9 - Cardiac Anomalies
Editors: Norris, John W.; Hachinski, Vladimir
Title: Stroke Prevention, 1st Edition
Copyright 2001 Oxford University Press
> Table of Contents > II - Secondary Prevention > 9 - Cardiac Anomalies
9
Cardiac Anomalies
G. Devuyst
J. Bogousslavsky
The aims in treating stroke are three-fold: (1) to reopen an occluded cerebral artery (thrombolysis), (2) to provide protection against the metabolic cascade caused by ischemic injury leading to neuronal death (neuroprotection), and (3) to prevent recurrent stroke (secondary prevention). Secondary prevention of stroke is the most important of these three since neither thrombolysis nor neuroprotection are currently practical in the majority of patients. In studies performed before the 1980s, stroke recurrence rate varied from 2% 13% in the first month, irrespective of treatment, and from 2% 22% in untreated patients. 1
No difference has been found in the early recurrence rate among patients with vascular causes compared to those with presumed cardioembolic stroke (CES).2,3 In strokes with cardiac causes, 13% 21% will experience a recurrence within two weeks, which worsens the prognosis.4,5,6,7 The Cerebral Embolism Study8 found the risk of recurrence was slightly higher during the first 6 days, and Yasaka et al.7 noted that recurrence was especially frequent 2 14 days after the initial stroke.
Little information exists about the recurrence rates of stroke for the various types of cardioembolic sources, except for rheumatic heart disease, in which recurrence rates differ among subgroups of patients with the same cardioembolic source, e.g. atrial fibrillation. Therapeutic strategies include anticoagulants, antiplatelet agents, and surgical procedures (e.g., closure of patent foramen ovale).
P.162
Three levels of credibility clinical diagnosis for stroke cardiac origin have been suggested possible, probable or definite depending on the source, and treatment is specific to each of these.9 This chapter provides an overview the recurrent stroke risk and the risk-benefit ratio for secondary preventive therapies in patients with stroke of cardiac origin.
Atrial Fibrillation (AF)
Approximately 16% (11% 29%) of all ischemic strokes are associated with nonvalvular AF,10 and among patients over 70 years old with ischemic stroke, more than one-third suffer AF.11,12 AF increases the relative risk of ischemic stroke about five-fold, roughly 1% 5% per year for elderly people. 10 Wolf et al.12,13 reported a five-fold increase in stroke incidence patients with nonrheumatic atrial fibrillation compared with a normal age matched population. The stroke risk associated with AF was 0.2 per 1,000 in the 30 39 year age group, and 39 per 1,000 in the 80 89 year age group. The risk of very early stroke recurrence among patients with AF (the most common cause of cardiogenic embolism) is estimated at 0.1% 1.3% per day during the first two weeks. 2,3,14,15,16,17,18,19,20,21,22,23,24 Moreover, AF patients with prior ischemic stroke or transient ischemic attack (TIA) have a high risk for recurrence of 12% per year for the subsequent two to three years.25,26 Those with more remote stroke or TIA have a similar high risk.27 These variations of recurrence rates are due to the retrospective design of most studies and also to the inclusion of AF patients irrespective a coexistent cardiac disorder.
Nine recent randomised clinical trials AFASAK, SPAF I, BAATAF, CAFA, SPINAF, SPAF II, EAFT, ESPS SPAF III have convincingly demonstrated the efficacy of anticoagulants and aspirin in stroke prevention nonvalvular AF,28,29 but only two EAFT 25 and ESPS II 26 dealt specifically with secondary prevention.
Five trials of primary prevention AFASAK, SPAF I, BAATAF, CAFA, SPINAF comparing warfarin vs. placebo found a relative risk reduction of 33% 86% per year for ischemic stroke and 2.5% 4.7% absolute rate reduction.10,30 The Atrial Fibrillation investigators, analyzing pooled data from the first five primary prevention trials, found an annual stroke rate of 4.5% in controls vs. 1.4% in the warfarin group (risk reduction = 68%). The death ra and combined outcome rate (stroke, death, systemic embolism) were also significantly reduced in the treatment group.
The efficacy of aspirin for stroke prevention in AF patients has been studied in only two of the original five primary prevention trials (AFASAK and SPAF I) and in one secondary prevention trial (EAFT), yielding a pooled risk reduction of 20%, a modest reduction compared to placebo.10 In the SPAF II trial of primary prevention, warfarin [international normalized ration (INR 2.0 4.5)] produced a 50% risk reduction compared to aspirin at 325 mg/day.31 Evaluation of
P.163
the combined results of AFASAK, SPAF I, BAATAF, CAFA, SPINAF, and EAFT, indicates that warfarin reduces ischemic stroke by nearly 70%, compared to placebo.10
The stroke prevention benefit of warfarin carried no serious risk major bleeding in most of these trials: 1.0% for placebo, 1.0% aspirin, and 1.3% warfarin.10,30 Also, the incremental increase in severe haemorrhage among elderly, anticoagulated AF patients in these trials was only 0.3% 2.0% per year with INR 1.5 4.0,10 although trial patients have a lower bleeding risk than those in clinical settings. The risk of major hemorrhage in AF patients receiving warfarin was related to the intensity of anticoagulation, patient age, and fluctuation in INRs.10 High-risk AF patients, defined as those with prior TIA or stroke, a history of hypertension, or a substantially impaired left ventricular systolic function, had a higher risk of stroke (>7% per year) that was significantly reduced by warfarin.10
In the SPAF III study,29 892 patients with AF who were at low risk of stroke and taking 325 mg aspirin per day were followed for a mean of 2.0 years. The rate of primary events (ischemic stroke and systemic embolism) was 2.2% per year, while for all ischemic stroke it was 2.0% per year and for disabling ischemic stroke it was 0.8% per year. Those with hypertension had a significantly higher rate of primary events (3.6% per year vs. 1.1% year), while the rate of disabling stroke was low. This study illustrates that AF patients with a low risk of ischemic stroke benefited less with anticoagulation than with aspirin.
Risk Stratification for Patients with AF Based on Primary Prevention Studies
The risk of stroke from AF depends on various factors, including age,13 duration of fibrillation, 32 coexisting heart failure and hypertension.33 One evaluation of pooled data from five randomized primary stroke prevention trials found that the major risk factors were prior stroke or TIA, diabetes, hypertension, and age, while angina, previous myocardial infarction, and congestive heart failure were also significant.34 Mitral stenosis and thyrotoxicosis were also associated with increased stroke risk in retrospective series.34
The annual rate of ischemic stroke in AF is about 5%, varying between 0.5% and 12% depending upon the subgroup at risk.28 Patients with paroxysmal AF tend to be younger and have less cardiovascular disease, so that their risk of stroke is less.28
In the SPAF III study,29 patients were divided into high-risk and low-risk groups depending upon four prespecified risk factors: (1) left ventricular function associated with congestive heart failure or reduced extraction fraction on echocardiography; (2) systolic blood pressure >160 mm Hg; (3) prior ischemic stroke, TIA, or systemic embolism; and (4) female older than 75 years. The results of this trial indicated 3 levels of risk: (1) low (about 1.0% per year) for those
P.164
without thromboembolic risk factors or hypertension, (2) moderate (about 3.5 % per year) for those with hypertension but no risk factors, and (3) high (about 8% per year) for those with all the risk factors.
Based on these findings, Hart et al.9,10 recommended aspirin at 325 mg/day for low-risk patients, aspirin or warfarin for moderate risk patients, and warfarin, INR 2.0 3.0, for patients <75 years, and 1.6 2.5 >75 years for high-risk patients.28
Echocardiography helps gauge the risk stratification, but it is unclear at present if left ventricular dysfunction, atrial size, and mitral annular calcification diagnosed by transthoracic echocardiography (TTE) represent consistent additional stroke risk factors in AF patients. A pooled analysis of three studies, BAATAF, SPINAF, and SPAF I, showed that moderate to severe left ventricular dysfunction diagnosed by TTE was an independent predictor of stroke, but not left atrial size.35,36 Similarly, Shively et al.37 noted increased stroke risk associated with decreased left atrial flow velocity (<15 cm/sec), ventricular dilatation, and decreased left atrial ejection fraction in patients with AF and atrial enlargement. In another study, spontaneous echo contrast was significantly associated with AF-related stroke, possibly by changing blood coagulability consecutive to atrial stasis.38
Transesophageal echocardiography (TEE) in the SPAF III study39 showed that the presence of complex aortic plaques ( 4 mm or mobile) carried an annual stroke risk of 16%, compared with 4% in high-risk patients without such plaques. Unlike TEE, TTE is very insensitive for atrial thrombi detection.40
The decision to use anticoagulant or aspirin therapy depends upon risk stratification of patients with AF. Aspirin carries a lower bleeding risk and requires less medical monitoring than do anticoagulants, and at 325 mg/day reduces the stroke risk in these patients from 6.3% per year in the placebo group to 3.6% year in the aspirin group, a risk reduction of 42%.36 This therapeutic effect was higher in noncardiac sources of stroke than those from arterial causes. In AF patients with a low stroke risk (1% per year) on aspirin, only small reductions in ischemic stroke could be expected from anticoagulation, but this causes a higher risk of intracranial bleeding. In those with a high risk of stroke (6% 12% per year) on aspirin, a much greater reduction can be expected with warfarin.
Secondary Prevention Strategies
The only large placebo-controlled trial of secondary prevention stroke in AF, the European Atrial Fibrillation Trial (EAFT),25,41 enrolled AF patients with prior TIAs or minor ischemic strokes and was divided into three groups: warfarin alone, aspirin 300 mg/day alone, and warfarin vs. aspirin. The rate of recurrent stroke, 12% per year in the placebo group, was reduced by 17% in the aspirin group (n.s.) and 66% in the warfarin group (p = 0.001).
P.165
In this trial, the INRs varied between 2.5 and 4.0, but values of 2.0 to 2.9 reduced the stroke risk (including hemorrhagic events) by 80%, compared to INRs of less than 2.0. INRs between 3.0 and 3.9 reduced the rate by 40 %. Only INRs higher than 3.9 increased the complication rate, principally because of hemorrhagic complications.
In the ESPS II trial,26 in which dipyridamole with aspirin reduced recurrent stroke, this therapeutic effect was not seen in the subgroup of patients with AF.26,42 In a similar secondary prevention study, Studio Italiano Fibrillazione Atriale,43 using indobufen (100 mg-200 mg twice a day) or warfarin (INR, 2.0 3.5) no superiority of one treatment over the other was detected, and bleeding complications were low. Hence, indobufen is an acceptable alternative therapy to anticoagulation in AF patients.
Some questions remain unanswered, such as the efficacy of ticlopidine and anti-glycoprotein Ilb/IIIa inhibitors in preventing recurrent stroke AF patients, especially in elderly or hypertensive patients whom anticoagulation is more risky, as well the efficacy of thrombolytic agents. Finally, there is no convincing evidence that restoring sinus rhythm by cardioversion reduces cerebral embolic potential (Table 9.1).
Atrial Flutter and Atrial Fibrillation-Flutter
Data concerning this uncommon cardiac disorder are scant, and the exact risk of stroke associated with atrial flutter is unknown. Nevertheless, in a recent small retrospective study in patients without history of brain ischemia, the annual risk of stroke was only 1.6%.44 Available data suggest that the risk of embolism from atrial flutter is less than AF following cardioversion. Atrial fibrillation-flutter carries the same risk of stroke as AF and so requires the management
Sick Sinus Syndrome (SSS)
In a recent prospective study of sick sinus syndrome, previous cerebral ischemic events, an age >65 years, left atrial spontaneous echocardiographic contrast and depressed atrial ejection force were independent risk factors for stroke.45 Those with AF showed a thromboembolic rate of 5% per year, compared to 3.5% per year in those without AF,10 though a more recent study reported stroke rate of 10% per year.45 Dual-chamber cardiac pacemakers reduced both the occurrence of AF as well as thromboembolism in comparison to ventricular pacing.
For secondary prevention in patients with well established SSS, anticoagulation should be considered, irrespective of the presence or absence AF.10 The value of antiplatelets, the optimal intensity anticoagulation, and the safety chronic anticoagulation in elderly patients remains uncertain.
TABLE 9.1. Prevention of Stroke in Atrial Fibrillation Patients: Recommendations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
P.166
P.167
Patent Foramen Ovale
During the last decade, there has been an increasing emphasis on the role of patent foramen ovale (PFO) in the genesis of ischemic stroke, particularly young. Several case control studies46,47,48,49,50,51,52,53,54 have shown that PFO was significantly associated with stroke in patients younger than 60 years of age. Cerebral paradoxical embolism is usually a presumed diagnosis, because direct evidence, such as a thrombus lodged in the PFO shown on transesophageal echocardiography or the discovery of a deep venous thrombosis, is commonly lacking.46,49,50,51,52,53,54,55,56 Despite these ongoing controversies, it is reasonable to incriminate a cerebral paradoxical embolism in young patients with no other identified cause of stroke than PFO.
The optimal treatment of these patients remains a matter debate, mainly because of a lack controlled clinical trials. There are four therapeutic options: antiplatelets drugs, anticoagulants, closure of PFO by transcatheterization or closure of PTO by surgery. The only two studies57,58 secondary prevention of stroke in patients with PFO show that the risk recurrent stroke is relatively low, about 1% per year, in patients treated with aspirin or shortterm anticoagulation. 10 In the Lausanne Study57 and the French Study Group,58 the annual rate of TIA was 3.8% and 3.4%, of stroke alone, 1.9% 1.2%, respectively.
At present, there is little information on the risk of stroke recurrence in those with PFO associated with an atrial septal aneurysm (ASA) compared to PFO alone, and some have suggested that PFO with an ASA, or large PFOs with rightto-left shunting, have more stroke risk.59,60,61,62 On these grounds, Nendaz et al.63 created a decision analysis model for the clinician. This model indicates that a stroke risk recurrence of 0.8% to 7% per year, there was more benefit from surgical closure of the PFO than from any other treatment. When the risk exceeds 0.8% 1.4% per year, anticoagulants and antiaggregants are better than placebo, while when it is <0.8% per year, neither medical nor surgical treatment is indicated. Further studies are planned to determine the stroke risk in subgroups of PFO patients using transcranial Doppler ultrasound with the microbubble technique, which may be more accurate than TEE.64 At present, treatment is limited to the application of empirical clinical criteria.
Surgical closure of PFO without recurrence stroke has been reported,65,66,67 but others have not been so fortunate.68 An alternate procedure consists of transcatheter closure of the PFO, which was effective in 82% of cases, but recurrence occurred in 4 of 34 patients on follow-up.69 Considerably more information is needed concerning the efficiency, safety, and long-term complications of the transcatheter technique before it can replace surgery.
The use of anticoagulants is risky in young patients with a long life expectancy because of the major bleeding risk, estimated at 1.5% 11% per year.67 The authors recommend anticoagulants when a deep venous thrombosis (DVT) is
P.168
demonstrated by ultrasound investigation or by venography, and before closing the PFO surgically in those with a presumed higher risk of stroke recurrence. In practice, and until results of future studies focusing on risk stratification are reported, the authors apply following criteria to decide secondary prevention therapy in patients with stroke and PFO: (1) more than one cerebrovascular event clinically or on MRI scan, (2) a history of Valsalva's manoeuvre just before the clinical event, (3) significant right-to-left shunting through the PFO documented by TEE or Doppler, and (4) PFO associated with ASA. In these patients we recommend aspirin of 300 mg/day, or closure the PFO by surgery catheter, depending upon the criteria listed above (Table 9.2).
Prosthetic Heart Valves (PHV)
Thromboembolic events occur at a rate of 1 5% per year in patients with prosthetic heart valves, despite oral anticoagulation, and 85% of these are cerebral.68 Stroke may occur from either inadequate anticoagulation or because thrombogenic factors are inadequately suppressed despite adequate anticoagulation therapy. The precise pathophysiology of thromboembolism in patients with PHV remains uncertain. Increased shear rates at the valve surfaces may activate platelets, generating platelet-derived microparticles, which could have potent procoagulant activity.71 Also, the presence of microemboli, frequently encountered in these patients, may result from harmless gaseous bubbles (cavitation) rather than from actual paniculate elements.70,71 High-intensity transient signals (HITS) detected by the Doppler technique are seen overwhelmingly with mechanical heart valves compared to biological prostheses, and these may produce a cognitive alteration.72 Even with the combination of anticoagulation and antiplatelets, the annual incidence rate of thromboembolism in patients with PHV remained at 2% to 3%.70
As yet, no prospective randomized studies have been done in patients with mechanical valves to assess the efficacy of antithrombotic therapy. In a meta-analysis comprising more than 53,000 patient-years, the major embolism rate without antithrombotic therapy was 4.0% per year, reduced to 2.2% year with antiplatelets and to 1.0% per year with anticoagulants.73 The embolic rate with a combination of anticoagulants and antiplatelets was higher, at 1.7% per year, than for anticoagulants alone, and much higher with dipyridamole, at 5.4% per year than with aspirin alone, at 1.4% per year. Major embolism is more frequent mitral valves, with mitral plus aortic valves, and with caged ball prostheses.
The exact level of anticoagulation needed to prevent thromboembolism in patients with mechanical valves remains uncertain. In the past, high-intensity anticoagulation was used, and a recent meta-analysis based on 12 studies found an INR of 2.5 3.6 was best, resulting in an American College Chest Physicians
P.169
P.170
recommendation of 2.5 3.5.74 A similar study involving St. Jude valves confirmed this level of anticoagulation.75 Another study showed that higher levels anticoagulation, with INRs of 3.0 4.0, were needed, but this may reflect a type valve with a particularly high embolic rate.76 The presence of other risk factors, such as AF, left ventricular dysfunction, spontaneous echocardiographic contrast (SEC) in the left atrium and increasing age increase the chance of embolism.77 A meta-analysis of five controlled trials that combined antiplatelets and anticoagulants noted a 67% reduction in embolism risk, but a 65% increased risk of hemorrhage and a 250% increase of major gastrointestinal bleeding. These trials used high doses of aspirin (>400 mg/day).78 Low doses (100 mg/day) are safe in combination with an INR of 2.5 3.5, but it is uncertain if the combined therapy is significantly more effective than anticoagulation alone with a target INR of 2.5 3.5.
TABLE 9.2. Secondary Prevention in Patients with Patent Foramen Ovale-Associated Stroke: Recommendations (Risk of stroke on aspirin: 1%/year [0 4% / year]) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||||||||||
Acute Myocardial Infarction (AMI)
About 1% to 5% of patients with AMI have an ischemic stroke, most of them cardioembolic, occurring within two to four weeks. Stroke occurred especially in those with anterior AMI, in whom the risk of ischemic stroke was 12%,10 and in patients with large anterior infarcts.79,80 In the first month after AMI, incidence rates were 1% 3.2%, and AF and ST segment elevation were significant risk factors.81
Left ventricular thrombi (LVT), in older patients with large infarcts, especially those with congestive heart failure, have an increased risk of stroke. TTE is needed to diagnose ventricular thrombi, but it should be performed at least 24 hours after AMI, because since these develop 1 10 days after AMI. Approximately 15% of AMI patients with recognised LVT will suffer stroke, while /3-adrenergic blocking drugs may favor the development of LVT.10
No randomised trials have been carried out comparing aspirin to anticoagulants to prevent stroke following AMI, though anticoagulants alone were shown effective in preventing recurrent AMI (INR 2.8 4.8) and stroke the Anticoagulants in Secondary Prevention of Events Coronary Thrombosis (ASPECT) trial. No comparison with aspirin was made.82 Early randomised trials showed that heparin followed by low-intensity oral anticoagulation (INR 1.6 2.5) reduced stroke by about 70% in the weeks following AMI (mean rate 2.9% 1.2%).10 Because the stroke rate three months after AMI is so low, long-term anticoagulation beyond three months is not justified unless other major cardiac embolic risk factors, such as mural thrombosis, are present.
A risk stratification approach may be useful. Early treatment with low-dose heparin and aspirin for those with uncomplicated AMI is recommended, but full dose anticoagulation is needed for patients with LVT detected by echocardiography.
P.171
Timing Of Anticoagulant Treatment
Prevention of recurrent stroke by anticoagulantion in patients with cardioembolic stroke remains controversial, and the stroke risk must be balanced against the risk of hemorrhagic transformation the cerebral infarct. The timing anticoagulation is uncertain. In the International Stroke Trial83 and other studies, neither heparin nor heparinoid were efficacious because the benefit of reducing recurrent ischemic strokes was offset by an increase in hemorrhagic strokes. Until adequate data are available from randomized trials, the therapeutic decisions for these patients will remain arbitrary.
References
1. Koudstaal PJ. Prevention of early recurrences in acute stroke. In: J. Bogousslavsky, ed. Acute Stroke Treatment. London: Martin Dunitz, 1997:285 296.
2. Sandercock P, Bamford J, Dennis M, et al. Atrial fibrillation and stroke: Prevalence in different types of stroke and influence on early long term prognosis. BMJ 1992; 305:1460 1465.
3. Broderick JP, Phillips SJ, O'Fallon WM, Frye RL, Whisnant JP. Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke 1992;23:1250 1256.
4. Leonard AD, Newburg S. Cardioembolic stroke. J Neurosci Nurs 1992;24:69 76.
5. Takano K, Yamaguchi T, Kato H, Omae T. Activation of coagulqtion in acute cardioembolic stroke. Stroke 1991;22:12 16.
6. Yasaka M, Yamaguchi T. Immediate anticoagulation for intracardiac thrombus in acute cardioembolic stroke. Angiology 1992;(Nov):886 891.
7. Yasaka M, Yamaguchi T, Oita J, Sawada Shichiri Omae T. Clinical features of recurrent embolization in acute cardioembolic stroke. Stroke 1993;24:1681 1685.
8. Devuyst G, Bogousslavsky J. Which cardiac diagnosis tests apply in the acute phase of stroke and when are they useful? In: J. Bogousslavsky, ed.: Acute Stroke Treatment. London: Martin Dumitz, 1997:65 78.
9. Hart RG. Cardiogenic embolism to the brain. Lancet 1992;339:589 594.
10. Hart RG, Albers GW, Koudstaal PJ. Cardioembolic stroke. In: Ginsberg MD, Bogousslavsky J, eds. Cerebrovascular Disease, Maiden, Mass.: Blackwell, 1998:vol 2, 1392 1429.
11. Asplund K, Carlberg B, Sundstrom G. Stroke in the elderly. Cerebrovasc Dis 1992;2: 152 157.
12. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: A major contributor to stroke in the elderly. Arch Intern Med 1987;147:1561 1564.
13. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The Framingham Study. Neurology 1978;28: 973 977.
14. Bogousslavsky J, van Melle G, Regli F, Kappenberger L. Pathogenesis of anterior circulation stroke in patients with nonvalvular atrial fibrillation: The Lausanne Stroke Registry. Neurology 1990;40:1046 4050.
15. Anonymous. Cariogenic brain embolism: The second report of the Cerebral Embolism Task Force. Arch Neurol 1989;46:727 743.
P.172
16. Hornig CR, Dorndorf W. Early outcome and recurrences after cardiogenic brain embolism. Acta Neural Scand 1993;88:23 31.
17. Gustafsson C, Britton M. Pathogenetic mechanism of stroke in non-valvular atrial fibrillation: Follow-up of stroke patients with and without atrial fibrillation. J Intern Med 1991;230:11 16.
18. Bogousslavsky J, Adnet-Bonte C, Regli F, van Melle G; Kappenberger L. Lone atrial fibrillation and stroke. Acta Neural Scand 1990;82:143 146.
19. Yamanouchi H, Shimada H, Tomonaga M, Matsushita S. Recurrence of embolic stroke in non-valvular atrial fibrillation (NVAF): An autopsy study. Acta Neural Scand 1989; 80:123 129.
20. Kelley RE, Berger JR, Alter M, Kovacs AG. Cerebral ischemia and atrial fibrillation: Prospective study. Neurology 1984;34:1285 1291.
21. Wolf PA, Kannel WB, McGee DL, Meeks SL, Bharucha NE, McNamara PM. Duration of atrial fibrillation and imminence stroke: The Framingham study. Stroke 1983;14:664 667.
22. Sage JI, Van Uitert RL. Risk of recurrent stroke in patients with atrial fibrillation and non-valvular heart disease. Stroke 1983;14:537 540.
23. Hart RG, Coull BM, Hart D. Early recurrent embolism associated with nonvalvular atrial fibrillation: A retrospective study. Stroke 1983;14:688 693.
24. Sherman DG, Goldman L, Whiting RB, Jurgensen K, Kaste M, Easton JD. Thromboembolism in patients with atrial fibrillation. Arch Neural 1984;41:708 710.
25. European Atrial Fibrillation Trial Study Group. Secondary prevention of vascular events in patients with nonrheumatic atrial fibrillation and recent transient ischemic attack or minor ischemic stroke. Lancet 1993;342:1255 1262.
26. Diener HC, Forbes C, Riekkinin PJ, Sivenius J, Smets P, Lowenthal A. European stroke Prevention Study II: Efficacy and safety data. J Neural Sci 1997;151:S13-S17.
27. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: The Stroke Prevention in Atrial Fibrillation III randomized clinical trial. Lancet 1996;348:633 638.
28. Hart RG, Sherman DG, Easton JD, Cairns JA. Prevention of stroke in patients with nonvalvular atrial fibrillation: Views and reviews. Neurology 1998;51:674 681.
29. The SPAFF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin. JAMA 1998;279:1273 1277.
30. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of anti-thrombotics therapy in atrial fibrillation: An analysis of pooled data from five randomized control trials. Arch Intern Med 1994;154:1449 1457.
31. Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention Atrial Fibrillation II Study. Lancet 1994;343:687 691.
32. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: A major contributor to stroke in the elderly. Arch Intern Med 1987;147:1561 1564.
33. Petersen P. Thromboembolic complications in atrial fibrillation. Stroke 1990;21:4 13.
34. Woolfenden AR, Albers GW. Cardioembolic stroke. In: Fisher M, Bogousslavsky J, eds. Current Review of Cerebrovascular Disease. Philadelphia: Current Medicine, 1999:93 105.
35. The stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Transesophageal echocardiographic correlates of thromboembolism in highrisk patients with nonvalvular atrial fibrillation. Ann Intern Med 1998;128:639 647.
P.173
36. Souvik S, Oppenheimer SM. Cardiac disorders and stroke. Curr Opin Neurol 1998; 11: 51 56.
37. Shively BK, Gelgland EA, Crawford MH. Regional left atrial stasis during atrial fibrillation and flutter. J Am Coll Cardiol 1996;27:1722 1729.
38. Chimowitz MI, De Georgia MA, Poole RM, Hepner A, Armstrong WM. Left atrial spontaneous echo contrast highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke 1993;24:1015 1019.
39. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Transesophageal echocardiographic correlates of thromboembolism in highrisk patients with nonvalvular atrial fibrillation. Ann Intern Med 1998; 128:639 647.
40. Mugge A, Kuhn H, Daniel WG. The role of transesophageal echocardiography in the detection of left atrial thrombi. Echocardiography 1993;10:405 417.
41. European Atrial Fibrillation Trial Study Group. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med 1995;333:5 10.
42. Diener HC, Lowenthal A. Antiplatelet therapy to prevent stroke: Risk of brain hemorrhage and efficacy in atrial fibrillation. J Neurol Sci 1997;153:112.
43. Morocutti C, Amabile G, Fattapposta F, et al. for the SIFA (Studio Italiano Fibrillazione Atriale) Investigators: Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. Stroke 1997;28:1015 1021.
44. Wood KA, Eisenberg SI, Kalman JM, et al. Risk of thromboembolism in chronic atrial flutter. Am J Cardiol 1997;79:1043 1047.
45. Mattioli AV, Castellani ET, Fusco C, Mattioli G. Stroke in paced patients with sick sinus syndrome: Relevance of atrial mechanical function, pacing mode and clinical characteristics. Cardiology 1997;88:264 270.
46. Harvey JR, Teague SM, Anderson JL, Voyles WF, Thadani U. Clinically silent atrial septal defects with evidence for cerebral embolization. Ann Intern Med 1986;105: 695 697.
47. Lechat PH, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N EnglJ Med 1988;318:1148 1152.
48. Webster MWI, Chancellor AM, Smith HJ, et al. Patent foramen ovale in young stroke patients. Lancet 1988;2:11 12.
49. Biller J, Adams HP Jr, Johnson MR, Kerber RE, Toffol GJ. Paradoxical cerebral embolism: Eight cases. Neurology 1986;36:1356 1360.
50. Jeanrenaud X, Bogousslavsky J, Stauffer JC, Payot M, Regli F, Kappenberger L. Foramen ovale permeable et infarctus cErEbral du sujet jeune. Schweiz Med Wochenschr 1990; 120:823 829.
51. Jeanrenaud X, Kappenberger L. Patent foramen ovale and stroke of unknown origin. Cerebrovasc Dis 1991;1:184 192.
52. Gautier JC, Diirr A, Koussa S, Lascault G, Grosgogeat Y. Paradoxical cerebral embolism with a patent foramen ovale. Cerebrovasc Dis 1991;: 193 202.
53. De Belder MA, Tourikis L, Leech G, Camm AJ. Risk of patent foramen ovale for thromboembolic events in all age groups. Am J Cardiol 1992;63:1316 1320.
54. Di Tullio M, Sacco RL, Gopal A, Mohr JP, Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992; 17:461 65.
55. Daniel WG. Transcatheter closure of patent foramen ovale: Therapeutic overkill or elegant management for selected patients at risk? Circulation 1992;86:2013 2015.
56. Ranoux D, Cohen A, Cabanes L, Amarenco P, Bousser MG, Mas JL. Patent foramen ovale: Is stroke due to paradoxical embolism? Stroke 1993;24:31 34.
P.174
57. Bogousslavsky J, Garazi S, Jeanrenaud X, Aebischer N, van Melle G. Stroke recurrence in patients with patent foramen ovale: The Lausanne Study, Lausanne Stroke with Paradoxal embolism Study Group. Neurology 1996;46:1301 1305.
58. Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm or both and cryptogenic stroke transient ischemic attack: French Study Group on Patent Foramen Ovale an Atrial Septal Aneurysm. Am Heart J 1995;130:1083 1088.
59. Homma S, Di Tullio MR, Sacco RL, Mihalatos D, Li Mandri G, Mohr JP. Characteristics of patent foramen ovale associated with cryptogenic stroke: A biplane transesophageal echocardiographic study. Stroke 1994;25:582 586.
60. Stone DA, Godard J, Coretti MC, Kittner SJ, Sample C, Price TR, Plotnick GD. Patent foramen ovale: Association between the degree of shunt by contrast transesophageal echocardiography and the risk of future ischemic neurologic events. Am Heart J 1996;131:158 161.
61. Hausmann D, Miigge A, Daniel WG. Identification of patent foramen ovale permitting paradoxic embolism. J Am Coll Cardiol 1995;26:1030 1038.
62. Steiner MM, Di Tullio MR, Rundek T, Gan R, Chen X, Liguori C, Brainin M, Homma S, Sacco RL. Patent foramen ovale size and embolic brain imaging findings among patients with ischemic stroke. Stroke 1998;29:944 948.
63. Nendaz MR, Sarasin FP, Junod AF, Bogousslavsky J. Preventing stroke recurrence in patients with patent oframen ovale: Antithrombotic therapy, foramen closure or therapeutic abstention? A decision analytic perspective. Am Heart J 1998;135:532 541.
64. Devuyst G, Despland PA, Bogousslavsky J, Regli F. Complementarity of contrast transcranial Doppler and contrast transesophageal echocardiography for the detection of patent foramen ovale in stroke patients. Eur Neurol 1997;38:21 25.
65. Harvey JR, Teague SM, Anderson JL, Voyles WF, Thadani U. Clinically silent atrial septal defects with evidence for cerebral embolization. Ann Intern Med 1986;105: 695 697.
66. Homma S, Di Tullio MR, Sacco RL, et al. Surgical closure of patent foramen ovale in selected patients with cryptogenic stroke: A preliminary experience (abstract). Stroke 1995;26:172.
67. Devuyst G, Bogousslavsky J, Ruchat P, Jeanrenaud X, Despland PA, Regli F, Aebischer N, Karpuz HM, Castillo V, Guffi M, Sadeghi H. Prognosis after stroke followed by surgical closure of patent foramen ovale: A prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler ultrasound. Neurology 1996;47:1162 1166.
68. Homma S, Di Tullio MR, Sacco RL, Sciacca RR, Smith C, Mohr JP. Surgical closure of patent foramen ovale in cryptogenic stroke patients. Stroke 1997;28(12):2376 2381.
69. Bridges ND, Hellenbrand W, Latson L, Filiano J, Newburger JW, Lock JE. Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. Circulation 1992;86:1902 1908.
70. Geiser T, Sturifenegger M, Genewein U, Haeberli A, Beer JH. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles inpatients with prosthetic heart valves. Stroke 1998;29:1770 1777.
71. Devuyst G. New trends in neurosonology. In: Fisher M, Bogousslavsky J. Current Review of Cerebrovascular Disease. Philadelphia: Current Medicine, 1999;65 76.
72. Deklunder G, Roussel M, Lecroart JL, Prat A, Gautier C. Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves. Stroke 1998;29:1821 1826.
P.175
73. Cannegieter SC, Rosendaar FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 1994;89:635 641.
74. Stein PD, Grandison D, Hua TA, et al. Therapeutic level of oral anticoagulation with warfarin in patients with mechanical heart valves: Review of literature and recommendations based on international normalzed ration. Postgrad Med 1994;70(suppl 1): S72-S83.
75. Horstkotte D, Schulte HD, Bircks W, Strauer BE. Lower intensity anticoagulation therapy results in lower complications rates with St. Jude medical prosthesis. J Thome Cardiovasc Surg 1994;107:1136 1145.
76. Cannegieter SC, Rosendaal FR, Wintzen AR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995;333:11 17.
77. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heart valves. N Engl J Med 1996; 335:407 16.
78. Captell E, Fiore LD, Brophy MT, et al. Efficacy and safety of combined anticoagulant and antiplatelet therapy versus anticoagulant monotherapy after mechanical heartvalve replacement: A meta-analysis. Am Heart J 1995; 130:547 552.
79. Sloan MA, Gore JM. Ischemic stroke and intracranial hemorrhage following thrombolytic therapy for acute myocardial infarction: A risk-benefit analysis. Am J Cardiol 1992;69:21A-38A.
80. Tanne D, Reicher-Reiss H, Boyko V, Behar S, for the SPRINT Study Group: Stroke risk after anterior wall acute myocardial infarction. Am J Cardiol 1995;76:825 826.
81. Mooe T, Eriksson P, Stegmayr B. Ischemic stroke after acute myocardial infarction: A population-based study. Stroke 1997;28:762 767.
82. Anticoagulants in the Secondary Prevention of Events Coronary Thrombosis (ASPECT) Research Group. Effective long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994;343:499 503.
EAN: 2147483647
Pages: 23