Paraspinous muscle gene expression profiling following simulated staged endovascular repair of thoracoabdominal aortic aneurysm: exploring potential therapeutic pathways.

OBJECTIVES: Thoracic endovascular techniques for aneurysm repair offer less invasive alternatives to open strategies. Both approaches, however, are associated with the risk for neurological complications. Despite adjuncts to maintain spinal cord perfusion, ischaemia and paraplegia continue to occur during thoracoabdominal aortic aneurysm (TAAA) repair. Staging of such extensive procedures has been proven to decrease the risk for spinal cord injury. Archived biopsy specimens may offer insight into the molecular signature of the reorganization and expansion of the spinal collateral network during staged endovascular interventions in the setting of TAAA. METHODS: Biological replicates of total RNA were isolated from existing paraspinous muscle samples from 22 Yorkshire pigs randomized to 1 of 3 simulated TAAA repair strategies as part of a previous study employing coil embolization of spinal segmental arteries within the thoracic and lumbar spine. Gene expression profiling was performed using the Affymetrix GeneChip Porcine array. RESULTS: Microarray analysis identified 649 differentially expressed porcine genes (≥1.3-fold change, P ≤ 0.05) when comparing paralysed and non-paralysed subjects. Of these, 355 were available for further analysis. When mapped to the human genome, 169 Homo sapiens orthologues were identified. Integrated interpretation of gene expression profiles indicated the significant regulation of transcriptional regulators (such as nuclear factor кB), cytokine (including CXCL12) elements contributing to hypoxia signalling in the cardiovascular system (vascular endothelial growth factor and UBE2) and cytoskeletal elements (like dystrophin (DMD) and matrix metallopeptidase (MMP)). CONCLUSIONS: This study demonstrates the ability of microarray-based platforms to detect the differential expression of genes in paraspinous muscle during staged TAAA repair. Pathway enrichment analysis detected subcellular actors accompanying the neuroprotective effects of staged endovascular coiling. These observations provide new insight into the potential prognostic and therapeutic value of gene expression profiling in monitoring and modulating the arteriolar remodelling in the collateral network.

Planned Staged Repair of Thoracoabdominal Aortic Aneurysms to Minimize Spinal Cord Injury: A Proof of Concept.

Management of thoracoabdominal aortic aneurysms (TAA) can lead to spinal cord injury. A variety of clinical adjuncts have proven to decrease the incidence of paraplegia; however, at least 10% patients remain at risk of developing paraplegia. Experimentally and in sporadic clinical experiences, the staged repair of TAAs can lead to better neurologic outcomes. We present two clinical cases with extensive TAA in which a deliberate staged repair leads to excellent neurologic outcomes.

Endovascular coil embolization of segmental arteries prevents paraplegia after subsequent thoracoabdominal aneurysm repair: an experimental model.

OBJECTIVES: To test a strategy for minimizing ischemic spinal cord injury after extensive thoracoabdominal aneurysm (TAAA) repair, we occluded a small number of segmental arteries (SAs) endovascularly 1 week before simulated aneurysm repair in an experimental model. METHODS: Thirty juvenile Yorkshire pigs (25.2 ± 1.7 kg) were randomized into 3 groups. All SAs, both intercostal and lumbar, were killed by a combination of surgical ligation of the lumbar SAs and occlusion of intercostal SAs with thoracic endovascular stent grafting. Seven to 10 days before this simulated TAAA replacement, SAs in the lower thoracic/upper lumbar region were occluded using embolization coils: 1.5 ± 0.5 SAs in group 1 (T13/L1), and 4.5 ± 0.5 SAs in group 2 (T11-L3). No SAs were coiled in the controls. Hind limb function was evaluated blindly from daily videotapes using a modified Tarlov score (0 = paraplegia, 9 = full recovery). After death, each segment of spinal cord was graded histologically using the 9-point Kleinman score (0 = normal, 8 = complete necrosis). RESULTS: Hind limb function remained normal after coil embolization. After simulated TAAA repair, paraplegia occurred in 6 of 10 control pigs, but in only 2 of 10 pigs in group 1; no pigs in group 2 had a spinal cord injury. Tarlov scores were significantly better in group 2 (control vs group 1, P = .06; control vs group 2, P = .0002; group 1 vs group 2, P = .05). A dramatic reduction in histologic damage, most prominently in the coiled region, was seen when SAs were embolized before simulated TAAA repair. CONCLUSIONS: Endovascular coiling of 2 to 4 SAs prevented paraplegia in an experimental model of extensive hybrid TAAA repair, and helped protect the spinal cord from ischemic histopathologic injury. A clinical trial in a selected patient population at high risk for postoperative spinal cord injury may be appropriate.

A prospective study of growth and rupture risk of small-to-moderate size ascending aortic aneurysms.

OBJECTIVE: The natural history of small-to-moderate size ascending aortic aneurysms is poorly understood. To follow these patients better, we have developed a method to objectively and reproducibly measure ascending aortic volume on the basis of gated contrast computed tomography scans. METHODS: From 2009 to 2011, 507 patients were referred for management of ascending aortic aneurysms. A total of 232 patients (46%) with small-to-moderate size aneurysms who did not have compelling indications for operation had measurement(s) of ascending aortic and total aortic volume; 166 patients had more than 1 scan, allowing measurement of growth. A total of 66 patients admitted to the emergency department without ascending aortic pathology served as a reference group. RESULTS: None of the patients experienced rupture, dissection, or death; 3 patients ultimately underwent operation. Ascending aortic volume and volume/total aortic volume differed for the surveillance and reference groups: 132.8 ± 39.4 mL versus 78.0 ± 24.5 mL; 38.3% ± 7.4% versus 29.1% ± 3.9%, respectively (both P < .001). Diameters at the sinotubular junction and mid-ascending aortic were 4.1 ± 0.6 cm and 4.4 ± 0.6 cm, respectively, for the surveillance group and 3.0 ± 0.4 cm and 3.2 ± 0.4 cm, respectively, for controls. The increase in ascending aortic volume was 0.95 ± 4.5 mL/year and 0.73% ± 3.7%/year (P = .007 and .012, respectively). Analysis of risk factors for ascending aortic growth revealed only the use of antithrombotic medication as possibly significant. CONCLUSIONS: Computed tomography volume measurements provide an objective method for ascertaining aortic size and monitoring expansion. Patients with small-to-moderate ascending aortic aneurysms who are carefully followed and managed appropriately have slow aneurysm growth and a small risk of rupture or dissection. Annual computed tomography screening may not be indicated, and elective resection-absent other surgical indications-is not necessary. The rupture/dissection risk for even larger aneurysms in carefully followed patients may be lower than currently believed.

The ARCH Projects: design and rationale (IAASSG 001).

OBJECTIVE: A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic. METHODS: High-volume aortic arch centres were identified from the literature and contacted for recruitment. A Research Steering Committee of expert arch surgeons was convened to oversee the direction of the research. RESULTS: The International Aortic Arch Surgery Study Group has been formed by 41 arch surgeons from 10 countries to better evaluate patient outcomes after aortic arch surgery. Several projects, including the establishment of a multi-institutional retrospective database, randomized controlled trials and a prospectively collected database, are currently underway. CONCLUSIONS: Such a collaborative effort will herald a turning point in the surgical management of aortic arch pathologies and will provide better powered analyses to assess the impact of varying surgical techniques on mortality and morbidity, identify predictors for neurological and operative risk, formulate and validate risk predictor models and review long-term survival outcomes and quality-of-life after arch surgery.

A meta-analysis of deep hypothermic circulatory arrest versus moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion.

INTRODUCTION: A recent concern of deep hypothermic circulatory arrest (DHCA) in aortic arch surgery has been its potential association with increased risk of coagulopathy, elevated inflammatory response and end-organ dysfunction. Recently, moderate hypothermic circulatory arrest (MHCA) with selective antegrade circulatory arrest (SACP) seeks to negate potential hypothermia-related morbidities, while maintaining adequate neuroprotection. The present meta-analysis aims to compare postoperative outcomes in arch surgery using DHCA or MHCA+SACP as neuroprotective strategies. METHODS: Electronic searches were performed using six databases from their inception to January 2013. Two reviewers independently identified all relevant studies comparing DHCA with MHCA+SACP, as defined by a recent hypothermia temperature consensus. Data were extracted and meta-analyzed according to pre-defined clinical endpoints. RESULTS: Nine comparative studies were identified for inclusion in the present meta-analysis. Stroke rates were significantly lower in patients undergoing MHCA+SACP (P=0.0007, I(2)=0%), while comparable results were observed with temporary neurological deficit, mortality, renal failure or bleeding. Infrequent and inconsistent reporting of systemic outcomes precluded analysis of other systemic outcomes. CONCLUSIONS: The present meta-analysis indicated the superiority of MHCA+SACP in terms of stroke risk.

Consensus on hypothermia in aortic arch surgery.

Considered a standard part of aortic arch surgery, hypothermia can sufficiently reduce cerebral metabolic demand to permit reasonable periods of circulatory arrest. Yet despite its ubiquitous application and critical importance, temperature classification in hypothermic circulatory arrest is still without clear definition. The following Consensus from experts in high-volume aortic institutions defines 'profound', 'deep', 'moderate', and 'mild' hypothermia and recommends standardized monitoring sites, so as to facilitate more consistent reporting and robust analysis.

A meta-analysis of deep hypothermic circulatory arrest alone versus with adjunctive selective antegrade cerebral perfusion.

INTRODUCTION: Recognizing the importance of neuroprotection in aortic arch surgery, deep hypothermic circulatory arrest (DHCA) now underpins operative practice as it minimizes cerebral metabolic activity. When prolonged periods of circulatory arrest are required, selective antegrade cerebral perfusion (SACP) is supplemented as an adjunct. However, concerns exist over the risks of SACP in introducing embolism and hypo- and hyper-perfusing the brain. The present meta-analysis aims to compare postoperative outcomes in arch surgery using DHCA alone or DHCA + SACP as neuroprotection strategies. METHODS: Electronic searches were performed using six databases from their inception to January 2013. Two reviewers independently identified all relevant studies comparing DHCA alone with DHCA + SACP. Data were extracted and meta-analyzed according to pre-defined clinical endpoints. RESULTS: Nine comparative studies were identified in the present meta-analysis, with 648 patients employing DHCA alone and 370 utilizing DHCA + SACP. No significant differences in temporary or permanent neurological outcomes were identified. DHCA + SACP was associated with significantly better survival outcomes (P=0.008, I(2)=0%), despite longer cardiopulmonary bypass time. Infrequent and inconsistent reporting of other clinical results precluded analysis of systemic outcomes. CONCLUSIONS: The present meta-analysis indicate the superiority of DHCA + SACP in terms of mortality outcomes.

Hypothermia for aortic surgery.

Hypothermic circulatory arrest has been used during aortic arch repairs with acceptable neurologic outcomes. Through the years, we have studied the effects of deep hypothermia on brain metabolism and perfusion both in a pig model and in surgical patients. Hypothermic circulatory arrest has also been used as a method of organ protection in the repair of thoracoabdominal aortic aneurysms. We summarize the clinical and laboratory studies to support the routine use of hypothermic circulatory arrest in clinical practice.

Predicting the risk for acute type B aortic dissection in hypertensive patients using anatomic variables.

OBJECTIVES: This study sought to identify possible anatomic predictors of acute type B aortic dissection (AAD) in hypertensive patients using multidetector computed tomography angiography (CTA). BACKGROUND: Although hypertension remains one of the most significant risk factors for AAD development, it is unlikely to be the only risk factor for AAD. Few studies have assessed anatomical predictors of AAD development. METHODS: CTA of normotensive patients without AAD (group 1, n = 35), hypertensive patients without AAD (group 2, n = 37), and hypertensive patients with AAD (group 3, n = 37) were compared. The length, diameter, volume, and tortuosity of the aorta as well as arch vessel angulation were measured for each patient and normalized to group 1 averages. Stepwise logistic regression identified significant anatomical associations; the model was validated based on 1,000 bootstrapped samples. RESULTS: The demographics of the groups were similar. The length of the proximal and entire aorta, the diameters in the proximal ascending aorta and aortic arch, and the aortic volumes were all greater (p < 0.0001, p = 0.0064 for ascending aortic diameter) in group 3 than in groups 1 and 2, as was entire aortic tortuosity (p < 0.0001). An AAD risk model was developed based on aortic arch diameter, length from the aortic root to the iliac bifurcation, and angulation of the brachiocephalic artery origin from the aorta. The bootstrap estimate of the area under the receiver operating curve was 0.974. CONCLUSIONS: Enlargement of the ascending aorta and aortic arch and increased aortic tortuosity reflect an aortopathy which enhances the probability of AAD. A model based on 3 anatomical variables demonstrates significant associations with AAD: it may allow identification by aortic imaging of the hypertensive patient most at risk, and permit implementation of aggressive medical management and consideration of pre-emptive surgery to prevent dissection.

Open repair of descending and thoracoabdominal aortic aneurysms and dissections in patients aged younger than 60 years: superior to endovascular repair?

BACKGROUND: The best option for repair of descending thoracic and thoracoabdominal aortic aneurysms (TAAA)-whether open operation or stent grafting-is increasingly a subject of controversy. We examined the results of open surgical repair in patients aged 60 years or younger to assess the value of conventional repair in younger patients. METHODS: From October 2002 to October 2010, 107 of 294 TAAA operations were in patients (75 men [70%]) aged a mean of 48 ± 9 years. Twelve patients (11%) had Marfan syndrome. Operations were elective in 101 (94%); previous aortic operations had been performed in 40 (37%). The most common indication for operation was chronic dissection, in 60 (56%); 5 (4.7%) had acute dissection, and rupture was present in 6 (5.6%). Descending repair was undertaken in 44 (41%), in 32 (73%) as an elephant trunk stage II. Deep hypothermic circulatory arrest was used in 46 (42.9%). Neurologic monitoring and cerebrospinal fluid drainage were routine. Median postoperative follow-up was 4.3 years (range, 2 days to 7.9 years). RESULTS: Overall 30-day mortality was 4.7%. Stroke occurred in 4 patients (3.7%) and paraplegia in 1 (0.9%). The linearized rate for reoperation for TAAA was 0.22/100 patient-years (1 patient in 448.8 patient-years). Survival at 1, 5, and 8 years was 90.5%, 89.4% and 80.5%, respectively. During follow-up, 1 patient with Ehlers-Danlos died of aortic complications at 4.5 years. CONCLUSIONS: Although direct comparison with stent grafting is limited by the diversity of patients and indications in published reports, our results suggest that open repair should be the modality of choice. Early mortality and neurologic complication rates are similar, if not superior, to endovascular repair for descending aortic and TAAAs. Open repair has proven durability and a very low rate of required reintervention, in contrast with endovascular repair.

Quality of life and survival of septuagenarians and octogenarians after repair of descending and thoracoabdominal aortic aneurysms.

OBJECTIVE: We assessed quality of life and survival in elderly patients after complex aortic operations to aid in surgical decision making. METHODS: A retrospective review was performed of 93 patients who underwent descending thoracic aneurysm or thoracoabdominal aortic aneurysm (TAAA) repair from 2002 to 2008. A Cox model was used for survival analysis. The SF-36 Item Health Survey was administered to assess postoperative quality of life in 39 patients and was compared with age- and gender-matched normal scores. RESULTS: The mean age at operation was 75 ± 4.1 years; 51% of patients were male. In-hospital mortality was 15%. One-year survival was 69%, and 5-year survival was 45%. Only acute respiratory distress syndrome was a predictor of in-hospital mortality (hazard ratio = 3.75; P < .01) and 1-year mortality (hazard ratio = 4.61; P < .001). After 1 year, patients enjoyed longevity equivalent to that of a normal age- and gender-matched population (standardized mortality ratio = 1.06; P = .81). Being male is a predictor of long-term survival (hazard ratio = 0.18; P < .05). For women, extremely low and high body mass indexes (quadratic term = 0.020; P < .05) with an inflection point of body mass index of 28 is a risk factor of long-term survival. Quality of life scores were similar to those of the general population except for lower vitality scores, (s-score = -0.67, 95% CI, -1.09 to -0.26). CONCLUSIONS: TAAA repair in this selected older surgical population yields acceptable survival beyond the first year. Among 1-year survivors, quality of life is similar to that of an age- and gender-matched population.

Imaging of vascular remodeling after simulated thoracoabdominal aneurysm repair.

OBJECTIVE: A better understanding of the response of the spinal cord blood supply to segmental artery (SA) sacrifice should help minimize the risk of paraplegia after both open and endovascular repair of thoracoabdominal aortic (TAA) aneurysms. METHODS: Twelve female juvenile Yorkshire pigs were randomized into 3 groups and perfused with a barium-latex solution. Pigs in group 1 (control) had infusion without previous intervention. Pigs in group 2 were infused 48 hours after ligation of all SAs (T4-L5) and those in group 3 at 120 hours after ligation. Postmortem computed tomographic scanning of the entire pig enabled overall comparisons and measurement of vessel diameters in the spinal cord circulation. RESULTS: We ligated 14.5 ± 0.8 SAs: all filled retrograde to the ligature. Paraplegia occurred in 38% of operated pigs. A significant increase in the mean diameter of the anterior spinal artery (ASA) was evident after SA sacrifice (P < .0001 for 48 hours and 120 hours). The internal thoracic and intercostal arteries also increased in diameter. Quantitative assessment showed an increase in vessel density 48 hours after ligation of SAs, reflected by an obvious increase in small collateral vessels seen on 3-dimensional reconstructions of computed tomographic scans at 120 hours. CONCLUSIONS: Remodeling of the spinal cord blood supply--including dilatation of the ASA and proliferation of small collateral vessels--is evident at 48 and 120 hours after extensive SA sacrifice. It is likely that exploitation of this process will prove valuable in the quest to eliminate paraplegia after TAA aneurysm repair.

Cerebral protection for aortic arch surgery: deep hypothermia.

The technical aspects of arch surgery have evolved considerably during the last 2 decades. The use of deep hypothermic circulatory arrest has been embraced by many cardiac surgeons to approach aortic arch aneurysms around the world. The branched graft technique that we have been using since the late 1990s has improved surgical outcomes and simplified the treatment considerably. We describe our technique of total arch replacement by using deep hypothermia and selective cerebral perfusion in aortic arch surgery.