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Objectives Both preoperative (disease-related) and operative (management-related) variables make the assessment of the outcomes of acute type A aortic dissection (ATAAD) surgery a difficult task. Our aim was to evaluate the impact of operative factors, including arterial cannulation site, route of cerebral perfusion and surgeon's specific experience with ATAAD ('aortic surgeon'), on the early results of surgical management, with particular attention to neurological injury. Methods Penn classification was used to identify clinically homogeneous risk groups of ATAAD patients undergoing surgery. Between January 2007 and June 2014, 111 of 183 ATAAD patients treated with open surgery in a single centre were in Penn Class Aa (no ischaemic complications at presentation). They were divided in two groups depending on the arterial cannulation site: femoral artery (FemA; 56 patients) or right axillary artery (RAxA; 55 patients). Study outcomes included: 30-day mortality, major adverse cardiac and cerebrovascular events at 30 days, neurological complications and in particular, patterns of stroke as defined by Bamford classification. Results No significant differences in preoperative variables were observed between cannulation-site groups, except for myocardial ischaemic time (60.9 ± 30.4 min in the RAxA group vs 81.7 ± 52.3 in the FemA group, P = 0.014) and cerebral perfusion time (42.1 ± 25.5 min in the RAxA group vs 52.9 ± 32.6 in the FemA group, P = 0.048). Outcomes in terms of mortality and neurological injury did not differ except for a higher incidence of lacunar cerebral infarction (LACI) in the RAxA group (14.5 vs 3.6%, P = 0.043), mainly but not exclusively explained by a higher incidence of LACI in unilateral (17.2%) than in bilateral cerebral perfusion (6.9%) within the RAxA group. The 'non-aortic surgeon' was associated instead with 30-day mortality and composite outcome in multivariable analysis (respectively, OR 6.40, P = 0.002 and OR 4.68, P = 0.001). Conclusions The RAxA cannulation and FemA cannulation are associated with comparable 30-day mortality following surgery for aortic dissection. However, the possible higher risk of LACI-type strokes in the RAxA group, especially when associated with unilateral brain perfusion, should be considered when RAxA cannulation is performed in ATAAD. The hypothesis that more experienced surgeons may produce better earlier outcomes warrants further investigation.

Background Evaluation of the impact of prosthesis-patient mismatch (PPM) on long-term outcome and quality of life (QOL) in elderly patients who underwent implantation of small size bileaflet prostheses for aortic stenosis. Methods Between September 1988 and September 2006, 377 patients aged greater than 70 years underwent aortic valve replacement with a small size bileaflet prosthesis (17, 19, and 21 mm) in one Institution. The study population's survivors (345 patients) were divided into three groups according to the indexed effective orifice area (EOAI): Group A included patients with EOAI less than 0.60 cm 2 /m 2 ; group B included patients with EOAI ranging between 0.61 and 0.84 cm 2 /m 2 ; and group C included patients with EOAI 0.85 cm 2 /m 2 or greater. Cumulative and comparative analyses of long-term outcomes and of left ventricular mass regression were performed. The QOL was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire. Results Overall hospital mortality was 8.5% (32 patients). Group A included 33 patients (9.6%), group B 175 (50.7%), and group C 137 (39.7%). Actuarial survival was 88.8% ± 0.016 at 1 year, 82.1% ± 0.022 at 5 years, and 76.7% ± 0.032 at 10 years. No difference emerged among the three groups. A significant reduction in left ventricular mass was observed in all groups and in all patient subsets of prosthetic size. The scores obtained in the SF-36 test were similar in the three groups and significantly higher than those of the general population ( p Conclusions Incidence of severe PPM is low after aortic valve replacement. Presence of severe or moderate PPM, did not influence long-term outcome, left ventricular mass regression and QOL in a population of septuagenarians.

Objectives Peak oxygen uptake (Vo 2 ) and ventilatory efficiency have prognostic implications in the population with congestive heart failure. This study evaluated quality-of-life functional capacity after the 2 treatment strategies of surgical ventricular restoration and transplantation for severe left ventricular dysfunction of ischemic cause. Methods The 75-patient study population (between 2004 and 2006) with severe heart failure included 35 patients undergoing surgical ventricular restoration (mean age, 62.6 ± 8.7 years), sometimes together with coronary artery bypass grafting or mitral surgery, and 40 cardiac transplant recipients (mean age, 55.6 ± 7.7 years). Preoperative and 6-month postoperative function (peak Vo 2 , the anaerobic threshold, and the slope of minute ventilation/carbon dioxide uptake), cardiac catheterization parameters (left and right), and hospital and early outcomes were evaluated. Results The 2 groups had comparable baseline functional impairment and experienced similar hospital stay and early outcomes. They also showed similar improvements in left ventricular volume indexes and hemodynamic parameters and sustained significant improvements of median Vo 2 , anaerobic threshold, and minute ventilation/carbon dioxide uptake values. Conclusions Both surgical strategies resulted in a significant and comparable improvement of functional capacity at the 6-month evaluation. These early studies must be repeated to determine the long-term benefits of surgical ventricular restoration because maximal Vo 2 and ventilatory efficiency lose their prognostic survival role after transplantation.

The aim of this study was to determine whether changes in prognosis and quality of life (QOL) after aortic valve replacement (AVR) in octogenarians differ depending on the choice of mechanical (MP) or tissue (BP) valves.Between July 1992 and September 2006, 160 consecutive octogenarians underwent AVR with (18.8%) or without concomitant coronary artery bypass grafting. At follow-up (mean 3.4 +/- 2.8 years, 552 patient-years, 98.3% complete), 121 were still alive and answered the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) QOL questionnaire.Group BP had 62 patients. Group MP had 98 patients. Preoperative risk factors were comparable except group BP was older. Global hospital mortality was 8.8%. There were 21 late deaths, 61.9% of which were not valve- or anticoagulation-related. A significant difference emerged in 1-, 3-, 5- and 8-year actuarial survival rates (BP: 86.4% +/- 0.04%, 76.9% +/- 0.06%, 58.1% +/- 0.1%, 46.5% +/- 0.14%, respectively, vs MP: 91.3% +/- 0.03%, 88.6% +/- 0.03%, 81.6% +/- 0.05%, 70% +/- 0.67%; p = 0.025) but not in terms of 8-year freedom from valve-related complications (82.6% +/- 0.1% vs 87% +/- 0.053%, p = 0.55). One anticoagulant-related hemorrhage occurred in group MP; one stroke occurred in group BP. Survivors had significant improvement in New York Heart Association functional class compared with preoperatively (1.1 vs 2.8, p0.001) Mean QOL scores were satisfactory and substantially comparable between the two groups; in seven domains, scores were higher than those of the age- and sex-matched general Italian population.Long-term survival after AVR in selected octogenarians was similar to that of the general elderly population. The device type exerted no influence on QOL.

Objective: This study aimed to describe the features and identify the predictors of ascending aorta dilatation in patients with congenital bicuspid aortic valve (BAV). Methods: In 280 adult patients with isolated BAV undergoing echocardiography, multivariate logistic regression models, including clinical and echocardiographic variables, were developed to predict dilatation (aortic ratio exceeding 1.1) at both ascending and root level. Factors predicting aneurysm with surgical indication were also investigated. Classification tree models were used to identify factors influencing the probability of having a small aorta, normal aortic dimensions, a dilated ascending aorta or a dilated root (aortic phenotypes). Results: Aortic dilatation was present in 83.2% patients, prevailing at the mid-ascending tract in 83.7% of them. Surgical indication criteria were reached in 43.2% patients. A small aortic root was found in 16 patients (5.7%), thereafter excluded from multivariate models predicting dilatation. Age (maximal risk at 50—60 years: OR = 13.7; reference category: 60 (OR = 2.6, p = 0.022) and severe regurgitation (OR = 3.9, p = 0.011) were determinants of root involvement, while stenosis (moderate; OR = 0.3, p < 0.001) was a protective factor. Aortic stenosis (any degree, OR = 2.4) and hypertension (OR = 4.3) were the most significant predictors of mid-ascending aneurysm reaching surgical indication. Classification analysis showed that increasing age significantly increased the prevalence of ascending dilation phenotype, stenosis increased the prevalence of small aorta phenotype, and male gender of root dilation phenotype. Once excluding patients with small aortas from the analysis, a positive correlation was observed between degree of stenosis and mid-ascending size (p = 0.016). Conclusions: BAV patients constitute an importantly heterogeneous population in terms of risk and features of aortic disease. The most common condition is an ectasia of the mid-ascending tract, with unaffected or mildly involved root. If further confirmed, this could suggest that surgical approach may spare the root in most BAV patients. Mid-ascending dilatation is proportional to stenosis severity, suggesting a post-stenotic causative mechanism. Root dilatation is rarer, mostly observed in younger men, and unrelated to the presence and severity of stenosis. The two different aortic dilatation phenotypes (mid-ascending and root) may be subtended by different pathogeneses. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Perioperative transfusions are known to increase morbidity and mortality after coronary artery bypass grafting (CABG). The aims of the study were (1) to identify the clinical profile of the patient subset at highest risk from transfusion and (2) to disclose causative relationship and dose-dependency of transfusion on hospital mortality.A prospective observational design was employed on a cohort of 1047 consecutive patients (median age 63.2 ± 9.3, 18.8% female, 30.6% diabetics, 31.9% urgent/emergent, 15.3% with low preoperative left ventricular ejection fraction (LVEF)) who underwent on-pump isolated CABG between January 2004 and December 2007. Univariate and multivariate regression analysis and post-hoc risk stratification, by means of propensity scoring and binary segmentation, were adopted.The following independent risk factors were identified: age, body surface area (BSA), preoperative glomerular filtration rate, preoperative haemoglobin, surgical priority, length of cardiopulmonary bypass, intraoperative haemodilution and early postoperative blood loss. The patient population was stratified in quintiles of transfusional risk, by means of propensity scoring. As to modifiable risk factors, patients in the highest quintiles of risk were those with BSA (1.73, preoperative haemoglobin12 g/dl, intraoperative haemoglobin8.0 g/dl and those undergoing cardiopulmonary bypass90'). Binary segmentation was performed to avoid any association between red cell transfusion and worse outcomes being causative and dose-dependent. A dose-dependent pattern was disclosed, with patients receiving5 units being at highest risk.High exposure to blood transfusions may be prevented by preoperative patient stratification and by the close tailoring of management strategies on planning and implementing surgical timing, as well as by cardiopulmonary bypass technique.

OBJECTIVES The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabetic patients with chronic coronary heart disease (CHD). BACKGROUND Diabetes is characterized by a decreased collateral vessel formation in response to coronary ischemic events, although the role of VEGF in human diabetic macroangiopathy has not been fully investigated. METHODS Biopsies of left ventricular (LV) myocardium were obtained from 10 patients with type 2 diabetes and 10 non-diabetic patients with chronic CHD, all undergoing surgical coronary revascularization. Right ventricle myocardial samples taken from normal hearts were used as control specimens. Vascular endothelial growth factor and VEGF-receptors (flt-1 and flk-1) were evaluated by Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Akt and endothelial nitric oxide synthase (eNOS) protein expression and their phosphorylated forms were also evaluated by Western blot. RESULTS Vascular endothelial growth factor, flt-1, and flk-1 messenger ribonucleic acid (mRNA) and protein expressions were increased in non-diabetic patients with CHD compared with control subjects. Remarkably, in diabetic patients, VEGF mRNA and protein levels were significantly higher, whereas flt-1, flk-1 mRNA, and protein were lower when compared with nondiabetic patients. Interestingly, phospho–flk-1 was reduced in diabetic patients compared with non-diabetic patients. As a consequence, Akt phosphorylation, eNOS protein and its phosphorylated form were significantly higher in the samples from non-diabetic patients compared with diabetic patients. CONCLUSIONS Chronic CHD in diabetic patients is characterized by an increased VEGF myocardial expression and a decreased expression of its receptors along with a down-regulation of its signal transduction. The latter could be partially responsible for the reduced neoangiogenesis in diabetic patients with ischemic cardiomyopathy

Objective: To evaluate the mid-term results of endovascular stent-grafting for type B aortic dissection, in comparison with those of standard medical therapy in uncomplicated cases. Methods: Between January 1999 and 2004, among 56 patients (mean age 59.5G11.5 years) with type B aortic dissection, hypotensive medical therapy was the only treatment in 28 uncomplicated cases, (group A), while stent-graft implantation was performed in 28 patients with uncontrolled hypertension, persistent pain or evidence of dissection progression or complication (group B). In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting procedures were monitored with intraoperative transesophageal echocardiography and cine-angiography. CT scan and trans-esophageal echocardiography were performed before hospital discharge, at 6 and 12 months and then yearly. Results: Follow-up (range 1–61 months, average 18.1G16.9 months) was 100% complete. In-hospital mortality was 10.7% (three patients, all belonging to Group B; PZ0.24). No spinal cord injuries were observed. Early endoleak occurred in one patient (3.5%). Mid-term mortality was lower in Group B, although the difference was not significant (10.7 versus 14.3% in Group A, PZ0.71). Follow-up CT scans evidenced complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A (PZ0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in Group B, 28.5% in Group A (PZ0.02). Conclusions: Although with still considerable early mortality, endovascular stent-graft implantation is an effective option for the treatment of complicated type B aortic dissection. Endovascular treatment achieved a better mid-term fate of the descending thoracic aorta than medical therapy alone, even in patients with worse preoperative conditions. Q 2005 Elsevier B.V. All rights reserved.

Objective: To review outcomes and quality of life following two surgical strategies for severe left ventricular dysfunction due to ischemic dilated cardiomyopathy. Methods: Hospital and follow-up records of 111 patients with extensive ischemic cardiomyopathy (mean age 57.3G 8.4) referring to our institution between January 1996 and December 2003 were reviewed. Group A included 42 patients (mean age 62.4G7.9) with morphological and functional cardiac parameters allowing for ventricular restoration (including endoventricular circular patch plasty, coronary artery by-pass grafting, and, when needed, mitral surgery). Group B included 69 patients (mean age 54.3G7.2), undergoing cardiac transplantation. Hospital mortality, treatment-related late mortality, incidence of cardiac events, freedom from cardiac failure, freedom from hospital re-admission, functional recovery at follow-up (3075.2 pts/months; 100% complete) and quality of life (WHOQOL test) were assessed. Results: Hospital mortality was 19% in group A and 8.7% in group B (PZ0.143). No treatment-related late deaths were observed in group A, while six deaths (9.5%) occurred in group B (PZ0.063). Incidence of cardiac events was comparable. At 60 months, freedom from cardiac failure was 93.5G0.04 and 86.2G0.05%, respectively (PZ0.23), freedom from hospital re-admission was 93.5G0.04 and 61.3G0.07% (PZ0.002). Exertion dyspnea was present in 40% patients in group A versus 13% in group B (PZ0.006). WHOQOL test showed a satisfying quality of life in both groups, although patients undergoing restoration reached higher scores in the psychological and social domains. Conclusions: Selected patients with ischemic cardiomyopathy, potentially eligible for transplantation, can be managed by ventricular restoration. In those patients post-operative quality of life is satisfactory, with comparable survival and low risk of re-hospitalization. q 2004 Elsevier B.V. All rights reserved.

Bleeding is an important predictor of morbidity and mortality rates after the Bentall operation. This study reports our recent experience with composite aortic root replacement via a slightly modified button-Bentall operation. Fifty-six consecutive patients underwent a Bentall operation on an elective basis from January 2008 through December 2009. In all cases, we used 2 modifications: we imbricated the pledgeted 2-0 polyester interrupted U stitches of the proximal suture line, and at that same suture line we sealed with fibrin glue the possible sources of oozing. The series featured high proportions of associated procedures (25%) and reoperations (23%). The mean cardiopulmonary bypass and aortic cross-clamp times were 166 ± 50 and 113 ± 27 min, respectively. No case of operative or hospital (30-day) death was observed. Postoperative drainage amounted to 705 mL (median) on the first postoperative day and 377 mL (mean) on the second. Surgical re-exploration for bleeding was needed in only 1 patient (1.8%). Postoperative acute kidney injury was observed in 5 patients, neurologic complications in 3, and respiratory insufficiency requiring prolonged mechanical ventilation in another 3. Both respiratory and renal complications were significantly associated with greater consumption of blood products (P=0.03 and P=0.001, respectively). We conclude that the combined use of imbricated proximal suture-line stitches and subsequent fibrin-sealant spraying were associated with no deaths and with low rates of bleeding and other adverse postoperative sequelae in our 2-year experience with the Bentall operation in an elective series of patients characterized by a difficult mixture of prognoses.

Objective: The aim of this study was to prospectively evaluate frequency, characteristics, and predictors of nosocomial infections (NI) in a tertiary care centre. Methods: Study population included 925 patients (mean age 62.3 ± 12.5, 32.3% females, 22.9% diabetics, 6.8% with previous cardiac procedures) operated on between June 2005 and December 2006 (CABG 48.72%, valvular procedures 30.05%, thoracic aortic 10.9%, heart transplantations 3.78% and miscellanea 6.55%, procedure status: elective 72.9%, urgent 15.9% and emergent 11.2%). The study population was divided in two groups according to development of NI. Primary endpoints were multiorgan failure (MOF) and hospital mortality in the two groups. Secondary endpoints were length of intubation, intensive care unit (ICU) stay and overall hospitalisation. Univariate and multivariate analysis of NI predictors was conducted between 115 perioperative variables. Results: Eighty-three patients (9%) developed a NI. Infections affected respiratory tract in 51.8%, blood stream in 20.5 and wound infection in 27.7 (13.3% deep wound). Staphylococcal species (60.6%) predominated in blood stream and surgical wound infections while Gram-negative species predominated in respiratory infections. Patients affected by NI experienced significantly higher incidence of MOF (12% vs 0.8%) and hospital mortality (24.1 vs 6.9%). Development of NI significantly lengthened all the steps of postoperative process of care (length of intubation: 49.9 ± 73 h vs 19.1 ± 35.2; ICU stay: 10.4 ± 12.8 days vs 3.4 ± 4.6 and hospitalisation 20.7 ± 15.3 vs 10.6 ± 7). Independent predictors of NI were immunosuppressive therapy [OR 12.9 (CI 5.07-31.2)], reintubation [OR 10.3 (CI 4.6-2.3)], stroke [OR 9.5 (CI 1.8-49)], resternotomy for bleeding [OR 6.7 (CI 1.9-23.6)], emergent/urgent status [OR 3.6 (CI 1.5-8.4)], CVVH [OR 3.2 (CI 1.4-7.5)] and length of intubation [OR 1.03 (CI 1.01-1.1)]. Conclusions: NI still represents a serious complication. Presence of identified determinants of NI should prompt modification of management algorithms.

Objective A follow-up study was performed to assess long-term survival, valve-related complications, and pregnancy outcomes in young rheumatic women undergoing isolated mitral mechanical replacement. The influence of prosthetic type on outcomes was also investigated. Methods Between 1975 and 2003, 267 isolated mitral mechanical prostheses were implanted. Follow-up reached 3707.8 patient-years. Results Actuarial survival at 1, 5, 10, 15, 20, and 25 years was 97% ± 0.01%, 90.4% ± 0.017%, 85.3% ± 0.023%, 82.3% ± 0.025%, 71.7% ± 0.036%, and 70.2% ± 0.038%, respectively. At multivariate analysis, atrial fibrillation at follow-up was identified as an independent risk factor for late mortality, whereas left ventricular ejection fraction at 12 postoperative months proved to be a protective factor. Freedom from thromboembolism at 1, 5, 10, 15, 20, and 25 years was 98.1% ± 0.01%, 94.1% ± 0.015%, 89.1% ± 0.021%, 85.9% ± 0.025%, 81.1% ± 0.031%, and 75.3% ± 0.063%, respectively. Atrial fibrillation and Carbomedics device were significantly associated with an increase in thromboembolic events. Freedom from reoperation at 1, 5, 10, 15, 20, and 25 years was 99.2% ± 0.005%, 95% ± 0.014%, 91.6% ± 0.018%, 88.6% ± 0.022%, and 85.7% ± 0.041%. Type of prosthesis (tilting disc) was identified as a predictor of reoperation. At the end of the study, 208 patients were still alive: 94.7% were in New York Heart Association class I or II. When receiving warfarin therapy, no patient undertaking pregnancy (n = 35) experienced adverse cardiac or valve-related events. Fetal events were significantly less frequent with a daily warfarin dose less than 5 mg. Conclusions Mechanical devices provided excellent performance, safety, and durability. The prognostic role of left ventricular function and atrial fibrillation overwhelmed any differences that might exist between different prosthetic designs. Pregnancies entail virtually no maternal risk and predictable fetal complications.

Objective: The present study investigated the outcomes of aortic valve replacement with 17-mm mechanical prostheses in patients with isolated aortic stenosis. Methods: Between January 1997 and January 2003, 35 patients (mean age, 63.4 +/- 17 years; median age, 70 years; age range, 16-84 years) underwent isolated aortic valve replacement with a 17-mm St Jude Medical Hemodynamic Plus (16 [45.7%] patients) or a St Jude Medical Regent prosthesis (19 [54.3%] patients). The paired Student t test or the paired Wilcoxon rank sum test were used to compare preoperative with follow-up echocardiographic measurements. Results: Thirty-two (91.4%) patients were female, mean height was 154.4 +/- 8.3 cm, mean weight was 62.2 +/- 9.2 kg, and mean body surface area was 1.59 +/- 0.13 m2. The preoperative average New York Heart Association class was 2.8 * 0.8. The mean preoperative left ventricular mass index was 135.2 +/- 31 g/m2. Preoperative echocardiography showed an average gradient of 65.7 +/- 19.2 mm Hg (mean) and 103.6 +/- 30.7 mm Hg (peak) and a mean indexed effective orifice area of 0.40 +/- 0.1 cm2/m2. Echocardiographic follow-up time averaged 28.2 +/- 22.7 months (range, 13-72 months). Follow-up was 100% complete (1131.7 patient-months). Hospital mortality was 8.6% (3 patients). Actuarial 5-year survival was 94.7%. The mean postoperative New York Heart Association class was 1.13 +/- 0.34 (P < .001), with 27 (87.1%) patients in class I and 4 patients in class II. A significant regression of the indexed left ventricular mass was found (postoperative mean value, 107.8 +/- 22.8 g/m2; P < .0001), despite a mean indexed effective orifice area of 0.67 +/- 0.14 cm2/m2 (median, 0.66 cm2/m2). Conclusions: Selected patients with aortic stenosis can experience satisfactory clinical improvement and significant indexed left ventricular mass regression after aortic valve replacement with modern small-diameter bileaflet prostheses.

We are grateful to Petricevic and co-workers for the interest they showed in reading our paper [1, 2]. Table 1 of the manuscript discloses the preoperative exposure of transfused and nontransfused subgroups to both aspirin (ASA) and clopidogrel (CLO). ASA and CLO did not prove to be independent predictors of blood transfusion requirement in this study. Anyhow, we fully agree with Petricevic that evaluating platelet function is a crucial tool in enhancing perioperative patient blood management, and we have added these measures to our transfusion algorithm in the most recent practice. More, as authoritatively stated by Ranucci et al. [3], ‘tests of platelet function, measured intraoperatively and postoperatively (not preoperatively), correlate best with the occurrence and time course of post-CPB bleeding ... The measure of platelet function during the intraoperative or postoperative period is thus critical to devising accurate and appropriate transfusion strategies so that bleeding patients can be treated with only those allogeneic blood products that they actually need. Open questions include which platelet function tests to use and which other measures should be included in a transfusion algorithm’. In this respect, the most recent research of Petricevic et al. [4] certainly adds to the current knowledge.

OBJECTIVE: The present study examined temporal and spatial patterns of extracellular matrix and smooth muscle cell changes in the ascending aorta with bicuspid and tricuspid aortic valve stenosis. METHODS: Wall specimens were retrieved from both the greater and the lesser curvature ("convexity" and "concavity") of 14 nonaneurysmal and 12 aneurysmal aortas (aortic ratios 1.2 and 1.5, respectively) and from 3 heart donors (normal). Immunochemistry was performed for detection of apoptotic (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling [TUNEL]-positive) and proliferating (Ki-67-positive) smooth muscle cells and for semiquantification of matrix proteins (collagens, fibronectin, tenascin, laminin). Co-immunoprecipitation assessed the extent of Bcl-2-modifying factor binding to Bcl-2, indicating a matrix-derived cytoskeleton-mediated proapoptotic signaling. Polymerase chain reaction allowed for quantification of messenger RNA expression for Bcl-2. RESULTS: In both bicuspid and tricuspid aneurysms, fibrillar collagens were reduced, whereas fibronectin and tenascin were increased compared with those in normal conditions. These matrix alterations were already evident in bicuspid nonaneurysmal aortas at the convexity, with significant elevation of apoptotic indexes (P = .02 bicuspid vs normal; P = .48 tricuspid vs normal). Apoptotic indexes correlated with aortic dimensions only in tricuspid aortas (P = .01). No significant increase in Ki-67 was found. Higher levels of Bcl-2-modifying factor-Bcl-2 binding were found in bicuspid nonaneurysmal aorta versus tricuspid (P = .03) and normal aortas (P = .01). Bcl-2 messenger RNA expression was reduced in the bicuspid aorta versus normal (P = .08). CONCLUSIONS: Smooth muscle cell apoptosis with bicuspid aortic valve stenosis occurred before overt aortic dilation, mainly at the convexity, where wall stress is expectedly higher. In this setting, a matrix-dependent proapoptotic signaling was evidenced by increased Bcl-2-modifying factor-Bcl-2 binding. Stress-dependent bicuspid aortic valve matrix changes may trigger early apoptosis by inducing cytoskeletal rearrangement.

OBJECTIVE: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease. METHODS: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling. RESULTS: Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity. CONCLUSIONS: In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.