FUNDAMENTO: O diagnóstico de Embolia Pulmonar (EP) ainda requer longos períodos de trabalho e inúmeros testes. OBJETIVO: Nosso objetivo é avaliar os desfechos clínicos após uma investigação negativa usando um protocolo combinado de angio TC de tórax e venografia por TC (CTA/CTV) como único teste de diagnóstico em pacientes não selecionados com suspeita de EP. MÉTODOS: Estudo de coorte retrospectivo que incluiu pacientes consecutivos com suspeita de EP que foram investigados com um protocolo combinado de CTA/CTV. Os pacientes que apresentaram inicialmente uma investigação negativa e não receberam anticoagulantes foram acompanhados por seis meses para ocorrência de eventos tromboembólicos venosos recorrentes. RESULTADOS: De 425 pacientes com suspeita de EP, 62 (14,6%) tiveram diagnóstico de tromboembolismo venoso no CTA/CTV inicial. A média de idades foi de 56 ± 19 anos, e 61% da população se enquadravam na categoria de baixa probabilidade clínica. A trombose venosa profunda isolada representou 21% de todos os eventos tromboembólicos venosos, e quando se considerou toda a população, a CTV foi associada a um incremento no rendimento diagnóstico de 3,1%. Nosso grupo era composto de 320 pacientes com CTA/CTV inicialmente negativo e que não receberam anticoagulantes. Após seis meses de acompanhamento, apenas três pacientes apresentaram recorrência de eventos tromboembólicos (0,9%, IC 95% -0,1% - 2,0%) e nenhum foi fatal. Não houve mortes relacionadas com a EP. CONCLUSÕES: Nosso estudo sugere que uma estratégia de diagnóstico que utiliza CTA/CTV como único teste de diagnóstico pode descartar EP com segurança, em população com risco baixo a moderado, e está associada a resultados favoráveis, com um valor preditivo negativo de 99,1%. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)
Desfechos clínicos após investigação para Embolia Pulmonar utilizando TC de tórax/membros inferiores
IInstituto Cárdio Pulmonar, Salvador, BA
IIHospital Aliança, Salvador, BA
IIIUniversidade Federal de Bahia, Salvador, BA
IVSanta Casa de Misericórdia, Salvador, BA
VHospital Sírio-Libanês, São Paulo, SP - Brasil
VIHospital Beneficência Portuguesa, São Paulo, SP - Brasil
A maioria dos pacientes com suspeita clínica de Embolia Pulmonar (EP) tem um diagnóstico alternativo para os seus sintomas, e a prevalência de EP confirmada entre esses casos suspeitos varia de 16% para 26% em series contemporâneas1-3. Assim, um dos maiores desafios no trabalho da EP é a exclusão rápida e segura da doença, evitando uma anticoagulação desnecessária, e acelerar a estratégia de diagnóstico.
A Tomografia Computadorizada (TC) tornou-se rapidamente o método preferido para excluir ou confirmar o diagnóstico de EP4-6. No entanto, a incerteza permanece sobre a sensibilidade da Angio TC (CTA) como único método de diagnóstico, e testes adicionais para a trombose venosa profunda (TVP) tornaram-se parte integrante da maioria dos algoritmos diagnósticos7. A venografia por TC (CTV) tem uma precisão comparável com a da ultrassonografia de compressão (USC) para o diagnóstico da TVP8, com a vantagem adicional de ser realizada em conjunto com a CTA (CTA/CTV). A combinação de CTA e CTV é uma estratégia muito conveniente porque é capaz, ao mesmo tempo e sem material de contraste adicional, de detectar embolias na circulação pulmonar e trombos residuais nas veias profundas das pernas2,8, embora os pacientes devam ser expostos a radiação adicional.
Os objetivos deste estudo foram determinar o valor diagnóstico da adição de CTV à CTA e avaliar os resultados clínicos após um CTA/CTV normal, como único teste de diagnóstico em pacientes não selecionados, com suspeita clínica de EP.
Um algoritmo baseado em TC que usa a combinação de CTA e CTV tem sido o melhor método diagnóstico de EP desde 1999 em nossa instituição, um hospital não acadêmico de alta complexidade. Usando o banco de dados do departamento de radiologia, relacionamos em forma retrospectiva todos os pacientes com suspeita clínica de EP, que foram investigados com CTA/CTV, entre janeiro de 2004 e dezembro de 2007. Isso representa uma população não selecionada, uma vez que as cintilografias ventilação-perfusão (V/Q) foram realizadas somente quando havia contraindicações para o uso de material de contraste, e a medida de D-Dimer não havia sido incorporada ao nosso algoritmo diagnóstico na época do recrutamento de pacientes para o estudo. Com base no relatório do radiologista, os estudos foram classificados da seguinte forma: positivo para EP, EP e TVP ou TVP isolada, negativo e inconclusivo. Os pacientes com estudos inconclusivos foram excluídos por limitações técnicas. Os pacientes com estudos negativos foram contatados por telefone, a fim de verificar a ocorrência de eventos tromboembólicos venosos recorrentes ou morte durante o período de seis meses que se seguiram ao CTA/CTV. Os pacientes que usavam anticoagulantes orais em qualquer momento e por qualquer período, dentro desse período de seis meses, também foram excluídos. Todos os dados clínicos e demográficos foram obtidos a partir do gráfico médico, registros radiológicos ou diretamente dos pacientes. A probabilidade clínica de EP foi estimada com base nos seguintes fatores de risco: neoplasia maligna (excluindo o câncer de pele); tromboembolismo venoso prévio; cirurgia dentro do mês da CTA/CTV (intra-abdominal, torácica e cirurgia ortopédica) e pacientes acamados. A presença de pelo menos um dos fatores de risco acima identificou o grupo de alto risco. O grupo de baixo risco foi composto de pacientes com nenhum dos fatores de risco9.
Durante a entrevista por telefone os pesquisadores utilizaram um questionário padronizado para determinar as condições de vida e as circunstâncias da morte, a ocorrência de eventos tromboembólicos venosos e uso de anticoagulantes. A causa da morte foi determinada com base na informação presente no atestado de óbito, prontuários dos pacientes, e em informações coletadas dos membros da família. A morte foi atribuída à EP se foi precedida por sintomas sugestivos de tromboembolismo venoso recorrente (TEV), se foi repentina, sem outra causa plausível ou se foi confirmada na autópsia. Um evento tromboembólico venoso recorrente foi definido como EP ou TVP confirmada por testes objetivos, ou morte atribuída à EP ocorrida dentro do período de seis meses após o estudo de TC.
O protocolo do estudo está em conformidade com as diretrizes éticas da Declaração de Helsinque de 1975, foi aprovado pelo Comitê de Ética em Pesquisa e o consentimento verbal foi obtido de todos os pacientes (IRB: MCO/UFBA - n° 70/2004).
Todos os estudos foram realizados em um tomógrafo GE, helicoidal de alta velocidade e detector único (General Electric Medical Systems, Milwaukee, Wisconsin). Os pulmões foram escaneados a partir da porção mais baixa do diafragma até cerca de 2 cm acima do arco aórtico em apneia de 25-30-segundos, e imagens sequenciais de 5 mm de espessura das extremidades inferiores foram adquiridas a intervalos de 2 cm, a partir de aproximadamente 10 cm acima da fossa poplítea até imediatamente acima da crista ilíaca, 3 minutos depois de terminada a CTA. Para todos os estudos, foram administrados 150 mL de contraste por via intravenosa a uma taxa de 3 mL por segundo.
Um total de 425 pacientes com suspeita de EP foi investigado com CTA/CTV. As características gerais dessa população são apresentadas na
Dos 425 estudos de CTA/CTV, apenas 9 (2,1%) foram considerados inconclusivos. Sessenta e dois pacientes (14,6%) tiveram exames positivos, e desses, 14 (22,6%) tinham EP isolada, 35 (56,4%) tinham EP e TVP, e 13 (21%) tinham TVP isolada (
Um total de 354 pacientes (83,3%) apresentaram estudos de CTA/CTV negativos. Durante o acompanhamento, 20 pacientes receberam anticoagulantes orais e foram excluídos: TEV previa (6); fibrilação atrial (6), insuficiência cardíaca (3); prótese valvar (2); lúpus + anticorpos antifosfolipídios (2); trombose arterial periférica (1). Além disso, 14 pacientes não puderam ser contatados e também foram excluídos. Os restantes 320 pacientes formaram nossa coorte retrospectiva.
Durante os seis meses de acompanhamento, eventos tromboembólicos venosos recorrentes foram diagnosticados em 3 dos 320 doentes com uma investigação inicialmente negativa (0,9%, IC 95% - 0,1% - 2,0%). Desses, 2 pacientes tiveram EP (0,6%) e 1 paciente, TVP (0,3%). O primeiro paciente apresentou dor precordial aos sete dias em uma internação para investigação de dor abdominal. A CTA/CTV foi negativa para TEV, mas um duplex scan realizado no mesmo dia revelou uma trombose parcial envolvendo as veias tibial e poplítea esquerdas. O segundo paciente com diagnóstico de longa data de insuficiência cardíaca congestiva apresentava dispneia progressiva. O CTA/CTV mostrou somente uma importante efusão pleural direita. Ela foi submetida a toracocentese terapêutica e três dias depois, já que os sintomas não diminuíam, uma nova CTA/CTV foi ordenada. Dessa vez, foi visualizado um êmbolo na artéria pulmonar interlobar direita. A terceira paciente ingressou no pronto-socorro com dispneia e a CTA/CTV não mostrou TEV. Ela recebeu alta e retornou dez dias depois, com piora dos sintomas. Uma nova CTA/CTV revelou êmbolos subsegmentares bilaterais.
O valor preditivo negativo calculado de CTA/CTV para TEV recorrente foi de 99,1%. A taxa de recorrência foi de 1,0% (IC 95% - 0,4% - 2,5%) e 0,8% (IC 95% - 0,8% - 2,3%) em pacientes de baixo e alto risco, respectivamente (
Desenvolver uma estratégia de diagnóstico simples, prática e segura, que seja amplamente disponível e aplicável para a maioria dos pacientes com suspeita de EP, é um objetivo altamente desejável. Nos últimos 20 anos, as estratégias de diagnóstico de EP se caracterizaram pelo número excessivo de exames sequenciais, longos períodos de diagnóstico e frequente necessidade de procedimentos invasivos10. A introdução de CTA pulmonar11, e subsequentemente CTV12 de membros inferiores, apresentou a possibilidade de vencer a maioria das limitações nas estratégias de diagnóstico mais velhas. O presente estudo confirma o significativo valor incremental de diagnóstico da CTV, que pode ser usada no lugar da USC, e a utilidade clínica da CTA/CTV para descartar o diagnóstico de EP, com segurança, como único teste de diagnóstico.
A precisão da CTV foi demonstrada em uma recente meta-análise de 13 estudos comparativos com USC (com exceção de um estudo que usava venografia), com estimativas combinadas de sensibilidade e especificidade de 96% e 95%, respectivamente8. Embora a maioria das diretrizes e especialistas recomende estudos de imagem de membros inferiores antes de descartar, com segurança, a EP, particularmente em pacientes com risco moderado a elevado7,13, alguns autores têm reclamado um debate quanto à necessidade absoluta para a busca sistemática de TVP em todos os pacientes com um CTA inicialmente negativa14,15. Nossos dados mostraram que 21% dos eventos de TEV eram TVP isolada detectada na CTV (13/61 pacientes), o que significa que esses pacientes com CTA negativas teriam sido indevidamente classificados como não tendo TEV e deixada sem tratamento. Encontramos um valor diagnóstico incremental de CTV para toda a população de 3,1% (IC 95% 1,4% - 4,7%). Esses dados estão de acordo com a literatura atual, que mostra valores incrementais que variam de 2,0% para 5,0%9,16-18, considerando toda a população estudada, em vez de apenas os casos de TEV. Mais recentemente, o estudo II PIOPED reiterou a importância dos testes sistemáticos de TVP, mostrando uma sensibilidade de 90% com o protocolo combinado CTA/CTV, em oposição a 83% com apenas o CTA2. Também conseguimos identificar um subgrupo de pacientes com maior probabilidade de EP, no qual o valor incremental de CTV foi de aproximadamente quatro vezes maior quando comparados com pacientes de baixo risco (5,5%
Outra contribuição importante do presente estudo é a demonstração de que uma estratégia baseada apenas no CTA/CTV está associada a desfechos favoráveis. Nossos dados mostraram que em pacientes que tiveram inicialmente CTA/CTV negativo, a anticoagulação poderia ter sido evitada, independentemente da probabilidade clínicas antes dos testes. Encontramos uma taxa de TEV recorrente de 0,9% durante os seis meses após o teste negativo, achado similar ao relatado por outros autores e outras estratégias de diagnóstico. Uma revisão sistemática de todos os estudos prospectivos utilizando angiografia pulmonar convencional mostrou que pacientes com resultados negativos tiveram uma taxa global de TEV recorrente de 1,719. Moores e cols.20 relataram resultados semelhantes em uma meta-análise mais recente sobre resultados de pacientes estudados com CTA, com uma taxa de TEV subsequente, após três meses de um teste negativo, de 1,4% (95% IC 1,1% - 1,8%). Segundo nosso melhor conhecimento, o outro estudo que utilizou o resultado CTA/CTV como o único teste de diagnóstico contou com apenas 181 pacientes da unidade de terapia intensiva, acompanhados por um mês, e encontrou um valor preditivo negativo de 97,121. O PIOPED II2, uma das investigações mais importantes sobre a precisão da CTA/CTV para o diagnóstico da EP, não relatou formalmente os resultados. Os autores utilizaram um padrão de referência composto compreendendo um número de testes não invasivos, a fim de excluir ou confirmar o diagnóstico de EP, e concluiu que a CTA/CTV foi diagnóstica apenas quando a avaliação clínica e os resultados dos testes eram concordantes. Testes adicionais foram recomendados em casos de inconsistências entre a avaliação de probabilidade clínica e resultados de imagem. O nosso estudo, por sua vez, mostrou valores preditivos negativos muito semelhantes, independentemente da probabilidade clínica pré-teste (
Os investigadores de PIOPED utilizaram um padrão de referência composto para diagnosticar e excluir a EP, que incluiu varredura de V/Q, USC de membros inferiores, e em 225 pacientes (27%) Angiografia Pulmonar Convencional (CPA). No nosso estudo, por sua vez, foram utilizados os resultados clínicos após a CTA/CTV como medida de segurança da estratégia de diagnóstico. A precisão de um teste diagnóstico é normalmente medida comparando seu desempenho com um padrão de referência ouro, e no caso de EP, a CPA tem sido considerada o teste de referência. No entanto, além de sua natureza invasiva, a CPA também tem suas próprias limitações no que diz respeito à precisão e concordância interobservador22,23. Tais limitações no padrão de referência comprometem parcialmente a avaliação das características de diagnóstico de novos testes. Estudos de resultados, por sua vez, avaliam novos testes diagnósticos com base na ocorrência de eventos clínicos após a aplicação dos testes, e não dependem das características diagnósticas de um ensaio de referência, assim, superam essas limitações.
Nosso estudo utilizou apenas TC com detector único (TCDU), e se os nossos resultados se aplicariam a uma tecnologia mais nova é discutível. O TC Multidetectores (TCMD) é tecnologia de ponta para o diagnóstico da EP, embora um número considerável de centros médicos no mundo ainda use o TCDU. A sensibilidade para o diagnóstico da EP melhorou de 66%-93%24 com TCDU a 83%-100% com TCMD2,25. Apesar dessa melhoria da sensibilidade, em alguns estudos, a utilização de TCMD não demonstrou reduzir a importância da CTV quando adicionada à CTA2,17. Portanto, a utilização de ambos os testes foi recomendada pela maioria dos investigadores do PIOPED II26. Além disso, em estudos de resultados, apesar de poder diagnosticar mais embolias pulmonares, a TCMD mostrou taxas de recorrência muito semelhantes, quando comparada com a TCDU3,15,27. Como a maioria das embolias diagnosticadas com TCMD são subsegmentares e o incremento na precisão do diagnóstico não se traduziu em melhores resultados, alguns autores lançaram dúvidas sobre o significado clínico da EP pequena e periférica, e aumentou a preocupação do sobrediagnóstico28. A embolia subsegmentar isolada responde por menos de 10% de todas as EP29, e quando não tratada tem sido associada com bons desfechos30,31. Em recente publicação, os autores relataram resultados clínicos de três meses de 93 pacientes nos quais tinham sido achadas embolias subsegmentares isoladas. No final do período de acompanhamento, nenhum dos pacientes que não receberam anticoagulação tinha apresentado evento recorrente30, achado confirmado em outra serie31. Um relatório interessante mostrou que a localização e o tamanho das embolias subsegmentares detectadas na CPA eram inconsistentes com os achados clínicos, radiológicos e cintilográficos, sugerindo que as microembolias isoladas são achados casuais, sem significância clínica32. Na verdade, a PE encontrada incidentalmente em tomografia com contraste, realizada por diferentes razões, é observada em cerca de 2% dos pacientes hospitalizados33.
Grandes estudos prospectivos recentes usando a CTA multidetector têm, no entanto, favorecido a sua utilização como teste independente34,35. Perrier e cols.34 avaliaram se uma estratégia de medida D-dimer e a TCMD, sem uso de USC ou CTV, pode descartar com segurança a EP. Todos os pacientes com resultados negativos na CTA foram submetidos a USC, mas apenas uma pequena proporção deles apresentou TVP (0,9%, IC 95% 0,3% - 2,7%)34. O mesmo grupo de investigadores testou a mesma hipótese em um estudo randomizado e demonstrou que, independentemente de se a estratégia de diagnóstico incluía a USC, o risco tromboembólico aos três meses era exatamente o mesmo35. É importante salientar que ambos os estudos recrutaram apenas um pequeno número de pacientes de alto risco, e, como demonstrado pelo presente estudo com TCDU e por outros com MDCT17, a utilização sistemática de CTV está associada com um valor diagnóstico incremental significativo e provavelmente deveria ser recomendado para esses pacientes de alto risco, independentemente da tecnologia utilizada.
Primeiro, como uma coorte retrospectiva, nosso estudo pode sofrer vieses inerentes ao processo de coleta de dados retrospectiva, revisão de prontuários e lembranças dos pacientes. Em segundo lugar, 14 pacientes com CTA/CTV inicialmente negativo não puderam ser contatados e foram, portanto, excluídos. A revisão das características clínicas desses pacientes revelou um grupo de indivíduos jovens e de baixo risco. A média de idades foi de 52 ± 16 anos, 50% eram do sexo feminino e nenhum deles apresentou um alto risco, conforme definido no presente estudo. Se considerarmos a taxa de recorrência encontrada em nossos pacientes de baixo risco (1,0%), seria de esperar, no máximo, apenas uma única recorrência de TEV adicional. Nesse caso, o número total de eventos de TEV recorrente seria 4 de 320 (1,2%, 95% CI 0,0% - 2,5%) e, portanto, não iria comprometer os resultados globais e as conclusões.
Até onde nosso conhecimento alcança, este é o primeiro estudo de resultados que utiliza uma combinação de CTA e CTV com único detector, como teste de diagnóstico único em pacientes não selecionados com suspeita de EP. Ao contrário da maioria dos estudos de resultados previamente publicados, este foi realizado inteiramente num hospital comunitário de alta complexidade, e assim, mais perto do ambiente onde pratica a maioria dos médicos internos. O nosso estudo sugere que a adição de CTV à CTA resulta em um aumento significativo no número de pacientes com diagnóstico de TEV, particularmente no grupo de alto risco. Além disso, uma estratégia que usa CTA/CTV como o único teste diagnóstico para descartar a EP está associada a resultados muito favoráveis, e parece ser segura na maioria dos pacientes com suspeita de EP. Essa estratégia deve ser testada em grandes estudos prospectivos e utilizando tecnologia de ponta.
Declaro não haver conflito de interesses pertinentes.
O presente estudo não teve fontes de financiamento externas.
Não há vinculação deste estudo a programas de pós-graduação.
1. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-53.
2. Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317-27.
3. van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, et al; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-9.
4. Stein PD, Kayali F, Olson RE. Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism. Am J Cardiol. 2004;93(10):1316-7.
5. Mullins MD, Becker DM, Hagspiel KD, Philbrick JT. The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism. Arch Intern Med. 2000;160(3):293-8.
6. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000;132(3):227-32.
7. Fedullo PF, Tapson VF. Clinical practice: the evaluation of suspected pulmonary embolism. N Engl J Med. 2003;349(13):1247-56.
8. Thomas SM, Goodacre SW, Sampson FC, van Beek EJ. Diagnostic value of CT for deep vein thrombosis: results of a systematic review and meta-analysis. Clin Radiol. 2008;63(3):299-304.
9. Hunsaker AR, Zou KH, Poh AC, Trotman-Dickenson B, Jacobson FL, Gill RR, et al. Routine pelvic and lower extremity CT venography in patients undergoing pulmonary CT angiography. AJR Am J Roentgenol. 2008;190(2):322-6.
10. Perrier A, Bounameaux H, Morabia A, de Moerloose P, Slosman D, Didier D, et al. Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study. Arch Intern Med. 1996;156(5):531-6.
11. Remy-Jardin M, Remy J, Wattinne L, Giraud F. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. Radiology. 1992;185(2):381-7.
12. Loud PA, Grossman ZD, Klippenstein DL, Ray CE. Combined CT venography and pulmonary angiography: a new diagnostic technique for suspected thromboembolic disease. AJR Am J Roentgenol. 1998; 170(4):951-4.
13. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-315.
14. Perrier A, Howarth N, Didier D, Loubeyre P, Unger PF, de Moerloose P, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001;135(2):88-97.
15. Van Strijen MJL, de Monye W, Schiereck J, Kleft GJ, Prins MH, Hulsman MV, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med. 2003;138(4):307-14.
16. Richman PB, Wood J, Kasper DM, Collins JM, Petri RW, Field AG, et al. Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments. J Thromb Haemost. 2003;1(4):652-7.
17. Ghaye B, Nchimi A, Noukoua CT, Dondelinger RF. Does multi-detector row CT pulmonary angiography reduce the incremental value of indirect CT venography compared with single-detector row CT pulmonary angiography? Radiology. 2006;240(1):256-62.
18. Nazaroğlu H, Ozmen CA, Akay HO, Kilinç I, Bilici A. 64-MDCT pulmonary angiography and CT venography in the diagnosis of thromboembolic disease. AJR Am J Roentgenol. 2009;192(3):654-61.
19. van Beek EJ, Brouwerst EM, Song B, Stein PD, Oudkerk M. Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review. Clin Radiol. 2001;56(10):838-42.
20. Moores LK, Jackson WL Jr, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med. 2004;141(11):866-74.
21. Ravenel JG, Northam MC, Nguyen SA. Negative predictive value of computed tomography pulmonary angiography with indirect computed tomography venography in intensive care unit patients. J Comput Assist Tomogr. 2009;33(5):739-42.
22. Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman , et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation. 1992;85(2):462-8.
23. Quinn MF, Lundell CJ, Klotz TA, Finck EJ, Pentecost M, McGehee WG, et al. Reliability of selective pulmonary arteriography in the diagnosis of pulmonary embolism. AJR Am J Roentgenol. 1987;149(3):469-71.
24. Eng J, Krishnan JA, Segal JB, Bolger DT, Tamariz LJ, Streiff MB, et al. Accuracy of CT in the diagnosis of pulmonary embolism: a systematic literature review. AJR Am J Roentgenol. 2004;183(6):1819-27.
25. Winer-Muram HT, Rydberg J, Johnson MS, Tarver RD, Williams MD, Shah H, et al. Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus digital subtraction pulmonary arteriography. Radiology. 2004;233(3):806-15.
26. Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med. 2006;119(12):1048-55.
27. Prologo JD, Gilkeson RC, Diaz M, Cummings M. The effect of single-detector CT vs MDCT on clinical outcomes in patients with suspected acute pulmonary embolism and negative results on CT pulmonary angiography. AJR Am J Roentgenol. 2005;184(4):1231-5.
28. Goodman LR, Lipchik RJ. Diagnosis of acute pulmonary embolism: time for a new approach. Radiology. 1996;199(1):25-7.
29. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA. 1990;263(20):2753-9.
30. Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res. 2010;126(4):e266-70.
31. Eyer BA, Goodman LR, Washington L. Clinicians’ response to radiologists’ reports of isolated subsegmental pulmonary embolism or inconclusive interpretation of pulmonary embolism using MDCT. AJR Am J Roentgenol. 2005 Feb;184(2):623-8.
32. Lette J, Cerino M, Eybalin MC, Levasseur A. Prevalence and clinical significance of solitary pulmonary sub-segmental microembolism. Nucl Med Rev Cent East Eur. 2004;7(1):39-42.
33. Gosselin MV, Rubin GD, Leung AN, Huang J, Rizk NW. Unsuspected pulmonary embolism: prospective detection on routine helical CT scans. Radiology. 1998 Jul;208(1):209-15.
34. Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005;352(17):1760-8.
35. Righini M, Le Gal G, Aujesky D, Roy PM, Sanchez O, Verschuren F, et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomized non-inferiority trial. Lancet. 2008;371(9621):1343-52.
Correspondência: Eduardo S. Darze Serviço de Medicina Cardiovascular. Instituto Cárdio Pulmonar Av. Garibaldi, 2199, 3º andar CEP 40170-130, Salvador, BA &– Brasil E-mail:
Artigo recebido em 30/07/11, revisado em 02/08/11, aceito em 03/02/12
BACKGROUND: The diagnosis of pulmonary embolism (PE) still requires long work-up periods and multiple tests. OBJECTIVE: We aim to assess clinical outcomes after a negative investigation using a combined protocol of CT pulmonary angiography and CT venography (CTA/CTV) as a sole diagnostic test in unselected patients with suspected PE. METHODS: This retrospective cohort study enrolled consecutive patients with suspected PE who were investigated with a combined CTA/CTV protocol. Patients who had an initially negative investigation and were not anticoagulated were followed for 6 months for the occurrence of recurrent venous thromboembolic events. RESULTS: Out of 425 patients with suspected PE, 62 (14.6%) had venous thromboembolism diagnosed on the initial CTA/CTV. The mean age was 56 ± 19 years and 61% of the population fell into the low clinical probability category. Isolated deep vein thrombosis represented 21% of all venous thromboembolic events, and when considering the whole population, CTV was associated with an increment in diagnostic yield of 3.1%. Our cohort was composed of 320 patients with initially negative CTA/CTVs and who were not anticoagulated. After 6 months of follow up, only three patients presented with recurrent thromboembolic events (0.9%; 95% CI -0.1% - 2.0%) and none was fatal. There were no PE-related deaths. CONCLUSION: Our study suggests that a diagnostic strategy that utilizes CTA/CTV as a sole diagnostic test can safely rule out PE in a low to moderate risk population and is associated with favorable outcomes with a negative predictive value of 99.1%. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)
Clinical outcomes after investigation for pulmonary embolism using CT angiography and venography
IInstituto Cárdio Pulmonar, Salvador, BA
IIHospital Aliança, Salvador, BA
IIIUniversidade Federal de Bahia, Salvador, BA
IVSanta Casa de Misericórdia, Salvador, BA
VHospital Sírio-Libanês, São Paulo, SP - Brazil
VIHospital Beneficência Portuguesa, São Paulo, SP - Brazil
The majority of patients with clinically suspected pulmonary embolism (PE) has an alternative diagnosis for their symptoms, and the prevalence of confirmed PE among these suspected cases ranges from 16% to 26% in contemporary series1-3 .Thus, one of the greatest challenges in the work up of PE is to rapidly and safely rule out the disease, avoiding unnecessary anticoagulation and expediting the diagnostic strategy.
Computed tomography (CT) has rapidly become the preferred method for excluding or confirming the diagnosis of PE4-6.However, uncertainty remains about the sensitivity of pulmonary CT angiography (CTA) as a single diagnostic method, and additional testing for deep vein thrombosis (DVT) has become an integral part of most diagnostic algorithms7. CT venography (CTV) has comparable accuracy as compression ultrasonography (CUS) for the diagnosis of DVT8 with the added advantage of being performed in conjunction with CTA (CTA/CTV). The combination of CTA and CT venography is a very attractive strategy because it is able, at the same time and with no additional contrast material, to detect emboli in the pulmonary circulation and residual thrombi in the deep veins of the legs2,8, although it exposes the patients to additional radiation.
The goals of this study were to determine the diagnostic value of adding CTV to CTA and assess clinical outcomes after a normal CTA/CTV as a sole diagnostic test in unselected patients with clinically suspected PE.
A CT based algorithm that uses the combination of CTA and CTV has been the method of choice for the work up of PE since 1999 at our institution, a tertiary care non-academic hospital. Using the radiology department's database, we retrospectively enrolled all patients with clinically suspected PE who were investigated with a CTA/CTV between January 2004 and December 2007. This represents an unselected population since ventilation-perfusion (V/Q) scintigraphies were performed only when there were contra-indications for the use of contrast material, and D-Dimer measurement had not been incorporated into our diagnostic algorithm at the time of patient recruitment for the study. Based on the report of the interpreting radiologist the studies were classified as following: positive for PE, PE and DVT or isolated DVT, negative and inconclusive. Patients were excluded if they had inconclusive studies due to technical limitations. Patients with negative studies were contacted by telephone in order to verify the occurrence of recurrent venous thromboembolic events or death during the 6-month period that followed the CTA/CTV. The patients that used oral anticoagulants at any time and for any duration within this 6-month period were also excluded. All clinical and demographic data were obtained from the medical chart, radiological records or directly from the patients. A clinical probability of PE was estimated based on the following risk factors: malignancy (excluding skin cancer); previous venous thromboembolism; surgery within a month the CTA/CTV (Intra-abdominal, thoracic and orthopedic surgery) and bed-ridden state. The presence of at least one of the above risk factors identified the high-risk group. The low-risk group was comprised of patients with none of the risk factors9.
During the telephone interview, the investigators utilized a standardized questionnaire to determine life status and circumstances of death, occurrence of venous thromboembolic events and use of anticoagulation. The cause of death was determined based on the information present in the death certificate, the patients' charts, and on information collected from the family members. Death was attributed to PE if it was preceded by symptoms suggestive of recurrent venous thromboembolism (VTE), if it was sudden with no other plausible cause or if it was confirmed on autopsy. A recurrent venous thromboembolic event was defined as PE or DTV confirmed by objective tests, or death attributed to PE occurring within the 6-month period following the CT study.
The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, was approved by the research ethics committee and verbal consent was obtained from all patients (IRB: MCO/UFBA – n° 70/2004).
All studies were performed on a GE High-Speed single-detector helical CT scanner (General Electric Medical Systems, Milwaukee, Wis.). The lungs were scanned from the lowest portion of the diaphragm to approximately 2 cm above the aortic arch during a 25 to 30-second single breath hold and sequential 5 mm-thick images of the lower extremities were acquired at 2 cm intervals from approximately 10 cm bellow the popliteal fossa up to just above the iliac crest, 3 minutes after completion of the CTA. For all studies, 150 ml of contrast was administered intravenously at a rate of 3 ml per second.
A total of 425 patients with suspected PE were investigated with a CTA/CTV. The general characteristics of this population are detailed in
Of the 425 CTA/CTV studies only 9 (2.1%) were considered inconclusive. Sixty-two patients (14.6%) had positive scans, and of those, 14 (22.6%) had isolated PE, 35 (56.4%) had PE and DVT, and 13 (21%) had isolated DVT (
A total of 354 patients (83.3%) had negative CTA/CTV studies. During follow up, 20 patients received oral anticoagulation and were excluded: Previous VTE (6); atrial fibrillation (6); heart failure (3); valve prosthesis (2); systemic lupus + anti-phospholipid antibodies (2); peripheral arterial thrombosis (1). Additionally, 14 patients could not be contacted and were also excluded. The remaining 320 patients comprised our retrospective cohort.
During the 6-month follow up period, recurrent venous thromboembolic events were diagnosed in three of the 320 patients with an initially negative investigation (0.9%; 95% CI -0.1% - 2.0%). Of these, two patients presented with PE (0.6%) and one other patient with DVT (0.3%). The first patient developed chest pain 7 days into a hospitalization for investigation of abdominal pain. A CTA/CTV was negative for VTE but a duplex scan done on the same day revealed a partial thrombosis involving the left tibial and popliteal veins. The second patient with a long-standing diagnosis of congestive heart failure presented with progressive dyspnea. The CTA/CTV showed only a large right pleural effusion. She was submitted to a therapeutic thoracentesis and three days later, since her symptoms did not abate, a new CTA/CTV was ordered. This time an embolus in the right interlobar pulmonary artery was visualized. A third patient presented to the emergency room with dyspnea and a CTA/CTV did not show VTE. She was discharged home and returned ten days later with worsening symptoms. A new CTA/CTV revealed bilateral subsegmental emboli.
The calculated negative predictive value of CTA/CTV for recurrent VTE was 99.1%. The recurrence rate was 1.0% (95% CI -0.4% - 2.5%) and 0.8% (95% CI -0.8% - 2.3%) in low and high-risk patients, respectively (
The development of a simple, practical and safe diagnostic strategy that is widely available and applicable to the majority of patients with suspected PE is a highly desirable goal. Over the past 20 years, the diagnostic strategies for PE have been marked by an excessive number of sequential tests, long workup periods and the frequent need for invasive procedures10. The introduction of pulmonary CTA11 and subsequently lower extremities CTV12 has presented the possibility of overcoming most of the above limitations of older diagnostic strategies. The current study confirms the significant incremental diagnostic value of CTV, which can be used in place of CUS, and the clinical utility of CTA/CTV for safely ruling out the diagnosis of PE as a sole diagnostic test.
The accuracy of CTV was demonstrated in a recent meta-analysis of 13 studies comparing it with CUS (except one study that used venography), with pooled estimates of sensitivity and specificity of 96% and 95%, respectively8. Although most guidelines and experts recommend lower-extremity imaging before safely ruling out PE, particularly in moderate to high risk patients7,13, some authors have charged the debate as to the absolute need for systematically searching for DVT in all patients with an initially negative CTA14,15. Our data showed that 21% of the VTE events were isolated DVT detected on CTV (13/61 patients), which means that these patients with negative CTAs would have been wrongly classified as not having VTE and left untreated. We found an incremental diagnostic value of CTV for the whole population of 3.1% (95% CI 1.4% - 4.7%). These data are in accordance to the current literature which shows incremental values that varies from 2.0% to 5.0%9,16-18 considering the entire study population rather than only the cases of VTE. More recently, the PIOPED II study reiterated the importance of systematic DVT testing by showing a sensitivity of 90% with the combined CTA/CTV protocol as opposed to 83% with CTA alone2. We were also able to identify a subgroup of patients with a higher probability of PE, in whom the incremental value of CTV was approximately 4-fold greater when compared to low risk patients (5.5% versus 1.5%). Therefore, our data show that CTV may replace CUS in those patients who require DVT testing and also help define a more select group of patients with a higher risk of PE, which may derive a greater diagnostic value from a strategy that combines CTA and CTV, reducing cost and radiation exposure.
Another important contribution of the current study is the demonstration that a diagnostic strategy based solely on CTA/CTV is associated with favorable outcomes. Our data showed that in patients who had an initially negative CTA/CTV, anticoagulation could be safely withheld irrespective of the pre-test clinical probability. We found a VTE recurrent rate of 0.9% during the 6 months that followed the negative test, a finding similar to that reported by other authors and other diagnostic strategies. A systematic review of all prospective studies using conventional pulmonary angiography found that patients with negative results had an overall rate of recurrent VTE of 1.7%19. Moores et al20 reported similar findings in a more recent meta-analysis of outcome studies of patients managed with CTA with a 3-month rate of subsequent VTE after a negative test of 1.4% (95% CI 1.1% - 1.8%). To the best of our knowledge, the only other outcome study that used CTA/CTV as the sole diagnostic test involved only 181 intensive care unit patients followed for one month and found a negative predictive value of 97.1%21. The PIOPED II2, one of the most important investigations on the accuracy of CTA/CTV for the diagnosis of PE, did not formally report outcome data. The authors used a composite reference standard comprising a number of non-invasive tests in order to rule out or confirm the diagnosis of PE and concluded that CTA/CTV was diagnostic only when clinical assessment and test results were concordant. Additional testing was recommended in cases of inconsistencies between the clinical probability assessment and imaging results. Our study, on the other hand, showed very similar negative predictive values regardless of the pre-test clinical probability (
The PIOPED investigators used a composite reference standard to diagnose and rule out PE that included V/Q scans, lower extremities CUS and in 225 patients (27%) conventional pulmonary angiography (CPA). In our study, on the other hand, we used clinical outcomes after CTA/CTV as a measure of safety of the diagnostic strategy. The accuracy of a diagnostic test is usually measured by comparing its performance with a reference gold standard, and in the case of PE, CPA has been considered the reference test. However, besides its invasive nature, CPA also has its own limitations concerning accuracy and interobserver agreement22,23. Such limitations of the reference standard partially compromise the assessment of the diagnostic characteristics of new tests. Outcome studies, on the other hand, assess new diagnostic tests based on the occurrence of clinical events after the tests are applied, and do not rely on the diagnostic characteristics of a reference test, thus, overcoming these limitations.
Our study used only single-detector CT (SDCT) scanners and whether our results are applicable to newer technology is debatable. Multi-detector CT (MDCT) is the state-of-the-art technology for PE diagnosis although a considerable number of medical centers around the world still use SDCT. Sensitivity for the diagnosis of PE has improved from 66%-93%24 with SDCT to 83%-100% with MDCT2,25. In spite of this improvement in sensitivity, in some studies the use of MDCT has not been shown to reduce the importance of CTV when added to CTA2,17. Therefore, the use of both tests were recommended by most PIOPED II investigators26. Additionally, in outcome studies, despite being able to diagnose more pulmonary emboli, MDCT has shown very similar recurrent rates when compared to SDCT3,15,27. Since most additional emboli diagnosed with MDCT are subsegmental and the increment in diagnostic accuracy did not translate into better outcomes, some authors have cast doubts upon the clinical significance of small peripheral PE and raised the concern of overdiagnosis28. Isolated subsegmental emboli answer for less than 10% of all PE29 and when left untreated has been associated with very good outcomes30,31. In a recent publication, the authors reported the 3-month clinical outcomes of 93 patients found to have isolated subsegmental emboli. At the end of the follow up period, none of the patients that did not receive anticoagulation had recurrent events30, a finding confirmed in another series31. An interesting report showed that the location and size of the subsegmental emboli detected on CPA were inconsistent with clinical, radiographic and scintigraphic findings, suggesting that isolated microemboli are serendipitous findings of no clinical significance32. In fact, incidentally found PE on contrast-enhanced CT done for different reasons is seen in approximately 2% of inpatients33.
Nonetheless, recent large prospective studies using multi-detector CTA have favored its use as a stand-alone test34,35. Perrier et al34 have assessed whether a strategy of D-dimer measurement and MDCT, without the use of CUS or CTV, might safely rule out PE. All patients with negative findings on CTA underwent CUS but only a very small proportion of them had DVT (0.9%; 95% CI 0.3% - 2.7%)34. The same group of investigators tested the very same hypothesis in a randomized trial and showed that regardless whether the diagnostic strategy included CUS, the 3-month thromboembolic risk was exactly the same35. It is important to emphasize that both studies recruited only a small number of high risk patients, and, as demonstrated by the current study with SDCT and by others with MDCT17, the systematic use of CTV is associated with a significant incremental diagnostic value and should probably be recommended for these high risk patients independent of the technology utilized.
First, as a retrospective cohort, our study may suffer from biases inherent to the process of retrospectively collecting data, relying upon revision of medical records and patients' recollections. Second, fourteen patients with an initially negative CTA/CTV could not be contacted and were, therefore, excluded. Reviewing these patients' clinical characteristics revealed a group of young and low risk individuals. The mean age was 52 ± 16 years, 50% were females and none of them presented a high-risk feature as defined in this study. If one considers the recurrent rate encountered in our low risk patients (1.0%), one would expect, at most, only a single additional VTE recurrence. In this case, the total number of recurrent VTE events would be 4 out of 320 (1.2%; 95% CI 0.0% - 2.5%) and, therefore, it would not compromise the overall results and conclusions.
To the best of our knowledge, this is the first outcome study to utilize a combination of single detector CTA and CTV as the sole diagnostic test in unselected patients with suspected PE. Unlike the majority of previously published outcome studies, this one was carried out entirely in a tertiary community hospital, and thus, closer to the environment where most internists practice. Our study suggests that the addition of CTV to CTA results in a significant increase in the number of patients diagnosed with VTE particularly in the high-risk group. Additionally, a strategy that uses CTA/CTV as the sole diagnostic test for ruling out PE is associated with very favorable outcomes and appears to be safe in the majority of patients with suspected PE. This strategy ought to be tested in larger prospective studies and utilizing state-of-the-art technology.
No potential conflict of interest relevant to this article was reported.
There were no external funding sources for this study.
This study is not associated with any post-graduation program.
1. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-53.
2. Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317-27.
3. van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, et al; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-9.
4. Stein PD, Kayali F, Olson RE. Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism. Am J Cardiol. 2004;93(10):1316-7.
5. Mullins MD, Becker DM, Hagspiel KD, Philbrick JT. The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism. Arch Intern Med. 2000;160(3):293-8.
6. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000;132(3):227-32.
7. Fedullo PF, Tapson VF. Clinical practice: the evaluation of suspected pulmonary embolism. N Engl J Med. 2003;349(13):1247-56.
8. Thomas SM, Goodacre SW, Sampson FC, van Beek EJ. Diagnostic value of CT for deep vein thrombosis: results of a systematic review and meta-analysis. Clin Radiol. 2008;63(3):299-304.
9. Hunsaker AR, Zou KH, Poh AC, Trotman-Dickenson B, Jacobson FL, Gill RR, et al. Routine pelvic and lower extremity CT venography in patients undergoing pulmonary CT angiography. AJR Am J Roentgenol. 2008;190(2):322-6.
10. Perrier A, Bounameaux H, Morabia A, de Moerloose P, Slosman D, Didier D, et al. Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study. Arch Intern Med. 1996;156(5):531-6.
11. Remy-Jardin M, Remy J, Wattinne L, Giraud F. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. Radiology. 1992;185(2):381-7.
12. Loud PA, Grossman ZD, Klippenstein DL, Ray CE. Combined CT venography and pulmonary angiography: a new diagnostic technique for suspected thromboembolic disease. AJR Am J Roentgenol. 1998; 170(4):951-4.
13. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-315.
14. Perrier A, Howarth N, Didier D, Loubeyre P, Unger PF, de Moerloose P, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001;135(2):88-97.
15. Van Strijen MJL, de Monye W, Schiereck J, Kleft GJ, Prins MH, Hulsman MV, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med. 2003;138(4):307-14.
16. Richman PB, Wood J, Kasper DM, Collins JM, Petri RW, Field AG, et al. Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments. J Thromb Haemost. 2003;1(4):652-7.
17. Ghaye B, Nchimi A, Noukoua CT, Dondelinger RF. Does multi-detector row CT pulmonary angiography reduce the incremental value of indirect CT venography compared with single-detector row CT pulmonary angiography? Radiology. 2006;240(1):256-62.
18. Nazaroğlu H, Ozmen CA, Akay HO, Kilinç I, Bilici A. 64-MDCT pulmonary angiography and CT venography in the diagnosis of thromboembolic disease. AJR Am J Roentgenol. 2009;192(3):654-61.
19. van Beek EJ, Brouwerst EM, Song B, Stein PD, Oudkerk M. Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review. Clin Radiol. 2001;56(10):838-42.
20. Moores LK, Jackson WL Jr, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med. 2004;141(11):866-74.
21. Ravenel JG, Northam MC, Nguyen SA. Negative predictive value of computed tomography pulmonary angiography with indirect computed tomography venography in intensive care unit patients. J Comput Assist Tomogr. 2009;33(5):739-42.
22. Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman , et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation. 1992;85(2):462-8.
23. Quinn MF, Lundell CJ, Klotz TA, Finck EJ, Pentecost M, McGehee WG, et al. Reliability of selective pulmonary arteriography in the diagnosis of pulmonary embolism. AJR Am J Roentgenol. 1987;149(3):469-71.
24. Eng J, Krishnan JA, Segal JB, Bolger DT, Tamariz LJ, Streiff MB, et al. Accuracy of CT in the diagnosis of pulmonary embolism: a systematic literature review. AJR Am J Roentgenol. 2004;183(6):1819-27.
25. Winer-Muram HT, Rydberg J, Johnson MS, Tarver RD, Williams MD, Shah H, et al. Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus digital subtraction pulmonary arteriography. Radiology. 2004;233(3):806-15.
26. Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med. 2006;119(12):1048-55.
27. Prologo JD, Gilkeson RC, Diaz M, Cummings M. The effect of single-detector CT vs MDCT on clinical outcomes in patients with suspected acute pulmonary embolism and negative results on CT pulmonary angiography. AJR Am J Roentgenol. 2005;184(4):1231-5.
28. Goodman LR, Lipchik RJ. Diagnosis of acute pulmonary embolism: time for a new approach. Radiology. 1996;199(1):25-7.
29. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA. 1990;263(20):2753-9.
30. Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res. 2010;126(4):e266-70.
31. Eyer BA, Goodman LR, Washington L. Clinicians’ response to radiologists’ reports of isolated subsegmental pulmonary embolism or inconclusive interpretation of pulmonary embolism using MDCT. AJR Am J Roentgenol. 2005 Feb;184(2):623-8.
32. Lette J, Cerino M, Eybalin MC, Levasseur A. Prevalence and clinical significance of solitary pulmonary sub-segmental microembolism. Nucl Med Rev Cent East Eur. 2004;7(1):39-42.
33. Gosselin MV, Rubin GD, Leung AN, Huang J, Rizk NW. Unsuspected pulmonary embolism: prospective detection on routine helical CT scans. Radiology. 1998 Jul;208(1):209-15.
34. Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005;352(17):1760-8.
35. Righini M, Le Gal G, Aujesky D, Roy PM, Sanchez O, Verschuren F, et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomized non-inferiority trial. Lancet. 2008;371(9621):1343-52.
Mailing Address: Eduardo S. Darze Cardiovascular. Instituto Cárdio Pulmonar Av. Garibaldi, 2199, 3º floor Postal Code 40170-130, Salvador, BA – Brazil E-mail:
Manuscript received July 30, 2011; manuscript revised August 02, 2011; accepted February 03, 2012.