Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management.

Heritable thoracic aortic disease puts patients at risk for aortic aneurysms, rupture, and dissections. The diagnosis and management of this heterogenous patient population continues to evolve. Last year, the American Heart Association/American College of Cardiology Joint Committee published diagnosis and management guidelines for aortic disease, which included those with genetic aortopathies. Additionally, evolving research studying the implications of underlying genetic aberrations with new genetic testing continues to become available. In this review, we evaluate the current literature surrounding the diagnosis and management of heritable thoracic aortic disease, as well as novel therapeutic approaches and future directions of research.

Computational fluid dynamics simulate optimal design of segmental arteries reattachment: Influence of blood flow stagnation.

Objectives: This study aimed to simulate blood flow stagnation using computational fluid dynamics and to clarify the optimal design of segmental artery reattachment for thoracoabdominal aortic repair. Methods: Blood flow stagnation, defined by low-velocity volume or area of the segmental artery, was simulated by a 3-dimensional model emulating the systolic phase. Four groups were evaluated: direct anastomosis, graft interposition, loop-graft, and end graft. Based on contemporary clinical studies, direct anastomosis can provide a superior patency rate than other reattachment methods. We hypothesized that stagnation of the blood flow is negatively associated with patency rates. Over time, velocity changes were evaluated. Results: The direct anastomosis method led to the least blood flow stagnation, whilst the end-graft reattachment method resulted in worse blood flow stagnation. The loop-graft method was comparatively during late systole, which was also influenced by configuration of the side branch. Graft interposition using 20 mm showed a low-velocity area in the distal part of the side graft. When comparing length and diameter of an interposed graft, shorter and smaller branches resulted in less blood flow stagnation. Conclusions: In our simulation, direct anastomosis of the segmental artery resulted in the most efficient design in terms of blood flow stagnation. A shorter (<20 mm) and smaller (<10 mm) branch should be used for graft interposition. Loop-graft is an attractive alternative to direct anastomosis; however, its blood flow pattern can be influenced.

Direct and indirect activation of the adenosine triphosphate-sensitive potassium channel to induce spinal cord ischemic metabolic tolerance.

OBJECTIVES: The mitochondrial adenosine triphosphate-sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide-dependent indirect activation of the adenosine triphosphate-sensitive potassium channel contribute to the induction of ischemic metabolic tolerance. METHODS: Spinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate-sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate-sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia. RESULTS: Motor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P < .001), but worse than in the Nicorandil group (P = .078). Motor preservation in the diazoxide group was similar to the Nicorandil + carboxy-PTIO group. There was no significant difference between the diazoxide and diazoxide + carboxy-PTIO groups. CONCLUSIONS: Both direct and nitric oxide-dependent indirect activation of the mitochondrial adenosine triphosphate-sensitive potassium channel play an important role in pharmacologically induced motor function preservation.

The fate of the downstream aorta after total arch replacement.

OBJECTIVES: The goal of this study was to evaluate the fate of the downstream aorta following total arch replacement. METHODS: Between October 1999 and March 2018, a total of 740 patients underwent total arch replacement. After excluding connective tissue disease, previous descending or thoracoabdominal aortic surgery, patients without adequate preoperative images or operative mortality, late outcomes consisting of additional surgery for distal dilation and distal aortic events were evaluated in 623 survivors (240 aortic dissections, including 139 patients with acute dissection and 383 with a non-dissection aneurysm). The mean follow-up was 5.0 ± 4.0 years. RESULTS: The mean preoperative maximum diameter of the descending aorta was 36.9 ± 8.0 mm. An elephant trunk was inserted in 232 patients, including 183 patients with aortic dissection. Freedom from additional surgery for distal dilation was 88.5% at 5 years and 80.2% at 10 years. Freedom from distal aortic events was 81.9% at 5 years and 70.5% at 10 years. Multivariable regression analysis demonstrated that the preoperative diameter of the descending aorta was a significant risk factor for unfavourable distal aortic events. Computed tomography evaluation demonstrated a significant increase in the descending aortic diameter over time (P < 0.001). Positive aortic remodelling was observed in the proximal descending (P < 0.001) to mid-descending (P < 0.001) aorta exclusively in patients with acute aortic dissection. CONCLUSIONS: The diameter of the descending aorta increased significantly after total arch replacement, particularly in the distal descending aorta. The preoperative descending aortic diameter portended a significant risk for unfavourable distal aortic events.

The Effect of Ascending Aortic Repair on Left Ventricular Remodeling.

Left ventricular (LV) hypertrophy is common in patients with thoracic aortic diseases and is associated with increased long-term mortality. Thoracic aortic aneurysms are reported to increase LV afterload because of kinetic energy loss within the aneurysm sac, which may improve after surgical repair. However, LV afterload may also increase because of the stiffness of prosthetics used for aortic repair. We sought to investigate the long-term effect of surgical aortic repair with prostheses on postsurgical LV mass. We reviewed patients who underwent ascending aortic replacement with a prosthesis at our institution from January 2008 to December 2018. We calculated the LV mass index based on pre- and postoperative echocardiogram measurements. The primary outcome was the change in LV mass index 6 months after aortic repair. Patients aged <18 years and those who had concomitant cardiac operations, severe aortic valve disease, or who had no echocardiographic data were excluded. Of 1,008 patients who underwent ascending aortic replacement, 134 (51 with acute aortic dissections) were included. The median baseline and follow-up LV mass index were 107 (90 to 135) g/m2 and 101 (83 to 123) g/m2, respectively. Overall, there was a significant reduction of LV mass index over time (p = 0.03). LV mass index decreased in 77 patients (59%). Presentation due to acute aortic dissection (p = 0.03) and baseline LV mass index (p <0.001) were significant predictors of LV mass reduction. In conclusion, LV mass index may significantly decrease over time after the aortic repair, but the course is highly variable. The largest decrease occurred in patients who presented because of aortic dissections rather than for elective repair of aneurysms.

Reoperative aortic valve replacement after bio-Bentall using a double sewing ring technique.

We report an 89-year-old haemodialysis patient with a structural valve deterioration following a Bentall-de Bono operation with a tissue valve using the double sewing ring technique. The bioprosthesis was extracted easily, and the aortic valve replacement was performed without any complications in a high-risk patient. This procedure may be feasible given the prospects of reoperation.

Direct Innominate Artery Cannulation versus Side Graft for Selective Antegrade Cerebral Perfusion during Aortic Hemiarch Replacement.

BACKGROUND: Selective antegrade cerebral perfusion (SACP) has become our preferred method for cerebral protection during open arch cases. While the initial approach involved sewing a graft to the innominate artery as the arterial cannulation site, our access strategy has since evolved to central aortic cannulation with use of a percutaneous cannula in the innominate for SACP. We hypothesized that SACP delivered via direct innominate cannulation using a 12- or 14-Fr cannula results in equivalent outcomes to cases utilizing a side graft. METHODS: This was a single-center, retrospective analysis of 211 adult patients who underwent elective hemiarch replacement using hypothermic circulatory arrest with SACP via the innominate artery between 2012 and 2020. Urgent and emergent cases were excluded. RESULTS: A side graft sutured to the innominate was utilized in 81% (n = 171) of patients, while direct innominate artery cannulation was performed in 19% (n = 40) of patients. Baseline patient characteristics were similar between groups aside from a higher baseline creatinine in the direct cannulation group (1.3 vs. 0.9, p = 0.032). Patients undergoing direct cannulation demonstrated shorter cardiopulmonary bypass time (132.7 vs. 154.9 minutes, p = 0.020) and shorter circulatory arrest time (8.1 vs. 10.9 minutes, p = 0.004). Nadir bladder temperature did not significantly differ between groups (27.2°C for side graft vs. 27.6°C for direct cannulation, p = 0.088). There were no significant differences in postoperative outcomes. CONCLUSION: Direct cannulation of the innominate artery with a 12- or 14-Fr cannula for SACP during hemiarch replacement is a safe alternative to using a sutured side graft. While cardiopulmonary bypass and circulatory arrest times appear improved, this is likely attributable to accumulation of experience and proficiency in technique. However, direct innominate artery cannulation may facilitate quicker completion of these procedures by eliminating the time necessary to suture a graft to the innominate artery.

Repair of insufficient aortic valve and single coronary artery with intramural course.

We report about a patient with severe bicuspid aortic valve insufficiency and a single coronary artery with an intramural course. Aortic valve repair with double plication and coronary translocation was satisfactory.

Optimizing Nicorandil for Spinal Cord Protection in a Murine Model of Complex Aortic Intervention.

There are currently no clinically utilized pharmacological agents for the induction of metabolic tolerance to spinal cord ischemia-reperfusion injury in the setting of complex aortic intervention. Nicorandil, a nitric oxide donor and ATP-sensitive potassium (KATP) channel opener, has shown promise in neuroprotection. However, the optimized clinical application of the drug and its mechanism of neuroprotection remains unclear. We hypothesized that 3-days pretreatment would confer the most effective neuroprotection, mediated by mitochondrial KATP channel activation. Spinal cord injury was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Time course: mice received 0.1 mg/kg nicorandil for 10 min, 4 hours, and 3 consecutive days prior to ischemia compared with control. Dose challenge: mice received 3-days nicorandil pretreatment comparing 0.1 mg/kg, 1.0 mg/kg, 5.0 mg/kg, and saline administration. Mitochondrial KATP channel blocker 5-hydroxy-decanoate (5HD) was co-administered to elucidate mechanism. Limb motor function was evaluated, and viable anterior horn neurons quantified. Nicorandil pretreatment at 4 hours and 3 days before ischemia demonstrated significant motor function preservation; administration 10 minutes before ischemia showed no neuroprotection. All nicorandil doses showed significant motor function preservation. Three days administration of Nicorandil 1.0 mg/kg was most potent. Neuroprotection was completely abolished by 5HD co-administration. Histological analysis showed significant neuron preservation with nicorandil pretreatment, which was attenuated by 5HD co-administration. Three days administration of Nicorandil 1.0 mg/kg showed near-total motor function preservation in a murine spinal cord ischemia-reperfusion model, mediated by the mitochondrial KATP channel.

The mid-term outcome of interventricular septal hematoma after ventricular septal defect closure.

We present the case report of a patient who developed interventricular septal hematoma as a complication during perimembranous ventricular septal defect closure. Although cardiopulmonary bypass was re-established and the hematoma was aspirated, postoperative echocardiography revealed that the hematoma reaccumulated in the interventricular septum. She suffered from low-cardiac-output syndrome for 1 week requiring a large amount of inotropic agents. Postoperative echocardiography revealed that the interventricular septal hematoma gradually disappeared. At 1 year follow-up, 99mTc-tetrofosmin myocardial single-photon emission computed tomographic revealed myocardial ischemia in the inferior and septal walls. At 4 years follow-up, her cardiac function has gradually improved. She has no symptoms of heart failure with angiotensin-converting enzyme inhibitor and beta-blocker.

Aortic endograft sizing and endoleak, reintervention, and mortality following endovascular aneurysm repair.

OBJECTIVE: Endograft sizing for endovascular abdominal aortic aneurysm repair (EVAR) is not consistent despite published instructions for use (IFU). We sought to identify factors associated with over/undersizing, determine sex influence on sizing, and examine sizing effects on endoleak, reintervention, and mortality by analyzing data obtained from the W.L. Gore & Associates Global Registry for Endovascular Aortic Treatment (GREAT). METHODS: All patients enrolled in GREAT undergoing EVAR were included for analysis. Proximal/distal aortic landing zones were compared with device implanted to assess sizing as related to IFU. χ2/Fisher exact tests were used to evaluate associations between IFU sizing and demographics. Logistic regression modeling was used to identify predictors of outside IFU sizing. Cox proportional hazards regression analyzed the relationship between sizing and endoleak, device-related reinterventions, and all-cause/aortic mortality. RESULTS: There were 3607 EVAR subjects enrolled in GREAT as of March 2020. Of them, 1896 (53%) were within IFU for sizing, 791 (22%) were oversized, 540 (15%) were undersized, and 380 (10%) had both over- and undersized components. Factors predictive of use outside of IFU included female sex (P = .001), non-white race (P = .0003), decreased proximal neck length (P < .061), or larger iliac diameters (P < .0001). Women were more likely than men to have proximal neck undersizing and iliac limb oversizing, and men were more likely to have iliac limb undersizing. On multivariate analysis, undersizing of the proximal graft was associated with endoleak (hazard ratio [HR], 1.8) and aortic (HR, 60.5) and all-cause (HR, 18.0) mortality. Undersizing of iliac limbs was associated with endoleak (HR, 1.5) and device-related reintervention (HR, 1.4). Iliac limb outside IFU sizing was associated with aortic (HR, 2.6) and all-cause (HR, 1.3) mortality. Proximal and distal oversizing was not associated with adverse outcomes. Female sex was associated with mortality on univariate but not multivariate analysis. CONCLUSIONS: Women undergoing EVAR with GORE EXCLUDER abdominal aortic aneurysm Endoprosthesis (W.L. Gore & Associates Inc, Flagstaff, Ariz) are more likely to have proximal stent-graft undersizing and iliac limb oversizing, whereas men are more likely to have undersized iliac limbs. Proximal aortic graft undersizing is associated with endoleak and all-cause/aortic mortality, whereas undersizing of iliac limbs is associated with endoleak and device-related reintervention. Oversizing was not associated with adverse outcomes.

Reactive Oxygen Species Mediate Nicorandil-induced Metabolic Tolerance to Spinal Cord Injury.

BACKGROUND: Spinal cord injury remains a devastating complication of thoracoabdominal aortic surgery. We previously demonstrated that pretreatment with nicorandil preserved motor function in a murine spinal cord injury model through mitochondrial adenosine triphosphate-sensitive potassium channel activation. We hypothesized that the neuroprotective effect of nicorandil is mediated by downstream generation of reactive oxygen species. METHODS: Spinal cord injury was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Five groups were evaluated: ischemic control (n = 19); nicorandil 1.0 mg/kg (n = 17); nicorandil 1.0 mg/kg plus N acetyl L-cysteine (NAC [reactive oxygen species scavenger, n = 18)]) 150 mg/kg; NAC 150 mg/kg (n = 13); and sham (n = 10). Limb motor function and the number of viable neurons within the anterior horn of the spinal cord were evaluated. RESULTS: Mice in the sham group showed no functional deficits after surgery. Compared with ischemic control, motor function was significantly preserved in the nicorandil pretreatment group at every timepoint after ischemia. In the nicorandil plus NAC group, the motor-preserving effect of nicorandil was completely abolished (P < .001). Viable neuron quantification showed significant neuron preservation in the nicorandil group (29.± 2.6) compared with the ischemic control group (18.5 ± 2.1, P = .024) and nicorandil plus NAC group (14 ± 8.3, P = .001); no significant difference was observed between the ischemic control group and nicorandil plus NAC group (P = 0.768). CONCLUSIONS: Reactive oxygen species generation plays a key role in the nicorandil-induced metabolic tolerance to spinal cord injury. Manipulation of mitochondrial adenosine triphosphate-sensitive potassium channels may lead to improvement in preventing spinal cord injury after thoracoabdominal aortic interventions.

Periodic changes in chemical composition and in vitro digestibility of locally available Gramineae feed resources in the Philippines.

Efficient utilization of locally available feed resources is needed for further development of livestock productions in the tropics. However, an inadequate supply of nourish grass is common, and limited information exists regarding the chemical composition and digestibility of locally available feed resources in the different season. There were few reliable information concerning nutritive value of Gramineae resources in dry and rainy seasons in the Philippines. Hence, the present study was conducted to identify the chemical composition and in vitro digestibility of nine kinds of locally available Gramineae feed resources in dry and rainy seasons in the Philippines. The concentration of dry matter (DM), crude protein, and crude fiber of grass samples did not differ among species and seasons. The concentration of organic matter (OM), ether extract (EE), crude ash (CA), nitrogen-free extract (NFE), acid detergent fiber, and neutral detergent fiber (NDF) of grass samples differed significantly among species in both seasons except the NDF in the rainy season. However, the OM, CA, and NDF concentrations of the samples showed no differences between seasons. Imperata cylindrica showed the highest concentration of OM among the samples. Brachiaria brizantha had the lowest EE concentration among the grasses. The lowest NFE concentration was identified in Panicum maximum among the grasses. Although the digestibility of DM (DMD), OM (OMD), and NDF (NDFD) of grass samples showed significant differences among species. The DMD, OMD, and NDFD of I. cylindrica were the lowest among the samples, though Pennisetum purpureum showed the highest DMD, OMD, and NDFD among the species. Relatively high nutritive values of P. purpureum were remarkable among the samples in the present survey area.

The fate of aortic root and aortic regurgitation after supracoronary ascending aortic replacement for acute type A aortic dissection.

BACKGROUND: The aim of this study was to evaluate the fate of the preserved aortic root after supracoronary aortic replacement for acute type A aortic dissection. METHODS: Between October 1999 and March 2018, 339 patients underwent supracoronary aortic replacement for acute type A aortic dissection at our institution. Late outcomes were evaluated, including overall survival, aortic-related death, and aortic root-related reoperation. The median follow-up was 3.7 years (1.4-8.4 years). RESULTS: Operative mortality was 46 patients (13.6%). The cumulative incidences at 5 years for aortic root-related reoperation, aortic-related death, and non-aortic related death were 2.5%, 14.5% and 12.4%, respectively. Multivariable Cox hazard regression analysis demonstrated greater sinus of Valsalva diameter and number of commissural detachments to be significant risk factors for a composite outcome consisting of aortic-related death or aortic root-related reoperation. Mixed-effects regression demonstrated that sinus of Valsalva diameter significantly increased with time (P < .001), and aortic regurgitation significantly worsened (P < .001). CONCLUSIONS: Sinus of Valsalva diameter and commissural detachment were independent predictors of unfavorable outcomes after supracoronary aortic replacement. Close follow-up is particularly necessary for these patients, and aortic root replacement at the time of initial operation may lead to more favorable late outcomes.

Utility of neuromonitoring in hypothermic circulatory arrest cases for early detection of stroke: Listening through the noise.

OBJECTIVE: Stroke remains a potentially devastating complication of aortic arch intervention. The value of neurophysiologic intraoperative monitoring (NIOM) in the early identification of stroke is unclear. We evaluated the utility of NIOM for early stroke detection in aortic arch surgery. METHODS: Across 8 years at our institution, 365 patients underwent aortic arch surgery with hypothermic circulatory arrest, and 224 cases utilized NIOM. One patient was excluded for intraoperative death. In the remaining cohort, we reviewed the incidence, timing, and location of strokes, and the incidence and nature of NIOM alerts. RESULTS: Hemiarch was performed in 154 patients and total arch replacement in 69 patients. Stroke occurred in 6.3% of all cases (14 out of 223), 15.9% of total arches (11 out of 69), and 2.0% of hemiarches (3 out of 154). There were 33 NIOM alerts (14.8%), and 9 patients had both alerts and stroke. Of these, NIOM deficits plausibly correlated with imaging findings in 7 cases (78%). Of the 5 stroke patients without NIOM alerts, 2 developed neurologic symptoms 3 days or more postoperatively, and infarcts in 3 patients did not result in sensory or motor deficits. Excluding 2 patients with late stroke, the sensitivity of NIOM for stroke detection was 75%, specificity was 88.5%, positive predictive value was 27.3%, and negative predictive value was 97.4%. CONCLUSIONS: Despite a low positive predictive value requiring a high level of discrimination when interpreting abnormal findings, NIOM has high sensitivity and specificity for the early stroke detection. Furthermore, its high negative predictive valve is reassuring for low risk of stroke in the absence of alerts.