Chronic mesenteric ischemia-induced intestinal dysbiosis resolved after revascularization.

Objective: Chronic mesenteric ischemia (CMI) is a debilitating condition arising from intestinal malperfusion from mesenteric artery stenosis or occlusion. Mesenteric revascularization has been the standard of care but can result in substantial morbidity and mortality. Most of the perioperative morbidity has been secondary to postoperative multiple organ dysfunction, potentially from ischemia-reperfusion injury. The intestinal microbiome is a dense community of microorganisms in the gastrointestinal tract that help regulate pathways ranging from nutritional metabolism to the immune response. We hypothesized that patients with CMI will have microbiome perturbations that contribute to this inflammatory response and could potentially normalize in the postoperative period. Methods: We performed a prospective study of patients with CMI who had undergone mesenteric bypass and/or stenting from 2019 to 2020. Stool samples were collected at three time points: preoperatively at the clinic, perioperatively within 14 days after surgery, and postoperatively at the clinic at >30 days after revascularization. Stool samples from healthy controls were used for comparison. The microbiome was measured using 16S rRNA sequencing on an Illumina-MiSeq sequence platform and analyzed using the QIIME2 (quantitative insights into microbial ecology 2)-DADA2 bioinformatics pipeline with the Silva database. Beta-diversity was analyzed using a principal coordinates analysis and permutational analysis of variance. Alpha-diversity (microbial richness and evenness) was compared using the nonparametric Mann-Whitney U test. Microbial taxa unique to CMI patients vs controls were identified using linear discriminatory analysis effect size analysis. P < .05 was considered statistically significant. Results: Eight patients with CMI had undergone mesenteric revascularization (25% men; average age, 71 years). Nine healthy controls were also analyzed (78% men; average age, 55 years). Bacterial alpha-diversity (number of operational taxonomic units) was dramatically reduced preoperatively compared with that of the controls (P = .03). However, revascularization partially restored the species richness and evenness in the perioperative and postoperative phases. Beta-diversity was only different between the perioperative and postoperative groups (P = .03). Further analyses revealed increased abundance of Bacteroidetes and Clostridia taxa preoperatively and perioperatively compared with the controls, which was reduced during the postoperative period. Conclusions: The results from the present study have shown that patients with CMI have intestinal dysbiosis that resolves after revascularization. The intestinal dysbiosis is characterized by the loss of alpha-diversity, which is restored perioperatively and maintained postoperatively. This microbiome restoration demonstrates the importance of intestinal perfusion to sustain gut homeostasis and suggests that microbiome modulation could be a possible intervention to ameliorate acute and subacute postoperative outcomes in these patients.

Comparative outcomes of open, hybrid, and fenestrated branched endovascular repair of extent II and III thoracoabdominal aortic aneurysms.

OBJECTIVE: Open repair of extent II and III thoracoabdominal aortic aneurysms (TAAA) is associated with substantial morbidity. Alternative strategies, such as hybrid operations combining proximal thoracic endovascular aortic repair with either staged open distal TAAA repair or visceral debranching (hybrid), as well as fenestrated/branched endografts (FEVAR), have been increasingly reported; however, benefits of these approaches compared with direct open surgery remain unclear. The purpose of this study was to compare outcomes of these three different strategies in the management of extent II/III TAAA. METHODS: All extent II/III TAAA repairs (2002-2018) for nonmycotic, degenerative aneurysm or chronic dissection at a single institution were reviewed. The primary end point was 30-day mortality. Secondary end points included incidence of spinal cord ischemia (SCI), complications, unplanned re-operation, 90-day readmission, and out-of-hospital survival. To mitigate impact of covariate imbalance and selection bias, intergroup comparisons were made using inverse probability weighted-propensity analysis. Cox regression was used to estimate survival while cumulative incidence was used to determine reoperation risk. RESULTS: One hundred ninety-eight patients (FEVAR, 92; hybrid, 40; open, 66) underwent repair. In unadjusted analysis, compared with hybrid/open patients, FEVAR patients were significantly older with more cardiovascular risk factors, but less likely to have a connective tissue disorder or dissection-related indication. Unadjusted 30-day mortality and complication rates were: 30-day mortality, FEVAR 4%, hybrid 13%, open 12% (P = .01); and complications, FEVAR 36%, hybrid 33%, open 50% (P = .11). Permanent SCI was not different among groups (FEVAR 3%, hybrid 3%, open 6%; P = .64). In adjusted analysis, 30-day mortality risk was greater for open vs FEVAR (hazard ratio, 3.6; 95% confidence interval, 1.4-9.2; P = .01) with no difference for hybrid vs open/FEVAR. There was significantly lower risk of any SCI for open vs FEVAR (hazard ratio, 0.3; 95% confidence interval, 0.09-0.96; P = .04); however, no difference in risk of permanent SCI was detected among the three groups. There was no difference in complications or unplanned reoperation, but open patients had the greatest risk of unplanned 90-day readmission. There was a time-varying effect on survival probability, with open repair having a significant survival disadvantage in the first 1 to 6 months after the procedure compared with hybrid/FEVAR patients (Cox model P = .03), but no difference in survival at 1 and 5 years (1- and 5-year survival: FEVAR, 86 ± 3%, 55 ± 8%; hybrid, 86 ± 5%, 60 ± 11%; open 69 ± 7%, 59 ± 8%; Cox-model P = .10). CONCLUSIONS: Extent II/III TAAA repair, regardless of operative strategy, is associated with significant morbidity risk. FEVAR is associated with the lowest 30-day mortality risk compared with hybrid and open repair when estimates are adjusted for preoperative risk factors. These data support greater adoption of FEVAR as first-line therapy to treat complex TAAA disease in anatomically suitable patients who present electively.

Haemodynamics of Different Configurations of a Left Subclavian Artery Stent Graft for Thoracic Endovascular Aortic Repair.

OBJECTIVE: Branched stent grafts represent a viable option for left subclavian artery (LSA) revascularisation in patients treated by thoracic endovascular aortic repair (TEVAR) for Zone 2 lesions. This study investigated the haemodynamic performance of different LSA branched stent graft configurations as potential determinants of thrombotic and stroke risks. METHODS: A three dimensional aortic arch geometry extracted from post-operative computed tomography images of a TEVAR patient using a single LSA branched aortic endograft was modified in silico to obtain ten potential LSA branched stent graft configurations: five down facing (0-5 - 10 mm aortic protrusion with 10-12 mm internal diameter), four curved (30-60° with antegrade/retrograde orientation), and one LSA orifice misalignment. The 0 mm down facing stent graft was considered base configuration. Computational fluid dynamic analyses were performed to identify differences in pressure, energy, and wall shear stress (WSS) based parameters. RESULTS: Total pressure drop and energy loss variations among configurations were not greater than 5 mmHg (6% of mean arterial pressure) and 5.7 mW (0.7% of cardiac power), respectively. Protrusions up to 5 mm created clinically insignificant flow disturbances. However, stent graft protrusions further into the aortic lumen created more complex haemodynamics, characterised by larger energy loss and more prominent flow recirculation. Protrusion greater than 5 mm into the lumen was associated with larger areas of elevated maximum WSS (>20 Pa) along the outer surface of the branched stent graft. CONCLUSION: Arterial haemodynamic characteristics are affected by LSA branched stent graft configurations, with pressure drops and energy losses likely to be clinically insignificant. The length of the stent graft protrusion into the aortic lumen generated the largest haemodynamic variations in the aortic system. Protrusions up to 5 mm have smaller risk of potential thrombus generation. Conversely, larger protrusions into the aortic lumen showed more disturbed haemodynamics, suggesting a greater risk of potential thrombus formation, which may be clinically important over time.

Anatomic and hemodynamic investigation of an occluded common carotid chimney stent graft for hybrid thoracic aortic aneurysm repair.

We examined the possible reasons for common carotid artery chimney stent graft occlusion through computational fluid dynamics analyses of follow-up imaging of a patient-specific aortic configuration reconstructed from computed tomography aortography. Anatomic and hemodynamic parameters were extracted for the bilateral common carotid and subclavian arteries before and after endograft placement. Results suggested that postoperative reduction in lumen diameter within the chimney stent graft combined with an increased flow rate led to complex hemodynamics with high wall shear stress, probably resulting in high-shear thrombogenesis and chimney stent graft occlusion 2.6 years after the primary repair. Early postoperative duplex ultrasound imaging might help identify at-risk conditions.

Outcomes of Thoracic Endovascular Aortic Repair for Acute Type B Dissection in Patients With Intractable Pain or Refractory Hypertension.

PURPOSE: To compare uncomplicated acute type B aortic dissection (UATBAD) patients with intractable pain/refractory hypertension treated with thoracic endovascular aortic repair (TEVAR) to UATBAD subjects without these features receiving best medical therapy (BMT). METHODS: Interrogation of the hospital database identified 101 consecutive UATBAD patients admitted between January 2011 and December 2014. Of these, 74 patients (mean age 62±13 years; 44 men) were treated with BMT; the other 27 UATBAD patients (mean age 63±13 years; 17 men) were subsequently treated with TEVAR for intractable pain (24, 89%) and/or refractory hypertension (3, 11%) at a mean 2.4±3.3 days (median 1, range 0-12) after admission. Mixed models were employed to determine differences in centerline measured aortic remodeling. Propensity analysis was employed to mitigate selection bias. Kaplan-Meier methodology was used to estimate reintervention and survival. RESULTS: The groups were well matched; there was no difference in demographics, comorbidities, or proportion with visceral involvement (70% for TEVAR vs 86% for BMT, p=0.08). There was no significant difference in length of stay (9.6±6.3 for TEVAR vs 10.3±7.8 for BMT, p=0.3), complications (19% for TEVAR vs 24% for BMT, p=0.6), or 30-day mortality (0 for TEVAR vs 7% for BMT, p=0.1). One (4%) TEVAR patient experienced retrograde dissection. BMT resulted in greater mean increase in discharge antihypertensive medications (1.7±1.9 vs 0.7±1.7 for TEVAR, p=0.03), but there was no difference in narcotic utilization. Mean follow-up was greater in the TEVAR group (17.9±16.0 months) compared with BMT patients (11.5±10.8 months, p=0.05). TEVAR significantly improved rates of aortic diameter change (1.5% vs 12.9% for BMT, p=0.007), complete false lumen thrombosis (41% vs 11% for BMT, p=0.004), and true lumen expansion (85% vs 7% for BMT, p<0.01). However, there was no difference in reintervention (25.9% for TEVAR vs 23% for BMT, p=0.2) or survival (log-rank p=0.8). CONCLUSION: TEVAR for UATBAD with intractable pain/refractory hypertension is safe but offers no short-term outcome advantage when compared to UATBAD patients without these features receiving BMT. A significant improvement in aortic remodeling was identified after TEVAR. The potential long-term reintervention and aorta-related mortality benefits of this favorable remodeling have yet to be defined and randomized trials are warranted.

Hemodynamic and Anatomic Predictors of Renovisceral Stent-Graft Occlusion Following Chimney Endovascular Repair of Juxtarenal Aortic Aneurysms.

PURPOSE: To identify anatomic and hemodynamic changes associated with impending visceral chimney stent-graft occlusion after endovascular aneurysm repair (EVAR) with the chimney technique (chEVAR). METHODS: A retrospective evaluation was performed of computed tomography scans from 41 patients who underwent juxtarenal chEVAR from 2008 to 2012 to identify stent-grafts demonstrating conformational changes following initial placement. Six subjects (mean age 74 years; 3 men) were selected for detailed reconstruction and computational hemodynamic analysis; 4 had at least 1 occluded chimney stent-graft. This subset of repairs was systematically analyzed to define the anatomic and hemodynamic impact of these changes and identify signature patterns associated with impending renovisceral stent-graft occlusion. Spatial and temporal analyses of cross-sectional area, centerline angle, intraluminal pressure, and wall shear stress (WSS) were performed within the superior mesenteric and renal artery chimney grafts used for repair. RESULTS: Conformational changes in the chimney stent-grafts and associated perturbations, in both local WSS and pressure, were responsible for the 5 occlusions in the 13 stented branches. Anatomic and hemodynamic signatures leading to occlusion were identified within 1 month postoperatively, with a lumen area <14 mm2 (p=0.04), systolic pressure gradient >25 Pa/mm (p=0.03), and systolic WSS >45 Pa (p=0.03) associated with future chimney stent-graft occlusion. CONCLUSION: Chimney stent-grafts at increased risk for occlusion demonstrated anatomic and hemodynamic signatures within 1 month of juxtarenal chEVAR. Analysis of these parameters in the early postoperative period may be useful for identifying and remediating these high-risk stent-grafts.