Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCfs8PCDpg9Ncn7pgYZrW4tBfS0066-782X201800140013210.5935/abc.20180141Short EditorialAtrial Fibrillation and Cryptogenic Thromboembolic EventsHenzBenhur DaviLeiteLuiz RobertoHospital do Coração do BrasilInstituto Brasília de ArritmiasBrasíliaDFBrazilInstituto Brasília de Arritmias - Hospital do Coração do Brasil (Rede Dor / São Luiz), Brasília, DF – BrazilMailing Address: Benhur Davi Henz Condomínio Estância Jardim Botânico, conjunto I, casa 19. Postal Code 71680-365, Brasília, DF – Brazil Email- benhurhenz@yahoo.com.br0820181112132133This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.KeywordsAtrial, FibrillationStrokeThromboembolismForamen Ovale,Patent
Annual stroke rates are extremely high, affecting around 15 million individuals worldwide, generating major public health and economic impact. Approximately 25% of stroke cases do not have a determined etiology, thus being denominated cryptogenic stroke (CS).1 Cryptogenic strokes do not have a definite cause; their identification occurs by exclusion, when they are not attributable to definite cardioembolism, large-vessel atherosclerosis of and small-vessel disease, despite extensive vascular, cardiac or serological investigation.2
CS rates vary significantly, depending on the degree of diagnostic investigation. Considering that most CS cases have an embolic origin, a new terminology has been recently created for non-lacunar cryptogenic ischemic strokes: “Embolic Stroke of Undetermined Source”.3
Approximately one-third of patients with CS have a new ischemic episode in 10 years,4 of which 63% are once again classified as cryptogenic.5 Possible causes for this recurrence, despite the primary event, are paroxysmal atrial fibrillation (AF), arterial thromboembolism, patent foramen ovale, structural heart disease or less common etiologies, such as thrombophilias. AF detection after a CS or ESUS offers the opportunity to reduce the risk of stroke recurrence by prescribing an oral anticoagulant.6 Without this diagnosis, the treatment for CS and ESUS consists only of platelet antiaggregation.7
Detection of subclinical atrial fibrillation in cryptogenic and embolic stroke of undetermined source
The use of long-term monitoring dramatically improved the ability to detect short, rare, and asymptomatic AF periods in stroke patients. The EMBRACE study evaluated 572 patients with ischemic stroke in the last 6 months, with no AF diagnosis, with randomization for 30-day continuous monitoring (287 patients) vs. 24-hour Holter (285 patients).
The AF detection rates (> 30 seconds) were 16.1% in the long-term monitoring group vs. 3.2% in the Holter group.8 Similarly, when Implantable Monitors (IM) were used, as in the CRYSTAL-AF (Cryptogenic Stroke and underlying Atrial Fibrillation) study, AF detection rates using IM were higher than the standard detection rates during a long-term follow-up: 8.9%, 12.4% and 30% vs. 1.4%, 2.0% and 3% in the period of 6, 12 and 36 months.9
In this issue, Sampaio et al.10 published an article on the evaluation of a continuous monitoring device (PoIP) when compared to 24-hour Holter in the diagnosis of atrial arrhythmias in patients with and without stroke, or transient ischemic attack (TIA), and without AF. Episodes of AF were detected in the group of patients with a history of stroke / TIA in 23.1% of patients in the PoIP group and in 3.8% of patients in the Holter group. Lower recording times were also observed in the first 24 hours in the PoIP group vs. Holter group. Atrial tachycardia rates were higher in patients in the stroke group when compared to controls. Significant loss of signal was observed in the PoIP group, of 11.4% due to network instability and different types of signal-sending technology, GPRS vs. 3-4G.
Even with a limited number of patients, the incidence of AF was higher in the long-term monitoring group, although it did not reach statistical significance. However, for this type of monitoring, we need to improve the quality of data transmission, the stability of networks and the technologies used for sending and receiving signals, aiming at lower losses and better quality of the received data.
Association between atrial fibrillation, cryptogenic and embolic stroke of undetermined source
Recently, several studies have evaluated the association of atrial tachyarrhythmias diagnosed in implantable devices with the risk of thromboembolic events. The MOST study11 showed that the detection of periods > 5 minutes of atrial heart rate > 220 bpm was associated with a six-fold increase in the risk of AF and a 2.8-fold increase in the risk of death or stroke in these patients with AF. The TRENDS study12 showed that patients with episodes of AF / AT > 5.5 hours / day had an increased risk of thromboembolism (hazard ratio = 2.2), when compared to those with AF / AT burden of zero. Similarly, the ASSERT study demonstrated that the presence of atrial heart rate > 190 bpm for a period of time > 6 minutes was associated with a 5.6-fold increase in the development of AF and 2.5-fold increase in new episodes of stroke or systemic thromboembolism.13 A more recent analysis of this study showed that high-frequency atrial episodes lasting > 24 hours increased the risk of ischemic stroke and systemic embolism to 3.1%/year – a risk comparable to that of clinical AF.14
Although the high atrial rate with an increased number of embolic episodes is well documented, the temporal and causal association require further elucidation. A sub-analysis of the TRENDS study demonstrated the presence of tachyarrhythmias prior to the embolic event in only 50% of the patients; 73% of them did not have tachyarrhythmias in the 30-day period before the embolic event. Also, the ASSERT study corroborated the results by showing AF rates in 51% of patients with thromboembolism, but only 8% of them had AF in the 30-day pre-stroke period.15 The evaluation of these studies suggest that the presence of AF could be simply a marker of thromboembolic risk and be indirectly associated with the occurrence of thromboembolism through a more complex mechanism than the previously expected one.16
Short Editorial regarding the article: Cryptogenic Acute Ischemic Stroke: Assessment of the Performance of a New Continuous Long-Term Monitoring System in the Detection of Atrial Fibrillation
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Lancet Neurol. 2015;14(9):903-13.LiLYiinGSGeraghtyOSSchulzUGKukerWMehtaZIncidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke A population-based studyLancet Neurol20151499039135 Ntaios G, Vemmos K, Lijo GY, Koroboki E, Manios E, Vemmou A, et al. Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source. Stroke. 2016;47(9):2278-85.NtaiosGVemmosKLijoGYKorobokiEManiosEVemmouARisk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined SourceStroke2016479227822856 Sanna T, Ziegler PD, Crea F. Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source. Clin Cardiol. 2018;41(3):426-32.SannaTZieglerPDCreaFDetection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined sourceClin Cardiol20184134264327 Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American. Stroke Association. 2014;45(7):2160-236KernanWNOvbiageleBBlackHRBravataDMChimowitzMIEzekowitzMDGuidelines for the prevention of stroke in patients with stroke and transient ischemic attack A guideline for healthcare professionals from the American Heart Association/AmericanStroke Association2014457216022368 Gladstone DJ. et al. Atrial Fibrillation in Patients with Cryptogenic Stroke. N Engl J Med. 2014;370(26):2467-77.GladstoneDJAtrial Fibrillation in Patients with Cryptogenic StrokeN Engl J Med201437026246724779 Sanna T, Dienner HC, Passman RS, Di Lazaro V, Bernstein RA, Morello CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014; 370(26):2478-86.SannaTDiennerHCPassmanRSDi LazaroVBernsteinRAMorelloCACryptogenic stroke and underlying atrial fibrillationN Engl J Med2014370262478248610 Sampaio RF, Gomes IC, Sternick EB. Artigo Original AVC Isquêmico agudo criptogênico: avaliação do desempenho de um novo sistema de monitorização contínua e prolongada. Arq Bras Cardiol. 2018; 111(2):122-131.SampaioRFGomesICSternickEBArtigo Original AVC Isquêmico agudo criptogênico avaliação do desempenho de um novo sistema de monitorização contínua e prolongadaArq Bras Cardiol2018111212213111 Glotzer TV, Hellkamps AB, Zimmerman J, Swoeney MO, Yee R, Marinchak R, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: Report of the atrial diagnostics ancillary study of the MOde Selection Trial (MOST). Circulation. 2003;107(12):1614-19.GlotzerTVHellkampsABZimmermanJSwoeneyMOYeeRMarinchakRAtrial high rate episodes detected by pacemaker diagnostics predict death and stroke Report of the atrial diagnostics ancillary study of the MOde Selection Trial (MOST)Circulation2003107121614161912 Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hillker C, et al. The Relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk the trends study. Circ Arrhythm Electrophysiol. 2009;2(5):474-80.GlotzerTVDaoudEGWyseDGSingerDEEzekowitzMDHillkerCThe Relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk the trends studyCirc Arrhythm Electrophysiol20092547448013 Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capurci A, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120-9.HealeyJSConnollySJGoldMRIsraelCWVan GelderICCapurciASubclinical atrial fibrillation and the risk of strokeN Engl J Med2012366212012914 Tomita H, Sasaki S, Hagü J, Metoki N. Covert atrial fibrillation and atrial high-rate episodes as a potential cause of embolic strokes of undetermined source: Their detection and possible management strategy. J Cardiology. 2018;72(1):1-9.TomitaHSasakiSHagüJMetokiNCovert atrial fibrillation and atrial high-rate episodes as a potential cause of embolic strokes of undetermined source Their detection and possible management strategyJ Cardiology20187211915 Brambatti M, Connolly SJ, Gold MR, Morillo CA,Capucci A, Muto C, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation. 2014;129(21):2094-99.BrambattiMConnollySJGoldMRMorilloCACapucciAMutoCTemporal relationship between subclinical atrial fibrillation and embolic eventsCirculation2014129212094209916 Van Gelder IC, Healy JS, Grijns HJ, Wang J, Hohnloser SH, Gold MR. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J. 2017;38(17):1339-144.Van GelderICHealyJSGrijnsHJWangJHohnloserSHGoldMRDuration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERTEur Heart J2017381713391144MinieditorialFibrilação Atrial e Eventos Tromboembólicos CriptogênciosHenzBenhur DaviLeiteLuiz RobertoInstituto Brasília de Arritmias - Hospital do Coração do Brasil (Rede Dor / São Luiz), Brasília, DF – BrasilCorrespondência: Benhur Davi Henz Condomínio Estância Jardim Botânico, conjunto I, casa 19. CEP 71680-365, Brasília, DF – Brasil Email- benhurhenz@yahoo.com.brPalavras-chaveFibrilação AtrialAcidente Vascular CerebralTromboemboliaForame Oval Patente
As taxas anuais de acidentes vasculares cerebrais (AVC) são extremamente elevadas, acometendo cerca de 15 milhões de pessoas no mundo, e gerando um grande impacto de saúde pública e econômico. Aproximadamente 25% dos AVC não têm etiologia determinada, sendo denominados Criptogênicos (AVCc).1 Os AVCc não apresentam causa definida; sua denominação ocorre por exclusão, quando eles não são atribuíveis a cardioembolismo definido, aterosclerose de grandes artérias e nem a doenças de pequenas artérias, a despeito de extensa investigação vascular, cardíaca ou sorológica.2
As taxas de AVCc variam significativamente, dependendo do grau de investigação diagnóstica. Dentro da perspectiva de que a maioria dos AVCc tem origem embólica, recentemente tem sido utilizada uma nova terminologia para os AVC isquêmicos criptogênicos não lacunares: “AVC Embólico de Origem Indeterminada” (ESUS, sigla do inglês Embolic Stroke of Undetermined Source).3
Aproximadamente um terço dos pacientes com AVCc apresenta novo episódio isquêmico em 10 anos,4 sendo que 63% são novamente classificados como criptogênicos.5 Possíveis causas para esta recorrência, a despeito do evento primário, são Fibrilação Atrial (FA) paroxística, tromboembolismo arterial, forame oval patente, doença cardíaca estrutural ou etiologias menos comuns, como trombofilias. A detecção de FA após AVCc ou ESUS oferece a oportunidade de reduzir o risco de recorrência de AVC, pela prescrição de um anticoagulante oral.6 Sem este diagnóstico, o tratamento para AVCC e ESUS é somente a antiagregação plaquetária.7
Detecção de fibrilação atrial subclínica em acidente vascular cerebral criptogênico e embólico de origem indeterminada
A utilização de monitorização prolongada melhorou dramaticamente a habilidade de detecção de períodos curtos, raros e assintomáticos de FA em pacientes com AVC. O estudo EMBRACE avaliou 572 pacientes com AVC isquêmico nos últimos 6 meses, sem diagnóstico de FA, com randomização para monitorização contínua de 30 dias (287 pacientes) vs. Holter de 24 horas (285 pacientes). As taxas de detecção de FA (> 30 segundos) foram de 16,1% no grupo com monitorização prolongada vs. 3,2% no grupo Holter.8 Da mesma forma, quando empregados Monitores Implantáveis (MI), como no estudo CRYSTAL-AF (Cryptogenic Stroke and underlying Atrial Fibrillation), as taxas de detecção de FA utilizando MI foram superiores às de detecção padrão em um seguimento prolongado: 8,9%, 12,4% e 30% vs. 1,4%, 2,0% e 3% no período de 6, 12 e 36 meses.9
Nesta edição, Sampaio et al.10 publicam avaliação de uso de dispositivo de monitorização continuada (PoIP) quando comparado a Holter 24 horas no diagnóstico de arritmias atriais em pacientes com e sem AVC, ou Ataque Isquêmico Transitório (AIT), e sem FA. Foram detectados episódios de FA no grupo de pacientes com histórico de AVC/AIT em 23,1% dos pacientes do grupo PoIP e em 3,8% dos pacientes do grupo Holter. Foram também observados menores tempos de gravação nas primeiras 24 horas no grupo PoIP vs. Holter. As taxas de taquicardia atrial foram maiores nos pacientes do grupo AVC quando comparados aos controles. Foi observada importante perda de sinal no grupo PoIP, de 11,4%, devido à instabilidade de rede e a diferentes tecnologias no envio de sinais GPRS vs. 3-4G.
Mesmo com um número restrito de pacientes, a incidência de detecção de FA foi maior no grupo de monitorização prolongada, apesar de não atingir significância estatística. Entretanto, para este tipo de monitorização, precisamos evoluir na qualidade do envio de dados, na estabilidade de redes e tecnologias empregadas para captura, e no envio de sinal, visando à menor perda e à melhor qualidade de dados recebidos.
Relação entre fibrilação atrial, acidente vascular cerebral criptogênico e embólico de origem indeterminada
Recentemente, diversos estudos avaliaram a relação de taquiarritmias atriais diagnosticadas em dispositivos implantáveis com o risco de eventos tromboembólicos. O estudo MOST11 demonstrou que a detecção de períodos > 5 minutos de frequência cardíaca atrial > 220 bpm era relacionada a risco aumentado de FA em seis vezes e a aumento de risco de morte ou AVC nestes pacientes com FA de 2,8 vezes. O estudo TRENDS12 mostrou que os pacientes que apresentavam episódios de FA/TA > 5,5 horas/dia tinham aumento do risco de tromboembolismo (hazard ratio 2,2), quando comparados àqueles com burden de FA/TA de zero. Da mesma forma, o estudo ASSERT demonstrou que a presença de frequência cardíaca atrial > 190 bpm por tempo > 6 minutos foi associada a aumento de 5,6 vezes no desenvolvimento de FA e 2,5 vezes em novos episódios de AVC ou tromboembolismo sistêmico.13 Análise mais recente deste estudo demonstrou que episódios de alta frequência atrial com duração > 24 horas aumentavam o risco de AVC isquêmico e embolia sistêmica para 3,1%/ano - risco comparável ao de FA clínica.14
Apesar de a elevada frequência atrial com aumento de episódios embólicos estar bem documentada, a relação temporal e causal necessita maior elucidação. Subanálise do estudo TRENDS demonstrou a presença de taquiarritmias previamente ao evento embólico em apenas 50% dos pacientes; 73% deles não apresentaram taquiarritmias no período de 30 dias antecedendo o evento embólico. Ainda, o estudo ASSERT corroborou estes resultados, ao apresentar taxas de FA em 51% dos pacientes com tromboembolismo, mas somente 8% deles apresentaram FA no período de 30 dias pré-AVC.15 A avaliação destes estudos nos sugerem que a presença de FA pode simplesmente ser um marcador de risco tromboemlólico e estar indiretamente ligado à ocorrência de tromboembolismos por mecanismo mais complexo que o anteriormente esperado.16
Minieditorial referente ao artigo: AVC Isquêmico Agudo Criptogênico: Avaliação do Desempenho de um Novo Sistema de Monitorização Contínua e Prolongada, via Telefonia Celular, na Detecção de Fibrilação Atrial