Risk for Systemic Embolization of Atrial Fibrillation Without Mitral Stenosis

Henry S. Cabin, MD, K. Soni Clubb, BS, Cynthia Hall, MD, Robin A. Perlmutter, MPH, and Alvan R. Feinstein, MD

trial fibrillation (AF) has often been associated The risk for systemic embolixation was studied in with systemic embolization.*-I’ In studies of ce- 272 patients wlthout mitral stenosis or prosthetic A rebrovascular events, 6 to 23% of strokes have valves who were referred to the echocardlography been attributed to cardiogenic emboli,8~12+13almost half laboratory with atrial fibrillation (AF). During a of which were in patients with AF.‘*Y’~Although it was mean follow-up perfod of 33 months (range artery disease,4thyro- she 14.0 cm, but not by age, hypertension or type toxicosis,* 8 systemic hypertensionl 9 or dilated left of AF (paroxysmal vs chronic). In multivariable atria.*O Patients with AF have seldom been followed, analysis, left atrial size 14.0 cm was the single however,to identify risk factors for subsequentsystemic strongest predkitor of htcreased risk for embolixa- embolization. We present such a study in a consecutive tion (p bruits, previous transient ischemic attacks and results of scansor carotid angiography. If the patient had a peripheral embolic event, the solicited data included results of peripheral angiography and embolectomy, if performed. In patients who died during the follow-up period, the circumstancesof death were appraised.A sudden death without a prior embolic event was not consideredto be an embolic event. The follow-up was consideredadequate if it was > 12 months or if the patient died or had an embolic event From the Yale University School of Medicine, Section of Cardiology,

1112 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65 maining 272 patients who comprised the group under In an embolic risk score constructed from the multi- analysis. variable results, patients were assigned 1 point for each Echocardiography: Echocardiography was done risk factor identified by Cox regression.Life tables for with an HP 77-020 phased array real time echocardio- each risk group were constructed by the Kaplan-Meier gram machine. Left atria1 size was measured from the method and were statistically compared using the gen- M-mode tracing using the American Society of Echo- eralized Savage log-rank test. cardiography standards.*’ Measurements were made at end-systole using leading edge echoes.The atria1 sizes RESULTS measured at the time of the original examination were Of the 272 patients under analysis after the index used in all but 15 patients, for whom the measurement echocardiogram,27 (10%) had a systemicembolic event had not been recorded. In those patients, the echocar- during the follow-up period, which ranged from bruit; previous ipsilateral tran- tients above and below the median age of 70 years; sient ischemic attack; hypertension and evidence of a mean age was 68. Women had a higher frequency of lacunar infarction; nonsudden onset of the neurologic embolic events than men (14 vs 6%, p = 0.02) and pa- deficit while awake; evidence of ipsilateral cerebrovas- tients with underlying structural heart diseasehad em- cular stenosis by angiography or noninvasive testing; bolic events more often than those without structural prior ipsilateral carotid endarterectomy; or nonembolic heart disease (14 vs 5%, p = 0.02). Systemic embolic stroke at autopsy.22 Patients having a transient cerebral eventsoccurred in 13%of patients with coronary artery ischemic event without a persistent deficit were consid- disease (myocardial infarction or angina pectoris), in ered embolic unless they had evidence of ipsilateral ca- 16% of patients with valvular heart disease(aortic ste- rotid diseaseor prior transient ipsilateral deficits. nosis or regurgitation or mitral regurgitation) and in Peripheral ischemic events were considered embolic 23% of patients with cardiomyopathy (dilated or hyper- unless there was evidence of associatedatherosclerotic trophic) when compared to 5% of patients with no un- peripheral vascular disease.All peripheral systemic em- derlying heart disease(p = 0.07, p = 0.06, p = 0.05, bolic events had either surgical embolectomyto confirm respectively). The frequency of embolic events did not the diagnosis or had associatedembolic events in other show a statistically significant difference according to locations. the type of AF (chronic [15%] vs paroxysmal [9%]). Strokes that occurred before the index echocardio- The presenceof systemic hypertension also did not sig- gram were not analyzed as a risk factor for subsequent nificantly alter the frequency of embolization. systemic embolization, becauseinformation was rarely There was a striking difference in embolic frequency available to allow the strokes to be categorized as em- according to left atria1 size. Of the 180 patients whose bolic or nonembolic. left atrium measured 24.0 cm, 25 (14%) had systemic Paroxysmal versus chronic atrial fibrillation: embolic events compared with only 2 of 92 patients Chronic AF was defined as >-2 documented episodesof (2%) whose left atrium was <4.0 cm (p = 0.003). AF, at least 1 month apart, with no documented inter- Of the 27 embolic events,23 (85%) were cerebrovas- vening or subsequentepisodes of normal sinus rhythm. cular and 4 (15%) were peripheral. A history of 2 1 Paroxysmal AF was defined as AF followed by an epi- month of therapeutic anticoagulation at some point be- sode of normal sinus rhythm. Thus, a patient was con- fore the embolic event was noted in 5 patients (19%) in sidered to have paroxysmal AF if a single episodeof AF the embolic group and in 37 patients (15%) in the non- was followed by normal sinus rhythm or if there were embolic group. Of the 5 patients who embolized with a multiple episodesof AF with intervening normal sinus history of therapeutic anticoagulation, only 3 were re- rhythm. The status of the AF was consideredunknown ceiving a therapeutically effective dosage(prothrombin if there was a single episodeof AF with no subsequent time 11.3 X control) at the time of the embolic event. documentation of either normal sinus rhythm or persis- To determine the relative contributions of the embol- tent AF. ic risk factors identified by bivariate analysis, Cox re- Statistical analysis: Bivariate analysis of clinical gression was performed. As listed in Table II, the fol- variables was performed using Pearson’schi-square test lowing 3 variables contributed significantly to the model for categorical data and Student’s t test (2-tailed) for predicting risk of embolization: left atria1 size 14.0 cm; continuous data. Cox regressionanalysis was then used female sex; and the presenceof structural heart disease. to determine the relative contribution of clinical vari- Each of these 3 factors was then assigned 1 point in a ables to predict embolic events. Variables were entered risk score. As listed in Table III, subsequent embolic sequentially into the Cox regressionmodel if their prob- events occurred in none of 24 patients with a risk score ability level for significance was

THE AMERICAN JOURNAL OF CARDIOLOGY MAY 1. 1990 1113 TABLE I Clinical Factors as Predictors of Risk for Systemic TABLE Ill Risk Score for Embolization Embolization No. (%) Pts with No. and % Pts Having Score No. Pts Systemic Embolization Systemic Embolization 0 24 0 (0) 1 83 Presence of Absence of 2 (2) 2 118 13 (11) Factors Factor (%) Factor (%) p Value 3 47 12 (26) Age 170 yrs (median) 17/129(13) lo/143 (7) NS Total 272 27 (10) Female 18/125(14) 9/147 (6) 0.023 Systemic hypertension 17/147(12) lo/125 (8) NS Atrial fibrillation and inconvenience of long-term anticoagulation are of- Chronic lo/65 (15) - ten believed to outweigh the risk of embolization. This Paroxysmal 17/192 (9) study, which was done to assessthe risk of embolization Unknown O/15 (0) - Underlying heart disease 21/155(14) 6/117 (5) 0.020 in patients without mitral stenosis,provides a schemeof Atherosclerotic* 15/119(13) 0.068’ stratification that offers a rational basis for decision Valvular* 5/32 (16) 0.059’ making. The risk of systemic embolization is increased Cardiomyopathy* 3/13 (23) 0.047’ by a large (24 cm) left atrium and, to a somewhatless- 0.003 Left atrial size 24.0 cm 25/180(14) 2/92 (2) er extent, by female sex and structural heart disease. * Patients with >l type of heart disease were counted in each applicable category of underlying heart disease; t compared against patients without underlying heart The risk is particularly high if all 3 factors are present. disease. NS = not sgnlftcant. Previous studies have produced conflicting informa- tion about these risk factors. Rheumatic heart disease has been well documented as a risk factor*6*20but there TABLE II Significant Predictors of Risk for Systemic is little consensusabout the impact of other types of Embolization in Cox Regression Analysis heart disease.In an autopsy study4 of patients with AF, Cox Regression the risk of systemic embolization was reported to be Parameter Coefficient p Value similarly high in patients with rheumatic heart disease Left atrial size 24.0 cm 2.1 <0.001 and coronary heart disease. .This conclusion was not Female sex 1.0 0.014 confirmed in the Framingham study, in which rheumat- Structural heart disease 0.9 0.037 ic but not coronary artery diseaseincreased the risk of systemic embolization.l 5,24 13 (11%) of 118 patients with a risk scoreof 2 and in 12 In this study, a clinical history of angina pectoris or (26%) of 47 patients with a risk score of 3. Life table myocardial infarction produced a distinct but statistical- analysis in Figure 1 shows the distinct gradients of risk ly nonsignificant increase in risk, when compared produced by this scoring. against patients with no heart disease.Similarly, the pa- tients with nonmitral stenotic valvular heart diseaseor DlSCUSSlON with cardiomyopathy had an increasedrisk of emboliza- Despite the reportedly increasedrisk of systemicem- tion that was borderline statistically significant. When bolization in patients with AF,1-11,23,24anticoagulant all patients with underlying heart diseasewere consid- therapy is routinely used only when mitral stenosis is ered as a single group, the risk was significantly in- present.” Because patients fibrillating without mitral creasedto 14% (p = 0.02) versus 5% in patients with no stenosis are thought to have a lower risk, the hazards structural heart disease.

FlGURE 1. Actuarial uuve of ridi ol sys- CUMULATIVE 0.6- temllem-byrlrkscere.l?ldr PROPORTtON scare3hadsign~nuymoreembolk FREE OF eventsth8nrkkscore2@=0.00@,1(p EVENT = 0.001) and0 (p = 0.004). Rlrk score 2 haddgnWcantlymoreembollcevemtsthan riskscare1(p=O.O3).Risksczareldid mtdlfferdgnWanBy fromrkkscoreo(p = Odl!i).

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ii 14 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65 The association of AF with left atria1 dilatation has AF and in patients who have already had an embolic been well described25and echocardiographic measure- event.5~17,27*32-34In a recent randomized trial of antico- ments of left atria1 size have been related to the likeli- agulation in patients with chronic nonrheumatic AF, hood of maintaining normal sinus rhythm after cardio- warfarin significantly decreasedthe frequency of em- version.25Autopsy studies have associatedthe presence bolic events compared to aspirin and placebo.35The of left atria1 clot with left atria1 dilatation, and left atri- proposedscoring system for risk of systemic emboliza- al size, as assessedby chest radiograph, has been related tion, in combination with the previously reported risk of to the frequency of systemic embolization in patients major bleeding with oral anticoagulation of 1 to 2%/ with mitral stenosis.20In other reports, however, left year,36-38can provide a valuable basis for decision mak- atria1 size was not found to be related to risk of embolic ing in AF patients without mitral stenosis. stroke.r2J4 Echocardiographic measurements of left atria1 size22,26were used in only 2 previous clinical studies of patients with AF and systemic embolization. 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