Pressure transmission through thrombus
Certain studies support the theory of pressure transmission though a thrombus or a clot. In an experimental study in a canine model, Marty et al. found that in the group of excluded aneurysms without an endoleak, intraaneurysmal pressure ratio showed a decline to a ratio of 0.34 compared to systemic pressure. In the group of aneurysms with an endoleak, pressure ratio stabilized at 0.75 and the aneurysms remained pulsatile, although the pressure pulse was lower (30 mmHg) than that of untreated aneurysms (62 mmHg). After “sealing” of endoleaks by coil embolization (arteriography and computed tomography confirmed the “sealing”), intraaneurysmal pressure ratio did not decrease (0.76) (Marty et al. 1998).
In another ex vivo study, Mehta et al. created endoleak channels of various lengths and diameters using polytetrafluoroethylene (PTFE) grafts. Peak systolic pressure was recorded in the aneurysm sac, distal to each endoleak channel, before and after the channels were filled with human thrombus. In the absence of thrombus the pressure did not change across the channels, regardless of its length or diameter. In contrast, when an endoleak was thrombosed, pressure reduction was directly proportional to the length and inversely proportional to the diameter of its channel. The authors concluded that thrombosis of endoleaks with short and wide channels may not result in substantial pressure reduction within the aneurysm sac and a successful outcome (Mehta et al. 2001).
Pressure transmission through the endograft
In an in vitro experimental study, Gawenda et al. analyzed the pressure transmission through the endoluminal graft to a latex aneurysm connected to a circulation model containing a pulsatile pump and a silicone tubing system (Gawenda et al. 2003). The authors found transmission of pulsatile pressure to the latex aneurysm through the graft and they hypothesized that the reason for this phenomenon was what they named “diaphragm effect”. Three different types of grafts were used: thin-wall PTFE, thick-wall polyethylene and thin-wall polyethylene. The conclusion was that transmitted pressure increased with augmenting systemic pressure and it depends on the graft material. Thus, transmitted pressure with PTFE grafts was significantly lower to that recorded with polyethylene grafts whereas pulsatile pressure was lower with low compliance grafts. One important limitation of this study was that commercially available stent-grafts, provided with a wire mesh to enhance columnar strength and radial fixation, were not included. In another experimental in vitro study, they compared the obtained pressures in aneurysm models with 6 or 12 layers, resulting in elastic and stiff compliance. They concluded that pressures were influenced by the compliance (Gawenda et al. 2004).
In contrast, in a more recent in vitro study in a latex model, Bosman et al. demonstrated that pressure transmission through the commercially available stent-grafts wall is clinically irrelevant (Bosman et al. 2009). Seven types of endografts were used: a 3-layer latex tube as reference, a knitted thick-wall Dacron tube graft, a woven thin-wall Dacron tube graft, a thick-wall expanded PTFE tube graft, an Excluder endoprosthesis (WL Gore & Associates, Flagstaff, AZ, USA), a Zenith stent-graft (Cook, Bjaeverskov, Denmark) and a AneuRx stent-graft (Medtronic Vascular, Santa Rosa, CA, USA). The latex reference was used to see if a very compliant “graft” would cause large pressure increases. The thick-wall and the thin-wall Dacron tube grafts, as well as the thick-wall expanded PTFE tube graft, were based on Gawenda’s research. Testing was conducted in an in-vitro pulsatile flow model that was previously described and validated. The systolic and diastolic intra-aneurysm pressures were measured, along with the pulse pressure. The mean intra-aneurysm pressure and pulse pressures were compared for each category of graft (stented/stentless) and for each graft. They found that with increasing systemic pressures, there was a small pressure increase in the aneurysm (< 5 mmHg). In addition, there was no significant difference among the various types of endografts in the dynamic or the static experiments, whereas the pulse pressures were almost identical for all the grafts, not correlating with the stiffness. Therefore, no significant difference in the pressure transmission between stented and stentless grafts was found. According to this finding, the influence of graft rigidity on endotension and the acclaimed “diaphragm-effect” seem less plausible. This study seriously called this effect into question.
Reliability of imaging methods
In a summary of opinions expressed at an international conference and published in 2002, consensus was reached that some endoleaks could not be detected with even optimal CT scanning. Some authors think that endotension is actually a not identified endoleak by conventional imaging (Lin et al. 2003; Meier et al. 2001; Blackwood et al. 2016). Supporting this theory, there is a reported case of an enlarging aneurysm that was diagnosed as endotension and during open surgery a type III endoleak was demonstrated (Yoshitake et al. 2015).
What seems true is that an ideal imaging technique for endoleak diagnosis is still not available. Duplex ultrasound (DUS), magnetic resonance angiography (MRA), conventional angiography and CT rely on a net movement of fluid or contrast within a certain defined period of time. With each method there is a limit of resolution at which point a small endoleak may remain hidden.
CT has traditionally been considered the gold standard and remains the preferred methodology to evaluate patients. Usually, type I and III endoleaks are detected in arterial phase, whereas type II are detected on a delayed phase. Most CT protocols do not perform delayed imaging with > 180 s postcontrast injection (Rozenblit et al. 2003; Iezzi et al. 2006). However, some studies recommend a delayed CT protocol of up to 300 s to identify low flow endoleaks (Iezzi et al. 2008). Recently, some authors have advocated for using a single-acquisition split-bolus protocol, with simultaneous acquisition of arterial and delayed phase imaging, which could reduce radiation dose by up to 43% (Javor et al. 2017). Photon-counting detector (PCD) CT is an emerging technology, with potential application in EVAR surveillance. The acquisition of CT images at greater than two energy bins allows for better tissue discrimination (Dangelmaier et al. 2018). Improved tissue and material discrimination with PCD CT has potential for both better visualization and dose reduction in the evaluation of endoleaks.
MRA is an alternative, but it requires caution if the stent-graft skeletal is made of steel. Furthermore, the endograft material can influence study quality because stainless steel cause significantly more susceptibility artifact that may preclude optimal assessment. To detect an endoleak, one study with 52 patients found an increased sensivity of 92.9% using magnetic resonance compared with 44% sensivity with biphasic CT, calling into question the superiority of CT (Pitton et al. 2005). Moreover, a meta-analysis showed MRA to be potentially more sensitive than CTA for the detection of endoleaks, particularly for type II endoleaks (Habets et al. 2013). Four-dimensional phase contrast MRA has the capacity to visualize flow dynamics within the aorta, and increased sensivity for the detection of endoleaks relative to CTA (Katahashi et al. 2019; Sakata et al. 2016).
Otherwise, DUS does not require nephrotoxic contrast or radiation. Several studies on color duplex ultrasound (CDUS) and contrast-enhanced ultrasound (CEUS) have had conflicting opinions regarding their diagnostic value relative to CTA. In a meta-analysis, CDUS sensivity to detect type I and III endoleaks was 0.83 and specificity was 1 (Karthikesalingam et al. 2012). The use of ultrasound contrast agent may allow identifying endoleaks that are not detected with CT (Napoli et al. 2004). Thus, some authors think that CEUS may replace CT in surveillance programs after EVAR (Bredahl et al. 2016). A meta-analysis of 42 studies found CEUS to be superior to CDUS for ruling in endoleaks (Abraha et al. 2017). Similarly, in another meta-analysis of 18 studies the authors found that CEUS had higher sensivity and comparable specificity to CTA for the detection of endoleaks (Harky et al. 2019). According to this, a systematic review found that CEUS and MRA are more accurate than CT for the detection of endoleaks, but they are not better than CT for detecting types I and III endoleaks specifically (Guo et al. 2016).
Regarding capability of angiography to detect endoleaks, a comparative analysis showed a sensivity of 63% whereas sensivity with CT was 96% (Armerding et al. 2000). More recent studies found a sensivity between 69% (Ashoke et al. 2005) and 86% (Manning et al. 2009). In the setting of an endoleak identified on the previously cited imaging methods, angiography is an essential modality for further diagnostic characterization and treatment.
Interestingly, and regarding the limitations of angiography, Blackwood et al. created an in vitro model in an experimental study. Measurements of pressure and angiography images were recorded in three scenarios: no endoleak, type I endoleak with inflow and sac outflow and a type I endoleak with inflow but no sac outflow. In the second scenario, aneurysm sac pressure was lower than the systemic and the endoleak was visible at 30 s. In the last scenario sac pressure was higher than the systemic so that net flow was zero and visibility of an endoleak was confirmed after 9 min. Consequently, they concluded that the endoleak could only be visualized with markedly delayed imaging and not with standard angiography like that used in clinical practice (Blackwood et al. 2016). Therefore, endotension may represent an undiagnosed endoleak, particularly type I.
The possible influence of fabric porosity in the pressure transmission to the aneurysm sac is another controversial point. Initially it was proposed as one of the possible causes of endotension although afterwards it was considered as type IV endoleak.
Available endografts are made of different materials and each one has its corresponding porosity grade. Initially, some clinical data suggested that PTFE stent-grafts could not prevent the sac enlargement despite of the aneurysm exclusion in the absence of endoleak. Moreover, some studies observed a lower incidence in the regression of the aneurysm sac in patients that underwent treatment with the original Excluder stent-graft in comparison with other devices (Cho et al. 2004; Bertges et al. 2003; Rhee et al. 2000; Trocciola et al. 2006). Because of the publication of these findings, the Excluder endograft was modified in 2004, incorporating an additional low-permeability layer to reduce porosity.
In an experimental study in a canine model, Trocciola et al. found that stent-graft treatment reduces intra-aneurysmal pressure to < 30% of systemic pressure (nonpulsatile). However, significantly greater pressure was observed after exclusion with PTFE stent-grafts compared with Dacron grafts (Trocciola et al. 2006). Histology showed that those aneurysms that were excluded with the original Excluder stent-graft (thin-wall ePTFE) contained poorly organized thrombus and fibrin deposition, which could be indicative of active remodeling and continued influx of transudated serum. In contrast, aneurysms excluded by Dacron stent-grafts resulted in thrombi that were well organized and chronically composed mostly of granulation tissue. Dense mature collagenous connective tissue was also found in this group.
Haider et al. compared the sac behavior after aneurysm treatment with the original Excluder device, with the low-permeability Excluder device or with the Zenith stent-graft. At 1 year, sac regression rate was 25%, 63.9% and 65.3%, respectively. Consequently, they concluded that low-porosity fabric seems to be an important factor in early aneurysm sac shrinkage (Haider et al. 2006). Reinforcing this conclusion, the long-term results with this new Excluder device confirmed sac regression in 63% at 5 years. Interestingly, sac enlargement was observed only in the setting of a current or previous endoleak, with no cases of hygroma formation noted (Hogg et al. 2011).
A previously cited experimental study compared the new Excluder stent-graft to other available devices (Zenith and AneuRx) and demonstrated that there were no significant differences in the transmitted pressure to the sac among the analyzed devices. In addition, the pulse pressure was identical for all of them (Bosman et al. 2009).
In another study, also in a canine model, Hynecek et al. made a comparison among three distinct stent-grafts: the Trivascular Enovus (nonporous PTFE), the original Excluder (porous PTFE) and the Medtronic AneuRx (Dacron) (Hynecek et al. 2007). Within 24 h after exclusion pulse pressure within the sac tapered to less than 20% of systemic pressure for all three stent graft types. However, throughout the postoperative period significantly lower intra-aneurysmal pressures were present in those aneurysms that were not treated with the porous PTFE device. Histologic analysis of the Excluder-treated aneurysms demonstrated poorly organized fibrin deposition suggestive of acute thrombus. Dacron-treated aneurysms demonstrated mature well-organized collagenous connective tissue. Those aneurysms treated with nonporous PTFE showed characteristics of acute and chronic thrombus. Authors did not find hygromas, although the study period did not exceed 30 days.
Regarding the fabric porosity, it should be underscored that although cases of sac enlargement without a detected endoleak were documented in patients treated with the original Excluder device, the endotension-related rupture incidence was very low. In fact, Kong et al. reviewed data from the multicenter phase I and II clinical trials and reported no endotension-related aneurysm rupture (Kong et al. 2005).
Regarding the fluid accumulation theory, some cases of hygroma have been reported, describing a gelatinous material within the aneurysm sac (Williams 1998; Risberg et al. 2001; Thoo et al. 2004). One study included four patients with aneurysm sac expansion: one patient had undergone open surgery using a PTFE graft, and three cases had undergone treatment with endografts (two PTFE endografts and one Dacron endograft). The aspirated fluid was described as highly viscous and the analysis reported local hyperfibrinolysis in the sac with signs of local coagulation activation. The authors, Risberg et al., proposed the hygroma theory as a pathophysiological mechanism for endotension (Risberg et al. 2001).
Another study included five cases of symptomatic patients with late sac enlargement, all of them had undergone open repair of abdominal aortic aneurysm using PTFE grafts. Four of them underwent laparotomy and a seroma containing firm rubbery gelatinous material was found in all cases (Thoo et al. 2004). This fact led the authors to suppose that the most likely cause of sac enlargement was the fluid flow from aortic lumen to the aneurysm sac through the graft. It is important to consider that the incidence of symptomatic aneurysm enlargement in the patients after open repair with PTFE grafts was low (2.3%). It also has to be highlighted that the PTFE grafts were thin-walled and differed in porosity compared with PTFE used in the manufacture of Excluder endografts.
Seven cases described as intermittent endoleaks and four cases described as posture-dependent endoleaks were reported in an article (May and Harris 2012). The first case was a patient with aneurysm sac enlargement and no demonstrated endoleak. When the patient underwent reintervention by open surgery, they found a jet of blood when the endograft was subjected to positional changes. They also reported two cases in which the endoleak could only be imaged, using duplex, by changing the patient’s position on the examination table. May et al. concluded that patients with this condition could be considered to have endotension and that the ultrasound would be the most suitable diagnosis test in these cases.