Stroke Iskemik + Atrial FibrillasiDr Kiking Ritarwan SpS(K), MKTDepartemen Neurologi FK USU/ RSUPAdam Malik Medan12042013

Definisi StrokeStroke adalah suatu tanda klinis yang berkembang cepat akibat gangguan otak fokal (atau global) dengan gejala-gejala yang berlangsung selama 24 jam atau lebih dan dapat menyebabkan kematian tanpa adanya penyebab lain yang jelas selain vaskuler (Guideline Stroke, 2011)Stroke Iskemik tanda-tanda klinis disfungsi atau kerusakan jaringan otak yang disebabkan kurangnya aliran darah ke otak sehingga mengganggu kebutuhan darah dan oksigen di jaringan otak (Caplan, 2000).

Tagawa et.al. PACE 2007;30:1121-1128HISTORY OF AF

ECG FINDINGS ON ADMISSIONSTagawa et.al. PACE 2007;30:1121-1128

Tagawa et.al. PACE 2007;30:1121-1128HOLTER ECG

Stroke pada usia dewasa muda sebagai stroke yang terjadi sebelum usia 45 tahun. Usia dewasa muda berkisar 6 20/100.000. Seperlima sampai dengan sepertiga kardioemboli, kelainan jantung bawaan, kelainan katup maupun aritmia.Sekitar 15 25 % dari stroke iskemik kardioemboli atrial fibrilasiPasien dengan AF yang disertai kelainan katup peningkatan resiko untuk menderita stroke 18 kali dengan insiden 0,5 17 % /tahun. Emboli pada penderita dengan mitral stenosis 10 20% 50 70 % dari emboli ini melibatkan otak.

*Tabel 1. Sumber-sumber kardioemboli Potensial Dikutip dari: Kelley RE, Minagar A. Cardioembolic Stroke : An Update. South Med J 2003;96(4):343 49.

Cardiac disorderEstimated percentageof yearly strokeAtrial fibrilation7Cardiac failure4Myocardial infark2Other (eg, prosthetic heart valve, interatrial septal defect, endocarditis)2Based on yearly stroke rate of approximately 750.000 in the United Stated and an estimated overall frequency of cardioembolic stroke of 15%.

Stroke Risk Factors12042013Kiking Ritarwan*

Kiking Ritarwan

Well-documented Risk FactorsHypertensionExposure to cigarette smoke DiabetesAtrial fibrillation and certain other cardiac conditionsDyslipidemiaAsymptomatic Carotid artery stenosisSickle cell diseasePostmenopausal hormone therapyPoor dietPhysical inactivityObesity and body fat distributionLess well-documented or potentially modifiable Risk FactorsMetabolic syndromeExcessive alcohol consumptionDrug abuseUse of oral contraceptivesSleep-disordered breathingMigraineHyperhomocysteinemiaElevated lipoprotein(a) HypercoagulabilityInflammationInfectionGoldstein et al. Published online in Stroke Dec. 2, 2010

STROKE SUBTYPES12042013Kiking Ritarwan*

Kiking Ritarwan

Kasus Blok EMSLembar 1Seorang laki-laki, berusia 45 tahun, pekerjaan wiraswasta, sudah kawin,datang ke Instalasi Gawat Darurat RS Adam Malik Medan, dengan keluhan lemah lengan dan tungkai kanan disertai dengan bicara pelo.

Lembar 2Hal ini sudah dialami penderita sejak bangun pagi subuh, dimana ketika penderita hendak mau ke kamar mandi, tiba-tiba penderita tidak bisa menggerakkan anggota gerak pada sisi sebelah kanan. Selain itu juga dijumpai sudut mulut yang jatuh ke sisi sebelah kanan. Sejak 6 bulan terakhir pasien merasakan denyut jantungnya tidak teratur

Lembaran 3.Tidak dijumpai sakit kepala, muntah dan kejang Dari pemeriksaan dijumpai sensorium compos mentis, TD 160/ 100 mmhg, nadi 110 x/I, irregular, pernafasan 24 x/I, temp 37 0C Dijumpai Parese N VII dekstra, disarthria Sistem Motorik : hemiparese dekstra, reflex fisiologis: Bicep/ triceps, APR/ KPR meninggi pada sisi sebelah kanan, Reflek patologis (-). Kekuatan otot: ESS 43333, EIS 33333. Sistem sensorik: tak

EKG: dijumpai atrial fibrillasi dengan VR 110 x/I, axis normal, LVH (+), deviasi segmen ST tidak dijumpai.

Hasil Head CT Scan : NCCT : Infratentorial cerebellum ventricle-4 normal. Supratentorial tampak hypodense lesion didaerah cortex dan subcortical temporofrontoparietal kiri serta basal ganglia kiri. Tidak tampak midline shift. Cortical sulci daerah fronto-parietal kiri obliterated. Ventricular system normal CECT : ------- Kesan : cerebral infarct didaerah cortex dan subcortical temporo-fronto-parietal kiri serta basal ganglia kiri.

Masalah PemicuMasalah yang dijumpai pada pasien adalah I. Keluhan lemah lengan dan tungkai kanan disertai bicara pelo II. Atrial Fibrillasi

Jawaban Learning IssuePeta Homonculus

The endothelium regulates blood-vessel homeostasis

Structure of the vascular endotheliumThe vascular endothelium is the inner lining of blood vessels, and is composed of a single layer of oblong-shaped endothelial cells

Thrombus Formation

Patofisiologi Kardio emboli strokeMaterial emboli fragmen pecahan trombus sekitar jantung. Sumber emboli lain artery-to-artery, intra artery, atau local embolism. Sebanyak 75 % dari emboli kardiogenik berada di otak. Penyebab yang paling umum atrial fibrilasi kronik lebih mudah untuk menderita stroke fungsi jantung yang normal. Gumpalan darah dari jantung gerakan kontraksi jantung ke sirkulasi sistemik. Kemungkinan ini menjadi sangat diperbesar bila terdapat pula fibrilasi atrial. Disamping mengobstruksi iritan vasospasme lokal atau difusSpasme tampaknya lebih sering penderita yang berusia lebih muda Emboli besar berbeda dari emboli kecil dalam 2 hal :Emboli besar kaya akan fibrin dibandingkan emboli kecil yang biasanya mengalami kalsifikasi, kaya akan platelet atau material septikEmboli besar cendrung ventrikel dan dinding atrium, dimana emboli kecil lebih sering berasal dari katup dan endokarditis Emboli yang berasal dari jantung menyebabkan 15-20% stroke iskemik. Diagnosis stroke kardioemboli berdasarkan riwayat pasien, gejala klinis dan pemeriksaan tambahan.

Menjelaskan tentang sumber emboli dari jantung yang terdiri dari resiko tinggi dan resiko sedang.

High risk embolic source Prosthetic cardiac valves Atrial fibrillation Aortic arch atheroma Recent myocardial infarction Dilated cardiomyopathy Left ventricular thrombus Mitral stenosis Infective endocarditis Marantic endocarditis Rheumatic valvular disease Atrial myxoma Low risk embolic source Mitral valve prolapse Mitral annular calcification Embolic source of uncertain significance Patent foramen ovale Atrial septal aneurysm

The presence of a potential cardioembolic source in the absence of cerebrovascular disease in a patient with a non-lacunar stroke Cerebral Embolism Task Force, 1989 in Cerebral Embolism Task Force, 1989Diagnosis of Cardioembolic Stroke

High RiskMedium RiskLow / Unclear Risk LV hypokinesia / aneurysmBioprostetic valveCongestive failureCardiomyopathyMyxomatous MVPPatent foramen ovale

Atrial septal aneurysm

Spontaneous echo contrastCardioembolic SourcesAtrial fibrillation

Recent anterior MI

Mechanical valve

Rheumatic mitralstenosis

Thrombus / tumor

Endocarditis

SAB13%Stroke Subtypes and Impact on Clinical OutcomesNINCDS Stroke Data Bank: Foulkes, et al. Stroke 1988;19:547.Hemorrhagic 26%ICB 13%Other 3%Small vessel 19%Large vessel 6%Cardioembolic 14%Unspecified 32%Ischemic 71%

Chart1

6

14

32

3

13

13

19

Sales

Sheet1

Sales

Large vessel6

Cardioembolic14

Unspecified32

Other3

ICB13

SAB13

Small vessel19

Indikasi RujukanPada pasien dengan atrial fibrilasi disebut mempunyai resiko tinggi jika ada riwayat trasient iskemik attack (TIA), stroke atau adanya embolisistemik, riwayat hipertensi, fungsi ventrikel kiri yang jelek, umur umur 75 tahun, penyakit katup mitral rematik dan katup jantung prostetik. Faktor resiko sedang adalah umur 65-75 tahun, dabetes melitus, penyakit arterikoronaria, maka rekomendasi untuk rujukan ke bagian kardiologi dan neurologi

*Tabel 2. Insiden stroke penderita AF berdasarkan CHADS2 skore *Score determined by: CHF, hypertension, age >75, and/or diabetes = 1 point; stroke or TIA = 2 pointDikutip dari: Hart RG, Palacio S. Cardioembolic Stroke. 2005. Available from: http://www.emedicine.com/EMERG/topic554.htm

Stroke Rates by CHADS2 Score*CHADS2 ScoreRiskStroke Rate Per Year0Low1 %1Low1.5 %2Moderate2.5 %3High5 %Very High> 7 %

CHADS2 risk stratification for stroke prevention in patients with AF*Congestive heart failure+1Hypertension+1Age 75 years+1Diabetes mellitus+1Prior Stroke or TIA+2

1 or 2 points are assigned as shown for each of the risk factorsaboveStroke risk low, intermediate, high is determined by the cumulative scoreGage BF et al, 2001; Fuster V et al, 2006; Singer DE et al, 2008.

Risk categoryScoreLow0Intermediate1Moderate to high2

*PENUNJANG DIAGNOSTIKHead CT SCAN Gambaran multipel infark di Transformasi hemoragik MRIMRI lebih sensitif Transformasi hemoragik 70 % dari stroke kardioemboli.

*Stroke kardioembolikSken otak inisialInfark hemoragik (-)Calon antikoagulasiYaUlangi sken otak 48 72 jam lagiInfark hemoragik (+)Perdarahan (-)Efek Massa (-)Infark luasEfek massa (+)Infark hemoragikAntikoagulanUlangi sken otakPenilaian ulang 6 minggu lagi

Heparinditeruskan warparin

7 10 hari lagi danPertimbangkan lagi antikoagulan Algoritma pemberian antikoagulan.

Dikutip dari: Guideline Stroke 2004. Kelompok Studi Serebrovaskuler. PERDOSSI.

ESC 2010 Guidelines: the role of CHA2DS2-VASc*Camm AJ et al, 2010.

Risk categoryCHA2DS2-VASc scoreRecommended antithrombotic therapy1 major risk factor or 2 clinically relevant non-major risk factors2OAC1 clinically relevant non-major risk factor1Either OAC or ASA 75325 mg dailyPreferred: OAC rather than ASANo risk factors0Either ASA 75325 mg daily or no antithrombotic therapyPreferred: no antithrombotic therapy rather than ASA

(Stroke. 2011;42:00-00.)AHA/ASA GUIDELINES FOR THE PREVENTION OF STROKE IN PATIENTS WITH STROKE OR TIA

Prevention with warfarin / VKAsEffective, but difficult to manageSuboptimal use: approximately 50% of eligible patients do not receive itIntracranial bleeding is the most feared complicationPhysicians often more influenced by events induced (bleeds) than those prevented (strokes)

Warfarin is more effective than aspirin for secondary stroke prevention in AFEAFT: European, multi-centre RCT1,007 patients with non-rheumatic AF and recent TIA or minor ischaemic stroke (mean follow-up 2.3 years)

EAFT Study Group. Lancet 1993;342:1255-62p

New Oral Anticoagulants for SPAFDirect Thrombin InhibitorsDabigatran

Factor Xa InhibitorsRivaroxaban Phase III data published Aug. 2011ApixabanPhase III data published Aug. 2011EdoxabanPhase III data expected Mar. 2013http://www.clinicaltrials.gov/ct2/searchAdapted from Turpie Eur Heart J 2008; 29:155XIXIXaVIIIaVaII FibrinogenTTP889Warfarin sites of actionDabigatranFibrin

Kriteria Siriraj Stroke Score(2,5 x kesadaran + 2 x sakit kepala + 2 x muntah + 0,1 x diastole 3 x riwayat ateroma 12(iskemik)-1 < x > 1 (perdarahan)

E = cardioembolic strokeL = lacunar strokeT = atherosclerotic stroke

E = cardioembolic strokeL = lacunar strokeT = atherosclerotic stroke*The endothelium has an important modulating effect on many of the key processes in atherosclerosis: Regulates the permeability of macromolecules, such as low-density lipoprotein, a key factor in foam-cell and fatty-streak formation Regulates leukocyte adhesion and subsequent invasion through the vessel wall, which drives the atherosclerotic process Endothelial tissue also controls vascular smooth muscle contraction, thereby regulating blood flow to the organs. *The vascular endothelium is the inner lining of the blood vessels and comprises a single layer of oblong-shaped endothelial cells. The diagram shows the vascular endothelium in relation to the blood-vessel wall as a whole.Talking PointsA rupture of blood vessels is the cause in hemorrhagic strokes (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]); they make up 26% of all strokes. They are associated with a very high rate of mortality and morbidity. Ischemic strokes appear when brain blood vessels are occluded by a buildup of arterial atherosclerotic plaques or by an embolus from another blood vessel. These stroke subtypes account for the majority (71%) of all cases of stroke.The distinction between hemorrhagic and ischemic stroke is critical in stroke diagnosis, because acute treatments and preventive strategies are often associated with a risk of hemorrhage, which would be detrimental in the setting of hemorrhagic stroke.

BackgroundThe prevalence of stroke subtypes differs between populations. For example, African-American and Asian populations have a higher incidence of hemorrhagic stroke, and according to evidence from the Northern Manhattan Stroke Study, Hispanic populations may also have a slightly higher incidence of hemorrhagic strokes.(7)

*CHADS2 risk stratification for stroke prevention in patients with AF For stroke prevention in AF, the type of guideline-recommended antithrombotic therapy depends on the individual patients magnitude of risk. CHADS21 is probably the risk stratification scheme used most frequently in routine practice.2A cumulative CHADS2 score (range 16) is calculated by assigning points, and risk assessed accordingly, as shown in the slide.The ACC/AHA/ESC 20063 and ACCP 20084 guidelines recommend ASA for patients at low risk, ASA or VKA for patients at moderate risk, and a VKA for patients at moderate-to-high risk of stroke.However, CHADS2 does not include some risk factors which have been shown to be important e.g. female gender and vascular disease (including MI, peripheral arterial disease and aortic plaque).5This means that stroke risk may be underestimated in some patients with AF, potentially leading to them not receiving anticoagulation and therefore remaining at increased risk of stroke.

AbbreviationsACC, American College of Cardiology; ACCP, American College of Chest Physicians; AHA, American Heart Association; ASA, acetylsalicylic acid; ESC, European Society of Cardiology; MI, myocardial infarction

References1.Gage BF et al. JAMA 2001;285:28642870.2. Banerjee A et al. Rev Esp Cardiol 2011; 64:639641.3.Fuster V et al. Circulation 2006;114:e257e354.4. Singer DE et al. Chest 2008;133:546S592S.5.Lip GY et al. Chest 2010;137:263272.*ESC 2010 Guidelines: the role of CHA2DS2-VAScA number of recently identified risk factors are excluded from the CHADS2 score, and a comprehensive stroke risk assessment would need to consider other stroke risk modifiers:1,2Major risk factors are prior stroke, TIA or thromboembolism, and older age (75 years)Clinically relevant non-major risk factors are heart failure (especially moderate-to-severe systolic left ventricular dysfunction, defined as LVEF 40%), hypertension or diabetesOther clinically relevant non-major risk factors include female sex, age 6574 years and vascular disease (specifically, MI, complex aortic plaque and peripheral artery disease)Risk factors are cumulative, and the simultaneous presence of two or more clinically relevant non-major risk factors was considered by the 2010 ESC guidelines2 to provide a sufficiently high stroke risk to warrant anticoagulation2The more recent CHA2DS2-VASc scheme is based on a point system in which 2 points are assigned for a history of stroke or TIA, or age 75; and 1 point each is assigned for age 6574 years, a history of hypertension, diabetes, recent cardiac failure, vascular disease and female sex:CHA2DS2-VASc extends the CHADS2 scheme by considering additional stroke risk factors that may influence a decision on whether or not to prescribe anticoagulant therapyPatients with no stroke risk factors (e.g. CHA2DS2-VASc=0) are at low risk and either ASA 75325mg daily or no antithrombotic therapy is recommended; no antithrombotic therapy is preferred2

AbbreviationsCHA2DS2-VASc, cardiac failure, hypertension, age 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 6574 and sex category (female); LVEF, left ventricular ejection fraction

ReferencesLip GY et al. Chest 2010;137:263262.Camm AJ et al. Eur Heart J 2010;31:23692429.***