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Objective: The benefit of adding ganglionated plexi ablation to the maze procedure remains controversial. This study aims to compare the outcomes of the maze procedure with and without ganglionated plexi ablation., Methods: This multicenter randomized study included 74 patients with atrial fibrillation associated with structural heart disease. Patients were randomly allocated to the ganglionated plexi ablation group (maze with ganglionated plexi ablation) or the maze group (maze without ganglionated plexi ablation). The lesion sets in the maze procedure were unified in all patients. High-frequency stimulation was applied to clearly identify and perform ganglionated plexi ablation. Patients were followed up for at least 6 months. The primary endpoint was a recurrence of atrial fibrillation., Results: The intention-to-treat analysis included 69 patients (34 in the ganglionated plexi ablation group and 35 in the maze group). No surgical mortality was observed in either group. After a mean follow-up period of 16.3 ± 7.9 months, 86.8% of patients in the ganglionated plexi ablation group and 91.4% of those in the maze group did not experience atrial fibrillation recurrence. Kaplan-Meier atrial fibrillation-free curves showed no significant difference between the two groups (P = .685). Cox proportional hazards regression analysis indicated that left atrial dimension was the only risk factor for atrial fibrillation recurrence (hazard ratio: 1.106, 95% confidence interval 1.017-1.024, P = .019)., Conclusion: The addition of ganglionated plexi ablation to the maze procedure does not improve early outcome when treating atrial fibrillation associated with structural heart disease., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: Consensus regarding an optimal atrial fibrillation (AF) ablation lesion set concomitant with aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG) has not been established., Methods: We enrolled 125 consecutive patients (89 men; 70 ± 8 years old) with persistent AF who underwent radiofrequency-based pulmonary vein isolation (PVI) (PVI group, n = 53) or a Cox-Maze procedure (Maze group, n = 72) with AVR and/or CABG. To reduce the impact of treatment bias and potential confounding in the direct comparisons between patients who underwent Cox-Maze with and those who underwent PVI, we established weighted Cox proportional-hazards regression models with inverse probability of treatment weighting. Mean follow-up was 63 ± 34 months (maximum, 154 months)., Results: There was 1 in-hospital death in each group. Patients who underwent Cox-Maze showed a higher freedom from AF at all follow-up examinations. After the operation, there were 32 deaths, 13 thromboembolisms, 8 hemorrhagic events, and 22 heart failure readmissions. The Maze group had higher rates for 5-year survival (88% vs 64%, P = .013) and freedom from composite events (74% vs 42%, P < .001). After adjustment with inverse probability of treatment weighting, the Cox-Maze procedure still showed a lower risk of overall mortality (adjusted hazard ratio, 0.38; 95% confidence interval, 0.21-0.66; P = .001) and composite adverse events (adjusted hazard ratio, 0.52; 95% confidence interval, 0.35-0.76; P = .001)., Conclusions: In patients with persistent AF indicated for nonmitral valve surgery, a concomitant Cox-Maze procedure resulted in superior AF- and event-free survival compared with PVI, without increased risk of early mortality. These findings may assist decision making for surgical management of persistent AF concomitant with AVR and/or CABG., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Perioperative stroke is a major complication after debranching thoracic endovascular aortic repair (TEVAR), with a reported incidence of 7.0-26.9%. Subsequent functional recovery is difficult in most cases. This study was performed to evaluate the efficacy of mini-cardiopulmonary bypass (mini-CPB) support in debranching TEVAR to prevent perioperative stroke., Methods: From December 2010 to July 2017, 32 patients with a shaggy aorta or intimal irregularity in the aortic arch identified on preoperative computed tomography underwent debranching TEVAR. Nineteen patients underwent debranching TEVAR without mini-CPB, and 13 patients underwent debranching TEVAR with a mini-CPB support. Mini-CPB support had been used in November 2014 to treat perioperative stroke, which had occurred in 8 (42%) patients at that time. The form of the debranching arch vessels was not changed; bypass from the right axillary artery to the left axillary artery was performed for one debranching, and bypass from the right axillary artery to the left common carotid artery and left axillary artery was performed for two debranchings. After establishment of mini-CPB support through this debranching graft and right femoral vein cannulation, all endovascular manipulations were initiated. The left subclavian artery was occluded with a plug at the end of the procedure., Results: The proximal landing zones of the endoprosthesis were as follows: zone 0 in 9 patients, zone 1 in 5 patients, and zone 2 in 5 patients in the no-CPB era and zone 1 in 3 patients and zone 2 in 10 patients in the CPB era. The mean mini-CPB support period was 51 minutes. Postoperative respiratory support and hospitalization were not prolonged with mini-CPB support. The incidence of perioperative stroke was 42% in the no-CPB era and 8% in the CPB era. No operative mortality was observed in the CPB era, although 5 (26%) patients died in the no-CPB era. The cause of operative mortality in the no-CPB era was perioperative stroke in 4 patients and acute myocardial infarction in 1 patient. No significant difference in the cumulative survival rate was found between patients with and without mini-CPB support., Conclusions: Our mini-CPB system may have the potential to prevent perioperative stroke during debranching TEVAR for treatment of aortic arch pathologies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Blood glucose management is important for cardiovascular surgery using cardiopulmonary bypass. The usefulness of an artificial pancreas apparatus (STG-55) to control blood glucose in patients undergoing cardiopulmonary bypass was investigated. Subjects comprised 44 patients using the artificial pancreas during cardiopulmonary bypass between June 2016 and March 2017; 55 were initially enrolled, but 11 were excluded because of blood removal failure. Patients were divided into a monitoring group in which blood glucose levels were only monitored using the artificial pancreas (11 patients: six people with diabetes and 5 people without diabetes) and a management group with glycemic control by automatic insulin administration using the artificial pancreas (33 patients: people with diabetes and 21 people without diabetes). Mean maximum blood glucose levels and variation ranges significantly differed between the monitoring and management groups (p = 0.02). The variation range significantly differed between people with and without diabetes in the monitoring group (p = 0.008), but not in the management group. The artificial pancreas apparatus continuously and accurately reflected glycemic variations, facilitating strict and favorable control.

Objective: The usefulness of abdominal duplex ultrasound (DUS) for the detection of endoleaks after endovascular aneurysm repair (EVAR) was evaluated. Materials and Methods: Among 286 patients who underwent EVAR between September 2007 and July 2017, 241 patients were followed up using abdominal DUS. Endoleaks were detected in 74 patients (31%), who were divided into enlarged and nonenlarged sac groups. Endoleak velocities and widths were measured using abdominal DUS every 6 months after EVAR and were compared between the 2 groups. Results: The aneurysm diameter in the nonenlarged sac group was 54.4±8.7 mm in the final follow-up. None of the patients in the nonenlarged sac group were subjected to reintervention, whereas all patients in the enlarged sac group were subjected to reintervention. The aneurysm diameter in the enlarged sac group was 62.8±8.8 mm at the time of reintervention, and the maximum endoleak flow velocities and endoleak widths were significantly higher in the enlarged sac group than in the nonenlarged sac group (p<0.05). The cutoff values on receiver operating characteristics curves for endoleak velocity and width were 83.4 cm/s and 4.0 mm, respectively. Conclusion: Follow-ups using abdominal DUS are useful after EVAR. Endoleak velocity and width measurements are important, and reintervention may be needed when these measurements exceed their cutoff values.

Objective : We have previously shown that pretreatment with the free radical scavenger edaravone (Radicut ® , Mitsubishi Tanabe Pharma Co., Japan) mitigated skeletal muscle damage due to ischemia reperfusion. In this study, we sought to validate its use in an experimental model of myonephropathic-metabolic syndrome (MNMS). Methods : Either edaravone (3.0 mg/kg; edaravone group; n=4) or saline (saline group; n=6) was intraperitoneally injected into male Lewis rats (508±31 g). Normal kidneys were harvested as control (n=3). MNMS was induced by bilaterally clamping the common femoral arteries for 5 h and declamping 5 h later. Kidney damage was evaluated by quantifying Periodic Acid Schiff (PAS)-positive area (glycogen storage) and esterase-positive cells (neutrophil infiltration). Results : The PAS-positive area in the saline group was significantly lower than that in the normal group (36.9±2.6 vs. 66.9±1.2%, P<0.01); the PAS-positive area in the edaravone group remained comparable to that in the normal group (52.9±0.9%, P<0.01). Esterase-positive cells in the saline group were significantly higher than in normal kidneys (62.4±5.6 vs. 17.5±2.4 cells/mm 2 , P<0.01), while they were significantly reduced in the edaravone group (32.8±5.7 cells/mm 2 , P<0.01). Conclusion : Edaravone pretreatment mitigates MNMS-induced kidney damage by reducing both glycogen depletion and neutrophil infiltration.

Objective: Mitral annular structure and dynamics after mitral ring annuloplasty using transesophageal echocardiography during the operation have been reported. We evaluated mitral annular structure and dynamics of three different rings in the mid-term period postoperatively., Methods: Thirty-one patients underwent mitral valve repair for degenerative mitral insufficiency. The MEMO 3D ring (semi-flexible), Carpentier-Edwards Physio II ring (semi-rigid), and St. Jude Medical Rigid Saddle Ring (rigid) were implanted in 15, 12, and eight patients, respectively, from September 2009 to February 2015. Electrocardiogram-gated three-dimensional computed tomography was performed in the mid-term period postoperatively., Results: The postoperative antero-posterior rate of reduction in diameter from end-diastole to end-systole was slightly larger in the MEMO3D (0.57 ± 0.69%) than in the Physio II (0.08 ± 0.60%) and Rigid Saddle Ring (0.11 ± 0.59%). There was no significant difference in the commissure-to-commissure rate of reduction in diameter among the groups. The postoperative end-systolic annular height to commissure width ratio was significantly larger in the Physio II (20.4 ± 1.7%) and Rigid Saddle Ring (21.3 ± 1.7%) than in the MEMO3D (10.8 ± 3.1%, both p < 0.0001). The rate of increase in the postoperative annular height to commissure width ratio from end-diastole to end-systole was significantly larger in the MEMO3D (2.1 ± 1.7%) than in the Physio II (0.1 ± 0.4%) and Rigid Saddle Ring (0.1 ± 0.6%)., Conclusions: The Physio II and Rigid Saddle Ring can restore the physiological and three-dimensional annular shape, and the MEMO3D can preserve physiological annular dynamics in mid-term period postoperatively.

An 81-year-old woman developed severe hemolytic anemia after aortic valve replacement. The anemia was not caused by paravalvular leakage, as in most cases. Instead, it occurred secondary to left ventricular outflow tract obstruction that had not been seen preoperatively and was induced by afterload reduction following aortic valve replacement. The hemolytic anemia was drug-refractory and finally treated with dual-chamber pacing, as for hypertrophic cardiomyopathy.

Objective: This study aimed to evaluate the efficacy of the Functional Independence Measure to assess preoperative frailty for elderly patients undergoing surgical aortic valve replacement., Methods: Eighty-five patients >65 years who survived elective isolated aortic valve replacement from January 2008 to October 2015 were included. The mean age at the operation was 78 ± 6 years old (n = 28 males, n = 57 females). The patients were divided into two groups according to their status at discharge: impossible to discharge home or hospitalization for >30 days (compromised group, n = 8), or unaffected (unaffected group, n = 77). Preoperative frailty was evaluated with the Functional Independence Measure, which comprises 18 items divided into six domains: self-care, sphincter control, mobility, locomotion, communication, and social cognition., Results: The preoperative total Functional Independence Measure score was significantly lower in the compromised group (79 ± 32) than in the unaffected group (120 ± 9, p < 0.01). The preoperative motor Functional Independence Measure score was significantly lower in the compromised group (45 ± 24) than in the unaffected group (85 ± 9, p = <0.01). The duration of postoperative intubation, intensive care unit stay, and postoperative hospitalization were significantly longer in the compromised group than in the unaffected group (48 ± 67 vs 16 ± 12 h, p < 0.01; 6.7 ± 5.3 vs 3.4 ± 2.0 days, p < 0.01; 34 ± 27 vs 23 ± 11 days, p = 0.02, respectively)., Conclusions: The preoperative Functional Independence Measure is effective for assessing preoperative frailty in elderly patients undergoing aortic valve replacement in terms of predicting operative morbidity.

Objectives: In thoracic and thoraco-abdominal aortic aneurysm repair, spinal cord injury (SCI) is devastating. Detection of the Adamkiewicz artery might be important for preventing SCI. Although thoracic endovascular stent grafts often occlude the segmental artery, the incidence of SCI in thoracic endovascular aortic repair is thought to be low compared with open repair. This study aimed to evaluate how the Adamkiewicz artery is supplied after segmental arteries are occluded by stent grafts., Methods: From March 2007 to August 2015, 32 patients were enrolled whose segmental arteries that were connected to the Adamkiewicz arteries were occluded by stent grafts. Segmental arteries, Adamkiewicz arteries, collateral circulation into the Adamkiewicz arteries, and anterior spinal arteries were pre- and post-operatively evaluated by computed tomography angiography., Results: Post-operatively, Adamkiewicz arteries were detected in 24 (75%) patients, except for two patients with paraplegia and six without paraplegia. Post-operative Adamkiewicz arteries were the same as pre-operative Adamkiewicz arteries, except for one Adamkiewicz artery that was located at two vertebral levels below the pre-operative level. SCI occurred in two (6.3%) patients. The distribution of feeding arteries into the Adamkiewicz artery post-operatively was divided into three patterns as follows: a segmental artery below the distal landing zone of the stent graft (53%), branches of the left subclavian artery (33%), and a branch of the left external iliac artery (13%)., Conclusions: The length of the stent graft should be as short as possible. Blood supply to the left subclavian artery should be maintained because segmental arteries below the segmental artery occluded by the stent graft and branches of the left subclavian artery can become collaterals post-operatively., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Debranching thoracic endovascular aortic repair for aortic arch pathology is an important alternative to total arch replacement. However, the problem of intraoperative stroke due to atherosclerotic changes in the aorta remains. We apply our minimally invasive mini-cardiopulmonary bypass system to prevent intraoperative stroke during the endovascular procedure. Once debranching from the right axillary artery to the left common carotid and the left axillary artery is constructed; only the brachiocephalic artery is a pathway to the brain. After mini-cardiopulmonary bypass using the debranching graft is established, all cerebral perfusions are not only maintained, but retrograde blood flow from the brachiocephalic artery to the aortic arch is secured. All endovascular procedures can be performed under this situation. Our technique could be effective for preventing intraoperative stroke for endovascular repair with the debranching method for aortic arch pathology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Various difficulties can occur in patients who undergo cardiac resynchronization therapy for drug-refractory heart failure with respect to placement of the left ventricular (LV) lead, because of anatomical features, pacing thresholds, twitching, or pacing lead anchoring, possibly requiring other pacing sites. The goal of this study was to determine whether Purkinje potential (PP) pacing could provide better hemodynamics in patients with left bundle branch block and heart failure than biventricular (BiV) pacing., Methods: Eleven patients with New York Heart Association functional class II or III heart failure despite optimal medical therapy were selected for this study. All patients underwent left- and right-sided cardiac catheterization for measurement of LV functional parameters in the control state during BiV and PP pacing., Results: Maximum dP/dt increased during BiV and PP pacing when compared with control measurements. This study compared parameters measured during BiV pacing with PP pacing and non-paced beats as the control state in each patient (717±171 mmHg/s vs. 917±191 mmHg/s, p<0.05; and 921±199 mmHg/s, p<0.005); however, the difference between PP pacing and BiV pacing was not significant. There was no difference in heart rate, electrocardiographic wave complex duration, minimum dP/dt, left ventricular end-diastolic pressure, left ventricular end-systolic pressure, pulmonary capillary wedge pressure, or cardiac index when comparing BiV pacing and PP pacing to control measurements., Conclusions: The hemodynamic outcome of PP pacing was comparable to that of BiV pacing in patients with advanced heart failure.

Objectives: Left atrial (LA) dimension can predict atrial fibrillation (AF) recurrence after catheter-based or surgical ablation. Pulmonary vein isolation (PVI) may be a surgical option during aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG), though consensus regarding patient selection and late outcome is lacking., Methods: We studied 160 patients (mean age 70 ± 9 years) with paroxysmal AF who underwent radiofrequency-based PVI during AVR and/or CABG, and were followed up postoperatively for at least 6 months. Mean preoperative LA dimension was 44 ± 7 mm. Serial echocardiography was performed to evaluate left ventricular (LV) and LA dimensions, E/e', estimated systolic pulmonary artery (PA) pressure and degree of valvular regurgitation. Follow-up was completed with a mean duration of 47 ± 25 months., Results: At the latest follow-up, 133 patients (83%) remained in sinus rhythm. Preoperative LA dimension was independently associated with increased risk of AF recurrence at 6 months after surgery [adjusted odds ratio 1.3 per 1-mm increase in LA dimension, 95% confidence interval (CI) 1.1-1.6, P < 0.001]. Receiver-operating characteristic curve analysis demonstrated an optimal cut-off value for preoperative LA dimension of 45 mm to predict sinus rhythm restoration (98% for <45 mm vs 55% for ≥45 mm, P < 0.001). Patients with LA dimension ≥45 mm had a significantly lower 5-year survival rate (62 ± 7 vs 82 ± 7%, P = 0.025) and freedom from adverse events defined as cerebral infarction/haemorrhage, admission for heart failure, catheter ablation and permanent pacemaker implantation (58 ± 7 vs 91 ± 4%, P < 0.001). Multivariate analysis showed that preoperative LA dimension ≥45 mm was independently associated with adverse events (adjusted hazards ratio 2.4, 95% CI 1.2-5.1, P = 0.019). Serial echocardiography demonstrated improvement in LV systolic function irrespective of LA dimension, whereas patients with LA dimension ≥45 mm showed less improvement in LA dimension and systolic PA pressure (interaction effect P < 0.001) and persistent higher E/e' (group effect P < 0.001), along with aggravated tricuspid regurgitation., Conclusions: In patients with paroxysmal AF related to aortic valve disease and/or coronary artery disease, a dilated left atrium (≥45 mm) was associated with inferior AF- and event-free survival after PVI, accompanied by persistent abnormalities in cardiac and haemodynamic function. These findings may assist patient selection for PVI during AVR and/or CABG., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We treated a 21-year-old man with right ventricular thrombus caused by nephrotic syndrome. The right ventricular thrombus was safely removed and his postoperative course was uneventful. Peri- and postoperative management after surgery for the worsened nephrotic syndrome was relatively unique and difficult, and critical care was essential for saving the patient's life and protecting renal function.

Objective: Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models., Approach and Results: Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive., Conclusions: Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression., (© 2015 American Heart Association, Inc.)

We treated a 57-year-old female patient with an atrial tumor that was widely attached to the atrial septum. The tumor was diagnosed as a cystic tumor of the atrioventricular node (CTAVN). This type of tumor is rare, and its antemortem diagnosis is difficult because it is usually asymptomatic. This tumor may cause sudden death; thus surgical resection is recommended. We performed partial resection instead of total resection to avoid pacemaker implantation., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate whether edaravone (Radicut(®), Mitsubishi Tanabe Pharma Co., Osaka, Japan) injected at the start of reperfusion can suppress myonephropathic-metabolic syndrome (MNMS). MNMS models were made by clamping the bilateral common femoral arteries for 5 hours. At de-clamping (at the start of reperfusion), they were intra-peritoneal injected with 9.0 mg/kg of edaravone (the edaravone group, n = 5) or an equal volume of saline (the control group, n = 5). At five hours after de-clamping, the lower extremity muscles were stained with hematoxylin & eosin (H&E) to count the viable cells, and periodic acid- Schiff (PAS) to assess the glycogen storage. The lungs were also stained with H&E to expresse the alveolar wall thickness, and naphthol AS-D chloroacetate esterase to label infiltrating active neutrophils. The viable muscle cells in the edaravone group was significantly greater than that of the control group (593 ± 60 vs. 258 ± 31 cells/mm(2), p < 0.01). The PAS-positive area in the edaravone group was also significantly higher than that in the control group (30.1 ± 6.9 vs. 7.3 ± 2.1%, p < 0.001). The alveolar wall thickness in the edaravone group was significantly lower than that in the control group (63.6 ± 5.6 vs. 17.2 ± 5.2%, p < 0.001). The active neutrophil infiltration in the edaravone group was also significantly lower than that in the control group (249 ± 59 vs. 68 ± 8 cells/mm(2), p < 0.001). We conclude that edaravone injected at the start of reperfusion can suppress not only muscle reperfusion injury but also lung damage.

Aim: to evaluate the strategy for open heart surgery after renal transplantation performed in a single institution in Japan., Methods: we reviewed 6 open heart surgeries after renal transplantation in 5 patients, performed between January 1992 and December 2012. The patients were 3 men and 2 women with a mean age of 60 ± 11 years (range 46-68 years). They had old myocardial infarction and unstable angina, aortic and mitral stenosis, left arterial myxoma, aortic stenosis, and native valve endocarditis followed by prosthetic valve endocarditis. Operative procedures included coronary artery bypass grafting, double-valve replacement, resection of left arterial myxoma, 2 aortic valve replacements, and a double-valve replacement. Renal protection consisted of steroid cover (hydrocortisone 100-500 mg or methylprednisolone 1000 mg) and intravenous immunosuppressant infusion (cyclosporine 30-40 mg day(-1) or tacrolimus 1.0 mg day(-1))., Results: 5 cases were uneventful and good renal graft function was maintained at discharge (serum creatinine 2.1 ± 0.5 mg dL(-1)). There was one operative death after emergency double-valve replacement for methicillin-resistant Staphylococcus aureus-associated prosthetic valve endocarditis. Although the endocarditis improved after valve replacement, the patient died of postoperative pneumonia on postoperative day 45., Conclusions: careful perioperative management can allow successful open heart surgery after renal transplantation. However, severe complications, especially methicillin-resistant Staphylococcus aureus infection, may cause renal graft loss., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background and Aim of the Study: Valvular calcification is a prominent feature of aortic valve stenosis (AS), and calcified aortic valves share several features with bone tissue. Hypoxia-inducible factor-2 (HIF-2) is activated by nuclear factor-κB (NF-κB) and plays a critical role in an osteoblastic differentiation. The study aim was to determine whether the NF-κB-HIF-2 pathway is involved in the pathophysiology of calcified aortic valve disease., Methods: A total of 50 specimens of aortic valve leaflets obtained from patients who had undergone aortic valve replacement for AS was examined. The aortic valve leaflets from 10 patients with annulo-aortic ectasia (AAE) served as controls. The stenotic valve leaflets were examined using immunohistochemistry to detect NF-κB, HIF-2α, vascular endothelial growth factor (VEGF), vascular endothelial cells, and collagen X. The calcification area was measured and any correlation between the calcification area and NF-κB-HIF-2 pathway was assessed., Results: NF-κB and HIF-2α were expressed in the leaflets from patients with AS, but not in those from AAE controls. Both factors were expressed around massive calcified lesions, and HIF-2α was co-localized with NF-κB. VEGF, neoangiogenesis and collagen X were located in the area where HIF-2α was expressed, and correlated positively with HIF-2α expression. The calcification area correlated positively with collagen X expression., Conclusion: The NF-κB-HIF-2 pathway was expressed in calcified aortic valves and associated with an increased expression of VEGF and collagen X. This signaling pathway may play important roles in the pathophysiology of AS.