Cerebral perfusion issues in acute type A aortic dissection without preoperative malperfusion: how do surgical factors affect outcomes?

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.

Blood transfusion after on-pump coronary artery bypass grafting: focus on modifiable risk factors.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 haemoglobin < 12 g/dl, intraoperative haemoglobin < 8.0 g/dl and those undergoing cardiopulmonary bypass > 90'). 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 receiving > 5 units being at highest risk. CONCLUSIONS: 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.

Hemostatic modifications of the Bentall procedure: imbricated proximal suture and fibrin sealant reduce postoperative morbidity and mortality rates.

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.

Prosthesis-patient mismatch in the elderly: survival, ventricular mass regression, and quality of life.

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 < 0.001 in all domains). 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.

Aortic valve replacement with 19-mm bileaflet prostheses in the elderly: left ventricular mass regression and quality of life.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate left ventricular mass (LVM) regression, survival and quality of life in elderly patients after aortic valve replacement (AVR) with small-sized bileaflet prostheses. METHODS: Between September 1988 and September 2005, a total of 147 patients aged > 70 years underwent AVR with 19-mm bileaflet prostheses for aortic stenosis. In order to evaluate the impact of prosthesis-patient mismatch (PPM) on long-term outcome, survivors were allocated to two groups according to the effective orifice area index (EOAI): group A, with EOAI < 0.85 cm2/m2, and group B with EOAI > or = 0.85 cm2/m2. Hospital survivors were interviewed using the SF-36 questionnaire, and the scores compared with those of age- and gender-matched members of the general Italian population. RESULTS: The mean patient age was 74.5 +/- 3.5 years, body surface area (BSA) 1.68 +/- 0.15 m2, and EOAI 0.73 +/- 0.2 cm2/m2. Hospital mortality was 8.8% (n = 13). Actuarial survival was 87.1 +/- 0.028% at one year, 81.3 +/- 0.035% at five years, and 77.2 +/- 0.044% at eight years. Eight-year survival was 74.0 +/- 0.062% in group A and 82.5 +/- 0.064% in group B (p = 0.29). Echocardiographic follow up showed a significant regression of LVM. Scores obtained in the SF-36 test were similar in the two groups, and significantly higher than those of the general Italian population matched for age and gender (p < 0.001 in all domains). CONCLUSION: The implantation of 19-mm bileaflet mechanical prostheses in the elderly allowed LVM regression and a good perceived quality of life. PPM did not influence the long-term survival of these patients.

Acute hemodynamic and functional effects of surgical ventricular restoration and heart transplantation in patients with ischemic dilated cardiomyopathy.

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.

Tissue versus mechanical prostheses: quality of life in octogenarians.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p < 0.001) 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. CONCLUSIONS: 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.

Microbiologically documented nosocomial infections after cardiac surgery: an 18-month prospective tertiary care centre report.

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.

Spatiotemporal patterns of smooth muscle cell changes in ascending aortic dilatation with bicuspid and tricuspid aortic valve stenosis: focus on cell-matrix signaling.

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.

Quality of life after implantation of bileaflet prostheses in elderly patients: an anticoagulation work group experience.

BACKGROUND: The aim of the study was to examine our experience with the implant of bileaflet mechanical prostheses and with a centralized management of anticoagulation and the related risks in patients aged older than 70 years, focusing on the resulting expectancy and quality of life. METHODS: Between January 1988 and January 2005, 681 consecutive patients older than 70 years (mean age, 73 +/- 3.3 years) underwent bileaflet prostheses implantation in an isolated procedure (77%) or concomitant with other procedures (23%). Data were retrospectively collected, and follow-up was conducted by mean of outpatient chart review and outpatient clinic controls. Follow-up included assessment of perceived quality of life through the Medical Outcomes Trust Short Form 36-Item Health Survey tool (SF-36). The scores obtained by the patients were compared with those of the Italian general population matched for age and sex. RESULTS: Hospital mortality was 11.8%, and 74 late deaths (12.3%) occurred. Mean follow-up was 4.38 +/- 2.85 years. Actuarial survival was 85.2% +/- 0.014% at 1 year, 77.9% +/- 0.017% at 5 years, 74.2% +/- 0.02% at 10 years, and 71.8% +/- 0.031% at 15 years. The mean international normalized ratio variability was 4.5% +/- 1.2%. Freedom from bleeding was 98.7% +/- 0.005% at 5 years and 98.3% +/- 0.007% at 10 and 15 years. Freedom from thromboembolism was 99.1% +/- 0.004% at 5 years, and 98.3% +/- 0.007% at 10 and 15 years. The mean SF-36 scores in the study patients were significantly higher than those of the general population matched for age and sex (p < 0.001 in all domains). CONCLUSIONS: Septuagenarian patients receiving mechanical valve prostheses did not experience increased rates of anticoagulation-related complications and perceived a satisfactory quality of life.

Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression.

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: <30 years) and severe aortic stenosis (OR=23.8) independently predicted mid-ascending dilatation (p<0.001). Male gender (OR=4.1, p=0.001), age >60 (OR=2.6, p=0.022) and severe regurgitation (OR=3.9, p=0.011) were determinants of root involvement, while stenosis (> or =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.

High-risk heart grafts: effective preservation with Celsior solution.

Celsior solution has already proved effective in heart graft preservation because it reduces myocardial edema, prevents free radical damage, and limits calcium overload. The aim of this study was to evaluate the effectiveness of Celsior solution as myocardial protection in high-risk transplantation. Hospital charts and follow-up data of 200 consecutive heart recipients (162 males, 38 females, mean age 47.4 +/- 12.6 years) were reviewed. Patients were divided into two groups: group A (73 patients) included recipients of high-risk grafts (at least two of the following: age >45; female sex; high preretrieval inotropic support, viz. dobutamine or dopamine >10 microg/kg per minute and/or infusion of norepinephrine regardless of its dosage; size mismatch >20%; ischemia time >180 min) and group B (127 patients) included recipients of standard grafts. Quality of preservation was assessed through enzyme release, echocardiographic evaluation, the need for inotropic support or pacemaker, and histology of biopsy samples. Hospital and 1-year mortality were also evaluated. Comparisons between the two groups were made through univariate analysis. Study groups proved homogeneous as to recipient age, pretransplant cardiomyopathy, status at transplantation, mean panel reactive antibodies, and redo cardiac surgery. Hospital mortality was 8% (11% vs 6.3%, P = 0.18) while 1-year mortality reached 12% (15.1% vs 10.2%, P = 0.6) without significant difference between groups. Graft performance as described by the need for inotropic support and/or pacemaker as well as echocardiography (left and right ventricular ejection fraction) proved comparable. There were no significant differences as to histology findings and patterns of enzyme release. Celsior provides optimal myocardial preservation in both standard and high-risk procedures. Such advances help to enhance donor pool expansion.

Aortic arch surgery: thoracoabdominal perfusion during antegrade cerebral perfusion may reduce postoperative morbidity.

BACKGROUND: This study aimed to assess the results of the introduction of thoracoabdominal perfusion (TAP) in the surgical strategy for aortic arch replacement with cerebral protection. METHODS: Two hundred two arch procedures performed with moderate hypothermia (22 degrees to 26 degrees C) and antegrade cerebral perfusion (ACP) were the objects of retrospective investigation. Acute type A dissection was the indication in 164 patients, aortic aneurysm in 38. In 80 patients, during ACP, the thoracoabdominal aorta was perfused either in an antegrade fashion through proximal descending aorta endoluminal cannulation (in 62 dissections), or retrograde through femoral artery cannulation with proximal descending aorta endoluminal occlusion (in 18 aneurysms). Hospital mortality and morbidity rates were compared between the two treatments (group A: ACP only, 122 patients; group B: ACP plus TAP, 80 patients) and the underlying aortic disease (dissection/aneurysm) was stratified. RESULTS: Cerebral perfusion (p = 0.008) and cardiopulmonary bypass times (p = 0.035) were significantly longer in group B. No complication related to the TAP technique was observed in group B. Overall hospital mortality was 12.9%, without significant difference between groups. No differences were found in terms of permanent neurological dysfunction between groups A (9.3%) and B (9.1%; p = 0.58). Group B patients showed lower rates of respiratory failure (18.2% versus 30.5% in group A; p = 0.038), shorter mechanical ventilation times (18.1 +/- 26 hours versus 57.9 +/- 70.1; p < 0.001) and lower incidence of acute renal failure (6.5% versus 18.6%; p = 0.012). Shorter intensive care and hospital stays were observed in group B (p = 0.02). CONCLUSIONS: The adjunction of TAP to ACP was associated with lower rates of end-organ complications, even in more extensive and time-consuming procedures.

Spatial patterns of matrix protein expression in dilated ascending aorta with aortic regurgitation: congenital bicuspid valve versus Marfan's syndrome.

BACKGROUND AND AIM OF THE STUDY: Aortic wall stress has been shown to increase locally at the convex aspect of the ascending tract when axial root motion is increased, as occurs in aortic valve regurgitation. The study aim was to assess the expression of extracellular matrix (ECM) proteins involved in stress-induced vascular remodeling in the convexity and the concavity of dilated ascending aortas with aortic valve regurgitation. METHODS: Aortic wall specimens, harvested at the convexity and concavity of eight dilated ascending aortas with severe aortic valve regurgitation underwent morphometry, Western blot, RT-PCR and confocal immunohistochemistry. Five patients (group A) had congenital bicuspid aortic valve (BAV), and three (group B) had Marfan's syndrome. Specimens from the aorta of three multi-organ donors served as controls. RESULTS: At morphometry, medial degeneration was more severe in the convexity than in the concavity, especially in group A. Western blot, RT-PCR and immunohistochemistry disclosed an asymmetric pattern in the expression of some ECM proteins (laminin, tenascin, fibronectin). Fibronectin was increased in the convexity of both groups compared to controls at Western blot. Immunohistochemistry confirmed this pattern only in BAV. Higher levels of tenascin were found in the convexity in group A. The laminin content was greater in the concavity than in the convexity of both groups, but in group B the type of laminin was different, with the beta2 chain particularly expressed, and almost absent in non-Marfan patients. Type I and type III collagens were more markedly reduced in the convexity than in the concavity in BAV. In group B, type I collagen was decreased and type III increased, but without any significant difference between the two aspects of the aorta. CONCLUSION: A tissue remodeling response to valve disease-related wall stress may underlie aortic dilatation with BAV regurgitation. Although morphometry showed similar changes in Marfan aortas, molecular investigations differentiated this condition, qualitatively, from BAV.

Infective endocarditis in intravenous drug abusers: patterns of presentation and long-term outcomes of surgical treatment.

BACKGROUND AND AIM OF THE STUDY: Few data exist on infective endocarditis (IE) in intravenous drug abuse (IVDA) patients. In particular, clinical features, site of involvement and bacteriologic findings are controversial. Little is also known on the results of surgical treatment and on the long-term prognosis. METHODS: The clinical and microbiological characteristics of IE in a series of 39 IVDA patients were retrospectively assessed and compared to those in 85 non-IVDA patients with a likely similar life expectancy. The total follow up of patients was 717.6 patient-years (119.9 pt-yr for IVDA, 597.7 pt-yr for non-IVDA). RESULTS: Although tricuspid involvement was significantly more frequent in IVDA cases than in non-IVDA cases (p = 0.001), left-sided endocarditis prevailed in both groups. In addition to Staphylococcus aureus (51.3%), Staph. epidermidis (15.4%) and streptococcal spp. (23.1%) were emerging pathogens in IVDA cases. A worse cardiac function (p < 0.002) and a higher rate of embolism (p = 0.04) characterized the preoperative status of IVDA patients. No difference was observed as to indications, emergency procedures and pathologic findings. Hospital and long-term survival did not significantly differ between the two groups. The rate of recurrence was higher in IVDA cases; this difference was mostly accounted for by early postoperative events. CONCLUSION: A new pattern of IE in IVDA is emerging, characterized by more frequent left heart involvement (61.5%), a severe clinical course, and a need for surgery in the active phase. Staph. epidermidis and streptococci are emerging pathogens. Drug abuse does not affect postoperative prognosis when an aggressive surgical attitude is combined with prolonged medical therapy. Higher rates of early recurrence are expected during the follow up period.

Echocardiographic anatomy of ascending aorta dilatation: correlations with aortic valve morphology and function.

BACKGROUND: Different anatomical forms of proximal aortic dilations associated with aortic valve disease can be distinguished by echocardiography. Differences in the anatomy could reflect different pathogeneses and need for different therapeutic approaches. The present study assessed the clinical features associated to each anatomical form, particularly focusing on the relations with valve morphology and function. METHODS: Trans-thoracic and trans-esophageal echocardiography reports of 552 adult patients (mean age 60.4+/-12.8 years; 379 male) with mild to severe proximal aorta dilation were reviewed. The relationships between the anatomy of aorta dilatation (distinguished into "root type" dilatation, with maximal enlargement at the sinuses, and "mid-ascending type", with maximal diameter at the mid-ascending tract) and aortic valve morphology (tricuspid/bicuspid) and function (normal/stenosis/regurgitation) were assessed. The relations with other clinico-echocardiographic variables were also tested in univariate and multivariate analysis. RESULTS: A "root type" dilatation was found in 4.9% tricuspid patients with stenosis, 32.3% with regurgitation, 22.5% with normal valve function (p=0.018). Dilatation prevailed at the mid-ascending tract in patients with bicuspid aortic valve, irrespective of valve function (stenotic: 92.9%, regurgitant: 87.9%, normal: 94.3%; p=0.23). Predominant root involvement was significantly more prevalent in male patients (24.8% versus 5.2% in females; p<0.001). In multivariate analysis, predominant aortic valve regurgitation (OR=1.83; p=0.028) independently predicted root site, while predominant aortic valve stenosis (OR=3.70; p=0.001), bicuspidity (OR=2.90; p=0.005) and female sex (OR=6.10; p<0.001) predicted mid-ascending site. CONCLUSIONS: Pathogenetical considerations arise from the evidence of preferential mid-ascending localization of bicuspid-associated aortic dilatations. This finding is consistent with previous studies on bicuspid valve models revealing a wall stress overload beyond the sino-tubular ridge.

Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease.

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 non-diabetic 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.

Different patterns of extracellular matrix protein expression in the convexity and the concavity of the dilated aorta with bicuspid aortic valve: preliminary results.

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.