Fenestrated Fontan-like circulation under durable left-ventricular assist device support in fulminant myocarditis.

Fulminant myocarditis is a fatal development from profound biventricular heart failure and often requires both right- and left-ventricular assistance to maintain hemodynamics, even at the risk of increased mortality and morbidity. Here, we present a 42-year-old female with profound biventricular failure due to fulminant myocarditis, resolved by an isolated durable left-ventricular assist device support under a fenestrated, Fontan-like circulation and managed low-pulmonary vascular resistance.

Changes in the Quality of Life of Patients with Left Ventricular Assist Device and their Caregivers in Japan: Retrospective Observational Study.

Left ventricular assist devices (LVAD) improve quality of life (QOL) in many patients with end-stage severe heart failure, but not in some patients. In addition, the burden on caregivers is expected to increase after LVAD patients are discharged. Our study aimed to investigate the impact of LVAD on the QOL of patients and caregivers. Thirty-two LVAD patients were assessed for changes in QOL, mental status, and activity level using the Euro QOL (EQ-5D-5L), Short Form 12 (SF-12), Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale (HADS), and Frenchay Activities Index. Twenty-four caregivers were assessed for changes in QOL, mental status, and burden of care using the EQ-5D-5L, SF-12, HADS, and Burden Index of Caregiver (BIC-11). The LVAD patients and caregivers responded contemporaneously regarding two points: pre-and post-LVAD. Patients' physical and mental QOL was significantly improved, but not social QOL and activity level. Caregivers' QOL and burden of care did not change, and anxiety was reduced (p = 0.028). The patients were divided into two groups based on whether EQ-5D-5L was improved: twelve patients in the unimproved group (UG) and twenty patients in the improved group (IG). In the UG, 50% had LVAD-related strokes (p = 0.001, IG: 0%), and their social QOL decreased (p = 0.023). The activity levels improved in the IG. Multi-dimensional analyses on the QOL in LVAD patients yielded mixed results. Anticipated benefits derived from LVAD therapy may be limited by LVAD-related complications such as stroke that negatively impacts on the QOL.

Individual Variability in von Willebrand Factor Fragility in Response to Shear Stress: A Possible Clue for Predicting Bleeding Risk.

Acquired von Willebrand syndrome (AVWS), characterized by reduced von Willebrand factor (VWF) large multimers, has recently been implicated as the principal mechanism underlying bleeding in patients implanted with left ventricular assist devices (LVADs). Hematological severity of AVWS varies among patients, even if an identical device is implanted. We investigated whether this diversity in hematological severity is due to individual variability in VWF fragility, according to responses to incremental shear stress. Whole-blood samples were sheared at 20,000-40,000 s -1 shear rate, an index of shear stress, using a custom-made shear stressor that could generate shear stress compatible with that produced by an LVAD. The degree of VWF large multimers degradation was evaluated using the VWF large multimer index. A significant inverse correlation was observed between the VWF large multimer index and LVAD-compatible magnitudes of shear stress: the VWF large multimer indices were 68.5 ± 18.3, 48.0 ± 13.9, 33.9 ± 12.1, 23.7 ± 7.9, and 18.7% ± 8.7% at 20,000, 25,000, 30,000, 35,000, and 40,000 s -1 of shear rates, respectively ( P < 0.0001). Furthermore, experimental VWF large multimer index values were compatible with those derived from patients with implanted LVADs (median; 28.9%). Finally, reduction in the VWF large multimer index corresponding to shear stress showed individual variation. We demonstrated that the combined use of a novel high shear stress loading device and quantitative evaluation of VWF large multimers may predict risk of bleeding before LVAD implantation.

Aortic Insufficiency Causes Symptomatic Heart Failure during Left Ventricular Assist Device Support.

De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

A Case of an Increase in Prothrombin Time-International Normalized Ratio by Interaction Between Warfarin and Baloxavir Marboxil in a Patient on Implantable Ventricular Assist Device.

BACKGROUND: Baloxavir marboxil (BM) is a novel drug with a cap-dependent endonuclease inhibitory action for influenza A or B; it is highly safe and requires just a single oral dose. Patients with severe heart failure use implantable ventricular assist device (iVAD) until transplantation, but they have an increased risk of thrombosis development. Their warfarin is administered based on point-of-care testing (POCT) with a strict control of prothrombin time-international normalized ratio (PT-INR). CASE REPORT: Here, we report a case of a patient with iVAD whose PT-INR was significantly increased from the target range after BM administration. The patient was a 45-year-old man and transplanted with iVAD; warfarin treatment was started when his PT-INR target range was 3.0-3.5. At home, he frequently self-measured PT-INR by POCT and precisely controlled the warfarin dose. He had a fever, was diagnosed with influenza A and was administered BM 40 mg. Thereafter, his PT-INR continued to increase, reaching 4.8 on day 12 of BM administration, exceeding his target range; warfarin was skipped for 1 day. In this case, based on the history of BM administration and clinical course, the increase in PT-INR could be due to BM. Considering the interaction between warfarin and BM, we suspected a possibility of competition for protein-binding sites. Increased PT-INR in the patient was detected early by POCT and thus severe bleeding was avoided. CONCLUSION: Strict monitoring of PT-INR when using BM in patients taking warfarin is of clinical importance.

Laparoscopic right hemicolectomy for an ascending colon cancer patient with an implantable left ventricular assist device: a case report.

BACKGROUND: Left ventricular assist devices (LVADs) currently play an important role in the treatment of patients with end-stage heart failure who require a bridge to heart transplantation or destination therapy. With the development and improvement of the LVADs, the morbidity and mortality rates are declining and life expectancies increasing, and the number of patients with LVADs requiring non-cardiac surgery is likely to increase. We present the case of a patient with implantable LVAD who underwent laparoscopic right hemicolectomy for ascending colon cancer. CASE DESCRIPTION: The patient was a 66-year-old man who underwent LVAD implantation as a BTT 3 years prior. He suffered from severe anemia at follow-up, and a colonoscopy revealed ascending colon cancer. The LVAD pump was implanted in the epigastrium. The long C-shaped subfascial driveline tunnel was made, and driveline exit site was located on the left lateral abdominal wall. We assessed the positional relationship between the tumor and the driveline using X-ray and three-dimensional computed tomography (3D CT) images. 3D CT image allowed us to easily identify the location of the driveline, and we determined to perform laparoscopic right hemicolectomy. The port sites were decided upon carefully to avoid the driveline injury, and the driveline was marked on the skin before surgery. There were no adhesions in the abdominal cavity, and both the LVAD and the driveline were observable. The trocars were in nearly the same positions as in a standard laparoscopic right hemicolectomy. During the operation, the LVAD and the driveline did not interfere with the trocars. We successfully completed a standard laparoscopic right hemicolectomy despite hemorrhagic tendency. The patient was discharged without any bleeding complications during the postoperative course. CONCLUSION: Laparoscopic surgery is feasible and safe for patients with LVADs with intensive preoperative simulation and perioperative prevention of infection.

[Effects of Olmesartan Medoxomil on Patients with Thoracic and Thoracoabdominal Aortic Aneurysm;Evaluation of Anti-hypertensive Effect and Possible Suppression of Aneurysmal Dilation( OLM 40 Study)].

We evaluated the blood pressure( BP) lowering effect and possible suppression of aortic enlargement by olmesartan (OLM) in patients with thoracic and thoracoabdominal aortic aneurysm. In this single center prospective, forced titration study, 50 patients were registered between 2008 and 2011. After all patients received any of OLM 10, 20, and 40 mg/day as an initial dose, the dosage of OLM was titrated up to 40 mg as needed during follow-up period. Home BP (HBPs), aortic aneurysm size assessed by computed tomography (CT) scan, indices of renal function were recorded at 3- and 6-months follow-up. Depending on whether 40 mg/day of prescription was continued for more than 4 months or not, the patients were divided into 2 groups:less than 40 mg (<40 mg) and 40 mg groups. Morning HBPs tended to decrease in both groups, and the percent changes in BPs were essentially the same regardless of dosage. The absolute value of aortic diameter tended to slightly enlarge only in <40 mg group. Also in the <40 mg group, the absolute differences in aortic diameter between those at the time of study registration and each follow-up were 0.5±1.8 mm at 3-month and 1.2±2.3 mm at 6-month (p=0.047),whereas the percent changes were 0.9±3.3% and 2.2±4.5% at 3 and 6 months, respectively( p=0.058). As for 40 mg group, the absolute differences and percent changes did not reach statistically significant increase during the follow-up period. No severe renal dysfunction related to OLM 40 mg prescription was observed. Our results imply that OLM 40 mg may suppress aortic aneurysmal dilation independently of blood pressure lowering effect. Further study with larger number of sample size is warranted to assure this observation.

Native Valve Endocarditis due to Staphylococcus warneri Developing in a Patient with Type 1 Diabetes.

A 59-year-old man with type 1 diabetes presented with heart failure. Echocardiography showed large vegetations on the mitral and aortic valves. Blood bacterial culture was positive for Staphylococcus warneri, a coagulase-negative staphylococcus (CoNS) family member. He was diagnosed with native valve endocarditis (NVE) induced by the resident bacteria and ultimately underwent double valve replacement. Retrospectively, slight laboratory data abnormalities and weight loss beginning four months before may have been signs of NVE. He had no history of immunosuppressive therapies or medical device implantation. Thus, CoNS can cause NVE after a long asymptomatic course in patients with poorly controlled diabetes.

Preventive effect of low-dose landiolol on postoperative atrial fibrillation study (PELTA study).

OBJECTIVE: To investigate the efficacy of prophylactic administration of low-dose landiolol on postoperative atrial fibrillation (POAF) in patients after cardiovascular surgery. METHODS: Consecutive 150 patients over 70 years of age who underwent cardiovascular surgery for valvular, ischemic heart, and aortic diseases were enrolled in this single-center prospective randomized control study from 2010 to 2014. They were assigned to three treatment groups: 1γ group (landiolol at 1 µg/kg/min), 2γ group (landiolol at 2 µg/kg/min), or control group (no landiolol). In the two landiolol groups, landiolol hydrochloride was intravenously administered for a period of 4 days postoperatively. Electrocardiography was continuously monitored during the study period, and cardiologists eventually assessed whether POAF occurred or not. RESULTS: POAF occurred in 24.4% of patients in the control group, 18.2% in 1γ group, and 11.1% in 2γ group (p = 0.256). Multivariate logistic regression analysis showed that the incidence of POAF tended to decrease depending on the dose of landiolol (trend-p = 0.120; 1γ group: OR = 0.786, 95% CI 0.257-2.404; 2γ group: OR = 0.379, 95% CI 0.112-1.287). Subgroup analysis showed a significant dose-dependent reduction in POAF among categories of female sex, non-use of angiotensin II receptor blockers (ARBs) before surgery, and valve surgery (each trend-p = 0.02, 0.03, and 0.004). CONCLUSIONS: These findings indicate that prophylactic administration of low-dose landiolol may not be effective for preventing the occurrence of POAF in overall patients after cardiovascular surgery, but the administration could be beneficial to female patients, patients not using ARBs preoperatively, and those after valvular surgery.

The incidence, risk factors, and outcomes of gastrointestinal bleeding in patients with a left ventricular assist device: a Japanese single-center cohort study.

Continuous flow-left ventricular assist devices (CF-LVADs) have become a therapeutic option in the management of advanced heart failure. Several studies show that patients with CF-LVAD are at an increased risk of gastrointestinal bleeding (GIB). However, few reports have presented the characteristics of GIB in Japanese populations. We investigated the incidence, etiology, and outcome of GIB in patients with CF-LVAD. Records of adult patients who received CF-LVADs between October 2008 and January 2017 were reviewed. GIB was defined as detection of bleeding sites by any type of diagnostic imaging. 54 patients received CF-LVAD, of which eight (14%) presented with overt GIB (12 events). GIB patients are significantly older (p = 0.04) and their pre-operative inferior vena cava diameter was larger (p = 0.02). Multivariate analysis revealed that the use of Jarvik 2000 (p = 0.003) was a risk factor for GIB. In total, 85.8% of patients were free from GIB at 1 year. The most common site was the small intestine (67%). The most common cause was angiodysplasia (50%). Six patients required blood transfusion (nine events) and four underwent endoscopic clippings (five events); however, no patients needed surgeries. The incidence of GIB in our cohort was similar to the global registry data. Double balloon endoscopy is useful for diagnosis and treatment of small intestinal lesions. Future efforts to further understand the incidence of GIB in Japanese populations by multicenter data are needed.

Maximization of the sealing effect of fibrin glue in aortic surgery.

OBJECTIVES: Fibrin glue is used to reinforce anastomosis in aortic surgery. There has not yet been a consensus on how it should be applied optimally. This study aimed to define the optimal condition of applying fibrin glue. METHODS: In experiment 1, we determined the optimal condition for spraying fibrin glue using an expanded polytetrafluoroethylene graft within a needle hole. The length and area of the fibrin cap within the hole were measured. In experiment 2, methods for applying fibrinogen were assessed by comparing brushing and spraying. In experiment 3, swine aorta segments sutured with a Dacron graft were divided into the following three groups: nothing was applied; fibrinogen was sprayed and rubbed using brush. The aorta was clamped and blood was infused from an occlusion catheter inserted into the graft. The pressure at the first appearance of blood leak was recorded. RESULTS: In experiment 1, among the four groups divided by the pressure and distance of spraying, the fibrin cap area in the group with 0.075 MPa and 2-cm spray distance was significantly larger than that in the group with 0.15 MPa and 2 cm (P < 0.01). In experiment 2, the fibrin cap area in the brushing group was significantly larger than that in the spraying group (P < 0.05). In experiment 3, the capacity to resist endoluminal pressure was higher in the brushing and combined spraying group compared with that in the sequential combined spraying group (P < 0.01). CONCLUSIONS: The brush and spray methods showed excellent hemostatic outcomes.

Temporary ventricular assist device implantation by sternotomy-avoiding technique for bridge-to-decision therapy: a comparison with conventional implantation.

OBJECTIVE: Temporary ventricular assist device (VAD) is a commonly used therapeutic option for cardiogenic shock. Patients requiring this treatment are often critical, and clinical outcomes remain unsatisfactory. This study evaluated the feasibility and efficacy of a sternotomy-avoiding technique for temporary VAD implantation to improve patient outcomes. METHODS: Between December 2012 and November 2018, seven patients underwent temporary VAD implantation by sternotomy-avoiding technique (SA group) and eight by median sternotomy technique (MS group). Pre- and intraoperative characteristics, postoperative 7-day hemodynamic parameters, 30-day mortality, and adverse events were compared between the groups. RESULTS: More than 50% of the patients were mechanically supported before temporary VAD implantation. Cardiopulmonary bypass time was significantly shorter in the SA than in the MS group (84 min vs 215 min; p = 0.011); surgical time tended to be shorter in the SA group (385 min vs 461 min; p = 0.064). Pump index, cardiac index, mixed venous oxygen saturation, and central venous pressure did not differ significantly during the first seven days of support. The 30-day incidence of any adverse event was not significantly different between the groups. No patients in the SA group needed re-exploration for surgical bleeding. Thirty-day all-cause mortality rates were 29% in the SA group and 0% in the MS group (p = 0.11). CONCLUSIONS: The sternotomy-avoiding and conventional techniques resulted in comparable short-term hemodynamic support. The sternotomy-avoiding technique was associated with a potential reduction in risk of re-exploration for bleeding. These results support the usefulness of the sternotomy-avoiding procedure for selected patients.

Nanobubble technology to treat spinal cord ischemic injury.

Background: Spinal cord ischemic injury is a severe complication of aortic surgery. We hypothesized that cerebrospinal fluid (CSF) oxygenation with nanobubbles after reperfusion could ameliorate spinal cord ischemic injury. Methods: Twenty white Japanese rabbits were categorized into 4 groups of 5 rabbits each: sham group, with balloon catheter insertion into the aorta; ischemia group, with spinal cord ischemic injury by abdominal aortic occlusion; nonoxygenated group, with nonoxygenated artificial CSF irrigation after spinal cord ischemic injury; and oxygenated group, with oxygenated artificial CSF irrigation after spinal cord ischemic injury. At 48 hours after spinal cord ischemic injury, the modified Tarlov score to reflect hind limb movement was evaluated. The spinal cord was histopathologically examined by counting anterior horn cells, and microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses were performed. Results: The oxygenated group showed improved neurologic function compared with the ischemia and nonoxygenated groups (P < .01 and P = .019, respectively). Anterior horn neuron prevention in the sham, nonoxygenated, and oxygenated groups was confirmed (mean modified Tarlov score: sham, 9.2 ± 1.9; nonoxygenated, 10.2 ± 2.2; oxygenated, 10.4 ± 2.2; ischemia, 2.7 ± 2.7). Microarray analysis identified 644 genes with twofold or greater increased signals between the ischemia and sham groups. Thirty-three genes related to inflammatory response were enriched among genes differentially expressed between the oxygenated and ischemia groups. Interleukin (IL)-6 and tumor necrosis factor (TNF) expression levels were significantly lower in the oxygenated group compared with the ischemia group, while qRT-PCR showed lower IL-6 and TNF expression levels in the oxygenated group compared with the ischemia group (P < .05). Conclusions: CSF oxygenation with nanobubbles after reperfusion can ameliorate spinal cord ischemic injury and suppress inflammatory responses in the spinal cord.

[Splenic Injury during Replacement of the Thoracoabdominal Aorta].

Extraperitoneal approach is commonly employed for thoracoabdominal aortic repair via Stoney incision. It is supposedly rare to encounter abdominal visceral bleeding during that procedure. However, the spleen may spontaneously adhere to the adjacent peritoneum, which could induce incidental injury to the spleen by its anterior mobilization during extraperitoneal approach. Unless we bare its potential risk in mind, bleeding from the spleen may be overlooked, which results in hemodynamic deterioration. We have experienced 3 cases of splenic injury that necessitated hemostatic maneuvers for bleeding during and just after the thoracoabdominal aortic repair.

Concomitant Valve-Sparing Aortic Root Replacement With Repair of Tetralogy of Fallot.

Valve-sparing aortic root replacement is one of the effective repairs for aortic regurgitation resulting from progressive dilatation of the aortic root late after surgical correction of conotruncal anomaly. However, feasibility and effectiveness of this procedure are unknown for unrepaired physiology. A 32-year-old man presented with unrepaired tetralogy of Fallot (TOF) and moderate aortic regurgitation with severe left ventricular dysfunction. Valve-sparing aortic root replacement and TOF repair were simultaneously performed. Six months after the surgical procedure, aortic regurgitation remained trivial. Concomitant valve-sparing aortic root replacement with TOF repair can be feasible and effective for unrepaired TOF with aortic regurgitation.

Differential selective hypothermic intercostal artery perfusion: a new method to probe spinal cord perfusion during thoracoabdominal aortic aneurysm repair.

OBJECTIVE: To prevent paraplegia in patients undergoing thoracoabdominal aortic aneurysm repair, the importance of preoperative identification of the Adamkiewicz artery and reconstruction of critical intercostal artery have been advocated. Conversely, significance of collateral network for spinal cord perfusion has been recognized. We invented a new system consisting of a direct monitoring of cerebrospinal fluid temperature (CSFT) and differential selective hypothermic intercostal artery perfusion (D-HIAP). METHODS: After exposing a critical intercostal artery, a 10-mm prosthetic graft was anastomosed in an end to side fashion. A balloon-tipped catheter was inserted into the graft to perfuse with 15 °C blood. Neighboring intercostal arteries were also perfused in the same fashion. Serial monitoring of CSFT was performed. Between January 2011 and January 2015, D-HIAP was employed in 50 patients with Adamkiewicz artery that located within a reconstructed area. RESULTS: Significant CSFT drop was recorded after initiation of D-HIAP in 42 (84%) patients. Of those, 34 (68%) patients showed significantly lowered CSFT with D-HIAP into a single critical intercostal artery. Perfusion into plural intercostal arteries was necessary for CSFT drop in 2 cases (4%), and plural intercostal artery perfusion further enhanced CSFT drop that had been modestly achieved by single intercostal artery perfusion in 6 cases (12%). Eight (16%) patients did not exhibit a significant drop in CSFT even when D-HIAP was employed for the critical and neighboring intercostal arteries. CONCLUSIONS: The detection of a disparity in temperature between the intrathecal space and blood generated by D-HIAP revealed individual variability in CSFT changes, which may imply a complexity in spinal cord perfusion. Intraoperative D-HIAP may help to identify a major blood supply for spinal cord perfusion and underlying collateral network.

[Preliminary Results with Implantation of Extracorporeal Ventricular Assist System without Sternotomy Incision].

Temporary mechanical circulatory support device has been highly advocated for severe cardiogenic shock patient. However, standard ventricular assist device (VAD) implantation is invasive procedure for these sick patients. Less-invasive cardiac procedures are known to be generally associated with many beneficial effects such as reduction of trauma, blood loss and risk of infection, and relatively short intensive care unit stay. Here we describe an alternative technique for less invasive extracorporeal VAD implantation.

Small GTP-Binding Protein GDP Dissociation Stimulator Prevents Thoracic Aortic Aneurysm Formation and Rupture by Phenotypic Preservation of Aortic Smooth Muscle Cells.

BACKGROUND: Thoracic aortic aneurysm (TAA) and dissection are fatal diseases that cause aortic rupture and sudden death. The small GTP-binding protein GDP dissociation stimulator (SmgGDS) is a crucial mediator of the pleiotropic effects of statins. Previous studies revealed that reduced force generation in aortic smooth muscle cells (AoSMCs) causes TAA and thoracic aortic dissection. METHODS: To examine the role of SmgGDS in TAA formation, we used an angiotensin II (1000 ng·min-1·kg-1, 4 weeks)-induced TAA model. RESULTS: We found that 33% of Apoe-/- SmgGDS+/- mice died suddenly as a result of TAA rupture, whereas there was no TAA rupture in Apoe-/- control mice. In contrast, there was no significant difference in the ratio of abdominal aortic aneurysm rupture between the 2 genotypes. We performed ultrasound imaging every week to follow up the serial changes in aortic diameters. The diameter of the ascending aorta progressively increased in Apoe-/- SmgGDS+/- mice compared with Apoe-/- mice, whereas that of the abdominal aorta remained comparable between the 2 genotypes. Histological analysis of Apoe-/- SmgGDS+/- mice showed dissections of major thoracic aorta in the early phase of angiotensin II infusion (day 3 to 5) and more severe elastin degradation compared with Apoe-/- mice. Mechanistically, Apoe-/- SmgGDS+/- mice showed significantly higher levels of oxidative stress, matrix metalloproteinases, and inflammatory cell migration in the ascending aorta compared with Apoe-/- mice. For mechanistic analyses, we primary cultured AoSMCs from the 2 genotypes. After angiotensin II (100 nmol/L) treatment for 24 hours, Apoe-/- SmgGDS+/- AoSMCs showed significantly increased matrix metalloproteinase activity and oxidative stress levels compared with Apoe-/- AoSMCs. In addition, SmgGDS deficiency increased cytokines/chemokines and growth factors in AoSMCs. Moreover, expressions of fibrillin-1 ( FBN1), α-smooth muscle actin ( ACTA2), myosin-11 ( MYH11), MYLLK, and PRKG1, which are force generation genes, were significantly reduced in Apoe-/- SmgGDS+/- AoSMCs compared with Apoe-/- AoSMCs. A similar tendency was noted in AoSMCs from patients with TAA compared with those from control subjects. Finally, local delivery of the SmgGDS gene construct reversed the dilation of the ascending aorta in Apoe-/- SmgGDS+/- mice. CONCLUSIONS: These results suggest that SmgGDS is a novel therapeutic target for the prevention and treatment of TAA.