LAE related rhythm disturbance that characterize atrial fibrillation is also associated with other atrial derangement such as endothelial dysfunction and impaired myocyte function.The role of LAEinacutecere bralinfarctionpatientisnot sufficient lydescribedinliterature.
2. KeywordsAtrium; Ischemic; TOAST; AtrialCardiopathy
3.IntroductionWellknowndefinitivemodifiableriskfactorforischemicstrokeinclude dyslipidemia,transientischemicattack,priorstroke,hypertension,diabetesmellitus,ischemicheartdisease,atrialfibrillation,valvularheartdisease,carotid stenosis,cigarettesmoking,obesity,alcoholconsumption,increasedfibrinogen,e levatedhomocysteine,lowserumfolate,oralcontraceptiveuseandelevatedanticar diolipinantibodies[1].Evenwithfulldiagnosticevaluation,specificcauseremainsunidentifiedinupto39%patientofacuteinfarctandarela beledascryptogenicstroke[2].Suchpatientofundeterminedaetiologyhassignificantlyhigherrateofrecurrentstroke[3]. Out of these many modifiable risk factor, atrial fibrillation needs particularattention.Patientwithatrialfibrillationhavehighriskof stroke.Thisriskhasbeenascribedtostasisofbloodandthrombus tion.Leftatrialappendageissiteforaround91%ofnon-rheumatic atrial fibrillation-related thrombi origin [4]. Although an single standard 12 lead ECG can pick up atrial fibrillation in some case but paroxysmal atrial fibrillation may be missed. In that case a standard 24 hours, 48 hours or even longer holter monitoring is used to diagnose paroxysmal atrial fibrillation. Long monitoring byImplantablelooprecorderscanalsobehelpfulindetectingparoxysmalatrialfibrillation[5].Somecardioembolicstrokemaystill bemissedandlabeledasstrokeundeterminedetiology.Inarecent study,despite3yearsofheartmonitoring70%ofpatientwithcryptogenic stroke had no evidence of atrial fibrillation [5]. While the role of atrial fibrillation in stroke is well established in literature, therearestudieswhicharepostulatingthatperhapsatrialfibrilla
4. MethodologyPatients who were admitted in the Indraprastha Apollo Hospital duringthestudyperiod(June2016toMarch2018)withadiagnosis ofacuteischemicstrokewerescreenedaccordingtoourinclusion and exclusion criteria, and those found suitable were enrolled for thestudy.Itwasaprospective,hospitalbased,observationalstudy. Weincludedallthecasesoffirsttimeacuteischemicstrokedefined as “abrupt onset of neuronal death due to vascular compromise causingneurologicaldeficitlastingmorethan24hoursassociated withCT/MRIfeaturesofinfarction”admittedinIAH,Delhiduring thestudyperiod.Patientswithhemorrhagicstroke,TransientIschemic Attack (TIA), and those with history of previous ischemic, hemorrhagic stroke or sinus thrombosis were excluded from the study.Patientsdetailedhistoryandthoroughphysicalexamination was performed and his/her demographic data, complete clinical profile,drughistoryandtraditionalstrokeriskfactorswerenoted. Routinehematological(CBC),biochemicalanalysis(RFT,Serum Electrolytes, RBS, Lipid profile), 12 lead ECG, Trans-thoracic Echocardiographywereperformedwithin24hoursofadmission. Neuro-radiological analysis that were required to diagnose stroke andrelatedtoaetiologydetermination[BrainCT,BrainMRI,Brain MRI Angiography, Carotid MRI Angiography], as required were performed. Other investigation like Carotid Doppler, 24 hours holter, HbA1C, Serum Homocysteine level, PT and other lab test for thrombophilia were performed in selected patient to establish aetiologyofstroke.Usingclinicaldata,radiologicalimagesandinvestigationresults,strokesubtypeofeachpatientwasdetermined basedonModifiedTrialofOrg10172inAcuteStrokeTreatment (TOAST) Classification system [17]. PwavemorphologyinleadV1ofECGwasevaluatedineachpatienttolookforleftatrialenlargementandPTFV1>4,000micro- volt ms were considered to have left atrial enlargement by ECG voltage criteria [18, 19]. Trans Thoracic Echocardiography was performed by cardiologist in every patient to determine left atri-al enlargement. Left atrial diameter (cm) in parasternal long axis view(atthelevelofaorticvalve)wasnoted.Leftatrialdiameterwas indexedtoBodySurfaceArea(BSA)(m2 ).IndexedLeftatrialdiameter(cm/m2 )morethanorequalto2.4cm/m2wasconsideredas leftatrialenlargementbyechocriteria[20].BodySurfaceAreawas calculatedaccordingtoDuBoisformula.Patientwhofulfilledleft atrialenlargementcriteriabothbyECGcriteriaandbyTransThoracicEchocardiographycriteriadefinedearlierwereconsideredto haveleftatrialenlargement.Afterclassifyingpatientsingroupsaccording to Toast criteria, distribution of left atrial enlargement in each group was analyzed and inference was drawn pertaining to the aims and objectives of the study.
5. StatisticalAnalysisCategorical variables were present as frequency and percentages whereaslinearvariableswereexpressedasmeanandstandarddeviation. The chi-square test was used to compare the categorical variables.UnpairedttestandANOVAtestfollowedbyTukey’spost hoctestswereusedtocomparelinearvariables. Thep-value< 0.05 wasconsidered significant. All theanalysiswascarriedoutonSPSS 16.0version (Chicago, Inc., USA).
6. ResultsandObservationsThepresentstudywasconductedintheDepartmentofNeurology, Indraprastha Apollo Hospital, and New Delhi with the objective to study the frequency of left atrial enlargement in different subtypes of ischemic stroke. A total of 154 stroke patients were included in the study. The mean age of male and female stroke patientswas61.13±14.51yearsand62.11±13.34yearsrespectively. Overallmeanageofpatientswas61.52±14.02years.Therewasno significant(p>0.05)associationofagewithstrokesubtype.Figure1 Table-2showsthecomparisonofLAEbyvoltageandECHOcri- teria. Both voltage and ECHO criteria for LAE was positive in 41.6% patients (Table 2). The percentage of positivity by voltage and ECHO criteria was almost similar constituting 42.9% and 42.2%respectively.LAdiameterwassignificantly(p=0.002)high- er among hypertensive (4.24±0.54) patients than non-hypertensive(3.96±0.48).LAdiameterwasinsignificantly(p>0.05)higher amongdiabeticpatientsthannon-diabetics.ThepercentageofAF was 25% among whom LAE was present and the association was statistically insignificant (p>0.05).
LAEbyvoltagecriteria:LAEbyvoltagecriteriaamongdif- ferent stroke subtype showed that percentage of Cardioembolic (39.4%) was higher than large (9.1%) and small (16.7%) artery among whom LAE was detected by ECG voltage criteria and the associationwasstatisticallysignificant(p=0.001).Thepercentage of undetermined cases was 34.8% in whom LAE was detected by voltagecriteria.
LAEamongdifferentstrokesubtype: UponcomparisonofLAE(positivebybothvoltageandechocriteria)withstrokesubtype,thepercentageofCardioembolic(40.6%) was higher than undetermined (35.9%) among whom LAE was present by both echo and voltage criteria and the association was statistically significant (p=0.001) (Figure 3).
Hypertension was most common risk factor among the stroke patient in this study (61.6%), followed by Left atrial enlargement (41.5%) and diabetes mellitus (38.3%). In previous studies also,it was considered that there could be a relationship between left atrialdilatation and HT[24]. It is not so clear if this relates to left ventricular hypertrophy or there is a direct relationship between HT and left atrial dilatation. With its thin wall, left atrium dilates easily.Asaresultofthis,LAdilatationinechocardiographymaybe evaluatedasanearlyfindingofhypertensiveheartdisease.Inthis study also, indexed left atrial diameter was significantly (p=0.02) higher among hypertensive (2.45±0.32 cm) patients than non-hypertensive (2.20±0.24 cm) highlighting relationship between hypertensionandleftatrialenlargement.Nosuchrelationwasnoted with D.M. in this study. In this study, we detected significant involvement of AF in cardioembolic strokes.This is expected also as Atrial fibrillation disturbs synchronous mechanical atrial activity and impairs the hemodynamics which can give rise to thrombus formationandembolismtothesystemiccirculationleadingtocardioembolic stroke. Similar observations were noted by Misirli et al[22]. Similarly, there was significant difference in Indexed LA diameter among stroke subtype in this study. Indexed LA diameter was significantly (p=0.001) higher in Cardioembolic (2.67±0.30) than large artery, small artery and undetermined stroke group. This higher LA diameter can result in new onset AF and thus explains associationofAFwithcardioembolicstroke.HyeYoungshinetal [25], also found higher mean indexed LA volume (ml/m2 ) in cardioembolicgroupandincreasedindexedLAvolumewasnotedto associatedwithcardioembolicstroke.LAvolumemeasurementis moreaccurateestimateoftrueLAsize,however,inthisstudyleft atrial volume was not measured. WhenTOAST classification[17] was followed, it was found that left atrial enlargement was most frequent in the cardioembolic group(40.6%).ThiswasquiteexpectedfindingsinceleftatrialdilatationwasobservedtogetherwithAFinthecardioembolicgroup. However,leftatrialdilatationhadthesecondhighestfrequencyin the undetermined cause group (35.9%), after the cardioembolic group, which was bit surprising. one probable explanation to this finding can be occult paroxysmal atrial fibrillation (AF) which is foundinasubstantialminorityofpatientswithcryptogenicstroke. Similarobservation was noted by Takoglu et al[26], in his study, whofoundleftatrialenlargementmostfrequentlyincardioembolicgroupfollowedbyunderminedcausegroupandfurthersuggestedthathavingonlyleftatrialdilatationintheundeterminedcause group should be evaluated as a risk factor. Contrarytothis,Misirlietal[22],notedfrequencyofLAenlarge- ment in the Cardioembolic group only, was significantly higher (p< 0.01)comparedtotheothergroups.Howeverhigherfrequency in the undetermined cause group is consistent with recent studies thatcallintoquestionwhetherAF—thedysrhythmiaitself—isalwaysanecessarystepinthepathogenesisofleftatrialthrombo-embolism [13]and Left atrial abnormality as indicated by left atrial enlargement can itself lead to thrombus formation and embolism, inwhichcase,becauseofabsenceofAF,strokewouldbelikelyla- beled as cryptogenic and thus stroke of undetermined aetiology and wouldbe proneto recurrentstroke. Sucha conditionmay ex- plain some proportion of the ischemic strokes that currently lacka known cause. It would be ideal to perform further studies with largernumberofpatientswithspecialemphasizeonatrialvolume.
Followingarethesalientfindingsofthepresentstudy:1. Of 154 stroke patients, percentage of undermined group (36.4%) was highest followed by cardioembolic group (22.1%).Smallarteryocclusionwasfoundamong20.1% patientsandlargearteryatherosclerosiswasseenamong 17.5%patients.Strokeofotherdeterminedaetiologywas noted in only 3.9% of stroke patient. 2. Hypertension was most common risk factor among the strokepatientinthisstudy(61.6%),followedbyLeftAtri- al enlargement (41.5%) and Diabetes mellitus (38.3%). 3. Indexed left atrial diameter was significantly (p=0.02) higher among hypertensive (2.45±0.32) patients than non-hypertensive(2.20±0.24). 4. IndexedLAdiameterwassignificantly(p=0.001)higher in Cardioembolic group (2.67±0.30) than large artery, small artery and undetermined stroke group. 5. Left atrial enlargement was most frequent in the cardioembolic group (40.6%) followed by undetermined cause group(35.9%).
Thisstudyhadfollowinglimitations: 1. We didn’t evaluate left atrial volume indexes relative to bodysurfaceareaorbodyheight,sincerecentliteratures concerning left atrial size have emphasized the importance of the left atrial volume rather than the left atrial dilatation. 2. Our study protocol did not include follow up of the patients to recognize increased risk for atrial arrhythmias, thrombi or recurrent stroke.
8. ConclusionSecond Highest frequency of LAE found in undermined group raises the possibility cardiogenic origin of stroke, at least in some of these patients. Paroxysmal AF or left atrial pathology without AFmayexplainthisphenomenon.Asthesepatientwouldbeprone to recurrent stroke, stroke patients of undermined aetiology with leftatrialenlagementshouldbeevaluatedindetailincludingmore prolongedholter.Furthergiventheprovenbenefitofanticoagulant therapyinpreventingleftatrialthromboembolisminpatientswith AF,furtherstudiesmaybeworthwhiletodetermineoptimalmarkersofatrialcardiopathyandtheeffectofanticoagulanttherapyin patientswithconclusiveevidenceofatrialcardiopathy,butnoclear evidence of AF.
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Citation:Tiram Y. The Association of Left Atrial Enlargementin Different Subtypes of Ischemic Stroke Basedon Toast Classification. Annals of Clinical and Medical Case Reports 2020