Outcomes of thoracic endovascular aortic repair using fenestrated stent grafts in patients with thoracic aortic distal arch aneurysms.

OBJECTIVES: Thoracic endovascular aortic repair (TEVAR) for aortic arch aneurysms is challenging because of anatomical restrictions and the presence of cervical branches. Revascularization of the cervical branch is required when conventional commercial stent grafts are used. TEVAR using fenestrated stent grafts (FSG) often does not require additional procedures to revascularize cervical branches. This study aimed to evaluate the features and initial and midterm outcomes of TEVAR using fenestrated stent grafts. METHODS: From April 2007 to December 2016, 101 consecutive patients underwent TEVAR using fenestrated stent grafts for distal aortic arch aneurysms at a single centre. Technical success, complications, freedom from aneurysm-related death, secondary intervention and aneurysm progression were retrospectively investigated. RESULTS: All the patients underwent TEVAR using fenestrated stent grafts. The 30-day mortality rate was zero. Cerebral infarction, access route problems and spinal cord injury occurred in 4, 3 and 2 patients, respectively. Each type of endoleak was observed in 38 of the 101 patients during the course of the study; 20/38 patients had minor type 1 endoleaks at the time of discharge. The endoleak disappeared in 2 patients and showed no significant change in 8 patients; however, the aneurysm expanded over time in 10 patients. Additional treatment was performed in 8 of the 10 patients with type 1 endoleaks and dilatation of the aneurysm. The rate of freedom from aneurysm-related death during the observation period was 98%. CONCLUSIONS: TEVAR with FSG is a simple procedure, with few complications. Additional treatment has been observed to reduce aneurysm-related deaths, even in patients with endoleaks and enlarged aneurysms. Based on this study, the outcomes of endovascular repair of aortic arch aneurysms using a fenestrated stent graft seem acceptable.

Effect of False Lumen Occlusion Treatment With AFX VELATM, Candy-Plug Technique for Chronic Aortic Dissection.

INTRODUCTION: We sought to examine midterm results and remodeling effect of false-lumen occlusion treatment using AFX VELA in case of chronic dissection repair. MATERIAL AND METHODS: From June 2019 to May 2022, we performed false lumen occlusion treatment using a modified Candy-Plug technique with AFX VELA on 8 chronic aortic dissection patients with a patent false lumen. We collected operative data, short-term clinical outcomes, mid-term clinical outcomes and imaging test results. We conducted follow-up examinations at postoperative, 6-month and 1-, 2- and 3-year intervals, including contrast-enhanced computed tomography to evaluate the diameter, false lumen thrombosis and any events. RESULTS: The average time from the symptom onset to the thoracic endovascular repair was 81.5 (35-155) months. The aorta showed aneurysmal dilation with an average maximum short-axis diameter of 58.9 (41-91) mm. Two cases needed emergency surgery due to rupture and impending rupture. There were no postoperative deaths. Complete thrombosis within the false lumen was achieved in 6 cases (75%), but 2 cases had incomplete thrombosis, requiring additional treatment. The mean maximum diameter showed a significant decrease at 6 months, 1 year and 2 years postoperatively compared to preoperative measurements (P < .05). CONCLUSION: We showed the results of false lumen occlusion treatment using the AFX VELA cuff. We observed favorable clinical outcomes and remodeling effects. While the long-term durability and efficacy of this technique in aortic remodeling will need to be monitored with further observation, the use of this cuff is considered a reliable approach to false lumen occlusion treatment.

Direct Coronary Artery Reimplantation of Anomalous Aortic Origin of the Right Coronary Artery: A Case Report.

Anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital cardiac abnormality. Although AAOCA can cause angina, syncope, palpitations, and sudden cardiac death, most patients remain asymptomatic. A 60-year-old woman experienced occasional chest discomfort. A coronary computed tomography (CT) showed that the right coronary artery (RCA) originated from the left sinus of Valsalva, indicating AAORCA. Exercise myocardial scintigraphy revealed ischemia in the inferior wall. Cardiac catheterization showed stenosis in the ostium of the RCA. Therefore, direct reimplantation of the RCA into the right sinus was performed under cardiopulmonary bypass. The patient recovered uneventfully, postoperatively. Postoperative coronary CT showed no evidence of bending or stenosis in the RCA. Moreover, exercise scintigraphy showed no ischemic changes. The patient was discharged on postoperative day 18 after the resolution of chest discomfort and remained healthy for the following one year. AAORCA is a rare congenital abnormality that could lead to sudden cardiac death. Appropriate imaging studies and surgery should be performed in symptomatic patients with AAORCA who have inter-arterial paths between the ascending aorta and pulmonary artery with right coronary ostial stenosis. Reimplantation of the RCA directly into the right coronary sinus with adequate mobilization of the RCA is a simple procedure that can return the anatomic and biophysiologic status of AAORCA patients to normal and resolve most morphologic abnormalities.

[Tricuspid Valve Replacement for Isolated Tricuspid Valve Infective Endocarditis without Risk Factor].

A 78-year-old Japanese male with previous gastric cancer and untreated diabetes mellitus was admitted to hospital for persistent fever and leg edema. Blood culture was positive for Streptococcus angino'sus, and echocardiography showed isolated tricuspid valve infective endocarditis. Infection was controlled with intravenous antibiotics, but surgery was indicated because of persistent severe regurgitation and large vegetation of 15 mm in size. As the tricuspid valve anterior leaflet was extensively damaged, he underwent valve replacement using a bioprosthetic valve. The patient was discharged 25 days postoperatively with additional antibiotics, and he has been free from recurrent endocarditis for 6 months.

Refractory diffuse coronary artery spasm post aortic valve replacement.

Postoperative coronary artery spasm occurs rarely after valve replacement surgery. We report the case of a 64-year-old man with normal coronary arteries who underwent aortic valve replacement. Nineteen hours postoperatively, his blood pressure plummeted with an elevated ST-segment. Coronary angiography demonstrated a 3-vessel diffuse coronary artery spasm, and direct intracoronary infusion therapy was performed with isosorbide nitrate, nicorandil and sodium nitroprusside hydrate within 1 h of onset. Nonetheless, there was no improvement, and the patient was resistant to treatment. The patient died due to prolonged low cardiac function and pneumonia complications. Prompt intracoronary vasodilator infusion is considered effective. However, this case was refractory to multi-drug intracoronary infusion therapy and was not salvageable.

Complete Resection of Phosphoglyceride Crystal Deposition Disease After Cardiac Surgery.

Phosphoglycerides are the major lipid component of all cell membranes. Phosphoglyceride crystal deposition disease (PCDD) is defined as the deposition of phosphoglyceride crystals and is considered a lipid metabolic disorder. It predominantly involves injured soft tissues, ultimately forming foreign body granulomas. We present a case of complete resection of PCDD in a 48-year-old woman, in whom the PCDD originated from a myocardial wound created at the time of surgical repair of a ventricular septal defect 40 years ago. We underscore that familiarity with this disease entity will help to stimulate accurate diagnosis and timely treatment.

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice.

Elimination of senescent cells (senolysis) was recently reported to improve normal and pathological changes associated with aging in mice1,2. However, most senolytic agents inhibit antiapoptotic pathways3, raising the possibility of off-target effects in normal tissues. Identification of alternative senolytic approaches is therefore warranted. Here we identify glycoprotein nonmetastatic melanoma protein B (GPNMB) as a molecular target for senolytic therapy. Analysis of transcriptome data from senescent vascular endothelial cells revealed that GPNMB was a molecule with a transmembrane domain that was enriched in senescent cells (seno-antigen). GPNMB expression was upregulated in vascular endothelial cells and/or leukocytes of patients and mice with atherosclerosis. Genetic ablation of Gpnmb-positive cells attenuated senescence in adipose tissue and improved systemic metabolic abnormalities in mice fed a high-fat diet, and reduced atherosclerotic burden in apolipoprotein E knockout mice on a high-fat diet. We then immunized mice against Gpnmb and found a reduction in Gpnmb-positive cells. Senolytic vaccination also improved normal and pathological phenotypes associated with aging, and extended the male lifespan of progeroid mice. Our results suggest that vaccination targeting seno-antigens could be a potential strategy for new senolytic therapies.

Single-stage hybrid procedure for ruptured calcified thoracic aortic aneurysm caused by Takayasu's arteritis.

A 68-year-old woman was referred to our hospital because of ruptured severely calcified thoracic aortic aneurysm on chest computed tomography. She was diagnosed with Takayasu's arteritis ~ 30 years ago and was treated with oral steroids daily. We performed total arch repair using uncalcified ascending aorta with open stent-grafting technique, and additional thoracic endovascular aortic repair immediately after open surgery to avoid type Ib endoleak. Continuous hemodiafiltration was needed owing to postoperative transient acute renal failure, following which the patient recovered. She was referred to another hospital 50 days after surgery. A single-stage hybrid procedure for ruptured severe calcified thoracic aortic aneurysm caused by Takayasu's arteritis was required in this case.

p53 plays a crucial role in endothelial dysfunction associated with hyperglycemia and ischemia.

p53 is a guardian of the genome that protects against carcinogenesis. There is accumulating evidence that p53 is activated with aging. Such activation has been reported to contribute to various age-associated pathologies, but its role in vascular dysfunction is largely unknown. The aim of this study was to investigate whether activation of endothelial p53 has a pathological effect in relation to endothelial function. We established endothelial p53 loss-of-function and gain-of-function models by breeding endothelial-cell specific Cre mice with floxed Trp53 or floxed Mdm2/Mdm4 mice, respectively. Then we induced diabetes by injection of streptozotocin. In the diabetic state, endothelial p53 expression was markedly up-regulated and endothelium-dependent vasodilatation was significantly impaired. Impairment of vasodilatation was significantly ameliorated in endothelial p53 knockout (EC-p53 KO) mice, and deletion of endothelial p53 also significantly enhanced the induction of angiogenesis by ischemia. Conversely, activation of endothelial p53 by deleting Mdm2/Mdm4 reduced both endothelium-dependent vasodilatation and ischemia-induced angiogenesis. Introduction of p53 into human endothelial cells up-regulated the expression of phosphatase and tensin homolog (PTEN), thereby reducing phospho-eNOS levels. Consistent with these results, the beneficial impact of endothelial p53 deletion on endothelial function was attenuated in EC-p53 KO mice with an eNOS-deficient background. These results show that endothelial p53 negatively regulates endothelium-dependent vasodilatation and ischemia-induced angiogenesis, suggesting that inhibition of endothelial p53 could be a novel therapeutic target in patients with metabolic disorders.

Progerin impairs vascular smooth muscle cell growth via the DNA damage response pathway.

Mutations of the lamin A gene cause various premature aging syndromes, including Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner syndrome. In HGPS (but not atypical Werner syndrome), extensive loss of vascular smooth muscle cells leads to myocardial infarction with premature death. The underlying mechanisms how single gene mutations can cause various phenotypes are largely unknown. We performed an interactome analysis using mutant forms of lamin A involved in progeroid syndromes. We found that the mutant lamin A responsible for HGPS, known as progerin, could not bind to proteins related to the DNA damage response, including DNA-dependent protein kinase (DNA-PK). In contrast, wild-type lamin A and lamin A mutants causing atypical Werner syndrome were able to bind to these molecules. We also found that forced expression of progerin in vascular smooth muscle cells led to activation of DNA-PK and cellular growth arrest, while knockdown of DNA-PK attenuated this. Deletion of p53 also improved the inhibition of cell growth due to forced expression of progerin. These findings suggested that progerin activates the DNA damage response pathway and that dysregulation of this pathway may be responsible for the development of cardiovascular pathology in patients with HGPS.

Surgical Resection for Solitary Myocardial Metastasis of Gastric Cancer.

Six years after primary surgical treatment for gastric cancer, fluoro-deoxy-glucose positron emission tomography/computed tomography was performed in a 72-year-old man, and demonstrated an increased fluoro-deoxy-glucose uptake in the apex of the left ventricle. Magnetic resonance imaging also revealed a solitary small myocardial tumor. Under cardiopulmonary bypass, tumorectomy was performed with a macroscopically sufficient margin. Histopathologic examination showed adenocarcinoma with poor differentiation developed in the myocardium and pericardial fat; these findings were compatible with the previously resected gastric cancer. The postoperative course was uneventful; the patient has been alive for 29 months without any evidence of local recurrence or cardiac events.

[Early and Late Outcomes of Valve Surgery in Active Infective Endocarditis Patients with Cerebral Complications].

We carried out a retrospective evaluation of the early and late outcomes of valve surgery for acute endocarditis patients with cerebrovascular disease. Between January 2002 and August 2014, a total of 17 patients (early group, n=10;delayed group, n=7) underwent valve surgery with or without an additional procedure. Craniotomy was performed in 1 patient in the early group and 2 patients in the delayed group before valve surgery. There was 1 in-hospital death due to acute respiratory distress syndrome in the early group and 1 death due to intestinal bleeding in the delayed group. Postoperative deterioration was observed in 1 in the delayed group. Overall survival in the early group was 90% and was not significantly different from survival in the delayed group (86%). In conclusion, our study demonstrated good early and mid-term outcomes for valve surgery in active endocarditis patients with cerebrovascular disease. There was no postoperative deterioration in the early group. Thus, an early operation for these patients may be acceptable.

Inhibitory effect of statins on inflammation-related pathways in human abdominal aortic aneurysm tissue.

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression.

Descending aorta-external iliac artery bypass for middle aortic syndrome.

We encountered a surgical case of middle aortic syndrome (MAS) in a 56-year-old man who had resistant hypertension. Computed tomography showed severe stenosis of the abdominal aorta from below the superior mesenteric artery to above the inferior mesenteric artery. Although bilateral renal artery stenosis was confirmed, renal function was within normal limits. A 10-mm vascular prosthetic graft was used to perform a descending aorta to left external iliac artery bypass. His hypertension was well controlled without medication. This extra-anatomic bypass may be a simple and useful approach for treating MAS if it is not necessary to reconstruct the renal artery or visceral artery.

Periostin links mechanical strain to inflammation in abdominal aortic aneurysm.

AIMS: Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, which contributes to the pathological remodeling of the extracellular matrix. Although mechanical stress has been suggested to promote inflammation in AAA, the molecular mechanism remains uncertain. Periostin is a matricellular protein known to respond to mechanical strain. The aim of this study was to elucidate the role of periostin in mechanotransduction in the pathogenesis of AAA. METHODS AND RESULTS: We found significant increases in periostin protein levels in the walls of human AAA specimens. Tissue localization of periostin was associated with inflammatory cell infiltration and destruction of elastic fibers. We examined whether mechanical strain could stimulate periostin expression in cultured rat vascular smooth muscle cells. Cells subjected to 20% uniaxial cyclic strains showed significant increases in periostin protein expression, focal adhesion kinase (FAK) activation, and secretions of monocyte chemoattractant protein-1 (MCP-1) and the active form of matrix metalloproteinase (MMP)-2. These changes were largely abolished by a periostin-neutralizing antibody and by the FAK inhibitor, PF573228. Interestingly, inhibition of either periostin or FAK caused suppression of the other, indicating a positive feedback loop. In human AAA tissues in ex vivo culture, MCP-1 secretion was dramatically suppressed by PF573228. Moreover, in vivo, periaortic application of recombinant periostin in mice led to FAK activation and MCP-1 upregulation in the aortic walls, which resulted in marked cellular infiltration. CONCLUSION: Our findings indicated that periostin plays an important role in mechanotransduction that maintains inflammation via FAK activation in AAA.

Important role of the angiotensin II pathway in producing matrix metalloproteinase-9 in human thoracic aortic aneurysms.

BACKGROUND: The precise pathologic mechanisms underlying human thoracic aortic aneurysms (TAAs) remain uncertain, except that matrix metalloproteinase-9 (MMP-9) is considered a key enzyme for the degradation of extracellular matrix in aneurysm walls. The aim of this study was to elucidate the significance of the angiotensin II (AngII) pathway to MMP-9 production in human TAA walls. METHODS AND RESULTS: We examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor ß (TGF-ß) pathways, and the expression of MMP-9 in human nonsyndromic TAA walls. We observed significant increases in Smad2 activation and MMP-9 expression, associated with disruption of elastic lamellae. Using human TAA walls in ex vivo culture, we investigated whether AngII and/or TGF-ß pathways are essential for MMP-9 production. Unexpectedly, TGF-ß receptor inhibitor had no effect on MMP-9 production. We used PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) activation, and demonstrated that PD98059 dramatically reduced MMP-9 production with attenuation of Smad2 activation. Moreover, exogenous AngII resulted in increases in Smad2 activation and MMP-9 production, in an ERK-dependent manner. CONCLUSION: Our findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.

Optimization of thromboelastography-guided platelet transfusion in cardiovascular surgery.

OBJECTIVES: Platelet dysfunction is a major cause of bleeding complications in patients undergoing cardiovascular surgery under cardiopulmonary bypass (CPB). Thromboelastography (TEG) can be used to assess post-CPB coagulopathy, but its utility in guiding platelet transfusion (PT) after CPB is unclear. This study assessed the utility of a TEG-guided PT protocol in patients undergoing cardiovascular surgery under CPB. METHODS: The platelet count and TEG maximum amplitude (MA) was measured in 100 patients undergoing valvular or thoracic aortic surgery under CPB. PTs were guided by an empiric protocol in 50 patients (group C) and by a TEG-guided protocol (MA <35 mm, platelet count <7 × 10(4)/mm(3)) in the other 50 patients (group T). RESULTS: PT was utilized significantly less in group T (11 patients; 22%) than in group C (24 patients; 48%) (P < 0.01). The difference in PT utilization was particularly marked in patients undergoing aortic arch aneurysm repair (20% in group T vs. 100% in group C; P < 0.01), yet there was no difference in bleeding complications between these two groups. CONCLUSIONS: Use of a TEG-guided transfusion protocol dramatically reduced PT after CPB, particularly in patients undergoing aortic arch aneurysm repair.

[Increased physical and intellectual activity and changes in cognitive function in elderly dwellers: lessons from a community-based dementia prevention trial in Suginami Ward, Tokyo].

PURPOSE: This study was conducted to examine the effect of increased physical and/or intellectual activities on changes in cognitive function in elderly dwellers. METHODS: The subjects comprised 61 residents aged 65 or over living in Suginami Ward, Tokyo, who took part in a community-based dementia prevention class aimed at increasing both physical and intellectual activities. Physical activity was evaluated by the number of daily steps using a pedometer. Intellectual activity was evaluated by the number of pictures taken by a cellular phone and/or submitted through an internet "Dress" system by cellular phone. These activities were classified into two groups (higher and lower activity groups) according to whether above or below the respective median value. For assessment, the subjects underwent tests of physical and cognitive functions before and after the 7-weeks intervention. RESULTS: Subjects with a greater increment in physical activity during the intervention period showed a greater improvement in usual and maximal walking speed than did those with a lesser increment in physical activity. Analysis using the general linear model demonstrated that increase in physical activity independently correlated with improvement in physical function, but did not correlate with cognitive function. Subjects with a greater increment in intellectual activity showed a greater improvement in weight, BMI and trail making test-task B. This association was independent of potential confounders. Further, those who used the "Dress" system more often showed a greater improvement in stress coping tests. Analysis using a general linear model indicated that increased intellectual activity was independently associated with changes in cognitive and mental function. CONCLUSION: The present findings suggest that community-based dementia prevention classes should be stressed not only for increasing physical activity but also in order to stimulate intellectual activity.