; 82 of these patients (0.65%) had quent CNS embolization (Lazar et al., 1995; Karalis an intracerebral hemorrhage. Female gender, advanced et al., 1996; Tunick and Kronzon, 2000). Among age, systolic hypertension on arrival (systolic blood pres20 679 patients who had percutaneous coronary intervensure > 160 mmHg) and history of prior stroke were identions, cerebrovascular events occurred in 92 patients tified as independent risk factors for intracerebral (0.3% of procedures); 13 patients had transient ischemic hemorrhage. Patients receiving streptokinase had a attacks (0.04%) and 79 patients (0.25%) had strokes lower risk of intracerebral hemorrhage, particularly (Dukkipati et al., 2004). Another study of 76 903 patients those of advanced age. Patients with myocardial infarcwho had coronary angioplasty found that 140 (0.18%) tion also had fewer systemic hemorrhages when treated had a stroke. Multivariate regression analyses demonwith tenecteplase versus recombinant tissue-type plasstrate that acute myocardial infarction or congestive minogen activator (Huynh et al., 2004). Overall, the risk heart failure on admission, advanced age, use of

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glycoprotein IIb/IIIa inhibitors, history of carotid artery disease, placement of an intraaortic balloon pump, and chronic renal disease were independent predictors for stroke-complicating PCI (Wong et al., 2005).

ETIOLOGY Strokes following ACS have numerous possible pathogenetic mechanisms. The connection between coronary artery disease and ischemic stroke is attributed to a common pathophysiologic process, atherothrombosis. Mural thrombi in areas of ventricular hypokinesis after myocardial damage are also a possible cause. New-onset atrial fibrillation following acute myocardial infarction has been associated with long-term risk for stroke (Milika et al., 2009). Reduced cardiac output may also be a contributory factor to hemodynamic-related strokes. Strokes occurring several weeks after myocardial infarction may be due to embolization from left ventricular thrombi, left ventricular dysfunction, or akinetic left ventricular segments. Cerebral microembolism is often detected by transcranial Doppler among patients with a history of acute myocardial infarction and reduced left ventricular function, akinetic segments, or left ventricular thrombi (Nadareishvili et al., 1999). For every decrease of 5% in the left ventricular ejection fraction, an 18% increase in the risk of stroke has been documented (Loh et al., 1997). Left ventricular thrombi (LVT) are associated with an increased embolic risk (Chiarella et al., 1998). The likelihood of developing a left ventricular thrombus following an acute myocardial infarction depends on infarct location and size, reduced left ventricular ejection fraction, new wall motion abnormalities, and LV aneurysm formation (Asinger et al., 1981; Chiarella et al., 1998). Left ventricular thrombi develop in one third of patients with anterior wall myocardial infarction, and in 5% of patients with inferior wall myocardial infarctions. The highest rate of LVT formation is found among patients with anterior infarcts and low ejection fraction or congestive heart failure (Chiarella et al., 1998). In a series of 30 patients evaluated in the prethrombolytic/prerevascularization era after an acute anterior MI, LV thrombus was identified in 27% at 24 hours, 57% at 48–72 hours, 75% at 1 week, and 96% at 2 weeks (Weinreich et al., 1984). Most thrombi develop within the first 2 weeks after myocardial infarction (Asinger et al., 1981; Nihoyannopoulos et al., 1989). However, some patients develop a new LVT after hospital discharge, often in association with worsening LV systolic function (Keren et al., 1990). In the GISSI-3 database of 8326 patients, where prior to discharge, a transthoracic echocardiogram was performed, LVT was present in 5.1% of patients; 11.5% had an anterior wall myocardial

infarction, and 2.3% had myocardial infarctions at other sites. Furthermore, a LVEF 40% is associated with an increase frequency of LVT with both anterior MI (17.8 versus 9.6% with a higher LVEF) and infarctions at other sites (5.4 versus 1.8%). These data must be interpreted with caution, as patients at high risk for LVT formation (severe heart failure and systolic blood pressure below 100 mmHg) were excluded (Chiarella et al., 1998). In addition, mobile or protruding LVT into the left ventricular cavity on echocardiography were also associated with an increased risk of thromboembolism.

CLINICAL FINDINGS, CLINICAL PRESENTATION, AND DIAGNOSTIC CRITERIA Myocardial infarction (MI) is characterized by the development of acute myocardial ischemia leading to myocardial injury or necrosis (Alpert et al., 2000; Thygesen et al., 2007). Criteria are fulfilled when there is a rise of cardiac biomarkers, along with supportive clinical evidence corresponding electrocardiogram changes, or imaging confirmation of new loss of viable myocardium or acute regional wall motion abnormality. Strokes may obscure the clinical course of patients presenting with acute myocardial infarction. Ischemic strokes are the main type of strokes observed in patients with non-ST-segment elevation ACS. Intracerebral hemorrhages comprise a considerable fraction of strokes after thrombolysis for acute ST-segment elevation myocardial infarction (Kassem-Moussa et al., 2004). Nearly all ischemic strokes after acute myocardial infarction involve the carotid circulation, and are nonlacunar (Mooe et al., 1999). About a third of strokes occur within 24 hours after admission, while two-thirds occur with in the first week after a myocardial infarction (Behar et al., 1991; Sloan et al., 1997). Intracerebral hemorrhage, the most alarming complication of thrombolytic therapy, typically occurs during the first 2 days after administration of thrombolysis (Gore et al., 1995; Gurwitz et al., 1998).

LABORATORY INVESTIGATIONS In patients presenting with a suspected acute MI, electrocardiogram (ECG), an abbreviated history, and physical examination should be obtained within 10 minutes of patient arrival (Diercks et al., 2006). Evaluation requires distinguishing ACS from nonischemic chest pain including potentially life-threatening conditions such as aortic dissection, pulmonary embolism, or esophageal rupture. Diagnosis of acute coronary ischemia depends on the characteristics of the chest pain, specific associated symptoms, ECG abnormalities, and laboratory investigation of serum markers reflecting cardiac injury.

NEUROLOGIC COMPLICATIONS OF MYOCARDIAL INFARCTION Table 8.1 Cardiac serum markers timeline in acute myocardial infarction Laboratory test

Onset (hours) Peak (hours) Duration

Creatine kinase (total and MB) Troponin Myoglobin Lactate dehydrogenase

3–12

18–24

36–48 hours

3–12 1–4 6–12

18–24 6–7 24–48

Up to 10 days 24 hours 6–8 days

Below are biomarkers used to evaluate patients with suspected acute MI (Table 8.1): An elevation in the concentration of troponin or CKMB is required for the diagnosis of acute MI. Troponin is the preferred biomarker for the diagnosis of myocardial injury because of better specificity and sensitivity compared to CK-MB (Alpert et al., 2000; Thygesen et al., 2007). The use of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) for AMI diagnosis has been recommended by the 2007 joint ESC/ACCF/AHA/ WHF Task Force for the definition of myocardial infarction (Goodman et al., 2006). An elevation in cardiac troponins must be interpreted within the proper clinical and ECG framework since troponin elevation can be seen in a variety of clinical settings and is therefore not specific for an acute coronary syndrome. ECG is imperative for identifying simultaneous acute cardiac ischemia and particularly important in the setting of stroke, as patients with ischemic stroke commonly harbor coronary artery disease but may not be able to report angina. Stroke can also be linked with ECG changes. In large strokes, especially in cases of subarachnoid hemorrhage, there are centrally (neurogenic) mediated changes in the ECG. The ECG and cardiac monitoring should be used during the first 24 hours after onset of ischemic stroke as they are vital for the detection of arrhythmias predisposing to embolic events and for providing indirect evidence of atrial/ventricular enlargement that may ultimately predispose to thrombus formation and other potentially serious cardiac arrhythmias (Adams et al., 2007). The utility of this approach is illustrated by a systematic review of five prospective studies including a total of 588 hospitalized patients with ischemic stroke who had Holter monitoring (Liao et al., 2009). Holter monitoring for 24–72 hours detected new-onset atrial fibrillation or atrial flutter in 4.6% of patients (95% CI 0–12.7%). Transthoracic and transesophageal echocardiography are also important as they adequately detect potential cardiac and aortic sources for cerebral embolism. Their use can be postponed until after the acute

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treatment phase, when patients are in a more stable clinical condition. Exceptions may include patients suspected of having strokes due to paradoxical embolism or aortic dissection.

NEUROIMAGING INVESTIGATIONS Neuroimaging is critical for distinguishing between ischemia and hemorrhage, estimating tissue at risk for infarction, and finally identifying the vascular lesion responsible for the ischemic deficit (Adams et al., 2007; Latchaw et al., 2009). Neuroimaging must assess the extracranial and intracranial circulation. Noninvasive methods are favored unless urgent endovascular therapy is planned. Catheter cerebral angiography is usually reserved for acute administration of intra-arterial thrombolysis and for follow-up when noninvasive studies are inconclusive. Magnetic resonance (MR) imaging is an important tool (Bittner and Felix, 1998). Few contraindications to MR imaging exist. Most contraindications are relative precautions; these can be divided into four groups: implanted devices and foreign bodies, unstable patients, pregnancy, and other (Kanal et al., 2004; Marcu et al., 2006). The American Society for Testing and Materials International developed the following terminology for labeling of implanted devices (American Society for Testing and Materials, 2005) (Table 8.2): ● ●

●

MR safe: an item that poses no known hazards in any MR environment MR conditional: an item that has been demonstrated to pose no known hazards in a specified MR imaging environment with specified conditions of use MR unsafe: an item that is known to pose hazards in all MR environments.

Currently, no guideline completely covers all devices. Referring to dedicated websites that list the safety or potential risk of particular devices is suggested (Levine et al., 2007; MRI Safety, 2008). A notable complication is nephrogenic systemic fibrosis (NSF), a fibrosing disorder seen in patients with moderate to severe kidney failure, mainly among patients on dialysis (Grobner, 2006; Sadowski et al., 2007). Increasing evidence has implicated gadoliniumcontaining contrast agents. More than 95% of patients have had recent exposure to gadolinium. The best estimate of risk of NSF following gadolinium exposure is approximately 2.5–5% among patients with severely impaired renal function (LeBoit, 2003). The inciting event is most likely the tissue deposition of gadolinium. Diagnosis is based upon histopathologic examination of a biopsy of an involved site. The US Food and Drug

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Table 8.2 Precautions in MR imaging Parameter for MRI precaution

ASTM designation*

● Coronary artery and peripheral vascular stents

Most labeled as MR safe Remainder MR conditional

– non-ferromagnetic – can be safely scanned at 3 T any time after implantation – weakly ferromagnetic – timing of imaging at < 3 T should be determined on an individual basis ● Aortic stent grafts

● Mechanical cardiac valves

The presence of a prosthetic heart valve or annuloplasty ring that has been formally evaluated for MR safety should not be considered a contraindication to MR examination at 3 T any time after implantation ● Sternal wires ● Cardiac closure and occluder devices – non-ferromagnetic – can be safely scanned at 3 T any time after implantation – weakly ferromagnetic – timing of imaging at < 3 T should be determined on an individual basis ● Inferior vena cava filters Most have been studied at 1.5 T although many have been studied at 3 T – non-ferromagnetic – can be safely scanned at 3 T any time after implantation – weakly ferromagnetic (e.g., Gianturco bird nest IVC filter (Cook), stainless steel Greenfield vena cava filter (Boston Scientific) wait at least 6 weeks ● Embolization coils – non-ferromagnetic – can be safely scanned at 3 T any time after implantation – weakly ferromagnetic – timing of imaging at < 3 T should be determined on an individual basis ● Loop recorder The patient should be warned that he/she may feel the device move since it contains ferromagnetic components ● Hemodynamic monitoring and temporary pacing devices – pulmonary artery hemodynamic monitoring/thermodilution catheters (e.g., the Swan–Ganz catheter) – temporary epicardial pacing wires – temporary pacemaker external pulse generators ● Permanent pacemakers and implantable cardioverter-defibrillators – risks include possible movement of the device, programming changes, asynchronous pacing, activation of tachyarrhythmia therapies, inhibition of pacing output, and induced currents in lead wires leading to heating and/or cardiac stimulation ● Hemodynamic support devices ● Other implanted electronic devices Nerve stimulators Cochlear implants ● Aneurysm clips – non-ferromagnetic – can be safely scanned at 3 T any time after implantation – weakly ferromagnetic – ferromagnetic ● Transdermal patches – cutaneously applied drug-eluting adhesive patches that contain aluminum or other metals in their nonadhesive backing – examples of metal-containing transdermal patches include certain patches containing clonidine, nicotine, scopolamine, testosterone, or fentanyl

Most labeled as MR safe MR unsafe – Zenith AAA endovascular graft (Cook) stent Most labeled as MR safe Remainder MR conditional

MR safe Most labeled as MR safe Remainder MR conditional

Most labeled as MR safe Remainder MR conditional

Most labeled as MR safe Remainder MR conditional

MR conditional – Reveal Plus ILR

MR unsafe MR safe MR unsafe MR conditional

MR unsafe MR unsafe

MR safe MR safe MR unsafe MR unsafe

*American Society for Testing and Materials (ASTM) International. ASTM F2503-05: Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment. ASTM International, West Conshohocken, PA. 2005.

NEUROLOGIC COMPLICATIONS OF MYOCARDIAL INFARCTION Administration (FDA) recommends that gadoliniumcontaining contrast agents, especially at high doses, be used only if clearly necessary and be avoided in patients with a diagnosis or clinical suspicion of NSF.

MRI issues at 3 tesla and coronary artery stents Revascularization in ACS by percutaneous intervention (PCI) may require either the development of a bare metal or a drug-eluting stent. MRI safety information for patients undergoing MR procedures at 3 tesla or less are shown in Table 8.3.

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The potential early and late effects of MRI on stent thrombosis and major adverse coronary events following coronary artery stent (CAS) implantation were investigated in 43 patients who had CAS implantation before MRI examination. An average of 1.3 stents per patient were implanted (1–4 stents); mean follow-up of this study, 36  15 months. In this pilot study, MRI was not associated with increased risk of major adverse clinical cardiac events on long-term follow-up (Kaya et al., 2009).

PATHOLOGY The inflammatory response plays an important role in the genesis and progression of atherosclerotic lesions

Table 8.3 MRI issues at 3 Tesla with coronary artery stents

Type of stent Endeavor Drug Eluting Coronary Artery Stent (Medtronic Vascular) TAXUS Express Paclitaxel-Eluting Coronary Stent (Boston Scientific Corporation) Liberte Coronary Artery Stent (bare metal coronary artery stent, Boston Scientific Corporation) TAXUS Liberte PaclitaxelEluting Coronary Stent (Boston Scientific Corporation) CYPHER Sirolimuseluting Coronary Stent (Cordis Corporation/ Johnson and Johnson)

MULTI-LINK VISION Coronary Stent

MRI safe field strength with no reported migration 3 T 3 T

Maximum whole body averaged specific absorption rate (SAR)

Timeframe MRI may safely be performed after stent implantation

Maximum temperature rise produced by stent

2.0 W/kg for 15 minutes of MR imaging 2.0 W/kg for 15 minutes of MR imaging

Immediately

0.5 C

Immediately

0.65 C

3 T

2.0 W/kg for 15 minutes of MR imaging

Immediately

0.65 C

3 T

2.0 W/kg for 15 minutes of MR imaging

Immediately

0.65 C

Single and two overlapping CYPHER stents have been shown to be MRI safe at field strengths of 3 T or less

4.0 W/kg for 15 minutes of MR imaging

Immediately

Static magnetic field strength of 3 T with a maximum spatial gradient magnetic field of 3.3 T/meter

2.0 W/kg for 15 minutes of MR imaging

Immediately

Single CYPHER stents up to 33 mm in length produced a temperature rise of less than 1 C Two overlapped 33 mm length CYPHER stents produced a temperature rise of less than 2 C 0.60 C

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(Pasceri et al., 2000; Buffon et al., 2002; Lombardo et al., 2004). Inflammation of vulnerable atherosclerotic plaques may contribute to the development of ACS. Plaque instability may extend to other vascular beds such as the extracranial and intracranial circulation. High levels of serum C-reactive protein are frequently observed in cases of unstable angina and AMI. This is mostly regulated by proinflammatory cytokines and is largely unaltered by the administration of anti-inflammatory medications (Pasceri et al., 2000). Such an inflammatory response induces a thrombogenic state that may be responsible for the increased risk of early ischemic strokes in patients with AMI (Van de Graaff et al., 2006). Additionally, sympathetic overactivity may have a possible role in promoting thrombosis via upregulation of platelet activation and factor VIII, and downregulation of the fibrinolytic system and inflammation via upregulation of T-helper cytokines (Yun et al., 2005). This evidence suggests that sympathetic activity along with inflammation can induce, and be further stimulated by, thrombotic events such as AMI and ischemic strokes. We find further support for this concept in the fact that increased heart rate, presumably a surrogate marker for sympathetic activity, is an independent predictor of ischemic stroke in patients with AMI (Mahaffey et al., 1998). Strokes complicating acute myocardial infarctions among the subset of patients not receiving thrombolysis are likely cardioembolic. This notion is further substantiated by their association with large anterior myocardial infarcts and left ventricular thrombi. LV thrombus is most often seen in patients with large anterior ST elevation myocardial infarctions with anteroapical aneurysm formation and akinesis or dyskinesis, expanding the apical zone of intraventricular stasis. Additionally, there is enhanced thrombogenicity in the setting of inflammatory changes at the endocardial surface (Visser et al., 1985; Nayak et al., 2004). A systemic hypercoagulable state may promote thromboembolism early after a coronary event, in comparison to a residual fresh thrombus, which may enhance coagulation during the first 3 months. Several predictors of embolization have been defined in patients who have left ventricular thrombi, in particular mobile and pendulous thrombi. However, the frequency of embolization in patients with thrombus protrusion into the left ventricle (22–100%), or thrombus mobility (35–100%) has varied widely (Haugland, 1984; Meltzer, 1984). Embolization risk from left ventricular thrombi is reflective of thrombogenicity within the left ventricle. This includes activation of the intrinsic coagulation system, endocardial injury, and regional circulatory stasis as well as the dynamic forces potentially propelling thrombotic material into the systemic circulation. Primary prevention studies of myocardial infarction show an increased risk for hemorrhagic stroke with aspirin

use, estimated at 0.2 events per 1000 patient-years. This is similar to the risk associated with aspirin use in secondary stroke prevention (Gorelick and Weisman, 2005). Glycoprotein IIb/IIIa inhibitors have also been implicated in increased bleeding risk. This member of the integrin family of receptors (Hynes, 1987) is of particular interest because of its central role in platelet aggregation. A meta-analysis compared pooled data of 14 randomized trials involving approximately 28 000 patients treated with one of these agents or placebo. The occurrence of intracerebral hemorrhage with heparin plus any GP IIb/IIIa inhibitor was comparable with heparin plus placebo (0.12 versus 0.09%, OR 1.3). There were no differences with a GP IIb/ IIIa inhibitor alone compared to heparin alone (0.07 versus 0.06%) (Memon et al., 2000). Then, the GUSTO V trial examined the risk of intracranial hemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction. This trial randomized 16 588 patients to half-dose reteplase plus abciximab or standard dose reteplase (Topol, 2001). The rates of intracranial hemorrhage and nonfatal strokes were similar overall in the two treatment groups. However, combination therapy was linked with a noteworthy increase in intracranial hemorrhage among patients over the age of 75 (2.1 versus 1.1%). The risk of intracranial hemorrhage in GUSTO V was also age-dependent (Savonitto et al., 2003). The dislodgement of an atherosclerotic plaque from the aortic arch serves as a potential source of emboli during invasive procedures such as cardiac catheterization, percutaneous coronary intervention, intra-aortic balloon pumping, and coronary artery bypass surgery (Kassem-Moussa et al., 2004). It has been suggested that the presence of heart failure on admission for an acute myocardial infarction increases in-hospital stroke risk. Using the VALsartan In Acute myocardial iNfarcTion (VALIANT) registry, Szummer and colleagues investigated the contribution of heart failure on admission for an acute myocardial infarction to the subsequent in-hospital stroke risk. HF was present on admission in 38% of patients who subsequently had a stroke. Older age, Killip class III or IV, history of hypertension, and history of stroke, were more common in patients who had in-hospital stroke. The study additionally suggested that heart failure treatments may modify the risk of stroke (Szummer et al., 2005).

MANAGEMENT The patient with myocardial infarction and concomitant cardioembolic stroke is at high risk for recurrent early embolic events. Moreover, the sympathetic response to stroke can lead to demand-induced myocardial ischemia and requires urgent supportive care and treatment. Treatment strategies in CABG, PCI, the use of anticoagulation and thombolytics will be discussed.

NEUROLOGIC COMPLICATIONS OF MYOCARDIAL INFARCTION

Antiplatelet therapy and acute coronary syndrome Atherosclerotic plaque rupture is often the inciting event in ACS, leading to ensuing thrombus formation. Platelets play a significant role in this process, with platelet adhesion, activation, and aggregation all stimulated during an ACS, and antiplatelet agents have been shown to improve clinical outcomes.

CLASSIFICATION OF ANTIPLATELET AGENTS Antiplatelet agents can impede a number of platelet functions and may be categorized according to their mechanism of action (Table 8.4). Data strongly suggest the early initiation of dual antiplatelet therapy with aspirin and either clopidogrel or GP IIb/IIIa inhibitor in all patients with non-ST elevation ACS, regardless of whether they are managed by a conservative or early invasive strategy (Mehta et al., 2001; Steinhubl et al., 2006). Meta-analysis performed by the Antithrombotic Trialists’ Collaboration revealed no significant variations in risk of extracranial bleeding at higher doses of aspirin from 75 to 325 mg/day (Antithrombotic Trialists’ Collaboration, 2002). In nonrandomized post hoc subgroup analyses from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) and the Blockade of the IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trials, bleeding risk was higher at larger doses within the low-dose range (Peters et al., 2003; Topol et al., 2003). In a 2006 systematic review of 22 randomized trials of low-dose aspirin (75–325 mg/day) and clopidogrel for adverse effects, low-dose aspirin increased the risk of any major bleeding, major GI bleeding, and intracranial bleeding 1.7 to 2.1 times compared to placebo. The absolute annual increase in risk was 1.3 per 1000 patients for all major bleeding episodes and 3 per 10 000 for intracranial bleeding (McQuaid and Laine, 2006). The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial shows additional data from post hoc subgroup analysis in which patients with either established cardiovascular disease (about 12 000) or at high risk (about 4000) were randomly assigned to clopidogrel 75 mg daily or placebo (Bhatt et al., 2006; Steinhubl et al., 2009). The incidence of severe or lifethreatening bleeding (primary safety end point) was examined at a median of 28 months in relation to the dose of aspirin ( 100 mg daily) and whether or not the patient received clopidogrel. When examining the adjusted hazard ratio for the incidence of severe or life-threatening bleeding, there were no noteworthy differences between the aspirin dose groups and no effect modification by clopidogrel.

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Thienopyridine therapy reduces the long-term occurrence of adverse cardiovascular outcomes in patients with non-ST elevation ACS, including patients treated with both conservative and invasive strategies. Clopidogrel is the best studied (Yusuf et al., 2001). The most significant frequent adverse effect related with thienopyridine therapy is bleeding. The combination of clopidogrel plus aspirin in CURE was associated with a significant increase in major (3.7 versus 2.7% with aspirin alone), minor (5.1 versus 2.4%), and gastrointestinal bleeding (1.3 versus 0.7%), but not life-threatening bleeding events (Yusuf et al., 2001). For very high-risk patients (e.g., markedly elevated troponin, recurrent ischemic discomfort, dynamic electrocardiographic changes, or hemodynamic instability) undergoing an invasive approach, GP IIb/IIIa inhibitors are recommended. This strategy may also be appropriate for high-risk patients managed with medical therapy. In stable patients managed with invasive strategy who have not received a GP IIb/IIIa inhibitor, the addition of one at the time of percutaneous coronary intervention is suitable in most cases. Evidence from TRITON-TIMI 38 and PLATO demonstrates evidence that the level of platelet inhibition is correlated with both efficacy and bleeding outcomes (Wiviott, 2005; Antman et al., 2008). Agents with increased levels of platelet inhibition, such as prasugrel have lower cardiovascular event rates but higher rates of bleeding. Prasugrel has an earlier onset of action and attains increased degrees of platelet inhibition than clopidogrel, while having a similar rate of bleeding (Wiviott et al., 2005). Based on the results of TRITON-TIMI 38, prasugrel should be considered in patients with STEMI and those with NSTEMI, where thienopyridine therapy will be held until after diagnostic coronary angiography, who are not at high risk of bleeding (age < 75 years, weight  60 kilograms, or those without prior transient ischemic attack or stroke), and favored in patients instead of clopidogrel in patients deemed to be at high risk for stent thrombosis. While there are no data on the efficacy or safety of pre-PCI loading with prasugrel, consideration must be given to weighing the increased efficacy and increased bleeding risk, and certainly if the patient is found to need CABG. The role of ticagrelor has yet to be determined as it has only been studied in one outcome trial and is not yet approved for in non-ST elevation ACS patients (Schomig, 2009).

Anticoagulation and acute coronary syndrome Anticoagulation is indicated in the treatment of NSTEMI and unstable angina. Several risk stratification systems to

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Table 8.4 Classification of antiplatelet agents Antiplatelet agents

Mechanism of action

Initial therapy and dose

Long-term therapy and dose

Aspirin Nonsteroidal antiinflammatory drugs Sulfinpyrazone

Inhibits cyclooxygenase (prostaglandin H synthase), the enzyme that mediates the first step in the biosynthesis of prostaglandins and thromboxanes (including TXA2) from arachidonic acid

The first aspirin tablet should contain 162–325 mg and should be chewed

Aspirin indefinitely No stent: aspirin 75–162 mg/day Bare metal stent (BMS): aspirin (162–325 mg daily) for 1 month Drug eluting stent (DES): sirolimus-eluting stent for 3 months paclitaxel-eluting stent for 6 months Indefinite therapy{ For those patients unable to tolerate aspirin: clopidogrel 75 mg daily or ticlopidine 250 mg twice daily

Dipyridamole

Blocks phosphodiesterasemediated breakdown of cyclic AMP, which prevents platelet activation by multiple mechanisms Inhibits the binding of ADP to a specific platelet receptor P2Y12, thereby inhibiting activation of the GP IIb/IIIa complex and platelet aggregation

Loading dose of clopidogrel is 300 mg and 600 mg if patient going to catheterization the same day Loading dose for prasugrel 60 mg

Clopidogrel 75 mg/day indefinitely or prasugrel for 15 months 10 mg for patients  60 kg or 5 mg for patients 160 mmHg, and diastolic pressure > 90 mmHg. sisted until the end of an average follow-up of Autopsy data demonstrate that cerebral amyloid angio8 months and was seen in both stented and nonstented pathy also predisposes to ICH with administration of thrombolytics. Life-threatening ventricular arrhythmias patients. There was no significant difference in major are also a risk factor for ICH. It is hypothesized that a bleeding episodes between the two groups. Large observational cohort studies have demonstrated period of hemodynamic instability alters cerebral perfuthat use of aspirin and clopidogrel does not increase stroke sion, and the wide variation in blood pressure experirisk above baseline, but the combination of aspirin and enced during CPR combined with thrombolytic therapy warfarin increases the risk of stroke to 0.9% per year commay incite ICH (Sloan et al., 1995). pared to 0.2% per year for aspirin alone (Buresly et al., In a clinical setting where the optimal treatment stra2005). Triple therapy with aspirin, clopidogrel, and warfategy is still contemplative for central nervous system bleeding, an early multidisciplinary effort involving rin places the patient at three to five times the risk of major input from neurologists, neurosurgeons, hematologists, bleeding, which includes an increased stroke risk (Patti and Di Sciascio, 2010). A major predictor of bleeding risk with and cardiologists is ideal. Neurosurgical intervention oral anticoagulation is increasing patient’s age. The incimay be needed to alleviate raised intracranial pressure dence of major hemorrhage in orally anticoagulated or to evacuate hematomas (Sloan et al., 1995). Mahaffey patients younger than 60 years is 1.5% per year, but this et al. examined neurosurgical evacuation of intracranial risk increases to 4.2% in patients older than 80 years hemorrhage after thrombolytic therapy for acute myo(Torn et al., 2005). Risk of major bleeding on oral anticoacardial infarction from the Global Utilization of Streptokinase and Tissue-Plasminogen Activator (tPA) for gulation increases by 3% per year in patients over the age Occluded Coronary Arteries (GUSTO-1) trial where they of 75 years (Patti and Di Sciascio, 2010). randomly assigned 41 021 patients with acute myocardial infarction to one of four thrombolytic strategies in Thrombolytic agents 1081 hospitals in 15 countries and found that rapid neuDespite the focus on catheter-based revascularization rosurgical intervention may be beneficial in selected strategies as treatment for ST elevation MI, fibrinolytic cases (Mahaffey et al., 1999a), but evidence from

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Table 8.5 Thrombolytic agents in acute coronary syndrome

Drug

Dose*

Advantage

Risks and limitations

Salient clinical trial associated with thrombolytic agent

Streptokinase

1.5 million units over 30–60 minutes

Less efficacious than alteplase

GISSI-1 ISIS-2

Alteplase

(1) 15 mg bolus (2) Then 0.75 mg/kg (maximum 50 mg) over 30 minutes (3) Then 0.5 mg/kg (maximum 35 mg) over the next 60 minutes

Most widely used agent worldwide as less costly Reasonable efficacy to safety ratio Lower risk of intracranial hemorrhage than alteplase Better outcomes than streptokinase in GUSTO-1 (30 day mortality 6.3% versus 7.3%)

More expensive than streptokinase Difficult to administer because of short half-life GUSTO-I found a 1.4% incidence of stroke (ICH in 0.7% and nonhemorrhagic stroke in the remaining patients)

GUSTO-1 COBALT

Tenecteplase (TNK-tPA)

Single bolus over 5–10 seconds based upon bodyweight: 18,000 patients. Circulation 104: 269–274. Cupples LA, Gagnon DR, Wong ND et al. (1993). Preexisting cardiovascular conditions and long-term prognosis after initial myocardial infarction: the Framingham study. Am Heart J 125: 863–872. Dacey LJ, Likosky DS, Leavitt BJ et al. (2005). Northern New England Cardiovascular Disease Study Group. Perioperative stroke and long-term survival after coronary bypass graft surgery. Ann Thorac Surg 79: 532–536. Diercks DB, Peacock WF, Hiestand BC et al. (2006). Frequency and consequences of recording an electrocardiogram >10 minutes after arrival in an emergency room in non-ST-segment elevation acute coronary syndromes (from the CRUSADE Initiative). Am J Cardiol 97: 437–442. Diez JG, Cohen M (2009). Balancing myocardial ischemic and bleeding risks in patients with non-ST segment elevation myocardial infarction. Am J Cardiol 103: 1396–1402. Dukkipati S, O’Neill WW, Harjai KJ et al. (2004). Characteristics of cerebrovascular accidents after percutaneous coronary interventions. J Am Coll Cardiol 43: 1161–1167. Elahi M, Battula N, Swanevelder J (2005). The use of the stroke risk index to predict neurological complications following coronary revascularisation on cardiopulmonary bypass. Anaesthesia 60: 654–659. Fuchs S, Stabile E, Kinnaird TD et al. (2002). Stroke complicating percutaneous coronary interventions: incidence, predictors, and prognostic implications. Circulation 106: 86–91. Goodman S, Steg P, Eagle K et al. (2006). The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 151: 654–660. Gordinier HC (1924). Coronary arterial occlusion, a perfectly definite symptom complex. Am J Med Sci 198: 181–201. Gore JM, Granger CB, Simoons ML et al. (1995). Stroke after thrombolysis. Mortality and functional outcomes in the GUSTO-1 trial. Circulation 92: 2811–2818. Gorelick PB, Weisman SM (2005). Risk of hemorrhagic stroke with aspirin use: an update. Stroke 36: 1801–1807. Grobner T (2006). Gadolinium – a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21: 1104–1108. Gurwitz JH, Gore JM, Goldberg RJ et al. (1998). Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Ann Intern Med 129: 597–604. Hachinski VC (1993). The clinical problem of brain and heart. Stroke 24: I1. Haugland JM, Asinger RW, Mikel FL et al. (1984). Embolic potential of left ventricular thrombus detected

108

M.N. HAQUE AND R.S. DIETER

by two-dimensional echocardiography. Circulation 70: 588–598. Heart Protection Study Collaborative Group (2002). MRC/ BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360: 7–22. Herlitz J, Holm J, Peterson M, et al., LoWASA Study Group (2005). Factors associated with development of stroke long-term after myocardial infarction: experiences from the LoWASA trial. J Intern Med 257: 201–207. Hurlen M, Abdelnoor M, Smith P et al. (2002). Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 347: 969–974. Huynh T, Cox JL, Massel D et al. (2004). Predictors of intracranial hemorrhage with fibrinolytic therapy in unselected community patients: a report from the FASTRAK II project. Am Heart J 148: 86–91. Hynes RO (1987). Integrins: a family of cell surface receptors. Cell 48: 549–554. Ikram MA, Hollander M, Bos MJ et al. (2006). Unrecognized myocardial infarction and the risk of stroke: the Rotterdam study. Neurology 67: 1635–1639. ISIS-2 (Second International Study of lnfarct Survival) Collaborative Group (1988). Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 332: 349–360. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group (1992). ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 299 cases of suspected acute myocardial infarction. Lancet 339: 753–770. Kanal E, Borgstede JP, Barkovich AJ et al. (2004). American College of Radiology White Paper on MR Safety: update and revisions. AJR Am J Roentgenol 182: 1111–1114. Karalis DG, Quinn V, Victor MF et al. (1996). Risk of catheterrelated emboli in patients with atherosclerotic debris in the thoracic aorta. Am Heart J 131: 1149–1155. Kassem-Moussa H, Mahaffey KW, Graffagnino C et al. (2004). SYMPHONY and 2nd SYMPHONY Investigators. Incidence and characteristics of stroke during 90-day follow-up in patients stabilized after an acute coronary syndrome. Am Heart J 148: 439–446. Kaya M, Okyay K, Yazici H et al. (2009). Long-term clinical effects of magnetic resonance imaging in patients with coronary artery stent implantation. Coron Artery Dis 20: 138–142. Keren A, Goldberg S, Gottlieb S et al. (1990). Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. J Am Coll Cardiol 15: 790–800. Komrad MS, Coffey CE, Coffey KS et al. (1984). Myocardial infarction and stroke. Neurology 34: 1403–1409. Korpelainen JT, Sotaniemi KA, Huikuri HV et al. (1997). Circadian rhythm of heart rate variability is reversibly abolished in ischemic stroke. Stroke 28: 2150–2154. Latchaw RE, Alberts MJ, Lev MH et al. (2009). Recommendations for imaging of acute ischemic stroke:

a scientific statement from the American Heart Association. Stroke 40: 3646–3678. Lazar JM, Uretzky BF, Denys BG et al. (1995). Predisposing risk factors and natural history of acute neurologic complications of left-sided cardiac catheterization. Am J Cardiol 75: 1056–1060. LeBoit PE (2003). What nephrogenic fibrosing dermopathy might be. Arch Dermatol 139: 928–930. Levine GN, Gomes AS, Arai AE et al. (2007). Safety of magnetic resonance imaging in patients with cardiovascular devices: an American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Council on Cardiovascular Radiology and Intervention: endorsed by the American College of Cardiology Foundation, the North American Society for Cardiac Imaging, and the Society for Cardiovascular Magnetic Resonance. Circulation 116: 2878–2891. Liao J, O’DonnellMJ, Silver FL et al. (2009). In-hospitalmyocardial infarction following acute ischaemic stroke: an observational study. Eur J Neurol 16: 1035–1040. Lichtman JH, Krumholz HM, Wang Y et al. (2002). Risk and predictors of stroke after myocardial infarction among the elderly: results from the Cooperative Cardiovascular Project. Circulation 105: 1082–1087. Lloyd-Jones D, Adams R, Carnethon M et al. (2009). Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation 119: e21–e181. Loh E, Sutton MS, Wun CC et al. (1997). Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 336: 251–257. Lombardo A, Biasucci LM, Lanza GA et al. (2004). Inflammation as a possible link between coronary and carotid plaque instability. Circulation 109: 3158–3163. Maggioni AP, Franzosi MG, Farina ML et al. (1991). Cerebrovascular events after myocardial infarction: analysis of the GISSI trial. BMJ 302: 1428–1431. Maggioni AP, Franzosi MG, Santoro E et al. (1992). The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic therapy. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico II (GISSI-2), the International Study Group. N Engl J Med 327: 1–6. Mahaffey KW, Granger CB, Sloan MA et al. (1998). Risk factors for in-hospital non-hemorrhagic stroke in patients with acute myocardial infarction treated with thrombolysis: results from GUSTO-1. Circulation 97: 757–764. Mahaffey KW, Granger CB, Sloan MA et al. (1999a). Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and tissue-plasminogen activator (tPA) for Occluded Coronary Arteries. Am Heart J 138: 493–499. Marcu CB, Beek AM, van Rossum AC (2006). Clinical applications of cardiovascular magnetic resonance imaging. CMAJ 175: 911–917.

NEUROLOGIC COMPLICATIONS OF MYOCARDIAL INFARCTION McQuaid KR, Laine L (2006). Systematic review and metaanalysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 119: 624–638. Mehta SR, Yusuf S, Peters RJ et al., for the CLopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators (2001). Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 358: 527–533. Meltzer RS, VIsser CA, Kan G et al. (1984). Two dimensional echocardiographic appearance of left ventricular thrombi with systemic embolic after myocardial infarction. Am J Cardiol 53: 1511–1513. Memon MA, Blankenship JC, Wood GC et al. (2000). Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials. Am J Med 109: 213–217. Milika AR, Zorana VM, Mihailo MD et al. (2009). The longterm risk of stroke in patients with acute myocardial infarction complicated with new-onset atrial fibrillation. Clin Cardiol 32: 467–470. Mooe T, Eriksson P, Stegmayr B (1997). Ischemic stroke after acute myocardial infarction. A population based study. Stroke 28: 762–767. Mooe T, Olofsson BO, Stegmayr B et al. (1999). Ischemic stroke. Impact of a recent myocardial infarction. Stroke 30: 997–1001. MR safety. Available at: http//www.acr.org/Secondary MainMenuCategories/quality_safety/MRSafety.aspx. MRI safety. Institute for Magnetic Resonance Safety, Education, and Research Web site Available at: http:// MRIsafety.com. Nadareishvili ZB, Choudary Z, Joyner C et al. (1999). Cerebral microembolism in acute myocardial infarction. Stroke 30: 2679–2682. Nayak D, Aronow WS, Sukhija R et al. (2004). Comparison of frequency of left ventricular thrombi in patients with anterior wall versus non-anterior wall acute myocardial infarction treated with antithrombotic and antiplatelet therapy with or without coronary revascularization. Am J Cardiol 93: 1529–1530. Nihoyannopoulos P, Smith GC, Maseri A et al. (1989). The natural history of left ventricular thrombus in myocardial infarction: a rationale in support of masterly inactivity. J Am Coll Cardiol 14: 903–911. Ozatik MA, Gol MK, Fansa I et al. (2005). Risk factors for stroke following coronary artery bypass operations. J Card Surg 20: 52–57. Pasceri V, Willerson JT, Yeh ETH (2000). Dirrect proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102: 2165–2168. Patti G, Di Sciascio G (2010). Antithrombotic strategies in patients on oral anticoagulant therapy undergoing percutaneous coronary intervention: a proposed algorithm based on individual risk stratification. Catheter Cardiovasc Interv 75: 128–134. Peters RJ, Mehta SR, Fox KA et al. (2003). Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes:

109

observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 108: 1682–1687. Rosamond W, Flegal K, Furie K et al. (2008). Heart disease and stroke statistics – 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117: e25. Saczynski JS, Spencer FA, Gore JM et al. (2008). Twenty-year trends in the incidence of stroke complicating acute myocardial infarction: Worcester Heart Attack Study. Arch Intern Med 168: 2104–2110. Sadowski EA, Bennett LK, Chan MR et al. (2007). Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 243: 148–157. Sampson UK, Pfeffer MA, McMurray JJ et al. (2007). Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT trial. Eur Heart J 28: 685–691. Savonitto S, Armstrong PW, Lincoff AM et al. (2003). Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction. Dichotomous response as a function of age in the GUSTO V trial. Eur Heart J 24: 1807–1814. Schomig A (2009). Ticagrelor – is there need for a new player in the antiplatelet-therapy field? N Engl J Med 361: 1108–1111. Schulman S, Beyth RJ, Kearon C et al. (2008). Hemorrhagic complications of anticoagulant and thrombolytic treatment. Chest 133: 257S–298S. Segal AZ, Abernethy WB, Palacios IF et al. (2001). Stroke as a complication of cardiac catheterization: risk factors and clinical features. Neurology 975–977. Sloan MA, Price TR, Petito CK et al. (1995). Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the thrombolysis in myocardial infarction (TIMI) II pilot and randomized clinical trial combined experience. Neurology 45: 649–658. Sloan MA, Price TR, Terrin ML et al. (1997). Ischemic cerebral infarction after rt-PA and heparin therapy for acute myocardial infarction. Stroke 28: 1107–1114. Steinhubl SR, Berger PB, Brennan DM et al. (2006). Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention. J Am Coll Cardiol 47: 939–943. Steinhubl SR, Bhatt DL, Brennan DM et al. (2009). Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med 150: 379–386. Szummer KE, Solomon SD, Velazquez EJ et al. (2005). Heart failure on admission and the risk of stroke following acute myocardial infarction: the VALIANT registry. Eur Heart J 26: 2114–2119. Tanne D, Gottlieb S, Hod H et al. (1997). Incidence and mortality from stroke associated with acute myocardial infarction in the prethrombolytic and thrombolytic eras. J Am Coll Cardiol 30: 1484–1490.

110

M.N. HAQUE AND R.S. DIETER

Thygesen K, Alpert JS, White HD et al., Joint ESC/ACCF/ AHA/WHF Task Force for the Redefinition of Myocardial Infarction (2007). Universal definition of myocardial infarction. Eur Heart J 28: 2525–2538. Topol EJ (2001). Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 357: 1905–1914. Topol EJ, Easton D, Harrington RA et al. (2003). Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation 108: 399–406. Torn M, Bollen WLEM, van der Meer FJM et al. (2005). Risks of oral anticoagulant therapy with increasing age. Arch Intern Med 165: 1527–1532. Tung CY, Granger CB, Sloan MA et al. (1999). Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO 1 Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study. Circulation 99: 370–376. Tunick PA, Kronzon I (2000). Atheromas of the thoracic aorta: clinical and therapeutic update. J Am Coll Cardiol 35: 545–554. Vaitkus PT, Barnathan ES (1993). Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol 22: 1004–1009. Vaitkus PT, Berlin JA, Schwartz JS et al. (1992). Stroke complicating acute myocardial infarction: a metanalysis of risk modification by anticoagulation and thrombolytic therapy. Arch Intern Med 152: 2020–2024. Van de Graaff E, Dutta M, Das P et al. (2006). Early coronary revascularization diminishes the risk of ischemic stroke with acute myocardial infarction. Stroke 37: 2546–2551. Virchow RLK (1856). Thrombose und Embolie. Gefa¨ssentz€ undung und septische Infektion. Gesammelte Abhandlungen zur wissenschaftlichen Medicin, Von Meidinger & Sohn, Frankfurt am Main, pp. 219–732. Translation in: Matzdorff AC, Bell WR (1998). Thrombosis and Embolie (1846–1856). Science History Publications, Canton, Massachusetts.

Visser CA, Kan G, Meltzer RS et al. (1985). Embolic potential of left ventricular thrombus after myocardial infarction: a two dimensional echocardiographic study of 119 patients. J Am Coll Cardiol 5: 1276–1280. Weinreich DJ, Burke JF, Pauletto FJ (1984). Left ventricular mural thrombi complicating acute myocardial infarction. Long-term follow-up with serial echocardiography. Ann Intern Med 100: 789–794. Westerhout CM, Hernandez AV, Steyerberg EW et al. (2006). Predictors of stroke within 30 days in patients with non-STsegment elevation acute coronary syndromes. Eur Heart J 27: 2956–2961. Witt BJ, Brown R Jr, Jacobsen SJ et al. (2005). A communitybased study of stroke incidence after myocardial infarction. Ann Intern Med 143: 785–792. Wiviott SD, Antman EM, Winters KJ et al. (2005). Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 111: 3366. Wong SC, Minutello R, Hong MK (2005). Neurological complications following percutaneous coronary interventions (a report from the 2000–2001 New York State Angioplasty Registry). Am J Cardiol 96: 1248–1250. Woods RM, Barnes AR (1941). Factors influencing immediate mortality rate following acute coronary occlusion. Proc Staff Meet, Mayo Clinic 16: 341. Woods SE, Michael Smith J, Engle A (2004). Predictors of stroke in patients undergoing coronary artery bypass grafting surgery: a prospective, nested, case-control study. J Stroke Cerebro 13: 178–182. Yun AJ, Lee PY, Bazar KA (2005). Can thromboembolism be the result, rather than the inciting cause, of acute vascular events such as stroke, pulmonary embolism, mesenteric ischemia, and venous thrombosis?: a maladaptation of the prehistoric trauma response. Med Hypotheses 64: 706–716. Yusuf S, Zhao F, Mehta SR et al. (2001). Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345: 494–502.