- Email: [email protected]
Nonvalvular atrial fibrillation
The benefit of long-term anticoagulation in the prevention of recurrent cerebral embolism associated with some types of heart disease is well established. While it is conventional wisdom that unexplained stroke in young adults rarely recurs, this is contrary to our experience. We believe that the prognosis is not benign (Table 15). Oral contraceptive use should be permanently discontinued. In patients with migraine headache and stroke of uncertain etiology, oral contraceptives, and probably ergot preparations, should be avoided. We have used long-term platelet antiaggregation agents in migraine patients with ischemic stroke based on reports of abnormal platelet aggregability. The importance of a thorough diagnostic evaluation to establish a cause for stroke in the young cannot be overemphasized? as it may allow for a specific treatment to prevent a recurrent stroke. b M.A. ENG1.E: The technique of digital subtraction angiography with injection into a peripheral vein may be safer than cardiac catheterization in this setting and may provide similar information of diagnostic importance.
NONVALVULAR
ATRIAL
FIBRILLATION
Atria1 fibrillation is the commonest sustained cardiac dysrhythmia occurring in man.lgl This dysrhythmia increases in prevalence with advancing age, so that 2%~5% of the general population over age 60 years have AF.lg2-lg6 Patients with NVAF have approximately the same stroke risk (6%/year) as patients who experience a TIA (see Table 6, Part I). As a group, patients with AF frequently have other forms of cardiovascular disease that either cause or accompany the atria1 dysrhythmia. Hypertension is present in roughly half of patients with AF.lg6 Rheumatic valvular disease and ischemic heart disease are the next most frequently identified cardiovascular disorders. From TABLE
~~.--Pw~~~;usIs
\ITTIIOR Hindfelt and Nilsson’h’ Snyder and Ramirez-Lassepas’” Grindal et al.‘“’ Jackson et al.lkti* Hart et a1.14’ “‘) “Subgroup ocardiography: ..I
IN CEREBRAL IN YOUNG
INFARCTION ADULTS
OF‘ I;KGSKAI~
N
'i RECURRICNT
34 20 ? 30 13
3 15 4 17 23
ETIOLUG'~-
MEAN FOLLOW-VI' (months)
of patients with mitral valve prolapse as determined 634 received antiplatelet agents or anticoagulants.
51 36 31 49 42 by ech
53
10% to 30% of patients with AF have no clinically identifiable cardiovascular disease and thus have “isolated” or “lone” AF.~~~, lg6 The remaining patients have a variety of disorders accounting for the AF, including thyrotoxicosis, cardiomyopathy, pericarditis and trauma. Some of these presumed “causes” of AF, e.g., hypertension and ischemic heart disease, are common in the older population, and one must be cautious in assuming a cause-and-effect relationship. Likewise, the occurrence of a cerebral infarction in AF patients may at times be incorrectly attributed to an embolus from the left atrium when in fact the ischemic event resulted from cerebrovascular disease which often coexists with AF in elderly, hypertensive patients. It is not clear exactly how frequently thrombi form in the left atrium of patients with NVAF. Autopsy studies have revealed left atria1 thrombus in 13%~50% of patients with NVAF.‘g7~‘gg In many institutions the routine autopsy practice of vigorously irrigating the heart to dispel postmortem clots can dislodge all but the most adherent thrombi, resulting in underdetection of atria1 thrombi. The most common site for left atria1 thrombi to form in NVAF patients is in the auricular appendage rather than on the atria1 wall (about 75% of the left atria1 thrombi are in the appendage).lg7, 2oo This is in contrast to valvular heart disease, where atria1 thrombi are about equally distributed between the atria1 wall and the appendage. One third of patients with valvular heart disease have atria1 thrombi at autopsy.lg7 Some authors maintain that left atria1 thrombi are present only in patients with mitral stenosis.201 Figures describing the frequency of atria1 thrombi represent minimal occurrence not only because of the possibility of missing clots at autopsy, but also because of the likelihood that some thrombi may have embolized into the systemic circulation or resolved, either spontaneously or during anticoagulant therapy. A number of factors have been postulated as being important in the genesis of atria1 thrombus in the presence of AF. The fact that they are more frequent in the presence of valvular disease suggests that increased left atria1 ressure and outflow obstruction may be important factors.1g7, ! O1 Obstruction at the mitral valve fosters left atria1 stasis, as does AF itself. Left atria1 enlargement is usually the result of, rather than the cause of AF, especially in NVAF. Left atria1 size increases with the duration of AF, as does the incidence of atria1 thrombus.“’ Diseases of the atria1 endothelial surface may also be an important factor in the genesis of AF and thrombus formation. Myocardial infarction, rheumatic endocarditis, and pericarditis may involve the sinoatrial node and produce AF. In addition, these disorders may produce a surface that promotes thrombosis. This endothelial damage may explain the greater occurrence of atria1 wall thrombi in rheumatic heart disease and in acute MI, in con54
trast to the NVAF.l97-1%
predominance
of appendage
thrombi
in chronic
AF is a substantial risk factor for stroke. From 10% to 20% of all patients with strokes have AF.202-206 The frequency with which one finds AF depends on the population being studied. General population surveys tabulating all types of cerebral vascular disease, i.e., TIA, subarachnoid and intracerebral hemorrhage, and hemispheric and brain stem infarction, reveal smaller proportions of patients with AF.202, 206, 207 Studies limited to ischemic cerebral hemisphere infarctions, excluding transient and brain stem ischemic e isodes, produce higher proporB tions of patients with AF.203. 2o,5, O8 More than one third of all AF patients have evidence of systemic embolism at autopsy.20g Some 20%-35% of all patients with AF suffer clinical embolic events during life,35’ 2o with a risk of stroke more than six times that of the general population.“07 The group of patients at greatest risk are those with AF and rheumatic valvular disease. These patients have a 17-fold increase in the risk for systemic embolism.207 In a study by Hinton et al., 41% of patients with rheumatic valvular disease had evidence of systemic embolism at autopsy.20g While patients with rheumatic valvular disease are at greatest risk for embolism, they account for less than one fourth of all patients with AF. The larger group of patients, those with NVAF, constitute the vast majority.210 Clinical and autopsy studies show that 35% of patients with NVAF will experience systemic embolism.20g~ 211 Epidemiologic studies show a sixfold increase in stroke risk associated with NVAF.207 In patients with “idiopathic” AF, 7% sustain an embolus within the first year and 14% do so within 5 years of identification of the dysrhythmia.210 Patients with NVAF commonly have other forms of vascular disease that predispose to stroke in the absence of AF. In a study of data from the Harvard Stroke Registry, it was estimated that of the patients with AF who had a stroke, three fourths probably had stroke on the basis of a cardiogenic embolus, with stroke in the remainder being due to cerebrovascular disease.206 Others have estimated that as many as one third of ischemic strokes in NVAF patients are due to concomitant cerebrovascular disease.26 Data from the Framingham Study suggest that AF is the important risk factor and that other cardiovascular risk factors are as common in control patients as in those with AF.207 Certainly not every patient with AF and a stroke has experienced an embolus from the left atrium. Some have atherosclerotic occlusive cerebrovascular disease, hypertensive hemorrhages, or lacunar infarctions. The clinical and radiologic findings may be helpful in separating patients with a cardiogenic embolus from those with other causes for their brain ischemia (see Part I). Another unresolved issue is whether there is a particularly 55
vulnerable period for the occurrence of an embolus in the course of AF. Clinical evidence suggests that emboli may occur with particular frequency in th;iOmzonhs immediately following the Patients who are identified as onset of this dysrhythmia. ’ having sustained AF are more likely to have had a stroke prior to the onset of AF than matched controls.rg6 One explanation for this curious observation is that unrecognized episodes of pares ysmal AF which precede sustained AF are associated with the formation of left atria1 thrombi that embolize either during the period of AF or at the time of spontaneous reversion to normal sinus rhythm.213 Chronic AF is frequently preceded by paroxysms of AF. The Framingham Study found that AF is intermittent in at least 25% of cases.lg6 A survey of more than 3,000 life insurance applicants with AF revealed that in this population, 90% had paroxysmal AF.214 Takahashi et al. found that 40% of all AF patients have paroxysmal AF, with chronic sustained AF beins most common in patients with rheumatic valvular disease. l5 The risk of embolism in paroxysmal AF is noted in patients with NVAF associated with thyrotoxicosis.216 Thromboembolic events occurred in 40% of those patients, and two thirds of patients with emboli had paroxysmal rather than sustained AF. One can speculate that with the onset of AF, and stasis within the left atrium, thrombus is most apt to dislodge early, when the clot is still friable and unorganized. Certainly it is most common for the AF and the stroke to be identified simultaneously or within a few days of one another.35’ 211 The importance of a changing rhythm in the genesis of systemic embolism is also suggested by the observation that approximately 2% of patients undergoing cardioversion experience an embolus in the first few days following conversion from AF to normal sinus rhythm.217 Although the Framingham Study data were interpreted as showing no particularly vulnerable period for stroke associated with NVAF, 4 of 20 events occurred in 78 patients within the initial 6 months, for a rate of 102 events per 1,000 patient-years, compared to 36 events per 1,000 patients-years occurring after 6 months,207 In Fisher’s clinical study, 27% of the AF-associated strokes occurred within 6 months of the diagnosis of AF.35 In Hinton et al’s autopsy study of 333 AF patients, there were three embolic events in 40 patients with AF of less than 3 weeks’ duration, an extrapolated incidence of 100% per year.20g These data also suggest that the embolism rate is highest early after the onset of the rhythm disturbance. Recurrence of thromboembolism is frequent. Up to 50% of patients with one embolism eventually sustain another embolic event.35’ lg7, 218,21g The period of greatest vulnerability for recurrence is within the first days and weeks following an embolus. Approximately 15% of patients experience recurrence within 2 \veeks,‘)% 26 ‘b$i,‘! 1 56
The clinical features of cardiogenic embolus have been outlined previously (see Part I). Systemic emboli arising from the left atrium in AF tend to produce large and disabling infarcts. Studies comparing the size and severity of infarctions produced by thrombotic and embolic mechanisms have consistently shown that large and fatal infarctions occur more often with embolism associated with NVAF than with other causes of stroke.220’ 221 About one third of patients with cerebral emboli from AF die within the first few weeks of their embolus.359 222*223 Death or severe disability can be anticipated in 50%-70% of atients who sustain a cerebral embolus in association with AF. 3! ’ 211*224 A reliable noninvasive method of identifying left atria1 thrombi in patients with AF and suspected embolism is needed. Echocardiography is useful in documenting the size of the left atrium but has not proved to be consistently reliable in identifying left atria1 clots. Two-dimensional echocardiography can identify large thrombi within the left atria1 body. These large thrombi are most commonly seen in patients with mitral stenosis. However, in patients with NVAF, clots form within the left atria1 appendage half of the time. Thrombi in this location are much more difficult to identify. Lovett et al. found only one left atria1 thrombus on two-dimensional echocardio aphy in 21 patients with NVAF and suspected embolism. 22’Riser and colleagues found that two-dimensional echocardiography was only 50% sensitive when a group of 93 patients were examined at surgery or autopsy for intracardiac thrombi following echocardiography.226 They also noted that if one cardiologist interpreted an echocardiogram as showing a thrombus, there was only a 50% chance that a second cardiologist would confirm the interpretation. Other investigators have suggested that CT of the heart may prove to be more valuable than echocardiography in identifying left atria1 thrombi.227 Prevention of embolic stroke in NVAF patients is difficult. The patients are usually fully functional prior to their stroke, the stroke is unheralded by warning TIAs, and it typically results in major and permanent morbidity.35 The aver;ge3Fatient is 70 years old and the majority are hypertensive. ’ Aside from correcting the hypertension, and the AF whenever possible, the only specific treatment that is generally considered for patients with NVAF is anticoagulation. There are no data proving that anticoagulation prevents stroke in patients with NVAF, and usually these patients have not been prophylactically anticoagulated. There are, however, good data to support the value of anticoagulation in the prevention of cardiogenic cerebral embolism in patients with rheumatic heart disease and acute MI (see next section).22 There is no information about the value of platelet antiaggregation agents in lowering the embolic stroke rate in AF patients. 4t present, there are no ancillary investigations (e.g., echocar57
diography, CT of the left atrium) to reliably identify subgroups of NVAF patients at special risk for embolic stroke. Two-dimensional echocardiography accurately determines left atria1 size but it may not show thrombi within the atrium. Figure 12 demonstrates a left atria1 thrombus in a patient with NVAF, a cerebral embolus, and a two-dimensional echocardiogram that showed an enlarged left atrium, but no thrombus. In the absence of direct data, we are inclined to extrapolate treatment outcomes of other cardiogenic cerebral embolism patients and use anticoagulation to prevent stroke in NVAF patients. Since AF has the same warning implications for stroke as TIA does (approximately 6% of patients with both disorders experience a stroke each year), we treat such patients vigorously. If they are in generally good health and have no relative contraindications to anticoagulation therapy, we recommend permanent anticoagulation in the mild to moderate range (prothrombin time of 1.5-2.0 times control). If the patient has one or more relative contraindications to anticoagulation, we empirically recommend antiplatelet aggregation therapy. If a patient with NVAF presents with a proved left atria1 thrombus or has experienced an acute cerebral embolism, heparin and coumarin anticoagulation are started immediately in the manner outlined for acute MI patients (see next section). Permanent oral anticoagulation is then recommended. Fig 12.-Computed tomogram of the heart showing left atrial thrombus. A 60year-old man with chronic, nonvalvular atrial fibrillation developed sudden hemiplegia. A two-dimensional echocardiogram did not show atrial thrombus; cardiac CT demonstrated a 2-cm thrombus (arrow) in the left atrium.
In summary, there are a large number of patients with NVAF, and they have a high stroke rate, resulting largely from emboli from the left atrium. The strokes that occur in these patients are frequently devastating and appear without warning. Consequently, the primary treatment must be preventive. We have become liberal in our recommendation that many of these NVAF patients be prophylactically anticnagulated against stroke. A prospective, randomized study comparing the risks and benefits of anticoagulant versus placebo in these patients is needed. ACUTE MYOCARDIAL AND PREVENTION
INFARCTION:
STROKE OCCURRENCE
Approximately 95% of the mort,ality following MI is attributable to electrical or pump failure. Nevertheless. a small percentage of deaths result from pulmonary and systemic arterial embolism. In addition,. cerebral infarction in this setting contributes to disability in MI survivors. While some of the strokes that occur in the days and weeks following an MI are undoubtedly caused by cerebral artery thrombosis due to atherosclerosis, the majority appear to be caused by emboli arising from the left heart, mostly from left ventricular mural thrombi WI’).
LEFT VENTRICULARMURALTHROMBI It is well known that MI causes ventricular mural thrombi to form which may then break away to become emboli in the arterial circulation. Cumulative data from several reports indicate that approximately 45% (ran~~Lsl~%-83%) of lethal MIS have associated mural thrombi.221’ Some authors report the clinical incidence of peripheral emboli following acute MI to be as low as 2%-3%, and cerebral emboli in lo%-90% of them. Other studies on autopsied patients with MI have shown peripheral infarcts, presumably embolic, in 45%234 to 60%,22g with approximately half being cerebral. Although the very high incidence was seen in patients who died and in whom the diagnosis was made by a careful search for infarcts at autopsy, it is clear that the incidence is substantial in this very common cardiac disease. Asymptomatic emboli must be common, perhaps two to three times as common as symptomatic ones. Overall, it appears that peripheral arterial embolism occurs clinically in approximately 3%-5% of acute MI patients, and the majority of these clinically apparent emboli are cerebra1.234-23g Of considerable importance is the time of occurrence of cere!lral rmboli after an acute MI Bean’“” found that 113 occur in
59
NONVALVULAR
ATRIAL
FIBRILLATION
Atria1 fibrillation is the commonest sustained cardiac dysrhythmia occurring in man.lgl This dysrhythmia increases in prevalence with advancing age, so that 2%~5% of the general population over age 60 years have AF.lg2-lg6 Patients with NVAF have approximately the same stroke risk (6%/year) as patients who experience a TIA (see Table 6, Part I). As a group, patients with AF frequently have other forms of cardiovascular disease that either cause or accompany the atria1 dysrhythmia. Hypertension is present in roughly half of patients with AF.lg6 Rheumatic valvular disease and ischemic heart disease are the next most frequently identified cardiovascular disorders. From TABLE
~~.--Pw~~~;usIs
\ITTIIOR Hindfelt and Nilsson’h’ Snyder and Ramirez-Lassepas’” Grindal et al.‘“’ Jackson et al.lkti* Hart et a1.14’ “‘) “Subgroup ocardiography: ..I
IN CEREBRAL IN YOUNG
INFARCTION ADULTS
OF‘ I;KGSKAI~
N
'i RECURRICNT
34 20 ? 30 13
3 15 4 17 23
ETIOLUG'~-
MEAN FOLLOW-VI' (months)
of patients with mitral valve prolapse as determined 634 received antiplatelet agents or anticoagulants.
51 36 31 49 42 by ech
53
10% to 30% of patients with AF have no clinically identifiable cardiovascular disease and thus have “isolated” or “lone” AF.~~~, lg6 The remaining patients have a variety of disorders accounting for the AF, including thyrotoxicosis, cardiomyopathy, pericarditis and trauma. Some of these presumed “causes” of AF, e.g., hypertension and ischemic heart disease, are common in the older population, and one must be cautious in assuming a cause-and-effect relationship. Likewise, the occurrence of a cerebral infarction in AF patients may at times be incorrectly attributed to an embolus from the left atrium when in fact the ischemic event resulted from cerebrovascular disease which often coexists with AF in elderly, hypertensive patients. It is not clear exactly how frequently thrombi form in the left atrium of patients with NVAF. Autopsy studies have revealed left atria1 thrombus in 13%~50% of patients with NVAF.‘g7~‘gg In many institutions the routine autopsy practice of vigorously irrigating the heart to dispel postmortem clots can dislodge all but the most adherent thrombi, resulting in underdetection of atria1 thrombi. The most common site for left atria1 thrombi to form in NVAF patients is in the auricular appendage rather than on the atria1 wall (about 75% of the left atria1 thrombi are in the appendage).lg7, 2oo This is in contrast to valvular heart disease, where atria1 thrombi are about equally distributed between the atria1 wall and the appendage. One third of patients with valvular heart disease have atria1 thrombi at autopsy.lg7 Some authors maintain that left atria1 thrombi are present only in patients with mitral stenosis.201 Figures describing the frequency of atria1 thrombi represent minimal occurrence not only because of the possibility of missing clots at autopsy, but also because of the likelihood that some thrombi may have embolized into the systemic circulation or resolved, either spontaneously or during anticoagulant therapy. A number of factors have been postulated as being important in the genesis of atria1 thrombus in the presence of AF. The fact that they are more frequent in the presence of valvular disease suggests that increased left atria1 ressure and outflow obstruction may be important factors.1g7, ! O1 Obstruction at the mitral valve fosters left atria1 stasis, as does AF itself. Left atria1 enlargement is usually the result of, rather than the cause of AF, especially in NVAF. Left atria1 size increases with the duration of AF, as does the incidence of atria1 thrombus.“’ Diseases of the atria1 endothelial surface may also be an important factor in the genesis of AF and thrombus formation. Myocardial infarction, rheumatic endocarditis, and pericarditis may involve the sinoatrial node and produce AF. In addition, these disorders may produce a surface that promotes thrombosis. This endothelial damage may explain the greater occurrence of atria1 wall thrombi in rheumatic heart disease and in acute MI, in con54
trast to the NVAF.l97-1%
predominance
of appendage
thrombi
in chronic
AF is a substantial risk factor for stroke. From 10% to 20% of all patients with strokes have AF.202-206 The frequency with which one finds AF depends on the population being studied. General population surveys tabulating all types of cerebral vascular disease, i.e., TIA, subarachnoid and intracerebral hemorrhage, and hemispheric and brain stem infarction, reveal smaller proportions of patients with AF.202, 206, 207 Studies limited to ischemic cerebral hemisphere infarctions, excluding transient and brain stem ischemic e isodes, produce higher proporB tions of patients with AF.203. 2o,5, O8 More than one third of all AF patients have evidence of systemic embolism at autopsy.20g Some 20%-35% of all patients with AF suffer clinical embolic events during life,35’ 2o with a risk of stroke more than six times that of the general population.“07 The group of patients at greatest risk are those with AF and rheumatic valvular disease. These patients have a 17-fold increase in the risk for systemic embolism.207 In a study by Hinton et al., 41% of patients with rheumatic valvular disease had evidence of systemic embolism at autopsy.20g While patients with rheumatic valvular disease are at greatest risk for embolism, they account for less than one fourth of all patients with AF. The larger group of patients, those with NVAF, constitute the vast majority.210 Clinical and autopsy studies show that 35% of patients with NVAF will experience systemic embolism.20g~ 211 Epidemiologic studies show a sixfold increase in stroke risk associated with NVAF.207 In patients with “idiopathic” AF, 7% sustain an embolus within the first year and 14% do so within 5 years of identification of the dysrhythmia.210 Patients with NVAF commonly have other forms of vascular disease that predispose to stroke in the absence of AF. In a study of data from the Harvard Stroke Registry, it was estimated that of the patients with AF who had a stroke, three fourths probably had stroke on the basis of a cardiogenic embolus, with stroke in the remainder being due to cerebrovascular disease.206 Others have estimated that as many as one third of ischemic strokes in NVAF patients are due to concomitant cerebrovascular disease.26 Data from the Framingham Study suggest that AF is the important risk factor and that other cardiovascular risk factors are as common in control patients as in those with AF.207 Certainly not every patient with AF and a stroke has experienced an embolus from the left atrium. Some have atherosclerotic occlusive cerebrovascular disease, hypertensive hemorrhages, or lacunar infarctions. The clinical and radiologic findings may be helpful in separating patients with a cardiogenic embolus from those with other causes for their brain ischemia (see Part I). Another unresolved issue is whether there is a particularly 55
vulnerable period for the occurrence of an embolus in the course of AF. Clinical evidence suggests that emboli may occur with particular frequency in th;iOmzonhs immediately following the Patients who are identified as onset of this dysrhythmia. ’ having sustained AF are more likely to have had a stroke prior to the onset of AF than matched controls.rg6 One explanation for this curious observation is that unrecognized episodes of pares ysmal AF which precede sustained AF are associated with the formation of left atria1 thrombi that embolize either during the period of AF or at the time of spontaneous reversion to normal sinus rhythm.213 Chronic AF is frequently preceded by paroxysms of AF. The Framingham Study found that AF is intermittent in at least 25% of cases.lg6 A survey of more than 3,000 life insurance applicants with AF revealed that in this population, 90% had paroxysmal AF.214 Takahashi et al. found that 40% of all AF patients have paroxysmal AF, with chronic sustained AF beins most common in patients with rheumatic valvular disease. l5 The risk of embolism in paroxysmal AF is noted in patients with NVAF associated with thyrotoxicosis.216 Thromboembolic events occurred in 40% of those patients, and two thirds of patients with emboli had paroxysmal rather than sustained AF. One can speculate that with the onset of AF, and stasis within the left atrium, thrombus is most apt to dislodge early, when the clot is still friable and unorganized. Certainly it is most common for the AF and the stroke to be identified simultaneously or within a few days of one another.35’ 211 The importance of a changing rhythm in the genesis of systemic embolism is also suggested by the observation that approximately 2% of patients undergoing cardioversion experience an embolus in the first few days following conversion from AF to normal sinus rhythm.217 Although the Framingham Study data were interpreted as showing no particularly vulnerable period for stroke associated with NVAF, 4 of 20 events occurred in 78 patients within the initial 6 months, for a rate of 102 events per 1,000 patient-years, compared to 36 events per 1,000 patients-years occurring after 6 months,207 In Fisher’s clinical study, 27% of the AF-associated strokes occurred within 6 months of the diagnosis of AF.35 In Hinton et al’s autopsy study of 333 AF patients, there were three embolic events in 40 patients with AF of less than 3 weeks’ duration, an extrapolated incidence of 100% per year.20g These data also suggest that the embolism rate is highest early after the onset of the rhythm disturbance. Recurrence of thromboembolism is frequent. Up to 50% of patients with one embolism eventually sustain another embolic event.35’ lg7, 218,21g The period of greatest vulnerability for recurrence is within the first days and weeks following an embolus. Approximately 15% of patients experience recurrence within 2 \veeks,‘)% 26 ‘b$i,‘! 1 56
The clinical features of cardiogenic embolus have been outlined previously (see Part I). Systemic emboli arising from the left atrium in AF tend to produce large and disabling infarcts. Studies comparing the size and severity of infarctions produced by thrombotic and embolic mechanisms have consistently shown that large and fatal infarctions occur more often with embolism associated with NVAF than with other causes of stroke.220’ 221 About one third of patients with cerebral emboli from AF die within the first few weeks of their embolus.359 222*223 Death or severe disability can be anticipated in 50%-70% of atients who sustain a cerebral embolus in association with AF. 3! ’ 211*224 A reliable noninvasive method of identifying left atria1 thrombi in patients with AF and suspected embolism is needed. Echocardiography is useful in documenting the size of the left atrium but has not proved to be consistently reliable in identifying left atria1 clots. Two-dimensional echocardiography can identify large thrombi within the left atria1 body. These large thrombi are most commonly seen in patients with mitral stenosis. However, in patients with NVAF, clots form within the left atria1 appendage half of the time. Thrombi in this location are much more difficult to identify. Lovett et al. found only one left atria1 thrombus on two-dimensional echocardio aphy in 21 patients with NVAF and suspected embolism. 22’Riser and colleagues found that two-dimensional echocardiography was only 50% sensitive when a group of 93 patients were examined at surgery or autopsy for intracardiac thrombi following echocardiography.226 They also noted that if one cardiologist interpreted an echocardiogram as showing a thrombus, there was only a 50% chance that a second cardiologist would confirm the interpretation. Other investigators have suggested that CT of the heart may prove to be more valuable than echocardiography in identifying left atria1 thrombi.227 Prevention of embolic stroke in NVAF patients is difficult. The patients are usually fully functional prior to their stroke, the stroke is unheralded by warning TIAs, and it typically results in major and permanent morbidity.35 The aver;ge3Fatient is 70 years old and the majority are hypertensive. ’ Aside from correcting the hypertension, and the AF whenever possible, the only specific treatment that is generally considered for patients with NVAF is anticoagulation. There are no data proving that anticoagulation prevents stroke in patients with NVAF, and usually these patients have not been prophylactically anticoagulated. There are, however, good data to support the value of anticoagulation in the prevention of cardiogenic cerebral embolism in patients with rheumatic heart disease and acute MI (see next section).22 There is no information about the value of platelet antiaggregation agents in lowering the embolic stroke rate in AF patients. 4t present, there are no ancillary investigations (e.g., echocar57
diography, CT of the left atrium) to reliably identify subgroups of NVAF patients at special risk for embolic stroke. Two-dimensional echocardiography accurately determines left atria1 size but it may not show thrombi within the atrium. Figure 12 demonstrates a left atria1 thrombus in a patient with NVAF, a cerebral embolus, and a two-dimensional echocardiogram that showed an enlarged left atrium, but no thrombus. In the absence of direct data, we are inclined to extrapolate treatment outcomes of other cardiogenic cerebral embolism patients and use anticoagulation to prevent stroke in NVAF patients. Since AF has the same warning implications for stroke as TIA does (approximately 6% of patients with both disorders experience a stroke each year), we treat such patients vigorously. If they are in generally good health and have no relative contraindications to anticoagulation therapy, we recommend permanent anticoagulation in the mild to moderate range (prothrombin time of 1.5-2.0 times control). If the patient has one or more relative contraindications to anticoagulation, we empirically recommend antiplatelet aggregation therapy. If a patient with NVAF presents with a proved left atria1 thrombus or has experienced an acute cerebral embolism, heparin and coumarin anticoagulation are started immediately in the manner outlined for acute MI patients (see next section). Permanent oral anticoagulation is then recommended. Fig 12.-Computed tomogram of the heart showing left atrial thrombus. A 60year-old man with chronic, nonvalvular atrial fibrillation developed sudden hemiplegia. A two-dimensional echocardiogram did not show atrial thrombus; cardiac CT demonstrated a 2-cm thrombus (arrow) in the left atrium.
In summary, there are a large number of patients with NVAF, and they have a high stroke rate, resulting largely from emboli from the left atrium. The strokes that occur in these patients are frequently devastating and appear without warning. Consequently, the primary treatment must be preventive. We have become liberal in our recommendation that many of these NVAF patients be prophylactically anticnagulated against stroke. A prospective, randomized study comparing the risks and benefits of anticoagulant versus placebo in these patients is needed. ACUTE MYOCARDIAL AND PREVENTION
INFARCTION:
STROKE OCCURRENCE
Approximately 95% of the mort,ality following MI is attributable to electrical or pump failure. Nevertheless. a small percentage of deaths result from pulmonary and systemic arterial embolism. In addition,. cerebral infarction in this setting contributes to disability in MI survivors. While some of the strokes that occur in the days and weeks following an MI are undoubtedly caused by cerebral artery thrombosis due to atherosclerosis, the majority appear to be caused by emboli arising from the left heart, mostly from left ventricular mural thrombi WI’).
LEFT VENTRICULARMURALTHROMBI It is well known that MI causes ventricular mural thrombi to form which may then break away to become emboli in the arterial circulation. Cumulative data from several reports indicate that approximately 45% (ran~~Lsl~%-83%) of lethal MIS have associated mural thrombi.221’ Some authors report the clinical incidence of peripheral emboli following acute MI to be as low as 2%-3%, and cerebral emboli in lo%-90% of them. Other studies on autopsied patients with MI have shown peripheral infarcts, presumably embolic, in 45%234 to 60%,22g with approximately half being cerebral. Although the very high incidence was seen in patients who died and in whom the diagnosis was made by a careful search for infarcts at autopsy, it is clear that the incidence is substantial in this very common cardiac disease. Asymptomatic emboli must be common, perhaps two to three times as common as symptomatic ones. Overall, it appears that peripheral arterial embolism occurs clinically in approximately 3%-5% of acute MI patients, and the majority of these clinically apparent emboli are cerebra1.234-23g Of considerable importance is the time of occurrence of cere!lral rmboli after an acute MI Bean’“” found that 113 occur in
59