Showing papers in "Journal of Heart Valve Disease in 2010"

Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves.

Abstract: Background and aim of the study: Bicuspid aortic valve (BAV), the most common form of congenital heart disease, is a leading cause of aortic stenosis (AS) and aortic insufficiency (AI). AS is typically caused by calcific valve disease. Recently, microRNAs (miRNAs) have been shown to modulate gene expression. The study aim was to examine the miRNAs that were altered in the aortic valve leaflets of patients with AS compared to those in patients with AI. In-vitro experiments were also carried out to determine if these miRNAs could modulate calcification-related genes. Methods: Aortic valve samples (fused and unfused leaflets) were collected from nine male patients (mean age 44.9 ± 13.8 years) undergoing aortic valve replacement (AVR). PIQOR TM miRXplore Microarrays containing 1,421 miRNAs were used and hybridized to fused leaflet samples labeled with Cy5; unfused samples were used as controls and labeled with Cy3. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the miRNA array results. Cultured human aortic valve interstitial cells (AVICs) were treated with miRNA mimics, and qRT-PCR was carried out to determine any changes in mRNAs. Results: By microarray analysis, seven miRNAs were shown to be statistically different between the AS and AI patients. In the stenotic samples, the MiR-26a and miR-195 levels were shown (by qRT-PCR) to be reduced by 65% and 59%, respectively (p <0.05), and MiR-30b to be reduced by 62% (p <0.06). Human AVICs treated with miR-26a or miR-30b mimics showed decreased mRNA levels of calcificationrelated genes. MiR-26a repressed BMP2 by 36%, alkaline phosphatase (ALPL) by 38%, and SMAD1 by 26%, while MiR-30b reduced the expression of SMAD1 by 18% and of SMAD3 by 12%. In contrast, miR-195-treated AVICs had increased mRNA levels of calcification-related genes, such as BMP2 by 68% and RUNX2 by 11%. Conclusion: MiR-26a, miR-30b, and miR-195 were each decreased in the aortic valves of patients requiring AVR due to AS, compared to those requiring replacement due to AI. These miRNAs appear to modulate calcification-related genes in vitro.

Unicuspid aortic valve in adults: a systematic review.

Abstract: BACKGROUND AND AIM OF THE STUDY: The natural history of the unicuspid aortic valve (UAV) is poorly described in the literature. In order to study the association between UAV with any other cardiac or extra cardiac abnormalities, an evidence-based systematic review was carried out. METHODS: A computerized search was carried out of the medical literature published between 1st January 1966 and 1st September 2008 of the following databases: MEDLINE; EMBASE; Web of Science; and the Cochrane Database. RESULTS: A total of 231 cases of adult UAV was identified in 38 articles. The mean patient age was 42 years, and the most common presenting symptoms reported (in 52 cases) included dyspnea (44%; n=23), angina (21%; n=11), and dizziness or syncope (8%; n=4). The most common lesion in UAV was isolated aortic stenosis (AS) (41%; n=95) and AS with or without aortic regurgitation (28%; n=64). The preoperative diagnosis of UAV is rare, and 139 cases (60%) of UAV were reported at autopsy or by examination of surgically excised valves. Aortic valve replacement was performed in 166 cases (82%). Concomitant aortic surgery was performed in 47 of the UAV cases (23%), either for a dilated or aneurysmal aorta. CONCLUSION: UAV shares many of the features of bicuspid aortic valve, including valvular dysfunction, aortic dilatation, aortic dissection, and dystrophic calcification, although these conditions develop at an earlier age and progress at a faster pace in UAV. Further investigations are warranted regarding the possibility of a familial incidence, associated histopathological changes in the aorta, preoperative diagnostic tools, ideal follow up and surgical intervention.

Insights into the Use of Biomarkers in Calcific Aortic Valve Disease

Abstract: Calcific aortic valve disease (CAVD) is the most common acquired valvular disorder in developed countries. CAVD ranges from mild thickening of the valve, known as aortic valve sclerosis (AVSc), to severe impairment of the valve motion, which is termed aortic valve stenosis (AVS). The prevalence of CAVD is nearing epidemic status: its preceding stage, in which there is aortic sclerosis without obstruction of the left ventricular outflow, is present in almost 30% of adults aged over 65 years. As there is no existing medical therapy to treat or slow the progression of CAVD, surgery for advanced disease represents the only available treatment. Aortic valve replacement is the second most frequently performed cardiac surgical procedure after coronary artery bypass grafting, and consequently CAVD represents a major societal and economic burden. The pathophysiological development of CAVD is incompletely defined. At the present time, the major methods for its diagnosis are clinical examination, echocardiography, and cardiac catheterization. Yet, due to the multiple biological pathways leading to CAVD, there are many potential biomarkers that might be suitable for deriving clinically useful information regarding the presence, severity, progression, and prognosis of CAVD. Although at the present time the available data do not permit recommendations for clinicians, they do support a paradigm of screening patients based on multiple biomarkers to provide the information necessary to optimize future therapeutic interventions. This review summarizes the results of several studies investigating the value of potential biomarkers that have been used to predict the severity, progression, and prognosis of CAVD.

Anti alpha-gal immune response following porcine bioprosthesis implantation in children.

Abstract: Background and aim of the study: Porcine bioprostheses have been widely used in cardiac surgery in the treatment of valvular heart disease. However, in younger patients, their use has been limited by early failures known to be associated with an immune response and subsequent degeneration. The natural antibodies directed at Galα1, 3-Galβ1-4GlcNAc-R(αGal), have been thought to initiate an immune response in humans transplanted with porcine organ xenografts. The study aim was to determine the anti α-Gal immune response following commercial porcine bioprosthesis implantation in children. Methods: Between January 2008 and April 2008, 19 consecutive patients underwent pulmonary valve replacement (PVR) with a commercially available porcine bioprosthesis for an incompetent pulmonary valve with congenital heart diseases. The median age at surgery was 132 months (range: 14-330 months). Previous PVR with a porcine bioprosthesis had been performed in seven patients at a median of 44 months (range: 26-117 months) before surgery (rePVR group). Sera were obtained sequentially five times: immediately before surgery, and at one day, one week, three weeks, and two months postoperatively. All serum samples were analyzed using an enzyme-linked immunosorbent assay to investigate the α-Gal immune response. Results: There were no operative deaths or complications. There was no statistically significant difference between the titers of anti α-Gal antibodies of the PVR and re-PVR groups. The titer of anti α-Gal antibodies (IgM and IgG) was decreased on the first postoperative day, but increased in the first postoperative week, regardless of the isotype. Whilst the titer of the anti α-Gal IgM antibody began to decrease after three weeks postoperatively, the titer of anti α-Gal IgG antibody remained increased after two months. Conclusion: The implantation of a porcine bioprosthesis elicits the increased formation of anti α-Gal antibodies during the early postoperative period in children, with different patterns between the two isotypes. The IgM antibody response was rapid and transient, while the IgG antibody response was longer and more delayed.

Propensity score-matched analysis of aortic valve replacement by mini-thoracotomy.

Abstract: BACKGROUND AND AIM OF THE STUDY Although minimally invasive aortic valve replacement (MIAVR) through an anterolateral mini-thoracotomy has been shown to reduce surgical trauma, the technique is utilized only at a few selected heart surgery centers. The study aim was to demonstrate the implementation of a MIAVR program at the Innsbruck Medical University, Austria. METHODS Between October 2006 and January 2009, a total of 315 patients underwent elective isolated aortic valve replacement (AVR). Of these patients, 87 (27.6%) received MIAVR, while the remainder (n = 228) underwent 'conventional' AVR by full sternotomy. In the MIAVR group, 76 patients (87%) were cannulated via the femoral artery. The mean EuroSCORE was 5.7 +/- 2.2 in the MIAVR group, and 6.7 +/- 2.9 in the AVR group (p < 0.001). Propensity score matching was used to reduce the impact of treatment selection in the comparison of MIAVR with conventional AVR. The propensity score was used to yield two matched groups by means of a 1:1 sample matching. RESULTS The total operative, cardiopulmonary bypass and aortic cross-clamp times were significantly longer in the MIAVR group compared to the matched AVR group. The actuarial one-year survival was 96% in the MIAVR group, and 98% in the propensity-matched AVR group (p = 0.57). Reoperation due to bleeding was necessary in 4.6% of the MIAVR group (four patients, three by mini-thoracotomy) compared to 5.7% in the matched AVR group (n = 5; p = 0.38). A total of six MIAVR patients (6.9%) had complications from the cannulated groin, predominantly lymphatic fistula formation. Additionally, there was a trend towards a higher rate of renal insufficiency in the MIAVR group (p = 0.07). CONCLUSION MIAVR can be safely implemented as routine cardiac surgery procedure, although the operative times are significantly longer. The early postoperative outcome was equal to that of the sternotomy approach, but postoperative complications were predominantly associated with femoral cannulation.

Induction of mesenchymal to endothelial transformation of adipose-derived stem cells.

Abstract: Background and aim of the study Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering and regenerative medicine Adipose-derived stem cells (ADSCs) are currently being investigated as a source of interstitial cells to populate tissue-engineered heart valve constructs However, the ability of these cells to differentiate into endothelial cells that would be required to cover the surface of the valve cusps has not been fully investigated Methods ADSCs were isolated and characterized using immunofluorescence and flow cytometry Endothelial differentiation was promoted by culturing confluent cells in the presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor Differentiation was evaluated by immunofluorescence staining for endothelial markers, and an analysis of acetylated low-density lipoprotein (Ac-LDL) uptake An assessment of tubular formation was performed using an in vitro angiogenesis assay Results Isolated ADSCs were positive for the mesenchymal markers CD105, CD73, CD29, CD90 and CD44, and negative for hematopoietic and endothelial markers After a seven-day treatment period, approximately 15% of ADSCs expressed the endothelial marker von Willebrand factor, and 70% had lost the expression of smooth muscle a-actin Treated cells also were able to incorporate Ac-LDL, and also to form tubular structures on Matrigel, unlike control cells Conclusion Based on these results, ADSCs are capable of differentiating into cells with phenotypic and functional features of endothelial cells These predifferentiated cells provide new options for the tissue engineering of heart valves, based on autologous mesenchymal stem cells

Mitral valve surgery: comparison of outcomes in matched sternotomy and port access groups.

Abstract: BACKGROUND AND AIM OF THE STUDY The 30-day outcomes were compared between matched groups of patients undergoing mitral valve procedures through Port Access (femoral cannulation, percutaneous retrograde cardioplegia and aortic occlusion), and through a sternotomy. METHODS By using a Society of Thoracic Surgeons (STS)-certified, audited database, a total of 1108 patients was identified who were operated on between January 1996 and November 2008. A total of 608 mitral valve repair (MV-Rpr) patients (including 241 with Port Access procedures) and 500 mitral valve replacement (MVR) patients (including 45 with Port Access procedures) was included. Matching groups were created for 177 MV-Rpr patients (matched on preoperative cerebrovascular accident (CVA), previous coronary artery bypass grafting (CABG) and valve procedures, urgent operative status, mitral stenosis, heart failure, NYHA class IV, and age) and for MVR patients with 43 matches (matched for previous CABG surgery, operative status, NYHA class IV, and mitral insufficiency). RESULTS Patients with Port Access procedures for MV-Rpr had a shorter length of hospital stay (5.4 +/- 2.8 versus 7.3 +/- 5.8 days), less postoperative ventilator usage (8.4 +/- 36.0 versus 24.8 +/- 81.6 h) and a shorter intensive care unit (ICU) stay (34.0 +/- 40.5 versus 81.7 +/- 133.8 h) when compared to sternotomy cases. Port Access also resulted in fewer patients requiring postoperative ventilation (50.3% versus 76.9%; p < 0.001) or reoperation for bleeding (2.3% versus 6.8%; p = 0.048). In MVR patients, Port Access use led to reductions in mortality (11.6% versus 0%; p = 0.021), ventilation time (13.8 +/- 40.3 versus 38.1 +/- 83.0 h), ICU stay (51.9 +/- 83.4 versus 152.4 +/- 125.0 h) and postoperative hospital stay (8.2 +/- 8.0 versus 11.0 +/- 8.6 days). In both groups, the cross-clamp time was longer with Port Access (107.7 +/- 26.8 versus 92.8 +/- 35.2 min for MV-Rpr; 130.2 +/- 44.2 versus 102.7 +/- 64.6 min for MVR). CONCLUSION The performance of mitral valve surgery through a Port Access approach led to a reduction in ICU time, ventilator time, and hospital stay when compared to sternotomy. No increase in morbidity was observed with Port Access compared to sternotomy.

In-vivo assessment of a novel polymer (SIBS) trileaflet heart valve.

Abstract: Background and aim of the study A novel trileaflet polymer valve, which is a composite design of a biostable and biocompatible polymer poly(styrene-block-isobutylene-block-styrene) (SIBS) with an embedded reinforcement polyethylene terephthalate (PET) fabric, is being developed with the intention of providing a valve that has low thrombogenicity, high durability and favorable hemodynamic performance. The study aim was to investigate the biocompatibility and performance of this SIBS valve prototype under physiological loading conditions similar to humans, using a large-animal model. Methods Four SIBS valves (two with surface modification using dimyristoyl phosphatidylcholine, DMPC), and two commercial Magna tissue valves, were implanted into sheep. Hemodynamic and blood chemistry measurements were performed periodically during the postoperative period. The explanted SIBS valves were extensively evaluated using macroscopic, histological, radiographical and scanning electron microscopy/energy-dispersive spectroscopy analysis. Results Three animals, one with the DMPC-coated SIBS valve, and two with the Magna valves, reached the end of the study in satisfactory clinical condition, and were euthanized after 20 weeks. The other three animals (two with SIBS valves, one with a DMPC-coated SIBS valve) died at 6, 6.5, and 10 weeks due either to material failure or myocardial infarction. The explanted valves exhibited stent deformation and cracks on the leaflets, which exposed the underlying PET fabric and resulted in severe blood and tissue reactions. Extrinsic calcification was identified on the leaflets, and was associated with the regions of surface cracks. Conclusion The SIBS valve failed in animal testing because of material failure and calcification. The physical properties of SIBS must be improved in order to provide the structural integrity required for long-term in-vivo use in the form of a heart valve.

Structural and cellular changes in canine myxomatous mitral valve disease: an image analysis study

Abstract: BACKGROUND AND AIM OF THE STUDY Myxomatous mitral valve disease (MMVD) is the single most common cardiac disease of the dog, and bears close similarities to chronic degenerative mitral valve disease in humans. However, limited quantitative data are available on cellular and morphological changes in both species. The study aim was to use an image analysis system to examine various morphological changes associated with MMVD, and in particular to measure changes in cell numbers in overtly myxomatous areas of the distal portion of the valve. METHODS Mitral valve complexes were collected from normal dogs and dogs with varying severity of myxomatous mitral valve disease (veterinary Whitney grades 1-4; a measure of disease severity and age-related disease progression in the dog). An image analysis technique (ImageJ; National Institutes of Health, USA) was used to measure valve leaflet length, thickness, connective tissue content and density, glycosaminoglycan (GAG) content, cell number and shape in normal and myxomatous areas of diseased valves. RESULTS There was a change in the valve leaflet anterior/posterior length ratio in the diseased valves, suggestive of valve lengthening. Distinct and statistically significant (p < 0.01) changes occurred in the valve thickness ratio for both anterior and posterior leaflets as the disease progressed, and the posterior leaflet thickness ratios were consistently higher than for the anterior leaflets. There was a statistically significant decrease in cell numbers in overtly myxomatous areas of the distal portion of affected valves compared to similar locations in normal valves, but there was no difference between the different grades of disease. The majority of cells in both diseased and normal valves had a circularity score typical of a spindle (elongated) shape. Connective tissue derangement was clearly seen in the myxomatous areas, and this was associated with a significant reduction in connective tissue density. The reduction in connective tissue density was associated with advancing disease severity (age). There was an increase in GAG expression with disease severity, as shown by the level of Alcian blue staining, but this could not be quantified with ImageJ. CONCLUSION Mitral valve myxomatous degeneration in the dog is associated with lengthening and thickening of valve leaflets, a loss of connective tissue, and a decrease in cell numbers in selected myxomatous areas, but no change in cell circularity. Some of these changes were age- (disease severity-) related.

Pulmonary hypertension and elevated transpulmonary gradient in patients with mitral stenosis.

Abstract: Background and aim of the study: Pulmonary hypertension frequently complicates mitral stenosis, with a subset of these patients exhibiting pressures well in excess of their mitral valve hemodynamics. The prevalence of this condition and its impact on clinical outcome following percutaneous balloon mitral commissurotomy (PBMC) is unknown. Methods: The transpulmonary gradient (TPG) was measured in 317 patients undergoing PBMC; patients were subsequently defined as having either an appropriate or excessive TPG (≤15 mmHg or >15 mmHg, respectively). Twenty-two patients were excluded due to valvuloplasty-related significant mitral regurgitation. The remaining 295 patients (250 females, 45 males; mean age 52 ± 13 years) were prospectively followed up, with each patient underwent serial echocardiography. Results: Among the patients, 214 (73%) had pulmonary hypertension (pulmonary artery pressure >25 mmHg) and 55 (19%) also had an elevated TPG. Females were almost fivefold more likely than males to have an elevated TPG (p = 0.003). Patients with an elevated TPG had a worse mean NYHA functional class than those with a normal TPG (3.0 ± 0.5 versus 2.7 ± 0.6, p = 0.01), while the mitral valve area (MVA) was slightly smaller in patients with an elevated TPG (1.0 ± 0.2 versus 1.1 ± 0.2 cm 2 , p = 0.003). All patients demonstrated a significant increase in MVA after commissurotomy (final MVA 1.7 ± 0.6 cm 2 , p <0.001 for elevated TPG; 1.8 ± 0.4 cm 2 , p <0.001 for normal TPG), and the NYHA class at six months was improved for all patients (2.8 ± 0.6 versus 1.6 ± 0.7, p <0.001). The improvements in NYHA class, TPG and MVA were sustained at 36 months. Conclusion: Pulmonary hypertension with elevated TPG occurs in patients with mitral stenosis, and is significantly more common in females. Despite worse symptoms and higher right-sided pressures, PBMC is equally successful in patients with a normal TPG, and provides sustained benefit for up to 36 months after the procedure.

The Freedom SOLO valve for aortic valve replacement: clinical and hemodynamic results from a prospective multicenter trial.

Abstract: BACKGROUND AND AIM OF THE STUDY The study aim was to investigate the early results, hemodynamics and left ventricular remodeling after aortic valve replacement (AVR) with the Freedom SOLO valve, a bovine pericardial valve bioprosthesis, using a single running suture line in a supra-annular position. METHODS Between July 2004 and September 2006, a total of 256 patients (116 males; 140 females; mean age 74.5 +/- 6.4 years; range: 41-89 years) who underwent AVR with the Freedom SOLO valve in nine European institutions were enrolled in the study. The indications for AVR were stenosis in 182 patients, regurgitation in 15, and combined in 57. Preoperatively, 37%, 59% and 4% of the patients were in NYHA classes I-II, III, and IV, respectively. Concomitant procedures were performed in 91 patients (36%). A patient subgroup underwent echocardiography preoperatively (n=192), and at one (n=194) and 12 (n=165) months postoperatively. RESULTS The early mortality was 2.3% (n=6). There were 18 late deaths (6.2%/pt-yr). After 12 months, 82% of the patients were in NYHA class I-II. Linearized rates were 0.69%/pt-yr for bleeding, 0.34%/pt-yr for thromboembolism, 0.0%/pt-yr for structural degeneration and thrombosis, 1.37%/pt-yr for paravalvular leak, and 2.06%/pt-yr for endocarditis. Five patients required reoperation. Twelve-month transprosthetic regurgitation was graded as absent in 92% of cases. The mean gradient was 42.3 +/- 20.2 mmHg preoperatively, 6.5 +/- 3.8 mmHg at one month, and 6.7 +/- 4.1 mmHg at 12 months. The effective orifice area was improved from 0.78 +/- 0.35 cm2 preoperatively to 1.90 +/- 0.56 cm2 at one month and 1.89 +/- 0.56 cm2 at 12 months. The left ventricular mass was decreased by 23%, from 217.8 +/- 77.2 g/m2 preoperatively to 167.4 +/- 68.2 g/m2 at one year. The mean left ventricular ejection fraction was 65.5 +/- 14.2% preoperatively, and 64.5 +/- 12.5% and 66.0 +/- 10.6% at one month and at 12 months, respectively. CONCLUSION The data obtained suggest that the Freedom SOLO stentless bioprosthesis shows excellent early clinical and hemodynamic results, resulting in a significant regression of left ventricular hypertrophy and improvement in left ventricular systolic function.

Tryptophan Hydroxylase 1 Expression is Increased in Phenotype-Altered Canine and Human Degenerative Myxomatous Mitral Valves

Abstract: BACKGROUND AND AIM OF THE STUDY Serotonin is a known mediator of myxomatous pathology in heart valves Tryptophan hydroxylase 1 (TPH1) is the limiting enzyme for peripheral serotonin synthesis, and its expression by valve interstitial cells (IC) could implicate an autocrine serotonin signaling mechanism in primary degenerative myxomatous mitral valve disease Thus, the expression of TPH1 in canine and human myxomatous mitral valves was determined, and IC phenotypes expressing TPH1 identified METHODS TPH1 expression was determined in canine and human myxomatous and normal mitral valves by immunoblot (IB) and immunofluorescence microscopy (IFM) Co-localization of TPH1 expression with markers of IC phenotype transformation, alpha-smooth muscle actin (a-SMA) and non-muscle embryonic myosin (SMemb) was determined using double-IFM RESULTS TPH1 expression by IB was increased (p < 005) by three- to five-fold in canine early-stage and late-stage myxomatous valves, and in human surgically excised myxomatous valves compared to canine and human normal control valves, respectively The number of TPH1 immunopositive cells per x400 field was increased (p < 0005) in canine (149 +/- 12) and human (149 +/- 29) myxomatous valves compared to canine (50 +/- 24) and human (29 +/- 06) normal control valves, respectively Patterns for alpha-SMA and SMemb IC phenotype transformation were distinctly different in myxomatous valves TPH1 expression was more closely associated with the SMemb IC phenotype in canine and human myxomatous valves CONCLUSION An increased expression of TPH1 in canine and human myxomatous mitral valves implicates an autocrine serotonin signaling mechanism in primary degenerative myxomatous mitral valves TPH1 expression is associated with the SMemb-positive IC phenotype

Infective endocarditis in patients with diabetes mellitus.

Abstract: Background and aim of the study Numerous studies have been conducted to investigate the conditions associated with poor outcome among patients with infective endocarditis (IE). Yet, diabetes mellitus alone has rarely been analyzed as participating in the prognosis, and few data are available relating to the clinical characteristics of IE in diabetics. The study aim was to assess the influence of diabetes mellitus on the characteristics and prognosis of IE, and to identify predictors of poor outcome among diabetic patients with this condition. Methods The study included consecutive patients with IE who had presented to a tertiary center between 1990 and 2006. All patients underwent transthoracic and transesophageal echocardiography. Three or more blood cultures were collected from each patient. Records of all patients were collected prospectively into a computerized database. Results Among 309 patients with definitive IE (according to modified Duke criteria), 38 (12%) had diabetes mellitus. Typically, diabetic patients were older than non-diabetics (67.1 +/- 10.4 versus 60.7 +/- 15.8 years; p 3 were associated with an increased mortality among diabetic patients. Conclusion Diabetes mellitus represents a relevant risk factor for a worse clinical course and outcome of IE.

Long-term follow up of patients undergoing reoperative surgery with aortic or mitral valve replacement using a St. Jude Medical prosthesis.

Abstract: BACKGROUND AND AIM OF THE STUDY Between June 1978 and September 2002, a total of 440 reoperative open-heart patients (mean age 62 +/- 14 years; range: 18-91 years), following various primary cardiac operations, underwent single-valve replacement with the St. Jude Medical (SJM) heart valve. Of 241 patients having aortic replacement (AVR) and 199 mitral valve replacement (MVR), 86 (35%) and 42 (21%), respectively, underwent concomitant coronary artery bypass grafting. The study aim was to document patient survival and valve-related events in an experience extending up to 24 years after reoperative open-heart surgery with a single model cardiac valve prosthesis. METHODS The Cardiac Surgical Associates Research Foundation (CSARF) has maintained an independent database of those patients with the SJM prosthesis since the world's first implant in October 1977. Patients were contacted by questionnaire and/or telephone between November 2002 and June 2003. The hospital course and valve-related events were verified by patient chart review and/or physician contact. RESULTS Follow up was 94% complete, for a total of 3,114 patient-years (1,671 pt-yr after AVR; 1,443 pt-yr after MVR). The average follow up was 7 +/- 6 years (range: 0.1-24.3 years). The operative mortality was 9% (10% AVR, 8% MVR). Five deaths (13%) were valve-related. Freedom from all late mortality at 10 and 20 years, respectively, was 57% and 35% for AVR and 52% and 22% for MVR, and for valve-related mortality was 89% and 77% for AVR and 84% and 22% for MVR. Freedom from thromboembolic events at 10 and 20 years, respectively, was 93% and 93% after AVR and 92% and 81% after MVR; from anticoagulant-related hemorrhage it was 78% and 76% after AVR and 81% and 67% after MVR; and from reoperation it was 94% and 94% after AVR and 95% and 89% after MVR. CONCLUSION Reoperative valve replacement carries a significant operative morbidity and mortality. Long-term results with the SJM valve demonstrated a durable prosthetic valve, excellent long-term patient survival, and freedom from valve-related events followed reoperative open-heart valve replacement surgery. However, the early postoperative period carried an increased risk for valve-related events.

Mitigation of calcification and cytotoxicity of a glutaraldehyde-preserved bovine pericardial matrix: improved biocompatibility after extended implantation in the subcutaneous rat model.

Abstract: Background and aims of the study Implanted non-crosslinked tissues suffer rapid degeneration, shrinkage and absorption, whereas standard crosslinked tissues cause local cytotoxicity and calcification. Both approaches diminish implant capacity for long-term function. The study aim was to examine the tissue-engineered characteristics (cytotoxicity, calcification potential, biocompatibility) of bovine pericardium, crosslinked with a low concentration of glutaraldehyde (GA) followed by ADAPT anti-mineralization, following prolonged implantation in a subcutaneous rat model. Methods Bovine pericardium was decellularized with Triton X-100, deoxycholate, IgePal CA-630, and nucleases. The resulting matrices were allocated to: group I (control, n=10), crosslinked in 0.2% polymeric GA; and group II (treatment, n=10), crosslinked in 0.05% monomeric GA + ADAPT. Cytotoxicity was determined by in vitro cell seeding with human fibroblasts, and quantified using an Alamar Blue assay. The matrices were then implanted in a subcutaneous rat model and retrieved after extended implantation times (26 and 52 weeks). This was followed by further histology, immunohistochemical staining, and measurement of calcium deposition. Results Complete acellularity and biostability were significantly (p Conclusion Acellular bovine pericardium, when crosslinked with a low concentration of GA and treated with ADAPT, retains and improves its integrity with a low immunoreactivity over a prolonged period. Host cell infiltration is also optimized over time. The maintenance of reduced calcification levels in group II suggests that such a biomaterial might have an advanced long-term in vivo potential.

Tricuspid regurgitation in patients with severe mitral regurgitation and normal left ventricular ejection fraction: risk factors and prognostic implications in a cohort of 895 patients.

Abstract: BACKGROUND AND AIM OF THE STUDY Although tricuspid regurgitation (TR) is common in patients with mitral regurgitation (MR), its frequency, determinants and prognostic implications in those with severe MR and a normal left ventricular ejection fraction (LVEF) are not fully known. The study aim was to evaluate the risk factors for, and prognostic implications of, TR in patients with severe MR and a normal LVEF. METHODS In this retrospective cohort study, the authors' echocardiographic database for the period between 1993 and 2003 was screened for patients with severe MR and LVEF > or = 55%. Chart reviews were performed for clinical, pharmacological and surgical details, while survival was analyzed as a function of TR severity. RESULTS Among 895 patients with severe MR and normal LVEF, 510 (57%) had grade > or = 2+ TR, while 219 (24%) had grade 3 or 4+ TR. Those patients with grade > or = 2+ TR were older (p or = 2+ TR was associated with a higher mortality (relative risk 1.4, 95% confidence interval 1.1-1.8, p = 0.02). Mitral valve surgery was associated with a better survival in those with grade > or = 2+TR (p = 0.0003). CONCLUSION Significant TR is a frequent occurrence in patients with severe MR and a normal LVEF, and is associated with older age, female gender, and a higher RVSP. TR is independently associated with a higher mortality, while mitral valve surgery seems to offer a survival benefit.

Rheumatic tricuspid valve disease: an evidence-based systematic overview.

Abstract: Background and aim of the study Right-sided valve abnormalities are less common than their left-sided counterparts. Furthermore, whilst organic rheumatic involvement of the tricuspid valve is not uncommon, it receives less attention than left-sided heart valves. An evidence-based systematic overview was carried out to assess the epidemiology, diagnosis and management of organic rheumatic tricuspid valve disease (RTVD) over the past half century. Methods A computed search spanning more than four decades was conducted to identify articles on various aspects of RTVD. The bibliographies of all relevant articles were also searched. Results A total of 2,497 rheumatic heart disease patients (mean age 25.5 years; female:male ratio 1.3:1) was included. RTVD was detected in 193 patients (7.7%). Echocardiography was used to detect tricuspid valve involvement in all patients. Associated mitral valve disease was present in 99.3% of the patients with RTVD. A total of 1,092 patients (mean age 45.4 years) was included from six studies on surgical correction of the tricuspid valve. Of these patients, 278 (25.4%) underwent tricuspid valve replacement, while 814 (74.5%) had tricuspid valve repair. The in-hospital mortality was 9.9%, and late mortality 33.2% Conclusion RTVD is not uncommon among patients with rheumatic heart disease, but attracts less attention and might, therefore, be overlooked. Echocardiography is the most common diagnostic tool. Although indications for surgical intervention are not well defined, valve repair may have a better outcome than replacement.

Treatment of prosthetic valve thrombosis: rationale for a prospective randomized clinical trial.

Abstract: based on the results of the recent reports. Results: Although surgical therapy has been the traditional therapeutic approach, studies with low-dose and slow-infusion rates of thrombolytic agents have revealed excellent results in these patients. Surgery should be considered first in patients with left atrial thrombus, active bleeding, and within the first four days after valve replacement. Patients with nonobstructive PVT can initially be managed with an intensification of anticoagulation. Conclusion: The management of PVT remains controversial. Clearly, a prospective randomized clinical trial is required, and this could be achieved by developing an international database for patient enrollment and randomization into available treatment strategies.

Thrombocytopenia after aortic valve replacement: comparison between mechanical and biological valves.

Abstract: Background and aim of the study: Concerns have been recently raised regarding the postoperative decrease in platelet count after aortic valve replacement (AVR). Thus, a retrospective analysis was conducted of patients after AVR with regards to postoperative platelet count. Methods: The data were analyzed from all patients undergoing AVR with (n = 829) or without (n = 1,230) coronary artery bypass grafting (CABG) at a single center between January 1998 and May 2009. The lowest (minimum) platelet count within the first five postoperative days was determined. Results: The patients received either an ATS mechanical prosthesis (ATS; n = 401), a St. Jude Medical mechanical prosthesis (SJM; n = 791), a CarpentierEdwards Perimount bioprosthesis (CEP; n = 618), a Medtronic Freestyle stentless bioprosthesis (FRE; n = 213), or a Sorin Freedom Solo stentless bioprosthesis (SFS; n = 36). By using a multivariate linear regression model, the following independent risk factors for a lower postoperative platelet count were revealed : age, body surface area, active endocarditis, preoperative platelet count, duration of extracorporeal circulation, number of grafts, valve size, and units of transfused fresh-frozen plasma and red blood cells. On entering the type of prosthesis into the multivariate linear regression analysis, together with the other risk factors, patients with CEP and FRE valve prostheses had a lower minimum postoperative platelet count than those with mechanical prostheses (ATS and SJM). Conclusion: Patients undergoing AVR with the Carpentier-Edwards Perimount bioprosthesis or a Medtronic Freestyle stentless bioprosthesis had a lower minimum platelet count within the first five postoperative days, compared to patients receiving ATS and St. Jude Medical mechanical prostheses. No differences were identified between the Sorin Freedom Solo and all other valve prostheses.

Risk factors for in-hospital mortality in infective endocarditis: five years' experience at a tertiary care hospital in Turkey.

Abstract: Background and aim of the study Despite recent improvements in diagnostic and therapeutic interventions, infective endocarditis (IE) is still associated with high in-hospital mortality rates. The study aim was to determine the clinical, laboratory and echocardiographic features of IE, and to evaluate the risk factors for in-hospital mortality. Methods A retrospective cohort study design was employed, with a main outcome measure of in-hospital mortality. A total of 107 patients (79 males, 28 females; mean age 45 +/- 16 years) admitted with the modified Duke criteria for definitive IE were included in the study during a five-year period between January 2004 and December 2008. Results Among the patients, the mitral valve alone was involved in 45% of cases, the aortic valve in 36%, tricuspid valve in 11%, and multiple valves in 8%. Forty-seven patients (44%) had prosthetic valves. Blood cultures were positive in 71 patients (66%). The most common isolated microorganisms were staphylococci, streptococci and Brucella melitensis. The in-hospital mortality rate was 27%. Leading causes of death were multi-organ failure and heart failure. In univariate analysis, factors associated with death were a longer duration of symptoms before hospitalization, previous history of IE, white blood cell count > or = 10,000/mm3, serum creatinine level > or = 2 mg/dl, vegetation size >15 mm, involvement of multiple valves, existence of severe regurgitation, cardiac abscess, and neurologic complications. Multivariate analysis showed that risk factors for mortality were multivalvular involvement (hazard ratio (HR) 4.7; 95% confidence interval (CI) 1.3-17.6; p = 0.021), vegetation size >15 mm (HR 5.5; 95% CI 2.1-14.6; p = 0.001), serum creatinine > or = 2 mg/dl (HR 4.1; 95% CI 1.8-9.4; p = 0.001), and previous history of IE (HR 3.5; 95% CI 1.2-11; p = 0.026). Conclusion Multivalvular involvement, vegetation length >15 mm, serum creatinine level > or = 2 mg/dl on admission, and a previous history of IE, were independent predictors for in-hospital mortality in IE.

Considerations in timing of surgical intervention for infective endocarditis with cerebrovascular complications.

Abstract: Background and aim of the study: The timing of the surgical intervention for active infective endocarditis (IE) is particularly difficult when there is a cerebrovascular complication. The study aim was to investigate the results of surgical treatment for active IE in patients with recent cerebrovascular events, and to evaluate the relationship between the size of cerebral infarction and timing of the surgical intervention. Methods: Between January 1991 and April 2009, the details of 21 patients with cerebrovascular complications before surgery were analyzed retrospectively. Types of complication included cerebral infarction (n = 13), hemorrhagic infarction (n = 4), and cerebral hemorrhage (n = 4). The surgical treatment was single valve surgery (n = 14), multiple valve surgery (n = 3), and modified Bentall surgery (n = 4). The mean interval between onset of the cerebrovascular event and surgical intervention was 27.0 ± 18.8 days. Results: Eight patients underwent surgery within two weeks; among these patient, seven had a small cerebral infarction (≤15 mm diameter) and one patient had a cerebral hemorrhage. Postoperative exacerbation of cerebral complications was not observed among the eight patients treated within two weeks. The interval between onset of the cerebral event and cardiac surgery was significantly shorter in patients with a small infarction (18 days) than with a large infarction (38 days) (p <0.05). None of the patients with a small infarction had postoperative exacerbation of their cerebral complication, even with a significantly shorter interval. However, postoperative hemorrhage into the infarction area was observed in one patient with a large infarction. Conclusion: The study results showed that IE patients with a small non-hemorrhagic cerebral infarction may safely undergo cardiac surgery, even within two weeks of the onset of a cerebrovascular event.

Risk model of valve surgery in Japan using the Japan adult cardiovascular surgery database

Abstract: Background and aim of the study Risk models of cardiac valve surgery using a large database are useful for improving surgical quality. In order to obtain accurate, high-quality assessments of surgical outcome, each geographic area should maintain its own database. The study aim was to collect Japanese data and to prepare a risk stratification of cardiac valve procedures, using the Japan Adult Cardiovascular Surgery Database (JACVSD). Methods A total of 6562 valve procedure records from 97 participating sites throughout Japan was analyzed, using a data entry form with 255 variables that was sent to the JACVSD office from a web-based data collection system. The statistical model was constructed using multiple logistic regression. Model discrimination was tested using the area under the receiver operating characteristic curve (C-index). The model calibration was tested using the Hosmer-Lemeshow (H-L) test. Results Among 6562 operated cases, 15% had diabetes mellitus, 5% were urgent, and 12% involved preoperative renal failure. The observed 30-day and operative mortality rates were 2.9% and 4.0%, respectively. Significant variables with high odds ratios included emergent or salvage status (3.83), reoperation (3.43), and left ventricular dysfunction (3.01). The H-L test and C-index values for 30-day mortality were satisfactory (0.44 and 0.80, respectively). Conclusion The results obtained in Japan were at least as good as those reported elsewhere. The performance of this risk model also matched that of the STS National Adult Cardiac Database and the European Society Database.

Minimally invasive right lateral thoracotomy without aortic cross-clamping: an attractive alternative to repeat sternotomy for reoperative mitral valve surgery.

Abstract: Background and aim of the study: The study aim was to determine the safety and benefits of minimally invasive mitral valve surgery without aortic crossclamping for mitral valve surgery after previous cardiac surgery. Methods: Between January 2006 and August 2008, a total of 90 consecutive patients (38 females, 52 males; mean age 66 ± 9 years) underwent minimally invasive mitral valve surgery after having undergone previous cardiac surgery. Of these patients, 80 (89%) underwent mitral valve replacement and 10 (11%) mitral valve repair utilizing a small (5 cm) right lateral thoracotomy along the 4th or 5th intercostal space under fibrillatory arrest (mean temperature 28 ± 2°C). The predicted mortality, calculated using the Society of Thoracic Surgeons (STS) algorithm, was compared to the observed mortality. Results: The mean ejection fraction was 45 ± 13%, mean NYHA class 3 ± 1, while 66 patients (73%) had previous coronary artery bypass grafting and 37 (41%) had previous valve surgery. Twenty-six patients (29%) underwent non-elective surgery. Cardiopulmonary bypass was instituted through axillary (n = 19), femoral (n = 70) or direct use aortic (n = 1) cannulation. Operative mortality was 2% (2/90), lower than the STS-predicted mortality of 7%. Three patients (3%) developed acute renal failure postoperatively, one patient (1%) required new-onset hemodialysis, and one (1%) developed postoperative stroke. No patients developed postoperative myocardial infarction. The mean postoperative packed red blood cell transfusion requirement at 48 h was 2 ± 3 units. Conclusion: Minimally invasive right thoracotomy without aortic cross-clamping is an excellent alternative to conventional redo-sternotomy for reoperative mitral valve surgery. The present study confirmed that this technique is safe and effective in reducing operative mortality in high-risk patients undergoing reoperative cardiac surgery.

Unicuspid aortic valve in children: a systematic review spanning four decades.

Abstract: BACKGROUND AND AIM OF THE STUDY To date, the natural history of the unicuspid aortic valve (UAV) has been poorly described in the literature. To study the association between UAV with associated cardiac and extracardiac abnormalities, a systematic review was conducted. METHODS A computerized search was conducted of the medical literature published between 1st January 1966 and 1st September 2008, using the databases MEDLINE, EMBASE, Web of Science and Cochrane database. RESULTS Nine articles with 60 pediatric cases (age <15 years) were identified. The mean age at diagnosis was 14 months, the most common presentation of UAV was congestive heart failure due to congenital aortic stenosis, and the most common lesion was isolated aortic stenosis, reported in 19 cases (32%). Associated anomalies included 22 cases (37%) of aortic coarctation, seven (12%) with ventricular septal defect (VSD), three (5%) with patent ductus arteriosus (PDA), and three (5%) with aortic aneurysm. The preoperative diagnosis of UAV was rare, and 33 cases (55%) of pediatric UAV were reported at autopsy or at pathological examination of the surgically excised valves. A total of 26 cases (43%) was treated with either balloon valvoplasty or surgical valvotomy or commissurotomy. CONCLUSION UAV shares many of the features of bicuspid aortic valve, including valvular dysfunction, aortic dilatation, aortic dissection, and dystrophic calcification. The importance of an early diagnosis of UAV lies in its risk of sudden cardiac death and association with other congenital anomalies, such as PDA, VSD, anomalous coronary arteries, and coarctation of the aorta. Further investigations of UAV are warranted in the pediatric age group with regards to familial incidence, associated aortic histopathological changes, the ideal follow up to monitor complications, and surgical intervention.

Aortic root reoperation: a technical challenge.

Abstract: Background and aim of the study It is well known that aortic root re-replacement presents a formidable technical challenge. Thus, the study aim was to describe the authors' experience with this high-risk cohort. Methods Between August 1996 and January 2009, a total of 26 patients (mean age 51 years; range: 16-72 years) underwent aortic root re-replacement surgery at the authors' institution. Previous aortic root operations included mechanical valved conduit (n = 9), tissue valved conduit (n = 5), Ross procedure (n = 4), homograft (n = 4), David procedure (n = 2) and Yacoub procedure (n = 2). The indications for surgery included endocarditis (n = 16), Ross procedure failure (n = 4), valve degeneration (n = 3), anastomotic aneurysm (n = 2), and severe valve insufficiency (n = 1). Results The reoperations performed were classified as follows: aortic homograft (n = 11), mechanical conduit (n = 9), tissue valved conduit (n = 4) and David procedure (n = 2). The mean cardiopulmonary bypass time was 219 min (range: 101-398 min), and the mean cross-clamp time 142 min (range: 89-253 min). The mean ICU stay was 8 days (range: 1-45 days), and the mean hospital stay 20 days (range: 3-64 days). Four rethoracotomies were performed for postoperative bleeding or tamponade (14%). Two patients (8%) died within 30 days of surgery, and three (12%) required pacemaker implantation due to atrioventricular block (grade III). Conclusion Aortic root reoperation, even in the setting of endocarditis, can be carried out with excellent results. The major goals of this concept include a clinical examination and preoperative diagnosis, in addition to computed tomography to identify possible pitfalls during re-sternotomy. Care must also be taken to provide adequate myocardial and organ protection, by utilizing blood cardioplegia and individual selective perfusion techniques.

Validation of the European system for cardiac operative risk evaluation (EuroSCORE) in Chinese heart valve surgery patients.

Abstract: BACKGROUND AND AIM OF THE STUDY The study aim was to assess the performance of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) model in Chinese patients undergoing heart valve surgery. METHODS Between January 2003 and December 2007, the data from a total of 1726 consecutive patients who underwent heart valve surgery at the authors' center were collected and scored according to the additive and logistic EuroSCORE models. The patients were allocated to three risk subgroups, and the entire cohort and each risk subgroup analyzed. Calibration of the EuroSCORE model was assessed by the Hosmer-Lemeshow (H-L) test. Discrimination was tested by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS Completed data from all 1726 patients were analyzed. There were significant differences in the prevalence of risk factors between the study sample and European cardiac surgery populations. The observed mortality was 4.46% overall, compared to 3.51% (additive) and 2.85% (logistic). The additive EuroSCORE model showed good calibration in predicting in-hospital mortality (H-L; p = 0.204), but the logistic EuroSCORE model underpredicted observed mortality (H-L; p = 0.038) in the entire cohort. Both, the additive and logistic EuroSCORE models showed good calibration in predicting in-hospital mortality in the medium- and high-risk subgroups, but overpredicted observed mortality in the low-risk subgroup. The discriminative power of both models for the entire cohort was poor (areas under the ROC curve of 0.644 and 0.647 for the additive and logistic models, respectively). CONCLUSION The additive and logistic EuroSCORE models gave an imprecise prediction for individual operative risk in heart valve surgery patients at the authors' center; thus, use of the EuroSCORE models for risk evaluation at this center may be unsuitable in the future. It will be necessary to re-examine the performance of the EuroSCORE model for predicting operative mortality in heart valve surgery on a multicenter database in China.

Lambl's excrescences: a rare cause of stroke.

Abstract: Cardiogenic cerebral embolism is believed to be responsible over 25% of all ischemic strokes. Since 1856, Lambl's description of small excrescences on the aortic valves has attracted widespread attention and controversy. With the increasing use of transesophageal echocardiography, ever-increasing valvular strands are being detected. The case is presented of a cardioembolic stroke secondary to Lambl's excrescences in a 59-year-old man. In addition, the current concepts regarding the importance of recognizing these valvular strands are discussed, and a brief review of the topic is provided.

EuroSCORE-predicted mortality and surgical judgment for interventional aortic valve replacement.

Abstract: BACKGROUND AND AIM OF THE STUDY Transcatheter aortic valve implantation (TAVI) is used as an alternative to conventional surgery in high-risk patients. The EuroSCORE quantifies the risk, and patients are selected for this procedure if their predicted mortality is high. The study aim was to evaluate the risk discrimination and calibration of the EuroSCORE, as well as the surgical judgment that is used when selecting the aortic valve replacement (AVR) approach. METHODS Between 2003 and 2006, a total of 2757 patients underwent isolated, open AVR. The EuroSCORE was compared to the observed in-hospital mortality. A survey among surgeons assessed the relevance of patient-specific factors towards the approach of TAVI versus open AVR. RESULTS Survivors of AVR had a lower additive EuroSCORE than non-survivors (7.2 +/- 3.34 versus 12.0 +/- 3.34; p < 0.001). The EuroSCORE demonstrated reasonable risk stratification (c-statistic 0.843, p < 0.001). However, none of the 67 non-survivors was correctly predicted (Hosmer-Lemeshow test; p < 0.001), and most patients with a high EuroSCORE survived AVR. The actual mortality was 2.8% as compared to a EuroSCORE-predicted mortality of 12.5 +/- 14.2% (p < 0.001). This poor calibration was worse with higher EuroSCOREs (Cusum test; p < 0.001). Surgeons identified a porcelain aorta as the only factor that warranted TAVI. Most EuroSCORE variables had either no relevance for treatment selection, or prompted open AVR. CONCLUSION Patient selection for TAVI cannot be based on the EuroSCORE, because it lacks discrimination and center-specific calibration. Thus, individual, surgical judgment that weighs institutional expertise for high-risk patients against a possible reduction of mortality by using interventional techniques, is recommended.

Minimally invasive isolated tricuspid valve surgery.

Abstract: BACKGROUND AND AIM OF THE STUDY Outcomes after minimally invasive isolated tricuspid valve (TV) surgery have not been well described. Hence, an assessment was made of the authors' results for minimally invasive, isolated TV surgery. METHODS Between September 2000 and January 2008, at the authors' institution, a total of 35 patients (15 males, 20 females; mean age 59.2 +/- 14.9 years) underwent isolated TV surgery for TV regurgitation, using a right lateral mini-thoracotomy. The preoperative left ventricular ejection fraction was 57 +/- 11%. The TV pathology included annular dilatation (n = 22), recurrent regurgitation after previous repair (n = 4), ruptured chordae (n = 4), endocarditis (n = 2), intracardiac tumor (n = 2), and blunt chest trauma (n = 1). Twenty patients had previously undergone a total of 30 cardiac operations, eight of which involved the TV. RESULTS A TV repair was performed in 27 patients (77%), and involved the implantation of an annuloplasty ring in all cases. A leaflet repair was performed in addition to an annuloplasty in two patients, and eight patients underwent TV replacement. The hospital mortality was 5.7%, with two deaths due to low cardiac output syndrome on days 1 and 9 after surgery. The latter patient underwent reoperation on day 7 for recurrent TV regurgitation and a ventricular septal defect. Early and mid-term echocardiographic follow up revealed no TV regurgitation in 19 patients, but trivial and mild regurgitation each in eight patients. The mean follow up time was 35 +/- 40 months, and was 100% complete. A Kaplan-Meier analysis revealed an estimated five-year survival of 90% (95% CI: 73-97). CONCLUSION Isolated TV surgery can be performed through a minimally invasive approach, with good results. A high repair rate can be achieved, and the procedure has been particularly valuable in redo surgery.