Bioreactance and fourth-generation pulse contour methods in monitoring cardiac index during off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC) is considered the gold standard for cardiac index monitoring. Recently new and less invasive methods to assess cardiac performance have been developed. The aim of our study was to assess the reliability of a non-invasive monitor utilizing bioreactance (Starling SV) and a non-calibrated mini-invasive pulse contour device (FloTrac/EV1000, fourth-generation software) compared to bolus thermodilution technique with PAC (TDCO) during off-pump coronary artery bypass surgery (OPCAB). In this prospective study, 579 simultaneous intra- and postoperative cardiac index measurements obtained with Starling SV, FloTrac/EV1000 and TDCO were compared in 20 patients undergoing OPCAB. The agreement of data was investigated by Bland-Altman plots, while trending ability was assessed by four-quadrant plots with error grids. In comparison with TDCO, Starling SV was associated with a bias of 0.13 L min-1 m-2 (95% confidence interval, 95% CI, 0.07 to 0.18), wide limits of agreement (LOA, - 1.23 to 1.51 L min-1 m-2), a percentage error (PE) of 60.7%, and poor trending ability. In comparison with TDCO, FloTrac was associated with a bias of 0.01 L min-1 m-2 (95% CI - 0.05 to 0.06), wide LOA (- 1.27 to 1.29 L min-1 m-2), a PE of 56.8% and poor trending ability. Both Starling SV and fourth-generation FloTrac showed acceptable mean bias but imprecision due to wide LOA and high PE, and poor trending ability. These findings indicate limited reliability in monitoring cardiac index in patients undergoing OPCAB.

Endovascular Treatment of Degenerative Aneurysms Involving Only the Descending Thoracic Aorta: Systematic Review and Meta-analysis.

PURPOSE: To determine the efficacy of thoracic endovascular aortic repair (TEVAR) for degenerative aneurysm involving only the descending thoracic aorta (DTAA). METHODS: An English-language literature review was performed through PubMed, Scopus, and Google Scholar to identify any study evaluating the outcomes of TEVAR for DTAA. The main endpoints of this analysis were all-cause 30-day and late postoperative mortality. Secondary outcome measures were procedure success, vascular access complications, paraplegia, stroke, early endoleaks during the index hospitalization, aneurysm-related death, reinterventions, and conversion to open repair. To control for the anticipated heterogeneity among small observational studies, absolute values and means were pooled using random effects models; the results are expressed as pooled proportions, means, or risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: Eleven studies reporting on 673 patients (mean age 72.6 years, mean aneurysm diameter 62.9 cm) with DTAA were selected for the analysis. Technical success was reported in 91.0% of patients, and vascular access complications requiring repair were encountered in 9.7% of cases. Pooled overall 30-day, 1-year, 2-year, and 3-year survival rates were 96.0%, 80.3%, 77.3%, and 74.0%, respectively. Five studies compared the results of TEVAR after elective (n=151) and urgent/emergent procedure (n=77); the latter was a predictor of 30-day mortality (17.1% vs 1.8%, RR 3.83, 95% CI 1.18 to 12.40, p=0.025). Paraplegia occurred in 3.2% of patients and was permanent in 1.4% of patients. The stroke rate was 2.7%. Early type I endoleak was observed in 7.3%, type II endoleak in 2.0%, and type III in 1.2% of patients. The mean follow-up of 9 studies was 22.3 months. At 3 years, freedom from reintervention was 90.3%. Death secondary to aneurysm rupture and/or fistula was reported in 3.2% of patients. CONCLUSION: Current results indicate that TEVAR for DTAA can be performed with rather high technical success, low postoperative morbidity, and good 3-year survival.

Postoperative stroke in patients on oral anticoagulation undergoing coronary artery bypass surgery.

OBJECTIVE: Patients on long-term warfarin treatment have an inherent high risk of stroke and here we aimed to identify the determinants of postoperative stroke after coronary artery bypass grafting (CABG) in these patients. METHODS: A consecutive series of 270 patients on long-term warfarin treatment who underwent isolated CABG in two university hospitals was assessed by logistic regression as well as classification and regression tree (CART) analysis. RESULTS: Postoperative stroke occurred in 10 patients during in-hospital stay (3.7%). Logistic regression showed that CHADS(2) > 2 (p = 0.036), recent thrombolysis (p < 0.0001) and history of deep vein thrombosis (p = 0.025) were independent predictors of postoperative stroke (area under the ROC curve 0.77). CART analysis showed that CHADS(2) > 2, history of stroke/TIA, no preoperative use of aspirin and preoperative use of low molecular weight heparins were associated with an increased risk of stroke (area under the ROC curve of 0.77). CONCLUSIONS: Both CART and logistic regression analyses showed that the patient characteristics included in CHADS(2) score are important also in the prediction of postoperative stroke risk. Preoperative antiplatelet treatment may be beneficial in the high risk patients and the preoperative bridging with low molecular weight heparins may even be harmful in this respect.

Increase in tissue endothelin-1 and ETA receptor levels in human aortic valve stenosis.

AIMS: Aortic valve stenosis (AS) is an actively regulated process like atherosclerosis, which is accompanied by changes e.g. in endothelin-related genes. However, the role of endothelin peptides in AS is unknown. METHODS AND RESULTS: We characterized the expression of the endothelin system in aortic valves of patients with normal valves (n = 12), regurgitation, and fibrosis (n = 6) and AS (n = 18) by reverse-transcriptase-polymerase chain reaction and immunohistochemistry. The number of endothelin-1 (ET-1) positive cells was higher in AS than in control valves, while levels of ET-1 mRNA did not differ between groups. Endothelin receptor-A (ET(A)) mRNA levels were upregulated in stenotic valves (4.3-fold, P = 0.032) associated with a remarkable increase in number of ET(A)-immunopositive cells. ET(B)-receptor mRNA levels did not change during disease progression. Endothelin-converting enzyme-1 (ECE-1) mRNA levels were 42% lower (P = 0.007) in stenotic valves. Finally, because ET-1 and ECE-1 have binding site for activator protein-1 (AP-1), we measured AP-1 DNA binding by gel shift assays, which showed significantly lower (76%, P = 0.003) activity in AS. CONCLUSION: AS is characterized by distinct upregulation of ET-1 and its target receptor ET(A), promoting growth, inflammation, and fibrosis. These findings suggest therapeutic potential for ET(A)-receptor antagonists in aortic valve calcification.

Apelin and its receptor APJ in human aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: Aortic valve stenosis (AS) is an actively regulated pathobiological process that shows some hallmarks of atherosclerosis. Apelin and its receptor, APJ, are highly expressed in the heart, and the proposed effects of the apelin-APJ system are opposite to those of the angiotensin II-AT1-receptor pathway. The role of the apelin-APJ signaling pathway in calcified aortic valve disease is unknown. METHODS: The study involved the characterization and comparison of expression of apelin and APJ as well as angiotensin II receptors (AT1 and AT2) in the aortic valves of patients with normal valves (n = 6), aortic regurgitation (n = 9 AR), regurgitation and fibrosis/mild sclerosis (n = 14), and AS (n = 25). RESULTS: By employing the reverse-transcriptase polymerase chain reaction (RT-PCR), the gene expression of apelin (3.63-fold, p = 0.001) and the APJ receptor (2.70-fold, p = 0.01) were shown to be significantly up-regulated in stenotic valves when compared to controls. In addition, APJ receptor mRNA levels were higher (2.9-fold, p = 0.010) in the AR + sclerosis group when compared to controls. Using immunohistochemistry, apelin was shown to be localized in stenotic aortic valves to the valvular endothelial layer of the aortic valve, to vascular endothelial cells in neovessels, and to fibroblasts and macrophages adjacent to vessels in the stromal area. AT2-receptor mRNA levels were 90% (p < 0.001) lower in stenotic valves. In contrast, the gene expression of AT1-receptors did not differ significantly among the groups. CONCLUSION: Aortic valve stenosis is characterized by an up-regulation of the apelin-APJ signaling pathway, revealing a possible novel target for drug discovery in calcified aortic valve disease by suppressing chemotaxis, angiogenesis and osteoblast activity, all of which are well-documented phenomena in the disease process.

Distinct downregulation of C-type natriuretic peptide system in human aortic valve stenosis.

BACKGROUND: Aortic valve calcification is an actively regulated process that displays hallmarks of atherosclerosis. Natriuretic peptides (A-, B-, and C-type natriuretic peptides [ANP, BNP, and CNP]) have been reported to have a role in the pathogenesis of vascular atherosclerosis, but their expression in aortic valves is not known. Here, we characterized and compared expression of natriuretic peptide system in aortic valves of patients with normal valves (n=4), aortic regurgitation (n=11), regurgitation and fibrosis (n=6), and aortic valve stenosis (n=21). METHODS AND RESULTS: By reverse-transcription polymerase chain reaction, all 3 natriuretic peptides were found to be expressed in aortic valves. CNP mRNA levels were 92% lower (P<0.001) in stenotic valves, whereas no significant changes in the expression of ANP and BNP genes were found compared with valves obtained from patients with aortic regurgitation. CNP was localized by immunohistochemistry with specific CNP (32-53) antibody to valvular endothelial cells and myofibroblasts. Gene expression of furin, which proteolytically cleaves proCNP into active CNP, was 54% lower in aortic valve stenosis (P=0.04). Moreover, natriuretic peptide receptor-A and natriuretic peptide receptor-B mRNA levels were 78% and 76% lower, respectively, in stenotic valves. In contrast, gene expression of corin, a proANP- and proBNP-converting enzyme, and natriuretic peptide receptor-C did not differ between groups. CONCLUSIONS: We show that natriuretic peptides, their processing enzymes, and their receptors are expressed in human aortic valves. Aortic valve stenosis is characterized by distinct downregulation of gene expression of CNP, its processing enzyme furin, and the target receptors natriuretic peptide receptor-B and natriuretic peptide receptor-A, which suggests that CNP acts as a paracrine regulator of the aortic valve calcification process.

Predicting immediate and late outcome after surgery for mitral valve regurgitation with EuroSCORE.

BACKGROUND AND AIM OF THE STUDY: The European system for cardiac operative risk evaluation score (EuroSCORE) has been shown to be a valid tool for predicting immediate and late outcome after coronary artery bypass surgery. As evidence also suggests its value in heart valve surgery, this issue was investigated in a series of patients who underwent surgery for mitral valve regurgitation. METHODS: Data obtained from 180 patients who underwent mitral valve repair (MVRep) or mitral valve replacement (MVR) were reviewed, and the patients' additive and logistic EuroSCOREs calculated. RESULTS: The 30-day postoperative mortality rate was 10.0% (n = 18); rates were 7.1% after MVRep and 20.5% after MVR (p = 0.013). The additive EuroSCORE (p <0.0001, area under the ROC curve: 0.804, 95% CI 0.689-0.919, SE 0.059), as well as logistic EuroSCORE (p <0.0001, area under the ROC curve: 0.806, 95% CI 0.695-0.918, SE 0.057) were predictors of 30-day postoperative death. The 10-year overall survival rate from any cause of death was 74.7%. Additive and logistic EuroSCOREs were significantly higher in the MVR group compared to the MVRep group (p <0.0001 in both cases), and also among operative survivors. Patients who underwent MVR had a significantly poorer long-term survival than those with MVRep (p = 0.01). Both the additive EuroSCORE (p <0.0001) and logistic EuroSCORE (p = 0.003) were predictors of late, all-cause mortality. Both scores remained significant predictors of late outcome also when adjusted for type of surgery (MVRep versus MVR). Survival was particularly dismal in patients with an additive EuroSCORE >6 (at 10 years, 54.4% versus 86.6%, p <0.00001) or a logistic EuroSCORE >4% (at 10 years, 58.7% versus 86.6%, p <0.00001). CONCLUSION: EuroSCORE is an important predictor of immediate and late outcome after surgery for mitral valve regurgitation.

Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis.

Changes in the collagenous matrix may contribute to the pathogenesis and progression of human aortic valve stenosis (AS). To evaluate the significance of collagen I and III in the pathogenesis of AS, we studied their synthesis in diseased valves. Type I and type III collagen mRNA expression and the immunohistochemical localization of the collagen antigens were studied from 36 AS and 2 normal aortic valves. The concentrations of propeptides and telopeptide structure of type I (PINP, PICP, and ICTP) and those of III collagens (PIIINP and IIINTP) were measured by radioimmunoassays in soluble tissue extracts and trypsin-solubilized calcified and non-calcified matrices of 11 AS and 24 healthy aortic valves of different ages. The synthesis of type I collagen, localized in the myofibroblasts adjacent to calcified nodules, was two- to three-fold in the AS samples compared to the controls. The proportion of collagen in the total protein fraction was 90% in the healthy valves, 50% in the non-calcified matrix, and 10% in the calcified matrix of AS valves. In the calcified valves, the ICTP content was six-fold compared to the age-matched controls and two-fold compared to the young control group. In the controls, the amount of ICTP in type I collagen decreased with age (r=-0.908, p<0.001) and was replaced by other cross-linked C-telopeptide structure. The concentration of type III collagen decreased during aging (r=-0.753, p<0.001). The decrease in total collagen content, despite the increase in type I collagen synthesis indicates an increase in collagen turnover in AS. The calcification of the aortic valves is accompanied by increased amount of ICTP in type I collagen.

Risk-scoring methods in predicting the immediate outcome after emergency open repair of ruptured abdominal aortic aneurysm.

BACKGROUND: Rupture of an abdominal aortic aneurysm (RAAA) is associated with a risk of death approaching 80%. Prediction of immediate postoperative death in this condition assumes obvious relevance because it may be helpful in preoperative risk stratification. METHODS: One hundred fourteen patients underwent emergency open repair of RAAA. Data were retrospectively collected, and preoperative risk assessment was done according to the Glasgow aneurysm score, the Hardman index, and the Chen calculated risk. RESULTS: Fifty-one patients (44.7%) died during the immediate postoperative period. The area under the receiver operating characteristics curve for the Glasgow aneurysm score, the Hardman index, and the Chen calculated risk was 0.906, 0.834, and 0.672, respectively. The mortality rate among patients with a Glasgow aneurysm score >85 was 88.9%, whereas in those with a lower score it was 15.9% (P < .0001). The mortality rate among patients with a Hardman index > or =2 was 81.1%, whereas it was 27.3% in those with a lower score (P < .0001). The mortality rate in patients with a Chen calculated mortality risk >37% was 62.0%, whereas it was 31.3% in those with a calculated risk < or =37% (P = .001). CONCLUSIONS: The present study showed that the Glasgow aneurysm score and, to a somewhat lower extent, the Hardman score are valuable predictors of immediate postoperative death after emergency open repair of RAAA.

Chemically modified tetracyclines (CMT-3 and CMT-8) enable control of the pathologic remodellation of human aortic valve stenosis via MMP-9 and VEGF inhibition.

OBJECTIVE: Tetracycline derivatives affect many cellular functions relevant to chronic cardiovascular pathologies, including cell proliferation, migration and matrix remodelling. Accordingly, we sought to determine whether they may modulate the pathologic characteristics known to be significantly involved in human aortic valve stenosis, such as gelatinase production, apoptosis, expression of vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-alpha). METHODS: The effects of tetracycline derivatives (tetracycline and CMTs-3, -5, -8) on MMP-2 and -9 and their endogenous tissue inhibitor (TIMP-1 and -2) production profiles in explanted human aortic valve pieces were examined by means of gelatine zymography and reverse zymography. Chemiluminescent ELISA was performed to assess VEGF and TNF-alpha concentrations in the medium, and in order to evaluate programmed cell death, in situ labelling of the 3'-ends of the DNA fragments generated by apoptosis-associated endonucleases was performed. RESULTS: CMT-3 and -8 lowered the MMP-9 and VEGF levels significantly in a drug-, dose-, and time-dependent manner. MMP-2 and TIMPs remained unchanged, emphasizing the specificity of CMTs to MMP-9 production on the one hand and restoring the beneficial equilibrium of MMP-9 and TIMPs on the other. Tetracycline was the only drug with a significant impact on net gelatinolytic activity, suggesting that the effect of tetracycline is more extensive concerning total MMP activity. CONCLUSIONS: Tetracycline derivatives may have therapeutic effects on the pathologic remodellation of advanced human aortic stenosis through the inhibition of MMP-9 and VEGF production.

Preoperative C-reactive protein is predictive of long-term outcome after coronary artery bypass surgery.

BACKGROUND: Increased levels of C-reactive protein (CRP) are associated with the presence and severity of atherosclerosis, and with increased risk of coronary events as well as of cardiac events after coronary percutaneous intervention. METHODS: We have investigated whether preoperative CRP had an impact on the long-term outcome of 843 patients who underwent on-pump coronary artery bypass surgery (CABG). RESULTS: Among operative survivors, patients with preoperative CRP < 1.0 mg/dL had significantly better 12-year overall survival rate (74.1% vs 63.0%, p = 0.004) and survival freedom from fatal cardiac event (86.7% vs 78.1%). Multivariate analysis including patients' age, extracardiac arteriopathy, urgent/emergent operation, recent myocardial infarction, congestive heart failure, left ventricular ejection fraction, atrial fibrillation, transient ischemic attack/stroke, number of distal anastomoses, diabetes, and preoperative CRP > or = 1.0 mg/dL or <1.0 mg/dL, showed that the latter was an independent predictor of late all-cause mortality (p = 0.017, RR 1.60, 95% CI 1.09-2.35). Its impact on overall survival was particularly evident in patients with left ventricular ejection fraction <50% (CRP < 1.0 mg/dL: 58.7% vs CRP > or = 1.0 mg/dL: 43.7%, p < 0.00001). CONCLUSIONS: Increased preoperative levels of CRP are associated with significantly decreased overall survival after primary on-pump CABG.

Progression of human aortic valve stenosis is associated with tenascin-C expression.

OBJECTIVES: We sought to assess tenascin-C (TN-C) expression and its possible pathobiological impact in human aortic valve stenosis. BACKGROUND: Tenascin-C, a large extracellular matrix glycoprotein, has lately been increasingly connected to cardiovascular pathologies. As TN-C is a multifunctional protein implicated in cell proliferation, migration and differentiation, we investigated the pattern of its expression in diseased human aortic valves. METHODS: Fifty-five tricuspid, non-rheumatic stenotic aortic valves were collected from patients undergoing aortic valve replacement, and the controls consisted of four normal valves from individuals who had suffered traumatic death and one from a patient operated on because of a noncalcified purely regurgitant valve. A monoclonal mouse antibody to human TN-C (143DB7) was used as the primary antibody in immunostaining. To study the source of TN-C messenger RNA synthesis, some tissue samples were also examined using in situ hybridization. In order to identify smooth muscle cell differentiation, commercially available antibodies against alpha-smooth muscle actin were used, and immunophenotypic analysis of inflammatory cells was carried out by using the monoclonal mouse antibodies UCHL-1, L26 and PGM-1. RESULTS: In normal valves, TN-C expression was associated with the basement membrane beneath the endothelial cells, whereas stenotic valves showed no such expression but rather immunoreactivity in the deeper layers of the valves. This reactivity was associated with the characteristics typical of the stenosing process and the increased mechanical loading caused by hypertension. CONCLUSIONS: We hypothesize that the overexpression of TN-C in stenotic human aortic valves may emphasize that this disease is an active rather than a degenerative process.

Quality of life after mitral valve repair.

BACKGROUND AND AIM OF THE STUDY: Mitral valve repair for degenerative and ischemic mitral valve regurgitation has been shown to be a durable procedure. The study aim was to evaluate the quality of life of patients who had undergone mitral valve repair, and to compare it to that of an age- and gender-adjusted Finnish general population. METHODS: Among 130 late survivors after mitral valve repair, 109 (83.8%) answered the RAND-36 Health Survey questionnaire; these patients form the basis of the present study. RESULTS: The Wilcoxon test showed significantly higher mental health (p = 0.04) and pain scores (p = 0.015) and a lower role functioning/physical score (p = 0.008) in the study group. The scores of the other RAND-36 Health Survey variables of the study group were similar to those of the age- and gender-adjusted general population. The mean total score for the study group was 512 (median 532, IQR 360-678), compared to 522 (median 538, IQR 468-549) in the general population (p = 0.72) (only 95 patients were included in the analysis due to isolated missing scores). CONCLUSION: The quality of life of long-term survivors after mitral valve repair, as assessed by the RAND-36 Health Survey, is similar to that of an age- and gender-adjusted general Finnish population.

Angiogenesis is involved in the pathogenesis of nonrheumatic aortic valve stenosis.

Angiogenesis is an essential biological process not only in embryogenesis, but also in the progression of several major diseases, including cancer, diabetes, and inflammation. Excessive vascularization can also contribute to some cardiovascular pathologies, such as atherosclerosis, but contradictory reports still prevail regarding its impact on aortic stenosis. Using immunohistochemical techniques, we assessed the vascular density and distribution of angiogenesis (FVIII) and vascular endothelial growth factor (VEGF) expression as well as the expression of 2 VEGF receptors, Flt-1 and Flk-1, in 55 nonrheumatic and 6 control aortic valves. In the light of the fact that the angiogenic effect of VEGF is mediated by sustained formation of nitric oxide, the samples were also immunostained with 3 nitric oxide synthase (eNOS, iNOS, and nNOS) antibodies. The immunohistochemical findings of VEGF and its receptors were verified by immunoblotting techniques. Vascular density was highest in the cases with moderate valve stenosis, and the mean number of FVIII-positive blood vessels was 1.7 +/- 1.9 vessels/mm(2) in the diseased valves, whereas the normal valves contained no blood vessels. Vascular density was significantly higher in the cases showing chronic inflammation (P = 0.007). Interestingly, the patients receiving statin therapy had significantly lower vascular densities than those not receiving such therapy (P = 0.001). Diseased valves showed distinct VEGF, Flt-1, Flk-1, and eNOS positivity of activated endothelial, stromal fusiform myofibroblastic, and histocytic cells. In contrast, immunoreactivity for iNOS and nNOS was seen only in nonendothelial stromal cells, and their expression was weaker. Enhanced vascular density was significantly associated with increased expression of Flk-1 (P = 0.028 for endothelial and P = 0.009 for stromal cells) and with endothelial eNOS expression (P = 0.024). A similar tendency was also observed for VEGF, but not for Flt-1. Our results show a distinct angiogenic response and the presence of angiogenic factors in nonrheumatic aortic valve stenosis, suggesting that angiogenesis may influence on the evolution of this disease.

Preoperative C-reactive protein and outcome after coronary artery bypass surgery.

BACKGROUND: C-reactive protein (CRP) is a predictor of early and late outcome after coronary angioplasty, but there is scant data on its impact on the outcome after coronary artery bypass grafting (CABG). METHODS: The predictive value of preoperative CRP was evaluated in a series of 764 patients who underwent on-pump CABG. RESULTS: During the in-hospital stay, 13 patients (1.7%) died, 45 (4.5%) developed low cardiac output syndrome, and 28 (3.7%) suffered minor or major cerebrovascular complications. Patients with a preoperative serum concentration of CRP>/=1.0 mg/dL had a higher risk of overall postoperative death (5.3% vs 1.1%, p = 0.001), cardiac death (4.4% vs 0.8%, p = 0.002), low cardiac output syndrome (8.8% vs 3.7%, p = 0.01), and any cerebrovascular complication (4.4% vs 3.5%, p = 0.66). Preoperative serum concentration of CRP>/=1.0 mg/dL was significantly more frequent among patients with history of myocardial infarction, diabetes, lower limb ischemia, low left ventricular ejection fraction, NYHA class IV, and in those undergoing urgent or emergency operation. At multivariate analysis, preoperative serum concentration of CRP >/= 1.0 mg/dL (p = 0.01, O.R.: 6.97) and left ventricular ejection fraction (p = 0.01, O.R.: 0.95) were independent predictors of postoperative death. Postoperative mortality rate was 0.3% among patients with preoperative CRP < 1.0 mg/dL and an ejection fraction >/=50%, whereas it was 21.4% among those with a preoperative CRP >/= 1.0 mg/dL and an ejection fraction less than 50% (p < 0.0001). CONCLUSIONS: Preoperative serum concentration of CRP in patients undergoing on-pump coronary artery bypass surgery is an important determinant of postoperative outcome.

Evidence for an altered balance between matrix metalloproteinase-9 and its inhibitors in calcific aortic stenosis.

BACKGROUND: Recently, aortic valve stenosis has been demonstrated to exhibit increased expression of certain matrix metalloproteinases (MMPs), and this has relevantly raised the question about possible interdependency between these and their tissue inhibitors. We sought to assess the expression of elastolytic MMPs and their inhibitors (TIMPs) in nonrheumatic aortic stenosis. METHODS: The study comprised 30 stenotic and six noncalcified human aortic valves. To measure the expression levels and the amount and molecular forms of gelatinases (MMP-2, MMP-9) and TIMPs (1, 2), in situ hybridization, gelatin zymography, and reverse zymography were carried out. Antielastin staining by a monoclonal BA-4 antibody was performed to investigate the changes of one of the main substrates of these MMPs, and to substantiate the nature of the putative MMP- synthesizing cell. The cases were also immunostained with an antibody to alpha-smooth muscle actin. Inflammatory cell characterization was managed by monoclonal mouse antibodies (UCHL-1, L26, and PGM-1). RESULTS: Compared with the controls, the calcific valves showed increased mRNA expression and activation of MMP-9, and this was associated with typical characteristics of valve disease. MMP-2 mRNA production was rare, but proMMP-2 protein was detected in all valves. In agreement with the interdependency between MMP-9 and its inhibitors, a suggestive imbalance came out in diseased valves. CONCLUSIONS: The disproportion between MMP-9 and its tissue inhibitors may favor a persistent MMP activation state within the calcific valve and likely contribute to the valvular remodeling process in the setting of developing aortic stenosis.

Postoperative atrial fibrillation is a major cause of stroke after on-pump coronary artery bypass surgery.

BACKGROUND: Atrial fibrillation, occurring after coronary artery bypass grafting (CABG), has been suggested to be associated with the development of postoperative stroke. However, it is not clear what is the incidence of atrial fibrillation-related postoperative stroke, the timing of its occurrence, and the outcome. These issues have been investigated in a consecutive series of patients who have undergone on-pump coronary artery bypass grafting (ONCAB). METHODS: Among 2,630 patients who underwent ONCAB, 52 patients (2.0%) experienced postoperative stroke and form the basis of the present study. RESULTS: Twelve patients (23.1%) died postoperatively. The ischemic cerebral event occurred after a mean of 3.7 days (range, 0 to 33). In 19 patients (36.5%), atrial fibrillation preceded the occurrence of neurologic complication. These patients experienced a mean of 2.5 episodes of atrial fibrillation before the occurrence of neurologic complication. The cerebrovascular event occurred after a mean of 6.0 days in patients in whom atrial fibrillation preceded it, after a mean of 1.2 days in those with calcified ascending aorta, and after a mean of 3.1 days in those without calcified ascending aorta or in whom atrial fibrillation did not precede the cerebrovascular complication (p < 0.0001). Stroke occurred a mean of 21.3 hours after atrial fibrillation. CONCLUSIONS: This study confirmed that atrial fibrillation, occurring after CABG, is a major determinant of postoperative stroke. Prevention of postoperative atrial fibrillation, and of formation of clots into the left atrium, may dramatically reduce the risk of postoperative stroke.

Ten-year outcome of patients with very small abdominal aortic aneurysm.

BACKGROUND: The long-term fate of very small abdominal aortic aneurysms (AAA) is not well known. METHODS: Forty-one patients with asymptomatic small AAA (range 25 to 40 mm) underwent ultrasonographic surveillance. RESULTS: The median follow-up period was 7.3 years. The median linear aneurysm expansion rate was 2.0 mm/year (range 0 to 8.4). Three patients experienced aneurysm rupture (7.3%) which resulted in 1 patient'death. Thirteen patients underwent aneurysm repair (31.7%) and 1 patient died postoperatively (7.7%). The survival rate at 10-year follow-up was 59.0%. The survival rate free from aneurysm rupture and repair at 10-year follow-up was 69.9%. The median time for occurrence of aneurysm rupture was 4.9 years (range 1.8 to 10.5) and the need for aneurysm repair was 4.5 years (range 1.4 to 10.4). CONCLUSIONS: The fate of very small AAA is to slowly enlarge in size, sometimes threatening the patient's life. These observations underline the importance of continuous surveillance and the potential benefits of any medical treatment in this patient population.

Predictors of development of anastomotic femoral pseudoaneurysms after aortobifemoral reconstruction for abdominal aortic aneurysm.

BACKGROUND: The pathogenesis of anastomotic femoral pseudoaneurysms (AFPs) is still unclear. We have performed this long-term retrospective study of patients who underwent aortobifemoral reconstruction for abdominal aortic aneurysm (AAA) in order to better establish the long-term rate of AFP and to identify the predictors of its late occurrence. METHODS: The long-term outcome of 178 patients who underwent and survived aortobifemoral reconstruction for infrarenal AAA was reviewed. RESULTS: During a median follow-up of 5.2 years, 28 AFPs developed in 19 patients. Six AFPs were recurrent. The mean linearized rate of AFPs was 1.88% per year. At 15 years, the survival-freedom rate from AFPs was 60%, and from repair of AFPs it was 62%. The survival-freedom rate from AFP was significantly poorer in patients with chronic obstructive pulmonary disease (P = 0.017; at 10 years: 64.3% versus 92.3%), hyperlipidemia (P = 0.0056; at 10 years: 59.2% versus 87.5%), current smoking (P <0.0001; at 10 years: 65.8% versus 94.5%), and postoperative inguinal wound infection (P <0.0001; at 10 years: 42.8% versus 86.8%). Multivariate analysis showed that chronic obstructive pulmonary disease (relative risk [RR]: 3.05, 95% confidence interval [CI]: 1.04 to 8.95), current smoking (RR: 5.38, 95% CI: 1.62 to 17.90), and postoperative inguinal wound infection (RR: 9.04, 95% CI: 2.76 to 29.96) were significantly associated with the development of AFPs. The linearized rate of AFPs was significantly higher only among current smokers (P <0.0001, 4.4% versus 0.8% per year) and among those who had inguinal wound infection (P = 0.001, 9.2% versus 1.5% per year). CONCLUSIONS: Current smoking and inguinal wound infection may contribute to the development of AFP after aortobifemoral reconstruction for AAA, likely by affecting reparative connective tissue mechanisms at the anastomotic site.