In the first debate of Sunday’s CX, the majority of delegates (71%) agreed with the motion that “we prefer external aortic wall diameters in screening”

Naghmana Riazuddin, Wycombe, UK, who was speaking for the motion, said that the inner wall of the aorta was difficult to see and that the external wall was “much clearer”.

To support her arguments, Riazuddin outlined the findings of the UK Small Aneurysm Trial, which showed that the “outer to outer” method of measuring aortic diameter (in abdominal aortic aneurysms) could be used without any problems. She added that there is approximately 3mm of difference between inner-to-inner measurements and outer-to-outer measurements.

She said, therefore, if a patient was found with an aortic diameter of 2.9cm, by using the inner-to-inner method, they could actually have a diameter of 3.2cm. Riazuddin explained that this could have implications for treatment. She said: “A 4.7cm aorta via an inner-to-inner method would not be referred for vascular surgery, but it would be 5cm via an outer-to-outer method.” The threshold for intervention is 5cm. Concluding, she said that the outer-to-outer method was traditionally used and most of the trial data was based on this method. She explained that in a poll of 41 centres across Europe, 32 said that they used the outer-to-outer method. She added: “Aortas scanned by others outside of the [UK National] screening programme are still using outer-to-outer, so will we have different actual measurements for the 5.5cm threshold?” 

Arguing against the motion was Tim Hartshorne (Leicester, UK). He outlined the benefits of the inner-to-inner method. He said a study, of which he was the lead author, found that (as Riazuddin argued) there was the expected difference between the inner-to-inner method and the outer-to-outer method in terms of diameter, but it also showed that there was better accuracy and reliability with the inner-to-inner method.

He said: “This is important in the context of National Screening Programmes to assure consistency between technicians and surveillance visits.” Countering Riazuddin’s argument that the outer-to-outer method should be used because the 5cm threshold is based on trials that used that method, he said: “The inner-to-inner method should be used given that that there is evidence of better reproducibility but it would be possible to adjust referral thresholds if it was found that there was an increased rupture rate in men under surveillance, for instance from 5.5cm to 5.2cm (inner-to-inner method).”

He added: “Screening programmes including the NHS abdominal Aortic Aneurysm Screening Programme will gather large amounts of data on the natural history of aortic aneurysms, providing information and evidence that may lead to modification and improvement of the present schedules.”

After the debate, Roger Greenhalgh, Imperial College, London, CX programme chairman, and chair of the first aortic session, also posed the question: “Is it crazy that we ever adopted a variety of ultrasound borders for determining aortic diameter for infrarenal aortic abdominal aneurysms? The delegates overwhelmingly voted “yes” , with only 17% saying “no”.

As Nicholay Volodos, who developed a self-fixing synthetic endoprosthesis in the former Soviet Union in 1984, was unable to make CX 34, Krassi Ivancev, London, UK, spoke about the early history of endovascular repair on his behalf. Commenting on Volodos’ work, Ivancev said he was the “pioneer who started the endovascular stent graft revolution.” 

Roger Greenhalgh, London, UK and CX programme chairman, also praised the work of Volodos and asked people to stand if they thought it was worthwhile sending a message, via Ukranian delegates, to Volodos about how much everyone appreciated Volodos’ achievements – the entire audience stood up to celebrate his work. Volodos used the self-fixing synthetic endoprosthesis to perform his first transfemoral remote endosprothesis implantation in an iliac artery. This was in May 1985.

Two years later, he performed an endovascular repair for an aneurysm in the descending section of the thoracic aorta. “The world’s first EVAR was performed in 1987 by professor Nicholay Volodos in Kharkov, Soviet Union, and introduced in an article written in 1988,” Ivancev said at CX.

The first EVAR procedure reported in the literature took place on 7 September 1990, when Juan Parodi, Julio Palmaz and HD Barone at the Instituto Cardiovascular de Buenos Aires, Argentina, treated an abdominal aortic aneurysm patient. The aneurysm was excluded endoluminally with a Dacron graft that was anchored at the proximal infrarenal neck with a stainless steel balloon-expandable stent. Ivancev said, “Volodos realised the mechanical properties required of a stent graft. He designed, manufactured and implemented the first stent graft and his principles are still valid and exploited by us today.”

Volodos’ early experience was recorded in a paper titled “Experience with endovascular stent grafts for arterial disease from 1985 to present”, which was presented at the 21st Annual Symposium on Current Critical Problems – New Horizons and Techniques in Vascular Surgery in 1994. He wrote: “Trying to realise more effectively Charles Dotter’s attractive idea of implanting a prosthesis in not easily approached vessels through a superficially lying vessel, we developed a self-fixing synthetic endoprosthesis in 1984. This endoprosthesis received the national patent of the former USSR on 22 May 1984. At that initial stage we called the method a remote endoprosthesis.” “The design feature of the endoprosthesis was a fixing element in the form of a radial zigzag shaped cylindrical spring. The spring was made from stainless steel wire 0.4–0.5mm in the diameter. 

The height of the fixing element was about 18mm. As a rule, the number of rings was six or seven,” Volodos reported. The first animal studies with the endoprosthesis were conducted in dogs, with the transfemoral prosthesis implanted in the thoracic aorta. “The results of the study showed good function of the endoprosthesis six months after the operation,” Volodos said. 

Volodos and colleagues used these results as the basis to perform endoprosthesis implantation in patients. “The first operation of transfemoral remote endoprosthesis implantation in the iliac artery in the clinic was performed on 4 May 1985. 

It was done in combination with a simultaneous femorotibial bypass,” he wrote. In the first report, Volodos said that 19 patients had been treated for stenosis and occlusions of the iliac arteries. “Positive results were achieved in 17 patients immediately after operation and in 15 patients in the late period (from one to eight years).” “Transfemoral remote endoprosthesis implantation with the self-fixing synthetic endoprosthesis in case of the traumatic aneurysm of the descending section of the thoracic aorta was performed on 24 March 1987. It was performed in four patients, with positive results in all of them. At 7.5 years of follow-up, it has shown good function of the endoprosthesis.” After that, Volodos performed endoprosthesis implantation of the abdominal aorta in five patients – two of them received a bifurcated synthetic endoprosthesis. “The accumulated experience with the self-fixing synthetic endoprosthesis permits us to consider that remote endoprosthetics should have a place in the treatment of patients with lesions of the aorta and main arteries,” Volodos concluded in the paper.

Matt Bown, Leicester, UK, led an international team of investigators which identified a single gene that is linked to the development of abdominal aortic aneurysm. During the discussion session, after the results were presented, the point was made that the interaction between the gene LRP1 and environmental factors was key. 

Bown told CX delegates on Sunday that the investigators carried out a genome-wide association discovery study of 1,866 patients with abdominal aortic aneurysm and 5,435 controls and replication of promising signals (lead single-nucleotide polymorphism [SNP] with a p value <1×10−5) in 2,871 additional cases and 32,687 controls and performed further follow-up in 1,491 abdominal aortic aneurysms and 11,060 controls. “In the discovery study, nine loci demonstrated association with abdominal aortic aneurysms (p<1×10−5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p=0.0042),” Bown said. “We confirmed the association of rs1466535 and abdominal aortic aneurysm in our follow-up study (p=0.035).

In a combined analysis (6,228 abdominal aortic aneurysms and 49,182 controls), rs1466535 had a consistent effect size and direction in all sample sets. No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to abdominal aortic aneurysms. “Our findings suggest a mechanism contributing to abdominal aortic aneurysm formation via the LRP1 pathway, and exploration of this mechanism could provide future therapeutic approaches to preventing the development and/or progression of abdominal aortic aneurysms,” Bown et al reported.

“This study identifies a biological process that could be altered using drugs and therefore treat aneurysms, either to prevent them completely or to prevent them growing,” Bown said. “The key challenges are to identify how the protein produced by this gene causes or protects against aneurysms and then work out ways to reduce or increase the activity of the protein or pathway that this protein is involved in. The next step is to find out how the protein produced by this gene is involved in the development of aneurysms,” he noted.

He concluded that the gene was aortic aneurysm specific and that it was biologically plausible. In the discussion after his study was presented, Martin Bjorck, Uppsala, Sweden, asked Bown about the possible interaction between the LRP1 gene and environmental factors. Bown said their data was limited and not powered to detect such an interaction. Janet Powell, London, UK, commented: “The reason why we white people get aneurysms must partly be because of our environment and partly because of our genes.”

The research, funded by The Wellcome Trust, was published in The American Journal of Human Genetics in November 2011.