Jornal Vascular Brasileiro
https://app.periodikos.com.br/journal/jvb/article/doi/10.1590/jvb.2014.040
Jornal Vascular Brasileiro
Editorial

Abdominal aortic aneurysm: while there is still no cure, the key question is which patients to select for intervention and which intervention to select!

Aneurisma da aorta abdominal: enquanto a cura não vem, a seleção do paciente para intervenção e qual intervenção é a questão!

Erasmo Simão da Silva

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In 1952, Dubost et al.1 began the era of effective repair of aneurysms of the infrarenal aorta using homologous cadaveric aorta grafts, after aneurysmectomy. Development of arterial substitutes, more rigorous surgical techniques, better understanding of the disease, and the advent of ultrasonography which increased diagnoses and perfected preoperative, intraoperative (anesthesia) and postoperative clinical control, surgery for infrarenal aneurysms came to be routine and results became ever more encouraging. The prospect of effective treatment began to raise doubts with relation to which patients with asymptomatic aneurysms were suitable candidates for treatment. An understanding of the natural history of the disease became indispensable and many studies were conducted to investigate this subject.

As the number of patients operated increased, it became clear that, although mortality rates linked to elective conventional surgery exhibited a reduction over the years (17.4% to 5.0% in 20 years,2 between 2.5% and 3.5% in Brazil),3 - 5 mortality from ruptured aneurysms remained elevated (over 50%).6 This finding led to an aggressive approach to treatment of aneurysms, with surgery prescribed even for low risk patients, the elderly and patients with aneurysms considered to be small.7 , 8 While this approach does eliminate the possibility of rupture in these patients, a considerable contingent of individuals, with small aneurysms, would be subjected to major surgical operations, which are never risk free and may be unnecessary, since many aneurysms remain stable9 , 10 and 75% of people who have aneurysms die of other diseases,11 in particular cardiovascular conditions.

It therefore became imperative to establish which patients are at greater risk of aneurysm rupture, in other words, which factors influence rupture of infrarenal aortic aneurysms.

Estes12 reported in 1952 that the primary cause of death among patients with abdominal aneurysms was rupture and, in second place, coronary disease. In 1962, Shatz et al.13 recorded a reduction in the number of ruptures, associated with the spread of surgical treatment of aneurysms. These authors considered aneurysms with a maximum transverse diameter of up to 7.5 cm to be small. These observations were corroborated by Szilagui et al. in 1966,14 who claimed that surgical repair of aneurysms resulted in equal survival to that observed in the normal population and recommended surgical treatment when the maximum aneurysm diameter reached 6.0 cm. Hollier et al.15 demonstrated that coronary disease limited survival of patients after aneurysm repair.

Currently, there is consensus that the single most important risk factor for rupture of an abdominal aortic aneurysm (AAA) is its maximum transverse diameter and this is therefore the factor that is most often used when prescribing surgery. Analysis of several different studies showed that larger aneurysms are more prone to rupture than those with smaller diameters.9 , 16

Controlled studies17 , 18 concluded that aneurysms with largest diameters of up to 55 mm in men and up to 50 mm in women have low rates of rupture. The threshold diameter for indication of interventions was therefore defined. However, other studies recommended that aneurysms from 4.0 to 5.0 cm should also be candidates for surgery,7 , 8 justifying this by the low mortality rates of elective surgery and the high mortality related to rupture.

It was against this backdrop that, from 1991 onwards, an important new factor began to make its own contribution to increasing the debates and controversy related to AAA: endovascular aneurysm repair (EVAR). It has been proven that this procedure offers favorable mortality and morbidity compared with traditional open repair, both during the perioperative period and during short-term patient follow-up.19 - 21 However, over the long-term EVAR has exhibited a higher incidence of failures with more frequent need for reoperation and a worrying number of ruptures.22 - 24 Added to this is the daunting requirement for follow-up with tomographic imaging studies, immediately and over the medium and long term. However, the discussion appears far from over because endoprostheses are always in a constant state of development and are achieving ever better long-term results. Technical developments are a challenge to randomized studies because by the time the results are published, the prosthesis, the technique and the experience have all moved on, reducing the study's external validity.25 In turn, diagnostic imaging methods for monitoring progress have also improved and follow-up is already being conducted using Doppler ultrasonography, Doppler ultrasonography with contrast and, just beginning, 3-D Doppler ultrasonography.26 , 27

Once more, selection of patients for intervention (endovascular or conventional) or observation can be based on a greater quantity of information and has become even more controversial.

Two features that are invariably highlighted are patients' clinical risk and the anatomy of the AAA, with relation to the neck and the iliac vessels. A patient with favorable anatomy and high risk should be selected for EVAR. A patient with low risk and unfavorable anatomy should be prescribed traditional open repair. But what is low and high risk? What is an unfavorable anatomy? These are concepts that are difficult to apply in real life. More and more often, endoprostheses are being employed outside of the applications in their Information for Use documentation.28 Ask a young vascular surgeon fresh out of residency. What would he tend to choose for AAA repair, bearing in mind that during his training he observed that 60 to 75% of AAAs are repaired by EVAR? With which technique can he explore the limits? Is he subject to a conflict of interests when choosing between one or another endoprosthesis? The patient is informed about techniques and already has a preference. Would the young surgeon know how to deal with this? In short, would he do what is best for the patient or what is 'modern'? Would he do what the patient requests or, rather, what the industry dictates?

Studies show that EVAR has better outcomes when used to repair small aneurysms, because of less remodeling of the aneurysm sac, when compared with large aneurysms.29 It is important to observe that, as the aneurysm grows in diameter it loses its proximal and distal necks and progresses to involve the iliac vessels,30 limiting use of EVAR. However, in countries whose health services map their populations, the number of patients selected for repair could double if the maximum diameter lower cutoff for indicating intervention for AAAs were to be reduced.31 , 32 The impact of the cost of such a policy is obvious.33

Considering that just 25% of aneurysms that are detected do actually rupture,11 , 34 it is clear that the most obvious option would be to identify which patients are candidates for this outcome.

Large transverse diameter is not an excellent indicator of rupture, since there are small AAAs that rupture and large ones that remain intact.

Analysis of the risk factors of rupture is important and should not be undervalued. The following predisposing situations have been identified:

• Young patients;

• Women;

• Active smokers;

• Patients with family history;

• Severe hypertension;

• Patients with COPD;

• Non-diabetics.

These factors are important, but are not sufficient to determine indications, because people who are at high risk from intervention may have all of these risk factors and yet the risks may still outweigh the benefits.

From a biomechanical point of view, an AAA ruptures when, at a given point in the wall, resistance reduces below the tension exerted against it.

Studies that have analyzed and calculated stress against the walls of AAAs, with a view to substituting diameter as a criterion for intervention, are very far from perfect although they have great appeal in terms of publication and dissemination in the medical world.35 , 36 In order to perform this calculation, three types of information are needed: the geometry of the AAA/thickness of the wall, the forces acting and counteracting against the wall and, finally, information about the mechanical properties of the wall. To date, AAA geometry has been based on tomography or magnetic resonance imaging; it is possible that in future 3-D Doppler USG will be used. The thickness of the wall cannot be measured on an individual basis with any clinically applicable method currently available and so a constant thickness (15 to 25 mm) is used in the stress calculation. The forces acting against the wall are based on arterial blood pressure, but the counteracting forces, exerted by the retroperitoneum and neighboring organs cannot be measured. In the field of the mechanical properties of the wall, Doppler ultrasonography can measure displacement of the wall (strain) in biplanar mode. Destructive methods used on specimens taken from people during operations are limited to samples from the anterior surface of the aneurysm, from a more complex whole. Samples of AAAs removed from cadavers make it possible to study several segments, but not all, using uniaxial or biaxial destructive testing (on a structure that is subject to multi axial forces).37 , 38 There are, therefore, severe limitations to knowledge about the biomechanical properties of the walls of AAAs.

In addition to these mechanical aspects of what is an entirely heterogeneous structure, there is also the question of mechanobiology, i.e., how the thrombus interacts with the wall. Does this thrombus protect the AAA from rupture or help to degrade still further the already destroyed wall?39 Does it interfere with proteolytic enzymes - elastases and collagenases - and their inhibitors,40 with the genetic expression of repair proteins, and with flow characteristics and their cellular interaction on remodeling of the wall?41

When imaging methods provide information on the thickness of the entire aneurysm (including points of weakness: blebs) and the mechanical properties of the entire three-dimensional volume of the AAA, it will become possible to improve the equations for calculating risk of rupture, but they are unlikely ever to be infallible. Until this is achieved, or a cure for the disease is found, selection of candidates for intervention and selection of which type of intervention appear to be the guarantee of good quality individual care and of the credibility and viability of the healthcare system in this area.

Resumo

Em 1952, Dubost et al.( 1 ) deram início à fase de correção efetiva do aneurisma da aorta infrarrenal por meio de enxerto homólogo de aorta de cadáver, após aneurismectomia. Com a evolução dos substitutos arteriais, o rigor na técnica cirúrgica, o melhor conhecimento da doença, o advento da ultrassonografia com expansão no diagnóstico e o apurado controle clínico pré, intra (anestesia) e pós-operatório, a cirurgia do aneurisma infrarrenal passou a ser rotineira e com resultados cada vez mais animadores. A perspectiva da possibilidade de tratamento efetivo começou a gerar dúvidas a respeito de quais seriam os pacientes, com aneurismas assintomáticos, candidatos ao tratamento. O conhecimento da história natural da doença tornou-se imprescindível e numerosos estudos abordaram esta questão.

Com o aumento do número de pacientes operados demonstrou-se que, embora as taxas de mortalidade para a cirurgia convencional eletiva apresentassem declínio no decorrer dos anos (17,4% para 5,0% em 20 anos( 2 ), entre 2,5% e 3,5% no Brasil)( 3 - 5 ), as taxas de mortalidade nos casos de aneurismas rotos permaneciam elevadas (mais de 50%).( 6 ) Este fato determinou uma conduta agressiva no tratamento dos aneurismas, com indicação cirúrgica mesmo para os pacientes de maior risco, idade elevada e com aneurismas considerados pequenos( 7 , 8 ). Apesar de esta conduta eliminar a probabilidade de rotura nestes pacientes, um considerável contingente de indivíduos, com aneurismas pequenos, seriam submetidos a um grande procedimento cirúrgico, não isento de riscos e talvez desnecessário, pois muitos aneurismas permanecem estáveis( 9 , 10 ) e 75% dos indivíduos com aneurismas morrem de outras doenças( 11 ), em especial as afecções cardiovasculares.

Portanto, tornou-se imperativo estabelecer qual o paciente tem maior risco de rotura do aneurisma, isto é, quais os fatores que influenciam a rotura dos aneurismas aórticos infrarrenais.

Estes( 12 ), em 1952, relatou que a principal causa de morte nos pacientes com aneurismas abdominais era a rotura e, em segundo lugar, estava a doença coronariana. Em 1962, Shatz et al.( 13 ) notaram uma diminuição do número de roturas, associada à expansão do tratamento cirúrgico dos aneurismas. Para esses autores, os aneurismas eram pequenos até atingir o diâmetro transverso máximo de 7,5 cm. Estes fatos foram corroborados por Szilagui et al.( 14 ), que afirmaram, em 1966, que a correção cirúrgica dos aneurismas equiparava a sobrevida destes pacientes à observada na população normal e recomendavam o tratamento cirúrgico quando o diâmetro máximo do aneurisma atingisse 6,0 cm. Hollier et al.( 15 ) demonstraram que a doença coronariana limitava a sobrevida dos pacientes após a correção dos aneurismas.

Atualmente, é consenso que o fator de risco isolado mais importante para a rotura do aneurisma da aorta abdominal (AAA) é o seu diâmetro transverso máximo; portanto, este é o fator mais utilizado na indicação cirúrgica. Por meio da análise de vários estudos, constatou-se que os aneurismas maiores são mais propensos à rotura do que aqueles de menor diâmetro( 9 , 16 ).

Estudos controlados( 17 , 18 ) concluíram que os aneurismas de até 55 mm de maior diâmetro apresentavam baixa taxa de rotura em homens e, nas mulheres, este valor era de 50 mm. Assim, definiu-se o limiar de diâmetro para indicação de intervenção. Porém, outros estudos preconizavam a indicação também para aqueles entre 4,0 e 5,0 cm( 7 , 8 ), com a justificativa de baixa mortalidade na cirurgia eletiva e alta mortalidade no caso de rotura.

É neste teatro que, a partir de 1991, outro importante fator contribuiu para aumentar a discussão e a polêmica em torno do AAA: a correção por via endovascular (EVAR). Comprovadamente, este procedimento é favorável, em termos de mortalidade e morbidade, em relação à correção aberta tradicional, no período perioperatório e na evolução do paciente em curto prazo( 19 - 21 ). Em longo prazo, a EVAR mostra-se com uma incidência maior de falhas, com necessidade maior de reintervenção e um número de roturas preocupante( 22 - 24 ). Adiciona-se o fato da exigência imperiosa de seguimento, com imagem tomográfica, imediato e em médio e longo prazo. Mas a discussão parece longe de ter fim, pois as endopróteses estão sempre em constante evolução e mostram resultados em longo prazo cada vez melhores. A evolução tecnológica coloca um desafio aos estudos randomizados, pois, quando os resultados são publicados, a prótese, a técnica e a experiência já mudaram, diminuindo a validade externa do estudo( 25 ). Por sua vez, os métodos diagnósticos de imagem para evolução também melhoram e já se realiza o seguimento com ultrassografia Doppler, com ultrassonografia Doppler com contraste e, começa a ser utilizada, a ultrassonografia Doppler 3D( 26 , 27 ).

Novamente, a seleção de pacientes para intervenção (endovascular ou convencional) ou observação apresenta-se com maior quantidade de informações e mais polêmica.

Dois aspectos constantemente destacados são o risco clínico do paciente e a anatomia do AAA, em relação ao colo e aos vasos ilíacos. Um paciente com anatomia favorável e alto risco seria selecionado para EVAR. Um paciente de baixo risco e anatomia desfavorável seria elencado para correção aberta tradicional. O que é baixo e alto risco? O que é anatomia desfavorável? São conceitos difíceis de serem aplicados na vida real. As endoproteses, cada vez mais, são utilizadas fora da Information for Use ( 28 ). Questione um Cirurgião Vascular jovem saindo da Residência. Qual será sua tendência de reparo de um AAA, sendo que ele viu, na sua formação, que 60% a 75% dos AAA são corrigidos pela via EVAR? Com qual técnica ele pode ir aos limites? Ele está sujeito a conflito de interesse entre uma ou outra endoprotese? O paciente já tem informação das técnicas e tem sua preferência. Ele saberá lidar com este aspecto? Em resumo, fará o que é melhor para o paciente ou o que é 'moderno'? Fará aquilo que o paciente pede ou, ainda, o que a indústria dita?

Estudos demonstram que a EVAR tem evolução melhor quando a correção é feita em aneurismas pequenos, devido ao menor remodelamento do saco aneurismático, quando comparado a aneurismas grandes( 29 ). É importante observar que, à medida que o aneurisma cresce em diâmetro, este perde o colo proximal e distal, e progride para o envolvimento dos vasos ilíacos( 30 ), limitando o uso do EVAR. Porém, o número de pacientes eleitos para correção poderia dobrar, caso o limite do diâmetro de indicação de intervenção do AAA diminuísse nos serviços de saúde de países que realizam mapeamento da população( 31 , 32 ). É evidente o impacto do custo desta política( 33 ).

Considerando-se que apenas 25% dos aneurismas detectados rompem( 11 , 34 ), torna-se claro que o mais óbvio seria identificar quais são os candidatos a esta evolução.

O maior diâmero transverso não é um excelente indicador da rotura, pois há AAA pequenos que rompem e grandes que permanecem íntegros.

A análise de fatores de risco de rotura é importante e não deve ser desprezada. Contemplam-se as seguintes situações predisponentes:

Jovens

Mulheres

Tabagistas ativos

Indivíduo com histórico familiar

Hipertensos graves

Portadores de DPOC

Não diabéticos

Esses fatores são importantes, mas não suficientes para determinada indicação, pois indivíduos de alto risco de intervenção podem ter todos estes fatores de risco e a balança risco-benefício não adequada.

Do ponto de vista biomecânico, a rotura de um AAA ocorre quando, em determinado ponto da parede, a resistência se torna menor do que a tensão exercida sobre essa parede.

Os trabalhos que analisam e calculam o estresse na parede dos AAA, como substituto ao diâmetro no critério de intervenção, são extremamente imperfeitos, embora com grande apelo para publicação e divulgação no meio médico( 35 , 36 ). Para este cálculo, são necessárias três informações: geometria do AAA/espessura da parede, forças atuantes e contra-atuantes na parede, e, por fim, informação sobre as propriedades mecânicas da parede. Até hoje se utiliza a geometria dos AAA baseada em imagens tomográficas e/ou de ressonância magnética; talvez, no futuro, utilize-se USG-DOPPLER 3D. A espessura não pode ser medida, em bases individuais, com nenhum método de aplicação clínica disponível e utiliza-se, na equação do cálculo do estresse, uma espessura constante (15 a 25 mm). As forças atuantes baseiam-se na pressão arterial, mas a contraforça, exercida pelo retoperitônio e pelos órgãos vizinhos, não é possível de ser mensurada. No campo das propriedades mecânicas da parede, a Ultrasonografia Doppler pode medir o deslocamento da parede (strain) de modo biplanar; note-se que os métodos destrutivos em espécimes, removidos de indivíduos operados, são amostras limitadas da face anterior do aneurisma, de um todo complexo. Amostras de AAA removidas de cadáveres permitem estudar vários segmentos, mas não todos, e com testes destrutivos uniaxiais ou biaxiais (em uma estrutura sujeita a forças multiaxiais)( 37 , 38 ). Existe, portanto, grave limitação no conhecimento das propriedades biomecânicas da parede dos AAA.

Além destes aspectos mecânicos de uma estrutura completamente heterogênea, existe a questão da mecanobiologia, isto é, como o trombo interage com a parede. Este trombo protege o AAA da rotura ou ajuda a degradar ainda mais a parede já destruída( 39 ), interfere com as enzimas proteolíticas - elastases e colagenases - e seus inibidores( 40 ), com a expressão genética de proteínas reparadoras e com as características do fluxo e sua interação celular no remodelamento da parede( 41 )?

Quando os métodos de imagem fornecerem as informações de espessura de todo o aneurisma (incluindo ponto de fraqueza, blebs) e as propriedades mecânicas de todo o volume 3D do AAA, as equações constitutivas de risco de rotura poderão ser melhoradas, mas dificilmente serão infalíveis. Até lá ou até a descoberta de uma cura para a doença, a seleção dos candidatos à intervenção e qual o tipo de intervenção parece ser a garantia de boa qualidade na assistência individual e de credibilidade e viabilidade do sistema de saúde nesta área.

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