A Case of Thoracic Aortic Endovascular Repair of a Ruptured Mycotic Aortic Aneurysm Due to Pasteurella Multocida.

An 81-year-old man was admitted for general fatigue of one month's duration. Two sets of blood cultures revealed bacteremia, due to Pasteurella multocida, while computed tomography (CT) revealed a 47-mm descending aortic saccular aneurysm. After transfer to our hospital, the saccular aneurysm rapidly grew to 54 mm. An emergency thoracic endovascular aortic repair was performed, due to the aneurysm immediately rupturing after the CT scan. The patient was discharged on postoperative day 28.

Dichloroacetate prevents restenosis in preclinical animal models of vessel injury.

Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States. In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (ΔΨm) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented ΔΨm hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal ΔΨm and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.

Outcomes of Early-Onset Acute Type A Aortic Dissection　- Influence of Etiologic Factors.

BACKGROUND: Outcomes of early-onset acute type A aortic dissection (ATAAD) associated with Marfan syndrome (MFS) are known, but not with other etiologies. Methods and Results: ATAAD patients from 2 centers (n=1,001) were divided into 2 groups: age ≤45 years (n=93) and age >45 years (n=908). Although in-hospital death and 10-year survival were similar (12% vs. 7% and 62.6% vs. 67.3%), the 10-year aortic event-free survival differed (50.0% vs. 80.2%; P<0.01). ATAAD patients from 3 centers (n=132), all aged ≤45 years, were divided into 5 groups: lone hypertension (HTN, n=71), MFS (n=23), non-syndromic familial thoracic aortic aneurysm and dissection (NS-FTAAD, n=16), bicuspid aortic valve (BAV, n=11), and no known etiologic factor (n=11). The incidence of severe aortic insufficiency varied between groups (HTN: 11%, MFS: 39%, NS-FTAAD: 38%, BAV: 55%, no known factor: 46%; P<0.01), whereas in-hospital death did not (14%, 22%, 0%, 0%, and 9%; P=0.061). The 10-year survival was 52.2%, 64.7%, 83.6%, 100%, and 90.9%, respectively, and 10-year aortic event-free survival was 55.6%, 36.3%, 77.5%, 90.0%, and 30.0%. Median descending aorta growth (mm/year) was 1.1 (0.1-3.4), 2.3 (0.3-5.3), 1.9 (1.3-2.7), 0.9 (-0.1-2.0), and 1.0 (-0.2-2.9) (P=0.15), respectively. CONCLUSIONS: Late aortic events are common in young ATAAD patients. Known etiologic factors, though not BAV, negatively influence late outcomes in these patients.

Acute type a aortic dissection associated with a sporting activity.

PURPOSE: To investigate the clinical characteristics of acute type A aortic dissection (ATAAD) occurring during a sporting activity. METHODS: The subjects of this study were 615 patients who underwent surgery for ATAAD between 1990 and 2015. The patients were divided into two groups according to whether the ATAAD was associated with a sporting activity (sports group: n = 25, mean age 62.3 years; non-sports group: n = 590, mean age 63.7 years). Specific activity was assessed in the sports group, and the characteristics and outcomes were compared between the groups. RESULTS: The sports group accounted for 5% of the patients with daytime onset ATAAD (25/479). The most common sport was golf (n = 8), followed by swimming (n = 4), cycling (n = 4), and weight lifting (n = 3). The average diameter of the ascending aorta on preoperative computed tomography was 4.8 cm. The dissection characteristics of the sports group included DeBakey type I (n = 23, 92%) and malperfusion (n = 9, 36%), which were similar to those of the non-sports group. The 30-day mortality rates were 16% (4/25) for the sports group and 8% (49/590) for the non-sports group (P = 0.33). CONCLUSIONS: The most common sport associated with ATAAD was golf, followed by swimming cycling, and weight lifting. The findings of this study reinforce that sports-related aortic dissection is not a unique clinical condition of young syndromic patients, but can occur in all age groups.

Orthotopic tracheal transplantation using human bronchus: an original xenotransplant model of obliterative airway disorder.

Bronchiolitis obliterans syndrome (BOS) is a main cause of allograft dysfunction and mortality after lung transplantation (LTx). A better understanding of BOS pathogenesis is needed to overcome this treatment-refractory complication. Orthotopic tracheal transplantation using human bronchus was performed in Brown Norway (BN) and nude (RNU) rats. Allografts were recovered in both strains at Day 7 (BN7 , n = 6; RNU7 , n = 7) or Day 28 (BN28 , n = 6; RNU28 , n = 6). Immune response of the host against the bronchial graft was assessed. Human samples from BOS patients were used to compare with the histological features of the animal model. Obstruction of the allograft lumen associated with significant infiltration of CD3+ and CD68+ cells was observed in the BN group on Day 28. Immune response from type 1 T-helper cells against the tracheal xenograft was higher in BN animals compared to nude animals on Days 7 and 28 (P < 0.001 and P = 0.035). Xenoreactive antibodies were significantly higher at Day 7 (IgM) and Day 28 (IgG) in the BN group compared to RNU (respectively, 37.6 ± 6.5 vs. 5.8 ± 0.7 mean fluorescence, P = 0.039; and 22.4 ± 3.8 vs. 6.9 ± 1.6 mean fluorescence, P = 0.011). Immunocompetent animals showed a higher infiltration of S100A4+ cells inside the bronchial wall after 28 days, associated with cartilage damage ranging from invasion to complete destruction. In vitro expression of S100A4 by human fibroblasts was higher when stimulated by mononuclear cells (MNCs) from BN rats than from RNU (2.9 ± 0.1 vs. 2.4 ± 0.1 mean fluorescence intensity, P = 0.005). Similarly, S100A4 was highly expressed in response to human MNCs compared to stimulation by T-cell-depleted human MNCs (4.3 ± 0.2 vs. 2.7 ± 0.1 mean fluorescence intensity, P < 0.001). Obliterative bronchiolitis has been induced in a new xenotransplant model in which chronic airway obstruction was associated with immune activation against the xenograft. Cartilage infiltration by S100A4+ cells might be stimulated by T cells.

[Two-staged hybrid surgery for an extended thoracic aortic aneurysm with Komerell's diverticulum].

We have successfully performed 2 staged hybrid operation for an extended thoracic aortic aneurysm with Komerell diverticulum, which lessened surgical stress of the patient with avoidance of postoperative complications. An 82-year-old man who had been under observation for thoracic aortic aneurysm was admitted to the hospital with continuous chest discomfort. The patient initially underwent graft replacement for an ascending and arch aneurysm by using the elephant trunk technique. Thirty-five days later, he underwent endovascular repair for the residual descending thoracic aneurysm. The postoperative course was uneventful, and postoperative computed tomography (CT) revealed no stent migration and just a little type II endoleak. This 2 staged hybrid approach might be less invasive than the conventional approach, and be a potential therapeutic option for high risk patients with an extended thoracic aortic aneurysm.

Cardiac Arrest in a 33-year-old Marathon Runner with Anomalous Right Coronary Artery Originating from the Pulmonary Artery.

A 33-year-old marathon runner presented with anomalous right coronary artery originating from the pulmonary artery after being admitted for cardiac arrest. Surgical re-implantation of the right coronary artery to the aortic root to re-establish right coronary ostial circulation was successful. The patient resumed exercise and required no further medical therapy.

Bicuspidalization of the Native Tricuspid Aortic Valve: A Porcine in Vivo Model of Bicuspid Aortopathy.

Objective: To examine early histologic changes in the aorta exposed to bicuspid flow. Material and Methods: A porcine bicuspid aortopathy model was developed by suturing aortic cusps. Of nine pigs, eight underwent sham surgery (n=3) or bicuspidalization (n=5); one was used as an intact control. Wall shear stress (WSS) was assessed by computational fluid dynamics (CFD). Animals were exposed to normal or bicuspid flow for 48 h and were then euthanized for histologic examinations. Results: No animal died intraoperatively. One animal subjected to bicuspidalization died of respiratory failure during postoperative imaging studies. Echocardiography showed the aortic valve area decreased from 2.52±1.15 to 1.21±0.48 cm2 after bicuspidalization, CFD revealed increased maximum WSS (10.0±5.2 vs. 54.0±25.7 Pa; P=0.036) and percentage area of increased WSS (>5 Pa) in the ascending aorta (30.3%±24.1% vs. 81.3%±13.4%; P=0.015) after bicuspidalization. Hematoxylin-eosin staining and transmission electron microscopy showed subintimal edema and detached or degenerated endothelial cells following both sham surgery and bicuspidalization, regardless of WSS distribution. Conclusion: A bicuspid aortic valve appears to increase aortic WSS. The endothelial damage observed might have been related to non-pulsatile flow (cardiopulmonary bypass). Chronic experiments are needed to clarify the relationship between hemodynamic stress and development of bicuspid aortopathy.

A Successful Treatment Strategy for Paradoxical Cerebral Embolism Accompanied by Entrapped Thrombus in Patent Foramen Ovale.

A 73-year-old man was transferred to our hospital with dyspnea and left hemiplegia. The diagnosis of pulmonary embolism, entrapped thrombus in patent foramen ovale (PFO), and internal carotid artery occlusion was made by imaging studies. We decided to perform endovascular treatment without the administration of tissue plasminogen activator (tPA) for cerebral embolism because of concern about further embolism caused by fragmented thrombi. After endovascular treatment, he successfully underwent surgical embolectomy for entrapped thrombus in PFO. Endovascular treatment without tPA administration and subsequent surgical embolectomy seems to be a viable treatment strategy for patients with occlusion of the large cerebral artery accompanied by entrapped thrombus in PFO.

Utility of double arterial cannulation for surgical repair of acute type A dissection.

OBJECTIVES: Outcomes of planned and unplanned (rescue) double arterial cannulation (DAC) in surgery for acute type A aortic dissection were investigated retrospectively. METHODS: The study involved 805 patients who were divided into 4 groups according to the cannulation strategy: single cannulation of the femoral artery (n = 338), axillary artery (n = 256), left ventricular apex (n = 52) or ascending aorta (n = 5) (total, n = 57), and DAC (n = 154). Patients who underwent DAC were divided between planned (n = 132) and rescue (n = 22) usage. Characteristics and outcomes were compared between groups. Both unmatched and propensity score-matched analyses were performed. RESULTS: Shock (39%, 19%, 33% and 14%, in the femoral artery, axillary artery, left ventricular apex/ascending aorta and DAC, respectively) and leg malperfusion (5%, 16%, 16% and 26%, respectively) differed significantly (P < 0.001), but in-hospital mortality did not (9%, 8%, 18% and 7%, respectively; P = 0.096). The 5-year survival rates were 79.4%, 79.7%, 78.6% and 82.2%, respectively. Propensity score-matched analysis showed no statistically significant differences in in-hospital mortality rates (10%, 12%, 14% and 9%, respectively; P = 0.78) and 5-year survival rates (78.4%, 72.3%, 82.3% and 78.0%, respectively). The leading vessel combination and indications for planned and rescue DAC were the femoral and axillary arteries (98%) and true lumen narrowing and/or leg malperfusion (34%), and the axillary followed by femoral (77%) artery and low cardiopulmonary bypass flow (36%). In-hospital mortality in the planned and rescue DAC groups was 7% and 9%, respectively. CONCLUSIONS: DAC seems effective for both prevention and management of intraoperative malperfusion.

Effects of Obesity on Outcomes of Acute Type A Aortic Dissection Repair in Japan.

Background: The prevalence of obesity among Japanese acute type A aortic dissection (ATAAD) patients and its effect on repair outcomes remain to be elucidated. Methods and Results: The prevalence of obesity (body mass index [BMI] ≥30.0 kg/m2) among 1,059 patients (mean [±SD] age 64.3±12.7 years) who underwent ATAAD repair between 1990 and 2018 was compared with that among the general Japanese population (National Health and Nutrition Survey data). The prevalence of obesity among male patients (17.1% [6/35], 20.0% [18/90], and 14.4% [20/139] for those aged 20-39, 40-49, and 50-59 years, respectively) was significantly higher than that among the age- and sex-matched general population. The 1,059 patients were divided into groups according to weight (normal [BMI <25.0 kg/m2; n=742], overweight [BMI 25.0-29.9 kg/m2; n=248], or obese [BMI ≥30.0 kg/m2; n=69]). Comparing the normal weight, overweight, and obese groups revealed significant differences among the 3 groups in median cardiopulmonary bypass time (143, 167, and 183 min, respectively), ventilation >48 h (44.5%, 60.1%, and 78.3%, respectively), and in-hospital mortality (7.0%, 7.3%, and 17.4%, respectively), but not in 30-day survival. Shock, visceral malperfusion, operation time >360 min, obesity, and coronary malperfusion were identified as predictors of in-hospital mortality. Conclusions: The prevalence of obesity is increased among Japanese male patients with ATAAD aged ≤59 years. Obesity may increase these patients' operative risk; overweight does not.

Common carotid artery true lumen flow impairment in patients with type A aortic dissection.

OBJECTIVES: Our aim was to evaluate clinical and neurological effects of common carotid artery (CCA) true lumen flow impairment or occlusion in patients with type A aortic dissection. METHODS: Characteristics and imaging data of patients with dissected CCA secondary to acute type A aortic dissection from 3 institutions were analysed. We defined true lumen blood flow as unimpaired when the maximum true lumen diameter exceeded 50% of the complete CCA diameter, as impaired when the true lumen was compressed to ˃50% of the complete lumen, or as occluded. RESULTS: Out of 440 patients, 207 presented unimpaired CCA flow, 172 impaired CCA flow and CCA occlusion was present in 61 patients. Preoperative shock (P = 0.045) or a neurological deficit (P < 0.001) were least common in patients with unimpaired CCA flow and most common in those with CCA occlusion. Non-cerebral, other-organ malperfusion was common in 37% of all patients, but the incidence was similar (P = 0.69). In patients with CCA occlusion, postoperative stroke (P < 0.001) and in-hospital mortality (0.011) were significantly higher, while the incidences were similar between patients with unimpaired and impaired CCA flow. Mixed-effects logistic regression models showed that CCA flow impairment (P = 0.23) or occlusion (P = 0.55) was not predictive for in-hospital mortality, but CCA occlusion was predictive for in-hospital stroke (odds ratio 2.166, P = 0.023). CONCLUSIONS: Shock and non-cerebral, other-organ malperfusion are common in patients with CCA dissection. While there is a high risk for stroke in patients with CCA occlusion, CCA flow impairment and occlusion were not predictive for in-hospital mortality. Surgery should not be denied to patients with CCA flow impairment or occlusion.

Preoperative neurological deficit in acute type A aortic dissection.

OBJECTIVES: Our goal was to evaluate postoperative outcomes in patients with type A aortic dissection with preoperative neurological deficits independent of shock. METHODS: Between 2002 and 2017, 150 of 1600 patients, operated on for aortic dissection type A in 3 centres, presented with preoperative new onset neurological deficits. Postoperative outcomes were classified using a modified Rankin Scale (mRS) as 'no to moderate disability' (mRS 0-3) or as 'poor clinical outcome' (mRS 4-6). Clinical and radiographic data were analysed. RESULTS: Ninety-three patients (62%) had no to moderate disability and 57 (38%) had a poor clinical outcome. The in-hospital mortality rate was 18% (28 patients). Patients with poor clinical outcomes were significantly older (P = 0.01) and had a significantly higher incidence of hypertension (P = 0.04), history of stroke (P = 0.03) and common carotid artery occlusion (left common carotid artery: P = 0.01; right common carotid artery: P < 0.01). One-third of all patients developed haemodynamic instability (P = 0.27). Cardiopulmonary bypass (P < 0.01) and cross-clamp (P = 0.03) times were significantly longer in patients with poor clinical outcomes. Age (odds ratio 1.041; P = 0.02) and history of stroke (odds ratio 2.651; P = 0.03) were predictive of poor clinical outcome; coma was not. Haemorrhagic transformation occurred in 7 patients without any independent predictors. CONCLUSIONS: Most patients with preoperative neurological deficit have no to moderate disability postoperatively but commonly develop preoperative haemodynamic instability. This study suggests that an immediate surgical approach may be reasonable in patients with preoperative neurological deficit or coma.

Redo Descending Aortic Replacement via Direct Anastomosis to J Graft Open Stent Graft.

A 64-year-old man with prior history of total arch replacement with frozen elephant trunk was admitted for an enlarging descending thoracic aortic aneurysm. Preoperative computed tomography revealed previously implanted J graft open stent graft, a frozen elephant trunk device approved in Japan, with enlarged dissected aortic aneurysm from distal anastomosis site to the level of the diaphragm. The patient underwent descending aortic replacement. Proximal anastomosis was directly performed at the distal end of the previously implanted J graft open stent graft. Hemostasis at the anastomosis site was uneventful and the patient was discharged from the hospital without any aneurysm-related complication.

Characteristics and Treatment Outcomes of Acute Type A Aortic Dissection With Elevated D-Dimer Concentration.

BACKGROUND: Clinical characteristics and treatment outcomes of acute type A aortic dissection with D-dimer elevation have not been clarified. METHODS AND RESULTS: D-dimer was measured preoperatively within 24 hours of symptom onset in 262 patients with acute type A aortic dissection. The median (and interquartile range) admission D-dimer concentration in our total patient group was 26.7 (8.3-85.9) µg/mL. Median (interquartile range) D-dimer concentrations were 5.0 (2.6-18.0) µg/mL for complete false lumen thrombosis (n=33), 60.9 (19.4-160.4) µg/mL for partial thrombosis (n=81), 26.5 (10.0-70.6) µg/mL for a patent false lumen (n=131), and 8.7 (3.2-26.9) µg/mL for ulcerlike projection (n=17) (P<0.01). With a D-dimer concentration of ≤8.3 µg/mL representing the lower quartile, we then investigated predictors of a low D-dimer level. Multivariate analysis showed dissection limited to the ascending aorta (P<0.01; odds ratio, 9.81) or descending aorta (P<0.01; odds ratio, 7.68), a completely thrombosed false lumen (P<0.01; odds ratio, 4.02), and absence of brain ischemia (P=0.013; odds ratio, 4.74) to be predictors of the lower D-dimer concentration. Compared with patients with a low D-dimer concentration (≤8.3 µg/mL, n=66), patients with a D-dimer concentration >8.3 µg/mL (n=196) had a reduced preoperative platelet count and increased operation time and transfusion volume. In-hospital mortality was elevated in this group (1.5% versus 11.2%; P=0.031), although 7-year survival did not differ for hospital survivors (lower versus higher, 93.1% versus 79.1%; P=0.21). CONCLUSIONS: D-dimer concentrations are strongly influenced by the extent of dissection and false lumen status. Operative risks are increased in patients with a relatively high D-dimer concentration.

Lifesaving Treatment of Acute Stanford B Aortic Dissection Complicated by Intestinal Ischemia with Stent Placement in the Superior Mesenteric Artery: A Case Report.

A 44-year-old man was transported to our hospital with chief complaints of back pain and paralysis of the leg. Contrast-enhanced computed tomography (CT) imaging revealed an acute Stanford B aortic dissection (AD), which was complicated by acute arterial occlusion of the left external iliac artery. The patient was treated by femorofemoral crossover bypass. Thereafter, abdominal pain was noted, and the patient was diagnosed with intestinal ischemia due to occlusion of the celiac artery and superior mesenteric artery (SMA). A stent was emergently placed into SMA. Subsequently, the patient demonstrated good postoperative progress and was discharged on hospital day 27.

Is right axillary artery cannulation safe in type A aortic dissection with involvement of the innominate artery?

OBJECTIVE: In patients with acute type A aortic dissection involving the innominate artery, it is unclear whether right axillary artery cannulation for arterial inflow is safe. We evaluated the surgical outcomes of patients with dissected innominate artery according to different arterial cannulation sites. METHODS: From 2005 to 2014, of 416 patients with acute type A aortic dissection and preoperative computed tomography angiography in 2 centers, 186 (aged 63 ± 13 years; 43% were female; 95% with DeBakey type I) had dissected innominate artery (84%, 9%, and 7% involving its entire length or more or less than half of its length, respectively). Neurologic complications, in-hospital mortality, and survival were compared between patients with right axillary (N = 84) and non-right axillary (N = 102) cannulation sites. Median follow-up was 30 months (range, 0-130 months). RESULTS: In-hospital mortality was 9.5% and 10.8% (P = .97) for patients with right and non-right axillary cannulation, respectively. Seven patients (8.3%) with right axillary cannulation and 9 patients (8.8%; P = .89) with non-right axillary cannulation had a new-onset postoperative stroke. The axillary artery was cannulated (although dissected) in 8 patients. None of them had a new-onset stroke or died perioperatively. The innominate artery remodeling was observed on follow-up computed tomography in 12% of right axillary cases and 14% of non-right axillary cases (P = .82). Survival did not differ between right axillary and non-right axillary cases, and measured 92% ± 3% versus 87% ± 4% and 85% ± 5% versus 73% ± 9% at 1 and 5 years, respectively (log rank, P = .29). CONCLUSIONS: The right axillary artery is safe to cannulate for arterial inflow in patients with type A aortic dissection with dissected innominate artery.

miR-21 promotes fibrosis in an acute cardiac allograft transplantation model.

AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood. METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts. CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts.