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1.
J Clin Monit Comput ; 36(3): 879-888, 2022 06.
Article in English | MEDLINE | ID: mdl-34037919

ABSTRACT

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.


Subject(s)
Coronary Artery Bypass, Off-Pump , Thermodilution , Cardiac Output , Humans , Monitoring, Intraoperative/methods , Prospective Studies , Reproducibility of Results , Thermodilution/methods
2.
J Endovasc Ther ; 23(2): 387-92, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26802610

ABSTRACT

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.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aged , Aorta, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/mortality , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Female , Humans , Male , Postoperative Complications/etiology , Risk Factors , Stents , Time Factors , Treatment Outcome
3.
Atherosclerosis ; 220(1): 66-71, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22035575

ABSTRACT

BACKGROUND: Active involvement of extracellular matrix (ECM) and its composition regulating factors may have a central role in the pathogenesis of calcific aortic valve disease (CAVD). Thrombospondins (TSPs) are highly conserved matricellular proteins regulating inflammation, angiogenesis and ECM remodeling. These processes are strongly associated with progression of aortic valve stenosis (AS). However, the expression of TSPs in CAVD is not known. METHODS: We characterized the expression of TSPs 1-4 in human aortic valves by real-time quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Control valves (n=8), thickened and stiffened fibro(sclero)tic valves (n=8), and calcified AS valves (n=24) were compared. Furthermore, potential factors regulating TSP-2 expression was studied by western blotting and gel mobility shift assay in another set of control (n=10) and AS (n=20) valves. RESULTS: TSP-2 mRNA levels were increased 4.9-fold (P=0.037) and 4.8-fold (P=0.001) in fibro(sclero)tic and stenotic valves, respectively, whereas the expression of other TSPs did not change significantly. All TSPs 1-4 were detected from aortic valves by immunohistochemistry. Positive TSP-2 immunostaining was seen in the valvular myofibroblasts and patchily in endothelial cells. Semiquantitative analysis of TSP-2 staining indicated increased immunoreactivity for TSP-2 in neo vessels of fibro(sclero)tic and calcified aortic valves. Finally, when compared to controls, AS was associated with significant down regulation of Akt-pathway and diminished binding activity of nuclear factor-κB (NF-κB). CONCLUSIONS: We report for the first time that TSPs 1-4 are expressed in human aortic valves. CAVD is characterized by myofibroblastic proliferation and neovascularization associated upregulation of TSP-2 expression, as well as inactivation of Akt and NF-κB.


Subject(s)
Aortic Valve Stenosis/metabolism , Aortic Valve/chemistry , Calcinosis/metabolism , Thrombospondins/analysis , Adult , Aged , Aged, 80 and over , Analysis of Variance , Aortic Valve/pathology , Aortic Valve Stenosis/genetics , Aortic Valve Stenosis/pathology , Blotting, Western , Calcinosis/genetics , Calcinosis/pathology , Case-Control Studies , Electrophoretic Mobility Shift Assay , Female , Fibrosis , Humans , Immunohistochemistry , Male , Middle Aged , NF-kappa B/analysis , Proto-Oncogene Proteins c-akt/analysis , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Sclerosis , Thrombospondin 1/analysis , Thrombospondins/genetics , Up-Regulation
4.
Scand Cardiovasc J ; 45(6): 360-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21615240

ABSTRACT

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.


Subject(s)
Anticoagulants/administration & dosage , Coronary Artery Bypass/adverse effects , Stroke/prevention & control , Administration, Oral , Aged , Anticoagulants/adverse effects , Coronary Artery Bypass/mortality , Drug Administration Schedule , Female , Finland , Hospital Mortality , Hospitals, University , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/etiology , Stroke/mortality , Time Factors , Treatment Outcome
5.
Atherosclerosis ; 216(1): 35-43, 2011 May.
Article in English | MEDLINE | ID: mdl-21316680

ABSTRACT

BACKGROUND: There is increasing evidence that renin-angiotensin system (RAS) may play a major role in the actively regulated fibrocalcific process in aortic valve stenosis (AS), but the gene expression or function of (pro)renin receptor ((P)RR), prorenin and renin or angiotensin converting enzyme 2(ACE2)/angiotensin-(1-7)/Mas receptor axis in calcific aortic valve disease is not known. METHODS AND RESULTS: We characterized expression of (P)RR, ACE2 and Mas receptor as well as renin, prorenin and angiotensin II type 2 (AT(2)) receptors in human aortic valves, and compared normal control valves (n = 11) with valves obtained from patients with aortic regurgitation (AR, n = 14), AR with fibrosis (n = 20) and AS (n = 61). By immunohistochemistry (P)RR positive staining was seen in the valvular endothelial cells of control and in the neovessels of stenotic valves. By RT-PCR, renin mRNA levels were 72% (P = 0.001) and prorenin mRNA levels 64% lower (P = 0.002) in stenotic aortic valves compared to control valves. ACE2, Mas receptor and AT(2)-receptor mRNA levels were 69% (P < 0.001), 58% (P = 0.008) and 75% (P = 0.001) lower, respectively, in stenotic valves. ACE2 positive staining, existing to lesser extent in stenotic aortic valves, was localized mainly to stromal area in spongiosa layer in control valves. CONCLUSIONS: (P)RR, prorenin and renin are expressed in human aortic valves. We also report for the first time expression of ACE2/angiotensin-(1-7)/-Mas receptor axis in human aortic valve cusps. The downregulation of ACE2/angiotensin-(1-7)/-Mas receptor axis as well as AT(2)-receptors may promote fibrosis, proliferation and inflammation in patients with AS.


Subject(s)
Aortic Valve Stenosis/metabolism , Aortic Valve/chemistry , Peptidyl-Dipeptidase A/analysis , Proto-Oncogene Proteins/analysis , Receptors, Cell Surface/analysis , Receptors, G-Protein-Coupled/analysis , Renin-Angiotensin System , Vacuolar Proton-Translocating ATPases/analysis , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , Aortic Valve/drug effects , Aortic Valve/pathology , Aortic Valve Insufficiency/metabolism , Aortic Valve Stenosis/drug therapy , Aortic Valve Stenosis/genetics , Aortic Valve Stenosis/pathology , Calcinosis/metabolism , Case-Control Studies , Female , Fibrosis , Finland , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Immunohistochemistry , Male , Middle Aged , Neovascularization, Pathologic/metabolism , Proto-Oncogene Mas , Proto-Oncogene Proteins/genetics , RNA, Messenger/analysis , Receptor, Angiotensin, Type 2/analysis , Receptors, G-Protein-Coupled/genetics , Renin/analysis , Renin/genetics , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/genetics , Reverse Transcriptase Polymerase Chain Reaction , Young Adult , Prorenin Receptor
6.
J Heart Valve Dis ; 18(6): 644-52, 2009 Nov.
Article in English | MEDLINE | ID: mdl-20099713

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis/metabolism , Aortic Valve/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Adult , Aged , Aged, 80 and over , Aortic Valve/pathology , Aortic Valve Stenosis/pathology , Apelin , Apelin Receptors , Calcinosis/metabolism , Calcinosis/pathology , Case-Control Studies , Down-Regulation , Female , Humans , Male , Middle Aged , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Signal Transduction , Young Adult
7.
Eur Heart J ; 30(2): 242-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19008257

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis/metabolism , Aspartic Acid Endopeptidases/genetics , Endothelin-1/metabolism , Metalloendopeptidases/genetics , Receptor, Endothelin A/metabolism , Adult , Aged , Aged, 80 and over , Aortic Valve Stenosis/genetics , Aspartic Acid Endopeptidases/metabolism , Down-Regulation , Endothelin-1/genetics , Endothelin-Converting Enzymes , Female , Gene Expression Regulation, Enzymologic , Humans , Immunohistochemistry , Male , Metalloendopeptidases/metabolism , Middle Aged , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Endothelin A/genetics , Reverse Transcriptase Polymerase Chain Reaction
8.
Hum Pathol ; 39(11): 1695-701, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18701137

ABSTRACT

Clinically, calcific aortic valve disease is a progressive continuum from obstructive fibro(sclero)tic valve thickening to aortic stenosis. Recent evidence suggests that, in addition to nonbone miscellaneous mineralization, calcified valves present distinct signs of active bone remodeling; and in this context, noncollagenous bone-associated proteins are assumed to have a critical role. The expression of 5 bone matrix proteins-bone morphogenetic protein-2 and -4, bone sialoprotein II, osteopontin, and osteoprotegerin-was examined by reverse transcriptase polymerase chain reaction (n = 31) and immunolabeling (n = 83) in the clinical continuum from healthy pliable valves to heavily calcified ones. As a known structural pathologic sign, the extent of neovascularization was also examined. We observed progressive increase in the gene expression of osteopontin (7.4-fold elevation, P < .001) and bone sialoprotein II (5.8-fold elevation, P < .05), and also 1.7-fold elevation (P < .05) in osteoprotegerin gene expression during the disease course. These findings were congruent with that of immunohistochemical analysis. Surprisingly, bone morphogenetic protein-2 and -4 showed a comparable significant decrease in messenger RNA levels in calcified valves (P < .01 and P < .05, respectively). Our results support the view that aortic valve calcification is an actively regulated process. Furthermore, the results suggest that the expression of pro- and anticalcific noncollagenous bone-associated matrix proteins is altered during the disease continuum and that this imbalance may contribute to the pathology of calcific aortic valve disease.


Subject(s)
Aortic Valve Stenosis/pathology , Aortic Valve/metabolism , Bone Morphogenetic Proteins/metabolism , Calcinosis/pathology , Cardiomyopathies/pathology , Adult , Aged , Aged, 80 and over , Bone Morphogenetic Protein 2/metabolism , Bone Morphogenetic Protein 4/metabolism , Female , Gene Expression Regulation , Humans , Immunohistochemistry , Integrin-Binding Sialoprotein , Male , Middle Aged , Neovascularization, Pathologic/physiopathology , Osteopontin/metabolism , Osteoprotegerin/metabolism , Sialoglycoproteins/metabolism
9.
Interact Cardiovasc Thorac Surg ; 7(4): 578-81, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18430763

ABSTRACT

The aim of this study was to evaluate the value of statins in reducing abdominal aortic aneurysm (AAA) growth rate and improving freedom from aneurysm repair or rupture. One hundred and twenty-one patients with AAA undergoing ultrasonographic surveillance for at least one year were included in this retrospective study. Patients treated with statins had a decreased linear aneurysm growth rate than those not receiving statins (1.9+/-1.8 mm/year vs. 2.6+/-2.4 mm/year, P=0.27), but this difference did not reach statistical significance. Statin users had a better survival freedom from aneurysm repair or rupture (at 5 years: 72.3% vs. 52.5%, P=0.048). The impact of treatment with statins was even more evident in patients with a baseline aneurysm diameter<40 mm (at 5 years: 84.0% vs. 58.8%, P=0.022). When adjusted for age, coronary artery disease and baseline aneurysm diameter, treatment with statins had significantly better survival freedom from aneurysm repair or rupture (P=0.012, RR 0.34, 95% CI 0.14-0.78). The use of statins seems to slightly decrease the AAA growth rate and to significantly improve freedom from aneurysm repair and rupture.


Subject(s)
Aortic Aneurysm, Abdominal/drug therapy , Aortic Rupture/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/diagnostic imaging , Aortic Rupture/etiology , Aortic Rupture/surgery , Disease Progression , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Ultrasonography , Vascular Surgical Procedures
10.
Circulation ; 116(11): 1283-9, 2007 Sep 11.
Article in English | MEDLINE | ID: mdl-17709640

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis/metabolism , Down-Regulation/physiology , Natriuretic Peptide, C-Type/antagonists & inhibitors , Natriuretic Peptide, C-Type/biosynthesis , Adult , Aged , Aged, 80 and over , Aortic Valve Stenosis/pathology , Female , Gene Expression Regulation/physiology , Humans , Male , Middle Aged , Natriuretic Peptide, C-Type/genetics
12.
J Heart Valve Dis ; 16(2): 116-21, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17484456

ABSTRACT

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.


Subject(s)
Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency/surgery , Aged , Female , Finland , Humans , Logistic Models , Male , Middle Aged , Mitral Valve Insufficiency/mortality , Predictive Value of Tests , Proportional Hazards Models , Research Design , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Survival Analysis , Time Factors , Treatment Outcome
13.
J Mol Cell Cardiol ; 41(4): 642-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16938307

ABSTRACT

Human bone-marrow-derived mesenchymal stem cells (MSC) are responsible the remodeling of human tissue. However, damaged aortic valves are lack the ability to regenerate which is an active cell-mediated process. Diseased aortic valve remodeling has similarities even to bone formation. In this study, the prerequisites for cultured MSCs to undergo osteoblastic differentiation on aortic valves were explored. An ex vivo model using a human aortic valve microenvironment was developed. The expression of type I procollagen, alkaline phosphatase activity, osteocalcin secretion and osteocalcin immunostaining were studied to evaluate the induction of osteogenesis of the MSCs on noncalcified and calcified human aortic valves. Aortic valves were exposed to freeze-thaw injury to devitalize valves in order to separately study the role of valve matrix vs. endothelial cells in the explants. Thus, valves were assigned to 1 of 4 treatment groups: noncalcified uninjured valves, calcified uninjured valves, noncalcified injured and calcified injured. Finally, valves were decalcified to separately explore the effect of a calcified matrix on the osteogenesis. In this co-culture system, the noncalcified uninjured valves inhibited osteogenesis of MSCs, whereas the calcified valves promoted differentiation towards osteoblastic lineage. Devitalization of the valve matrix inflicted a significant increase in the osteogenesis of co-cultured MSCs. Calcified matrix in the valves seemed to have a role in the spontaneous osteogenesis of the MSCs. This spontaneous matrix induced differentiation of MSCs into osteoblast lineage could not be inhibited by pravastatin, indomethacin or tetracycline. In conclusion, these results suggest that interactions between MSCs and aortic valve matrix components and cells modulate MSC phenotype in this environment. Further studies are required to characterize this interesting phenomenon in greater detail.


Subject(s)
Aortic Valve/physiology , Bone Marrow Cells/physiology , Calcinosis/physiopathology , Mesenchymal Stem Cells/physiology , Osteogenesis , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biomarkers/analysis , Cell Cycle Proteins/pharmacology , Cell Differentiation , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Mesenchymal Stem Cells/drug effects , Models, Biological , Osteoblasts/physiology , Peptide Elongation Factor 1
14.
Ann Thorac Surg ; 82(1): 57-61, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16798188

ABSTRACT

BACKGROUND: The European system for cardiac operative risk evaluation score (EuroSCORE) has been shown to be of value in identifying patients at high risk for adverse immediate postoperative outcome after adult cardiac surgery. The aim of the present study was to evaluate EuroSCORE in predicting the 12-year outcome of patients who underwent on-pump coronary artery bypass surgery (CABG). METHODS: We calculated the EuroSCORE in 917 patients who underwent CABG. The median follow-up was 11.7 years. RESULTS: Both additive and logistic EuroSCORE had an area under the receiver operating characteristic curve of 0.856 for prediction of 30-day postoperative death. Among 912 operative survivors, the 10-year survival rates according to quintiles of additive EuroSCORE were 87.9%, 83.9%, 85.2%, 76.0%, and 51.3% (p < 0.0001). The 10-year survival rates according to quintiles of logistic EuroSCORE were 87.9%, 85.4%, 86.5%, 76.9%, and 58.9% (p < 0.0001). CONCLUSIONS: EuroSCORE is a relevant predictor of immediate and late outcome after on-pump CABG.


Subject(s)
Coronary Artery Bypass , Postoperative Complications/mortality , Severity of Illness Index , Aged , Female , Follow-Up Studies , Forecasting , Humans , Life Tables , Male , Middle Aged , Proportional Hazards Models , ROC Curve , Risk Assessment , Survival Rate , Treatment Outcome
15.
Am J Surg ; 192(1): 19-23, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16769269

ABSTRACT

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.


Subject(s)
Aortic Aneurysm, Abdominal/mortality , Aortic Rupture/mortality , Vascular Surgical Procedures/methods , Aged , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Emergencies , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Factors , Survival Rate
16.
Eur J Cardiothorac Surg ; 29(6): 983-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16682213

ABSTRACT

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.


Subject(s)
C-Reactive Protein/analysis , Coronary Artery Bypass , Coronary Disease/blood , Aged , Biomarkers/blood , Coronary Artery Bypass/mortality , Coronary Disease/surgery , Epidemiologic Methods , Female , Finland/epidemiology , Humans , Male , Middle Aged , Preoperative Care/methods , Prognosis , Treatment Outcome
17.
Atherosclerosis ; 189(1): 91-8, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16405893

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis/metabolism , Collagen Type III/biosynthesis , Collagen Type I/biosynthesis , Extracellular Matrix/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Aging/metabolism , Aortic Valve Stenosis/pathology , Biomarkers/metabolism , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Disease Progression , Extracellular Matrix/pathology , Female , Gene Expression , Humans , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Peptides/metabolism , RNA, Messenger/biosynthesis , Radioimmunoassay
18.
Int J Cardiol ; 111(3): 358-64, 2006 Aug 28.
Article in English | MEDLINE | ID: mdl-16242193

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis/metabolism , Tetracyclines/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Aortic Valve Stenosis/pathology , Apoptosis/physiology , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Gelatinases/metabolism , Humans , In Vitro Techniques , Tissue Inhibitor of Metalloproteinases/metabolism
19.
J Heart Valve Dis ; 14(6): 722-6, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16359050

ABSTRACT

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.


Subject(s)
Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Quality of Life , Aged , Female , Humans , Male , Middle Aged , Mitral Valve Insufficiency/mortality , Reoperation , Surveys and Questionnaires , Survival Rate
20.
Scand Cardiovasc J ; 39(4): 229-36, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16118071

ABSTRACT

BACKGROUND: Several studies reported excellent long-term results after mitral valve repair for regurgitation, however a number of patients still experience recurrent mitral valve regurgitation which requires reoperation. We have evaluated the long-term outcome of a consecutive series of patients who underwent mitral valve repair for regurgitation in an attempt to identify the risk factors associated with late failures. PATIENTS AND METHODS: One-hundred and sixty-four patients underwent mitral valve repair for ischemic and degenerative mitral valve regurgitation. Seventy-two patients underwent echocardiographic evaluation a median of 5.6 years after surgery. RESULTS: Ten-year survival freedom from any fatal cardiac event was 75.9% and survival freedom from redo mitral valve surgery was 93.8%. Multivariable analysis showed that residual mitral valve regurgitation grade>1 as assessed during the immediate postoperative period (at 10-year, 60.6% vs. 95.7%, p=0.001, RR 20.7, 95%C.I. 3.4-125.3) and chronic obstructive pulmonary disease/asthma (at 10-year 66.8% vs. 95.2%, p=0.013, RR 12.0, 95%C.I. 1.7-85.2) were predictors of redo mitral valve surgery. The same findings were observed also among patients with myxomatous degenerative disease. At echocardiographic follow-up, no significant improvement was detected in terms of left ventricular ejection fraction, whilst mitral valve regurgitation grade (median, 3 to 1), New York Heart Association class (median, 2 to 1) and left atrium diameter (median, 50 to 44 mm) decreased significantly. CONCLUSIONS: This study confirms the excellent clinical long-term results after mitral valve repair. An adequate repair technique is advocated in order to decrease the immediate postoperative rate of residual regurgitation>1 as this is a main determinant of late failures requiring redo mitral valve surgery. Further studies are required to better define the possible causative role of chronic obstructive pulmonary disease and any underlying connective tissue metabolic disorder in late failures after mitral valve repair.


Subject(s)
Mitral Valve Insufficiency/surgery , Aged , Disease-Free Survival , Echocardiography , Female , Finland , Follow-Up Studies , Heart Failure/epidemiology , Heart Failure/etiology , Heart Failure/surgery , Heart Valve Prosthesis Implantation , Humans , Male , Middle Aged , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/epidemiology , Multivariate Analysis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Predictive Value of Tests , Reoperation , Risk Factors , Time , Treatment Outcome
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