Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases.

Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.

Long-term results of Freestyle stentless bioprosthesis in the aortic position: a single-center prospective cohort of 500 patients.

OBJECTIVE: Stentless xenograft bioprostheses may be the future valve of choice for aortic valve replacement. The study aim was to investigate the long-term clinical outcome after aortic valve replacement with the Medtronic Freestyle bioprosthesis (Medtronic Inc, Minneapolis, Minn). METHODS: Between April 1997 and November 2004, a total of 500 patients (mean age, 74.5±9.6 years; 52% were male) underwent aortic valve replacement with a Freestyle bioprosthesis, without population selection. The surgical procedure used a modified subcoronary technique in 479 patients and a complete root replacement in 21 patients, conducted with mini-extracorporeal circulation. Concomitant procedures included coronary artery bypass grafting in 122 patients (24%) and mitral valve repair/replacement in 11 patients. RESULTS: The mean cardiopulmonary bypass time was 98±26 minutes, and total aortic crossclamp time was 77±19 minutes. Operative mortality was 5.2%. The median follow-up time was 104.8±5.7 months. During this period, there were 224 deaths (n=122 cardiovascular and n=102 noncardiovascular deaths). The actuarial survivals from cardiovascular and valve-related mortality were 67%±3% and 70%±4%, respectively, at 10 years. Freedom from structural valve deterioration at 10 years was 94%±2%. The linearized structural valve deterioration incidence was 0.6% per patient/year. Multivariate Cox regression analysis revealed that older age, impaired renal function, and coronary artery disease were independent predictors of cardiovascular death. In the subgroup of patients aged less than 65 years at implantation (n=45), the actuarial cardiovascular survival was 83%±8% and freedom from structural valve deterioration was 89%±6% at 10 years. CONCLUSIONS: The use of the Freestyle bioprosthesis for aortic valve replacement resulted in good long-term cardiovascular survival and freedom from structural valve deterioration in this cohort regardless of age at implantation.

Aortic wrapping for stanford type A acute aortic dissection: short and midterm outcome.

BACKGROUND: Conventional surgical treatment of Stanford type A acute aortic dissection (AAD) is associated with considerable in-hospital mortality. As regards very elderly or high-risk patients with type A AAD, some may meet the criteria for less invasive surgery likely to prevent the complications associated with aortic replacement. METHODS: We have retrospectively analyzed a cohort of patients admitted to our center for Stanford type A AAD and having undergone surgery between 2008 and 2012. The outcomes of the patients having had an aortic replacement under cardiopulmonary bypass (group A) have been compared with the outcomes of the patients who underwent off-pump wrapping of the ascending aorta (group B). RESULTS: Among the 54 patients admitted for Stanford type A AAD, 15 with a mean age of 77 years [46 to 94] underwent wrapping of the aorta. Regarding the new standard European system for cardiac operative risk evaluation (EuroSCORE II), the median result in our group B patients was 10.47 [5.02 to 30.07]. In-hospital mortality was 12.80% in group A and 6.6% in group B (p=0.66). For patients who underwent external wrapping of the ascending aorta, follow-up mortality rate was 13.3% with a median follow-up of 15 months [range 0 to 47]. CONCLUSIONS: The gold standard in cases of Stanford type A AAD consists of emergency surgical replacement of the dissected ascending aorta. In some cases in which the aortic root is not affected a less invasive surgical approach consisting of wrapping the dissected ascending aorta can be suggested as an alternative.

Transcatheter aortic valve implantation through carotid artery access under local anaesthesia.

OBJECTIVES: Trans-femoral and transapical are the most commonly used accesses for transcatheter aortic valve implantation (TAVI). However, when these approaches are unsuitable, alternative accesses are needed. We report a series of 19 patients undergoing TAVI through common carotid artery (CCA) access under local anaesthesia in order to assess its feasibility and safety. METHODS: From November 2008 to September 2013, 361 patients underwent TAVI at our institution. Nineteen of them (14 men) with mean age 82.2 ± 6.2 years, EuroSCORE 25.2 ± 15.7, Society of Thoracic Surgeons score 11.9 ± 5.1 and with severe peripheral arteriopathy were unsuitable for usual approaches and underwent TAVI through CCA access under local anaesthesia. Preoperative computed tomography assessed suitable carotid artery anatomy. Common carotid cross-clamping test allowed verifying patient's neurological status stability. An 18-Fr or 20-Fr sheath inserted into the CCA down into the ascending aorta was used for the delivery catheter. Valve implantation procedures were as usual. After sheath removal, the CCA was surgically purged and repaired. Feasibility and safety end points (VARC-2) were collected up to 30 days. RESULTS: Transcarotid insertion of the delivery sheath was successful in all cases (8 right, 11 left) and accurate deployment of the device was achieved in 18 patients (4 Edwards SAPIEN XT and 14 Medtronic CoreValve). There was 1 intraoperative death by annulus rupture during preimplant balloon valvuloplasty, and 1 in-hospital death due to multisystem organ failure. There was no myocardial infarction, stroke or major bleeding. Third-degree atrioventricular block requiring pacemaker implantation occurred in 3 patients. No vascular access-site, access-related or other TAVI-related complication occurred. Echocardiography revealed good prosthesis functioning with none, mild and moderate paravalvular leak in, respectively, 8, 9 and 1 patients. Patient ambulation was immediate after TAVI and hospital stay was 4.6 ± 2.3 days. CONCLUSIONS: TAVI through the CCA approach under local anaesthesia is feasible and safe. It allows continuous clinical neurological status monitoring with low risk of stroke, bleeding events, vascular access-site and access-related complications and immediate patient ambulation. It appears to be a valuable alternative access for patients who cannot undergo trans-femoral TAVI.

Recurrence of thymoma in the right atrium arising from the coronary sinus.

Invasive thymoma is a malignant tumor of the anterior mediastinum that could have intravenous affinity associated with a high recurrence rate. This report highlights the need of coronary sinus exploration when intraatrial thymoma recurrence is diagnosed. Surgical resection of invaded coronary sinus can be achieved safely with a good result.

Early and mid-term cardiovascular outcomes following TAVI: impact of pre-procedural transvalvular gradient.

OBJECTIVE: To assess the relation of aortic transvalvular gradient with outcomes following transcatheter aortic valve implantation (TAVI). BACKGROUND: Relatively little is known about the predictors of adverse outcomes in patients with severe aortic stenosis following TAVI. METHODS: We studied 126 consecutive patients (mean age 83.2 ± 6.3 years; 59% women) who underwent TAVI (23% transapical; 77% transfemoral) at our institution. All patients were followed for the incidence of major adverse cardiovascular events (MACE), including myocardial infarction, heart failure, stroke, and cardiovascular death. RESULTS: The acute procedural success rate was 98%; at 1 year, the cumulative incidence of MACE and cardiovascular death was 29% and 10%, respectively. In multivariable analyses adjusting for clinical and echocardiographic risk factors, presence of a baseline mean transvalvular gradient (MTG) <40 mmHg was a significant predictor of 30-day MACE in the total sample (OR 4.4, 95% CI 1.7-11.4; P=0.003) as well as in patients with an ejection fraction ≥ 50% (OR 10.3, 95% CI 3.0-33.4; P<0.001). In multivariable analyses, low MTG was also associated with 2-fold and 4-fold increased hazards for MACE (HR 4.2, 95% CI 2.0-8.9; P<0.001) and cardiovascular death (HR 4.2 95% CI 1.2-14.9; P=0.03), respectively, within 1 year following TAVI. CONCLUSION: Presence of a low MTG (<40 mmHg) prior to TAVI was associated with a greater risk of major adverse events, including cardiovascular death, up to 1 year following the procedure. Pre-procedural MTG could be used to identify patients at a high risk for adverse outcomes following TAVI.

Incidence, predictors and prognostic value of serious hemorrhagic complications following transcatheter aortic valve implantation.

BACKGROUND: TAVI is an alternative solution for patients with aortic valve stenosis (AS) who are refused for conventional surgery. We sought to evaluate the incidence, characteristics, predictors and prognosis impact of serious hemorrhagic complications following transcatheter aortic valve implantation (TAVI). METHODS: One hundred and seventy one consecutive patients with symptomatic severe AS (83.5 ± 6.1 y; 53% women; mean EuroSCORE=22.1 ± 12.3) underwent transapical (TA) or transfemoral (TF) TAVI in our institution using Edwards SAPIEN© and Medtronic CoreValve© devices. The primary evaluated criterion was the incidence of any bleeding complication, according to the Valve Academic Research Consortium (VARC) criteria. RESULTS: VARC serious hemorrhagic complications occurred in 34.5% of patients (n=23 life-threatening/disabling (LT/D) and n=36 major bleedings). Most of these complications were related to access site complications (69%). Multivariable analysis revealed that TA access, low weight and underlying coronary artery diseases were independent predictors for development of serious bleeding. The mortality was significantly higher in patients with serious events compared to patients without bleeding (p=0.008, log-rank analysis). Although the survival didn't significantly differ in patients with major hemorrhagic events, subjects with LT/D bleeding events had a higher mortality than the subjects with no hemorrhagic complications (p<0.001, log-rank analysis). Occurrence of VARC LT/D event independently predicted all-cause mortality (HR=5.35 [2.51-11.43], p<0.001) during the first year following TAVI in multivariate Cox regression analysis. CONCLUSION: Severe bleeding is frequent following TAVI procedure and is mainly related to local hemorrhage. VARC LT/D events are associated with decreased survival after AS correction.

Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery.

OBJECTIVES: Prothrombin complex concentrates (PCCs) are sometimes used as 'off label' for excessive bleeding after cardiopulmonary bypass (CPB). The main objective of this study was to retrospectively evaluate the clinical and biological efficacy of PCC in this setting. METHODS: We reviewed the charts of all patients who had undergone cardiac surgery under CPB in our institution for 2 years. Patients treated for active bleeding with haemostatic therapy were identified. Chest tube blood loss was quantified postoperatively in the first 24 h. Coagulation parameters were recorded at intensive care unit admission and in the patient's first 24 h. Thromboembolic complications were also ascertained. RESULTS: Seventy-seven patients out of the 677 studied (11.4%) were included: PCC was solely administered in 24 patients (group I), fresh frozen plasma in 26 (group II) and both in 27 (group III). The mean dose of PCC was 10.0 UI/kg ± 3.5 for group I vs 14.1 UI/kg ± 11.2 for group III (P = 0.09). Initial blood loss in the first hour was different between the three groups (P = 0.05): 224 ± 131 ml for group I, 369 ± 296 ml for group II and 434 ± 398 ml for group III. Only group I vs group III presented a significant difference (P = 0.02). Variations of blood loss over time were no different according to the treatment groups (P = 0.12). Reductions in blood loss expressed in percentage showed no difference between the three groups after 2 h: 54.5% (68.6-30.8) for group I; 45.0% (81.6-22.2) for group II; 57.6 (76.0-2.1) for group III; (P = 0.89). Re-exploration for bleeding involved 1 patient in group I (4%), 2 in group II (8%) and 10 in group III (37%) (P = 0.002). Except for fibrinogen, variations of prothrombin time, activated partial thromboplastin time and platelets with time were not different according to the treatment groups. Cerebral infarction occurred in one patient in group II. CONCLUSIONS: Administration of low-dose of PCC significantly decreased postoperative bleeding after CPB.

Wrapping of the ascending aorta in acute type A retrograde aortic dissection.

We describe off-pump wrapping of the ascending aorta in 3 high-risk patients with acute type A aortic dissection when the primary intimal tear was not located in the ascending aorta and in the absence of aortic insufficiency. A Teflon plaque (Bard Inc, Murray Hill, NJ) was tailored to tightly wrap the aorta from the coronary ostia to the innominate artery. The mean age of the patients was 80.3 years. All patients were at high risk for conventional surgery. A postoperative computed tomographic scan showed a reapplication of the intimal flap and containment of the false lumen in the reinforced ascending aorta in all patients.

Comparison of 64-slice computed tomography planimetry and Doppler echocardiography in the assessment of aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare, prospectively, the planimetry of aortic stenosis on 64-slice computed tomography (CT), with the area calculated by Doppler transthoracic echocardiography (TTE) in symptomatic patients evaluated before potential aortic valve replacement. METHODS: Fifty-two consecutive patients (27 males, 25 females; mean age 74 +/- 10 years) admitted to the authors' institution during 2005 were evaluated with 64-slice CT and Doppler TTE. The time interval between the two evaluations was 2 +/- 1 weeks. Planimetry of the anatomic orifice area (AOA) drawn on 64-slice CT was compared to the effective area determined by Doppler TTE by Bland and Altman analysis, and the anatomic area threshold value corresponding to a significant effective aortic stenosis (50.75 cm2) was determined by receiver operating characteristic (ROC) analysis. RESULTS: The aortic orifice area measured by 64-slice CT correlated well with the effective area (r = 0.76; p <0.0001), but was significantly greater, with a systematic overestimation (0.132 cm(2)) and a variability of 0.239 cm(2). There was good agreement between planimetry determined by two independent radiologists (difference = 0.002, variability = 0.115 cm(2)). ROC analysis showed that a threshold value of 0.95 cm(2) as measured by 64-slice CT planimetry identifies significant aortic stenosis with sensitivity, specificity, accuracy, positive and negative predictive values of 82%, 77%, 81%, 91% and 59%, respectively. CONCLUSION: 64-slice CT is a reproducible and reliable non-invasive method to evaluate aortic valve stenosis compared to the reference method of Doppler TTE. Indeed, the CT approach could replace the latter evaluation when measurements used in the continuity equation are inadequate.

Exclusive internal thoracic artery grafting in triple-vessel-disease patients: angiographic control.

BACKGROUND: The internal thoracic artery (ITA) is considered to be the conduit of choice for coronary artery bypass grafting surgery (CABG). In triple-vessel-disease patients, CABG can be performed exclusively using both ITAs in a Y fashion with multiple sequential side-to-side coronary anastomoses. The aim of this prospective study was to evaluate by early postoperative angiographic control, the patency and particularly the quality of ITA grafts and coronary anastomoses in this configuration. METHODS: Between October 2002 and October 2003, 92 triple-vessel-disease patients underwent CABG with this technique and consented to immediate postoperative angiographic control. The right ITA was divided at its origin and connected to the in-situ left ITA (ITA-Y anastomosis). The left ITA was anastomosed to anterior coronary arteries and the right ITA was anastomosed to lateral and inferior coronary arteries, for a total of 374 coronary anastomoses (4.1 anastomoses per patient; range, 3 to 6). RESULTS: There was 1 hospital death by septic shock. Two patients were reoperated on for superficial wound infection. There was no postoperative myocardial infarction or stroke. On postoperative angiograms, all ITA-Y (92) and ITA-coronary anastomoses (374) were patent. Competition of flow in right ITA to the moderately stenosed right coronary artery was observed in 9 patients, and there were 4 distal ITA-coronary stenoses, both without clinical consequences. CONCLUSIONS: In triple-vessel-disease patients, this procedure allows CABG without increasing operative risk. ITA-Y anastomoses and multiple sequential side-to-side ITA-coronary anastomoses are safe to perform and demonstrate excellent patency and quality in early postoperative angiographic control, particularly when coronary artery stenoses are significant (>70%).

Compact extracorporeal circulation: reducing the surface of cardiopulmonary bypass to improve outcomes.

We have introduced a number of modifications to minimize the deleterious effects of cardiopulmonary bypass (CPB) by reducing the surface of the extracorporeal circulation (ECC), the length of the ECC circuit, the contact surface of the oxygenator, and the volume of priming solution, in addition to employing biocompatible systems and isolation of excess blood volumes of venous reservoirs in transfusion bags very early in CPB. Encouraged by the results of our initial "Compact ECC," we have decided to improve it by implementing other techniques such as controlled hemodilution of the patient by reducing the diameter of ECC venous tubing (from 1/2 in. to 3/8 in.), limiting contact surface of the oxygenator and venous reservoir, positioning the oxygenator and venous reservoir at the level of the patient's shoulder, and employing venous cannulae adapted to vacuum assisted venous drainage (VAVD) to replace venous drainage by gravity. The purpose of this study is to evaluate postoperative outcomes of Compact ECC. Three groups of patients undergoing coronary artery bypass graft (CABG) are compared. Our new Compact ECC shows improved outcomes through reduced postoperative ventilation time, blood loss, intensive care stay, need for blood transfusion, and levels of lactate dehydrogenase despite the patients' pathologies and surgeries being more complex.

Heart tumors in children and adults: clinicopathological study of 59 patients from a surgical center.

BACKGROUND: Heart tumors are rare lesions with variegated histological types. Their clinicopathological features could be more comprehensively categorized. METHODS: This is a 19-year retrospective study of 17 infants/toddlers (<2 years of age) and 42 patients aged between 14 and 79 years (mean = 51.5) in a surgical center. RESULTS: Congenital tumors (n = 17; 29%), including rhabdomyomas (n = 9), ventricular fibromas (n = 6), and hemangiomas (n = 1), required surgery mainly because of mass effect. Familial myofibromatosis was the only embolic congenital lesion. Acquired benign tumors (n = 28; 47%) included myxomas (n = 21), fibroelastomas (n = 3), myofibroblastic inflammatory tumors (n = 2), and lipomas (n = 2). Eight (29%) were revealed by systemic embolization. These benign noncongenital tumors were all treated by complete resection, except for an incompletely resected lipoma of the mitral valve. Postoperative arrhythmia (n = 1) and pericardial effusion (n = 3) were the only complications. Primary sarcomas (n = 8; 14%) were mostly vascular tumors (five of eight), and patients with high-grade tumors had a mean survival of 15 months (n = 5). Cardiac metastases (n = 6; 10%) were from carcinomas (n = 3) or sarcomas (n = 3); apart from a necrotic metastasis, all patients died (mean survival of 6 months). CONCLUSIONS: This study shows that, regardless of patients' age, heart tumors can be classified as: (a) congenital lesions, which are spontaneously nonprogressive or regressive lesions possibly requiring surgery mainly because of mass effect; (b) acquired benign tumors, which are lesions requiring surgery often because of embolization risk; and (c) primary and secondary malignant tumors, which are lesions with globally poor prognosis but with some indications for resection.

Aortic valve translocation for severe prosthetic valve endocarditis: early results and long-term follow-up.

BACKGROUND: Surgical management of ventriculo-aortic disconnection and aortic root abscesses after prosthetic aortic valve endocarditis carries high mortality and morbidity. Initial experience with translocation of the aortic valve and distal coronary artery bypass grafting was disappointing in terms of short-term and long-term success in the few published reports. We describe a technique of translocation of the aortic valve into the ascending aorta with direct antegrade myocardial revascularization. METHODS: Between 1980 and 1992, we included 21 patients and evaluated their long-term outcome. The surgical technique included extracting the aortic valve prosthesis, resecting all infected tissue, restoring the left ventricular outflow tract, and translocating the aortic valve into the ascending aorta, associated with myocardial revascularization of the left main trunk and the proximal right coronary artery. RESULTS: All patients required emergency surgery: 15 patients were in severe congestive heart failure, 3 patients were in cardiogenic shock, and 3 patients had multiple neurologic and peripheral signs of distal embolization. Fifteen patients had active prosthetic valve endocarditis. Intraoperative findings dictated the translocation. The overall hospital mortality was 14%. None of the 18 hospital survivors had prosthetic aortic valve endocarditis recurrence. All patients were observed from 12 to 22 years, are alive, and have resumed normal activities. CONCLUSIONS: In severe forms of prosthetic valve endocarditis, this technique provides a safe and reliable alternative to homograft replacement. The long-term results are satisfactory.