Bioprostheses Research Articles

Outcomes of valve replacement with mechanical prosthesis versus bioprosthesis in dialysis patients: A 16-year multicenter experience

ObjectiveTo evaluate the long-term outcomes of heart valve replacement with mechanical prosthesis (MP) versus bioprosthesis (BP) in patients on dialysis. MethodsA retrospective review was performed at 7 hospitals. Patients on dialysis who underwent valve replacement were included. Survival, reoperation, bleeding, and embolic events were compared across the MP and BP groups. ResultsBetween April 2000 and April 2016, 312 patients on dialysis were enrolled in our study (MP: 94 patients [30.1%], BP: 218 patients [69.9%]). Mean follow-up was 3.4 ± 3.6 years. Five-year and 10-year survival rates were similar in both groups (MP: 57.4 ± 5.5% at 5 years and 46.3 ± 6.4% at 10 years, BP: 50.2 ± 4.1% at 5 years and 38.8 ± 4.5% at 10 years, P = .305). Multivariate Cox hazard analysis demonstrated that diabetic nephropathy (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.31-2.73, P < .001), New York Heart Association functional classification ≥III (HR, 2.16; 95% CI, 1.37-3.35, P = .001), and mitral valve replacement (HR, 2.36; 95% CI, 1.58-3.49, P < .001) were significant risk factors for late death. Valve selection was not a significant risk factor. Freedom from valve-related embolic event at 5 years was significantly lower in the MP group (MP: 88.3 ± 4.3% at 5 years, BP: 97.2 ± 1.6% at 5 years, P = .007). Freedom from valve-related reoperation or hemorrhagic events was similar across both groups. ConclusionsValve selection was not associated with late survival outcomes in patients on dialysis. However, BP may have an advantage in preventing embolic events without increasing the incidence of valve-related reoperation when compared with MP.

Rate, Timing, Correlates, and Outcomes of Hemodynamic Valve Deterioration After Bioprosthetic Surgical Aortic Valve Replacement.

The incidence of structural valve deterioration after bioprosthesis (BP) aortic valve replacement (AVR) established on the basis of reoperation may substantially underestimate the true incidence. The objective is to determine the rate, timing, correlates, and association between hemodynamic valve deterioration (HVD) and outcomes assessed by Doppler echocardiography after surgical BP AVR. A total of 1387 patients (62.2% male, 70.5±7.8 years of age) who underwent BP AVR were included in this retrospective study. Baseline echocardiography was performed at a median time of 4.1 (1.3-6.5) months after AVR. All patients had an echocardiographic follow-up ≥2 years after AVR (926 at least 5 years and 385 at least 10 years). HVD was defined by Doppler assessment as a ≥10 mm Hg increase in mean gradient or worsening of transprosthetic regurgitation ≥1/3 class. HVD was classified according to the timing after AVR: "very early," during the first 2-years; "early," between 2 and 5 years; "midterm," between 5 and 10 years; and "long-term," >10 years. A total of 428 patients (30.9%) developed HVD. Among these patients, 52 (12.0%) were classified as "very early," 129 (30.1%) as "early," 158 (36.9%) as "midterm," and 89 (20.8%) as "long-term" HVD. Factors independently associated with HVD occurring within the first 5 years after AVR were diabetes mellitus ( P=0.01), active smoking ( P=0.01), renal insufficiency ( P=0.01), baseline postoperative mean gradient ≥15 mm Hg ( P=0.04) or transprosthetic regurgitation ≥mild ( P=0.04), and type of BP (stented versus stentless, P=0.003). Factors associated with HVD occurring after the fifth year after AVR were female sex ( P=0.03), warfarin use ( P=0.007), and BP type ( P<0.001). HVD was independently associated with mortality (hazard ratio, 2.18; 95% CI, 1.86-2.57; P<0.001). HVD as identified by Doppler echocardiography occurred in one third of patients and was associated with a 2.2-fold higher adjusted mortality. Diabetes mellitus and renal insufficiency were associated with early HVD, whereas female sex, warfarin use, and stented BPs (versus stentless) were associated with late HVD.

Effect of size and position of self-expanding transcatheter valve on haemodynamics following valve-in-valve procedure in small surgical bioprostheses: an in vitro study.

The valve-in-valve (ViV) procedure has become a valuable alternative for the treatment of failed surgical bioprostheses (BP) in high-risk patients. However, in small BP, the clinical outcomes have been suboptimal due to high post-procedural gradients. We aimed to examine the effect of size and position of the self-expanding transcatheter heart valve (THV) CoreValve on the haemodynamics of ViV within small BP. Sizes 23 and 26 mm of the CoreValve were implanted in sizes 19 and 21 mm of three BP models: Trifecta, Mitroflow and Epic Supra. The THV was tested in three positions -normal (manufacturer recommendation), low (4 mm below normal) and high (4 mm above normal)- using a pulse duplicator. Haemodynamics were assessed by Doppler echocardiography and flowmeter, and GOA with a high-speed camera. Higher implantation was associated with lower residual gradients (normal position: -9%, high: -25% versus low). High position was, however, associated with increased risk of regurgitation in the Mitroflow and embolisation in the Epic Supra. Using a 26 mm THV instead of a 23 mm was associated with larger EOAs in the Trifecta, smaller in the Mitroflow, and increased risk of embolisation in the Epic Supra. Supra-annular positioning of the CoreValve THV is associated with improved post-ViV haemodynamics in small surgical BP. The haemodynamic outcomes are highly dependent on the model and size of surgical BP.

Прогнозирование риска кальцификации биопротезов клапанов сердца на основании комплексной оценки клинических факторов реципиентов и их приверженности к терапии

The development of the prediction methods of calcification risk of heart valve bioprostheses (BP) based on comprehensive assessment of the impact of clinical factors of the recipients and their adherence to medication. We performed a retrospective study of clinical status and adherence to drug therapy of 170 recipients of heart valve BP with (n=63) and without (n=109) calcification. We used the method of comprehensive assessment of the analyzed parameters with estimation of prognostic coefficients for each of them, followed by calculation of integral indicators and construction on their basis of prognostic models for the various intervals of BP functioning. The most important risk factors of calcium-associated BP dysfunctions at any duration of observation were heart failure decompensation, as well as the discontinuation of ACE inhibitors and β-blockers. At duration of BP functioning up to four years negative effect on prognosis produced the presence of concomitant multifocal atherosclerosis, during additional 4 (from 4 to 8) years - diabetes mellitus, and afterwards (over 8 years) - coronary artery disease. Lowering of probability of BP calcium degeneration was related to regular use of aldosterone antagonists during first 4 years after BP implantation and regular subsequent use of statins. Based on the comprehensive assessment of clinical status of patients and their compliance to medication it is possible to make adequate prediction models for assessment of the risk of structural dysfunctions due to BP calcification at various time intervals of remote postoperative period.

Incidence, predictors, and impact of bioprosthesis valve hemodynamic deterioration following aortic valve replacement

Bioprosthesis (BP) structural deterioration after aortic valve replacement (AVR) is generally defined by re-operation for BP failure. This approach underestimates the incidence of structural valve deterioration. We intended to determine the incidence, predictors and impact of valve hemodynamic deterioration (VHD) assessed by echocardiography (TTE). A total of 1387 patients (62.2% male; 70.5 ± 7.8 years old) were retrospectively included. A baseline TTE was performed at a median time of 4.1 (1.3–6.5) months post-AVR. TTE follow-up was performed at least 2-years post-AVR in all patients, at least 5-years in 926 patients and at least 10-years in 385 patients. VHD was defined as: > 10 mmHg increase in mean gradient (MG) and/or worsening of regurgitation > 1/3 grade from baseline to last TTE follow-up. Overall, VHD was identified in 428 patients (30.9%). The VHD occurred within the first 5 years in 181 (42.3%) patients and after 5 years in 247(57.7%) patients. VHD was a predictor of death (HR: 2.18, 95% CI: 1.86 to 2.57, P < 0.001). Diabetes (HR: 1.33, 95% CI: 1.06 to 1.66, P = 0.01), post-surgery MG > 15 mmHg (HR: 1.30, 95% CI: 1.05 to 1.62, P = 0.02), severe PPM (HR: 1.85, 95% CI: 1.12 to 2.87, P = 0.02) and type of BP ( P < 0.001) were associated with VHD. Predictors of early VHD identified (within the first 5-years post-AVR) were: diabetes ( P = 0.01), active smoker status ( P = 0.01), renal insufficiency ( P = 0.01), post-surgery MG > 15 mmHg ( P = 0.04), post-surgery > mild transprosthetic regurgitation ( P = 0.04) and type of BP ( P = 0.003). Predictors of late VHD (i.e. after the 5 years) were: female sex ( P = 0.03), coumadin ( P = 0.007) and type of BP ( P < 0.001). VHD as documented by TTE is frequent (30%) following AVR and associated with 2.2-fold increase in mortality. The main factors associated with VHD were female sex, diabetes, smoking, coumadin, presence of severe prosthesis-patient mismatch, high residual gradient, and/or regurgitation early after AVR.

INCIDENCE, PREDICTORS, AND IMPACT OF BIOPROSTHETIC VALVE HEMODYNAMIC DETERIORATION FOLLOWING AORTIC VALVE REPLACEMENT

The occurrence of structural biological valve deterioration after aortic valve replacement (AVR) is generally defined by the need for reoperation due to valve failure. However, this approach significantly underestimates the incidence of structural valve deterioration. We intended to determine the incidence, predictors and impact of bioprosthesis (BP) valve hemodynamic deterioration (VHD) assessed by Doppler-echocardiography according to the postoperative time period. A total of 1387 patients (62.2% male; 70.5±7.8 years old) were included in this retrospective study. A baseline echocardiography was performed at a median time of 4.1 (1.3–6.5) months post-AVR. Doppler-echocardiography follow-up was performed at least 2-years post-AVR in all patients, at least 5-years in 926 patients and at least 10-years in 385 patients. VHD was defined as: ≥10mmHg increase in mean transprosthetic gradient (MG) and/or worsening of transprosthetic regurgitation ≥1/3 grade from baseline to last echocardiography follow-up. Overall, VHD was identified in 428 patients (30.9%). The VHD occurred within the first 5 years in 181 (42.3%) patients and after 5 years in 247 (57.7%) patients. VHD (expressed as time-dependent variable) was a significant predictor of death (HR: 2.18, 95% CI: 1.86 to 2.57, p < 0.001) (Figure). Age at the date of first detection of VHD was not a predictor of VHD. Diabetes (HR: 1.33, 95% CI: 1.06 to 1.66, p=0.01), post-surgery MG ≥15mmHg (HR: 1.30, 95% CI: 1.05 to 1.62, p=0.02), severe prosthesis–patient mismatch (HR: 1.85, 95% CI: 1.12 to 2.87, p=0.02) and type of BP (protector effect of stentless vs. BP, p < 0.001) were independently associated with VHD during follow-up. Predictors of early VHD identified (within the first 5-years post-AVR) were: diabetes (p=0.01), active smoker status (p=0.01), renal insufficiency (p=0.01), post-surgery MG ≥15mmHg (p=0.04), post-surgery ≥mild transprosthetic regurgitation (p=0.04) and type of BP (protector effect of stentless vs. stented BP, p=0.003). Predictors of late VHD (i.e. after the 5 years) were: female sex (p=0.03), use of coumadin (p=0.007) and type of BP (stented vs. stenless, p < 0.001). The results of this large series reveals that VHD as documented by Doppler-echocardiography is frequent (30%) following AVR and is associated with 2.2 fold increase in mortality. The main factors associated with increased risk of VHD were female sex, diabetes, smoking, use of Coumadin, presence of severe prosthesis-patient mismatch, high residual gradient, and/or transprosthetic regurgitation early after AVR

P2996Antithrombotic strategies in patients with aortic bio prostheses, what is the optimal treatment

P2996Antithrombotic strategies in patients with aortic bio prostheses, what is the optimal treatment

Bioprosthetic mesh of bacterial cellulose for treatment of abdominal muscle aponeurotic defect in rat model.

The use of meshes for treatment of hernias continues to draw attention of surgeons and the industry in the search of an ideal prosthesis. The purpose of this work is to use meshes manufactured from bacterial cellulose, evaluate their organic tissue interaction and compare with an expanded polytetrafluorethylene (ePTFE's) prosthesis used to repair acute defect of muscle aponeurotic induced in rats. Forty-five male Wistar rats were classified using the following criteria: (1) surgical repair of acute muscle aponeurotic defect with perforated bacterial cellulose film (PBC; n=18); (2) compact bacterial cellulose film (CBC; n=12) and (3) ePTFE; (n=15). After postoperative period, rectangles (2×3cm) including prosthesis, muscles and peritoneum were collected for biomechanical, histological and stereological analysis. In all cases, the maximum acceptable error probability for rejecting the null hypothesis was 5%. Between PBC and CBC samples, the variables of strain (P=0.011) and elasticity (P=0.035) were statistically different. The same was found between CBC and ePTFE (elasticity, P=0.000; strain, P=0.009). PBC differed from CBC for giant cells (P=0.001) and new blood vessels (P=0.000). In conclusion, there was biological integration and biomechanical elasticity of PBC; therefore, we think this option should be considered as a new alternative biomaterial for use as a bio prosthesis.

Optimized Outcomes Using a Standardized Approach for the Treatment of Patients with Carcinoid Heart Disease

Background: Carcinoid heart disease (CHD) is common in patients with carcinoid syndrome (CS). Surgical treatment improves the poor prognosis of CHD, although the reported peri-operative mortality is high (∼17%). We attempted to improve outcomes by implementation of a protocol for the management of patients with CHD at a UK Neuroendocrine Centre of Excellence and report our experience. Methods: All patients treated for CHD between 2008 and 2015 were included. Peri-operative treatment included surgical features such as invasive pulmonary valve (PV) inspection and preservation of the tricuspid subvalvular apparatus. Results: A total of 11 patients were treated; the median age was 63 years (IQR: 56-70). Ten patients underwent both pulmonary valve replacement (PVR) and tricuspid valve replacement (TVR); 1 patient underwent isolated TVR. One patient had additional aortic valve replacement (AVR), another one coronary artery bypass grafting. Bioprostheses (BP) were used in all patients, stented for TVR and AVR, stentless for PVR. Invasive PV inspection caused unplanned PVR in 3 cases (27.3%). All patients were discharged home. One patient (9.1%), who had had previous TVR by another surgeon, had right heart failure (RHF) during follow-up. One death occurred due to progression of CS (day 346). The carcinoids' primary was resected in 5 patients (45.5%) 10 months (4.5-19.5) after cardiac surgery. Conclusion: Excellent results were achieved in patients with CHD. PV stenosis can be underestimated by echocardiography; therefore, intraoperative inspection is recommended. Right ventricular geometry should be respected to prevent RHF. BP should be used, as these patients are likely to undergo future non-cardiac surgeries.

Suture less Aortic Bio Prostheses a Reliable Tool for Minimally Invasive AVR in High Risk Patients

Background: Surgical aortic valve replacement (SAVR) with extracorporeal circulation (ECC) is currently the treatment of choice for patients with severe aortic stenosis. High-risk patients may benefit from reduced ECC time, crossclamp time (CCT) and a minimally-invasive approach. Minimally invasive aortic valve replacement (MIAVR) was first described by Cosgrove and Sabik [1] and have increasingly gained acceptance in the surgical realm, with the aim of achieving equivalent or superior out- comes compared with conventional AVR (CAVR). A new generation of “suture less” bioprostheses has recently been introduced in clinical practice. Sutureless fixation of the valve combines the advantages of open SAVR, i.e. complete removal of pathological tissue, with reduced ECC and CCT, and facilitates small incision surgery. Methods: Between November 2012 and October 2015 we operated on 70 consecutive patients with aortic valve stenosis, using suture less valves. Patients (25 males, mean age 77.9 ± 6.3 years, range 63-91) had a mean logistic Euro SCORE of 11.9 ± 10.8. Fifty-five patients received a Medtronic 3f Enable and 15 a Sorin Perceval S valve; 48 patients were operated through minithoracotomy, and 22 through ministernotomy. Results: Valve implantation resulted in a significant improvement in patients’ symptoms; mean preoperative and postoperative transvalvular gradient was 60 mmHg (120-40) and 8.5 mmHg (17-7), respectively. CCT time was66 ± 14.4 min, mean ECC time 71 ± 19.8 min, mean implant time 9 min. 30-day mortality was 1,5%. Early incidence of grade I paravalvular leakages and pacemaker implantation was, respectively, 2.0 % and 4%. 1 late PVL grade 2 was registered. Conclusion: MIAVR with suture less aortic bioprosthesisin high risk patients represents a safe and effective treatment for aortic valve stenosis, providing excellent hemodynamic and clinical results. A larger study is needed to confirm these initial promising results.

EVALUATION OF THE CALCIUM-PHOSPHOR HOMEOSTASIS AND PROINFLAMMATORY STATUS OF RECIPIENTS WITH CALCIUM DEGENERATION OF CARDIAC VALVES PROSTHESES

Aim. To study calcium-phosphor homeostasis and proinflammatory status of the cardiac valves bioprostheses (BP) recipients related to their interference with calcium degeneration of biomaterials. Material and methods. A retrospective assessment was performed of the calcium-phosphor metabolism and markers of non-specific inflammatory response in recipients of BP in mitral position: with histologically confirmed calcification — group I (n=22) and with normal morphology and prosthesis function — group II (n=48). Results. In patients with BP degeneration, comparing to the recipients of biological prostheses with normal function at the background of moderate hypovitaminosis D (34,0 [21,0; 49,4] versus 40 [27,2; 54,0] pmol/L, р>0,05), osteoprotegerine deficiency (82,5 [44,2; 115,4] versus 113,5 [65,7; 191,3] pg/ml, р>0,05) and osteopontine (4,5 [3,3; 7,7] versus 5,2 [4,1; 7,2] ng/ml, р>0,05) there was statistically significant decrease of the bone isoenzyme of alkaline phosphatase (17,1 [12,2; 21,4] versus 22,3 [15,5; 30,5] E/L, р=0,01), and significant decrease of IL-8 (9,74 [9,19; 10,09] pg/ml versus 13,17 [9,72; 23,1] pg/ml, р=0,045) with general increase of proinflammatory serum markers activity. Conclusion. Into the group of probable predictors determining the tempos of BP calcification, the following could be included: specifics of recipient metabolic status defined by the activity of bone resorption processes, and local and systemic inflammation.

Abstract 16300: Efficacy and Safety of Anticoagulation Following Bioprosthetic Aortic Valve Replacement: A Meta-analysis

Background: The American College of Cardiology (ACC) guidelines recommend three months of anticoagulation (AC) after replacement of the aortic valve with a bioprosthesis (BP). However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether AC in the setting of a new BP was associated with improved outcomes and/or greater risk of bleeding. Methods: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed AC with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks (TIA) and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa scale and random effects was used to pool the data from the available studies. I2 testing was done to assess the heterogeneity of the included studies. Results: After screening through 170 papers, a total of 13 studies (cases=6431, controls=18210) were included in the final analyses. Use of warfarin use was associated with a significantly increased risk of overall bleeding (OR= 1.96, 95% CI 1.25-3.08, P&lt;0.0001) or bleeding risk at 3 months (OR= 1.92, 95% CI 1.10-3.34), P&lt;0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke or TIA) at 3 months, no significant difference was seen with warfarin (OR= 1.13, 95% CI 0.82-1.56, P=0.67). Moreover AC was also not shown to improve outcomes at time interval &gt;3 months (OR= 1.12, 95% CI 0.80-1.58, P=0.79). Conclusion: Contrary to the current guidelines, a meta-analysis of prior studies suggests that AC in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable impact on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

0026 : Transfemoral tricuspid valve-in-valve and valve-in-ring implantation using the Edwards SAPIEN XT valve: one-year follow-up

Redo tricuspid surgery may be at high risk or even contraindicated in patients with comorbidities. Transcatheter valve implantation (TVI) has been recently reported in this setting. The aim of this study was to evaluate the early and 1-year outcomes of TVI with Edwards SAPIEN XT valves in failed tricuspid bioprostheses (BP) and ring annuloplasty (RA). TVI was performed in 6 patients for failed tricuspid surgical valves (3 BP, 3 RA). Median patient age was 58 years, all were in New York Heart Association (NYHA) class≥III and 5 out of 6 had previously undergone at least 2 cardiac interventions. The procedure was successful in the 3 patients with BP and 2 with RA; one patient had a moderate paravalvular regurgitation at the level of the open portion of a rigid incomplete ring. Otherwise, regurgitation was absent in 3 patients, trace in 1 and mild in 1. The transvalvular gradient decreased from 8 mmHg at baseline to 4 mmHg at day 7. At 1-year follow-up, survival was 100%. Tricuspid gradients remained stable in all but 1 patient, as well as regurgitation grades. Only 1 patient was in NYHA class III, 2 were in class II and 3 in class I. Transfemoral TVI with SAPIEN XT valves after failed tricuspid surgery is feasible in selected high-risk patients, with good early and 1-year hemodynamic and clinical results. However, RA may raise issues due to their oval shape and open configuration.

Lp‐PLA2 is associated with structural valve degeneration of bioprostheses

In this study, we sought to determine the metabolic markers associated with structural valve degeneration (SVD). Structural valve degeneration (SVD) is the major cause of bioprosthetic valve failure leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the SVD of BPs. We included 197 patients who underwent aortic valve replacement with a bioprosthetic valve and had echocardiographic follow-up to evaluate valve function. Moreover, explanted BPs (n=39) were analysed by immunohistochemistry for the expression of Lp-PLA2. After a mean follow-up of 7·9±0·2years, forty-one patients (21%) were identified as developing SVD. Patients with SVD had significantly higher plasma level of Lp-PLA2 mass (151·8±9·2ng/mL vs. 133·2±3·4ng/mL, P=0·03) and activity (27·6±0·9nmol/min/mL vs. 25·0±0·4nmol/min/mL, P=0·005). Multivariate analysis revealed that Lp-PLA2 activity (OR: 1·09, 95% CI: 1·01-1·18; P=0·03) was the strongest independent predictor of SVD. Immunohistochemistry studies of explanted BP showed that 77% of explanted BPs had the expression of Lp-PLA2, which correlated with the density of macrophages (CD68), and ox-LDL levels in bioprosthetic tissues. Increased blood plasma activity of Lp-PLA2 is associated with higher prevalence of SVD. These findings open new avenues for the identification of patients at risk for SVD and for the development of pharmacotherapy aiming at the prevention of SVD.

Blood Plasma LP-PLA2 Activity Is Associated With an Increased Risk of Bioprosthetic Valve Degeneration

In this study, we sought to determine the metabolic markers associated with SVD. Background: Structural valve degeneration (SVD) is the major cause of bioprosthetic valve failure leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the SVD of BPs.

The imbalance between proliferation and apoptosis contributes to degeneration of aortic valves and bioprostheses

The pathomechanisms underlying aortic valve degeneration are incompletely understood. Therefore, the aim of our work was to assess the quantitative changes of proliferation and apoptosis accompanied by cellular phenotype alternations and matrix secretionin aortic sclerotic and stenotic valves and degenerative bioprostheses, as well as to detect the expression pattern of the rapamycin receptor FKBP12 across these three valve types. Mild-to-moderate sclerotic and stenotic valves and degenerative bioprostheses from 30 patients (n = 10 per group) were collected at autopsy or by surgery. Ki67+, FKBP12+, alpha-actin+, HSP47+ and TUNEL+ apoptotic cells were analyzed by immunohistochemistry. The main finding was the reduced proliferation and increased apoptosis in stenotic valves (ST) compared to the sclerotic ones (SC) (proliferation: ST: 20.8 ± 2.0% vs. SC: 30.1 ±2.2%, apoptosis: ST: 40.7 ± 5.0% vs. SC: 28.0 ± 5.1%, p < 0.05, respectively). Analogical alternations were found in degenerative bioprostheses (BP) (proliferation: 4.8 ± 2.3%; apoptosis: 13.1 ± 6.8%). Corresponding changes were observed in the valve cellularity (ST: 893 ± 168, SC: 1034 ± 284, BP: 385 ± 179 cells/mm2, p < 0.05, respectively). The FKBP12 signaling was reduced in diseased valves and bioprostheses (ST: 28.1 ± 3.6%, SC: 42.2 ± 3.8%, BP: 5.8 ± 1.9%, p < 0.05, respectively). Further, the augmented alpha-actin expressionwas observed as the degenerative process progressed (ST: 30.3 ± 5.0%, SC: 22.6 ± 2.7%, BP:8.7 ± 4.0%, p < 0.05, respectively), followed by the upregulation of HSP47 (ST: 22.6 ± 2.8%,SC: 15.4 ± 2.1%, BP: 3.4 ± 1.0%, p < 0.05, respectively) and consecutive matrix accumulation. The imbalance between proliferation and apoptosis with cellular phenotypical shift and subsequent matrix secretion may contribute to aortic valve stenosis and bioprosthesis degeneration. The identification of FKBP12 expression may implicate potential therapeutic strategies.

306: Pregnancy Following Aortic Valve Replacement - Cardiac, Maternal and Fetal Outcomes

The choice of aortic valve substitute in young women should take the desire for pregnancy into account. Currently however, little is known about pregnancy-related outcomes following aortic valve replacement (AVR). The aim of this study was to assess cardiac, maternal and fetal-related outcomes in female patients with AVR during and after pregnancy. A retrospective study of all AVRs performed in women under the age of 40 years at our institution was undertaken. These patients were prospectively followed at our dedicated valve clinic. Patients with Turner syndrome or having undergone a hysterectomy and/or tubal ligation were excluded. Cardiovascular, maternal and fetal outcomes were gathered from medical records and telephone interviews. From 1976 to 2011, 77 women underwent 86 isolated AVRs: 65 mechanical prostheses (MPs) and 21 bioprostheses (BPs). The follow-up was 81% complete. Ten patients (13%) had 19 pregnancies at a mean age of 28±6 years. Of those, 5 ended in miscarriages (26%; n=4 BPs and n=1 MPs). Twelve (63%) pregnancies occurred in patients with BPs. The following adverse events were reported: two hospitalizations for syncope (25%), functional prosthetic valve deterioration during pregnancy necessitating reintervention 6 months post-partum (12%) and 4 miscarriages (33%). Nine of the 65 women (14%) with MPs had a hysterectomy or endometrial ablation for excessive uterine bleeding, precluding childbearing potential. In total, 7 pregnancies were reported in women with MPs. Two of them were terminated (n=1, medical advice and n=1 embolic myocardial infarction). The following peri-partum complications occurred: two embolic myocardial infarctions (33%), a postpartum bleeding (16%) and an urgent caesarean for placental abruption (16%). No fetal adverse events were observed. Findings from this study suggest that pregnancy in women with prosthetic AVR is associated with an increased risk of cardiac adverse outcomes.

Noninferiority of Closely Monitored Mechanical Valves to Bioprostheses Overshadowed by Early Mortality Benefit in Younger Patients

Confidence in bioprosthetic durability without anticoagulation has led to a contemporary trend of offering tissue valves to younger patients. Close monitoring of mechanical valve patients at lower international normalized ratio (INR) thresholds may reduce anticoagulation morbidity. We prospectively compared results of bioprostheses (BP) and a bileaflet mechanical prosthesis (MP) monitored at low INR thresholds. Patients received an isolated Carpentier-Edwards bovine or Medtronic porcine BP or the On-X MP. INR targets were 2.0 for MP recipients undergoing aortic valve replacement and 2.5 for mitral valve replacement, using point-of-care home monitoring. Operations consecutively performed between September 2003 and August 2007 were propensity matched using logistic regression by preoperative covariates of age, sex, valve position, New York Heart Association class, ejection fraction, atrial fibrillation, and creatinine. Of 469 operations consecutively performed, 172 patients were matched for analysis. Mean age was 56.2±9.6 years (range, 24 to 72 years). Median follow-up was 4.0 years (total follow-up, 667.0 patient-years). No late bleeding events occurred. The thromboembolic complication rates per patient-year were 0.77% for MP and 0.78% for BP (p=0.67). There were 9 BP deaths vs 4 MP (2.35% vs 1.41%/patient-year; BP hazard ratio, 0.60; 95% confidence interval, 0.13 to 2.15). Postoperative linearized mortality benefit of MP was observed as early as 5 years, reaching significance at 7.5 years (p=0.04). Patients aged 65 years or younger with MP and closely monitored anticoagulation display noninferiority to BP from bleeding and thromboembolic complications. MP valves begin to confer mortality benefit over BP as early as 7.5 years postoperatively. Because this predates the timeline of typical structural valve degeneration, equipoise is suggested when choosing a BP in a young patient with future expectations of valve-in-valve intervention.

Lipid‐mediated inflammation and degeneration of bioprosthetic heart valves

The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs. Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM). The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets. These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.

Perforation of the left atrium by a chest tube in a patient with cardiomegaly: Management of a rare, but life-threatening complication

Perforation of the heart is a rare, but life-threatening complication of chest tube thoracostomy. We report the very unusual case where right-sided insertion of a Matthys catheter (6 F) due to pleural effusion resulted in a left atrium perforation. Heart injury was immediately considered as a continuous flow of bright red blood emerging through the chest drain. Diagnosis was confirmed by computertomography also revealing a massive cardiomegaly due to pre-existing mitral valve regurgitation. In two consecutive thoracotomies, first the Mathys drain was removed and the heart defect closed and then the mitral valve was replaced by a bio prosthesis. The extent of the cardiomegaly and the position of the left atrium were not detected pre-operatively by chest X-ray or ultrasonic device. Despite a nosocomial pneumonia, the patient fully recovered. This case shows that extreme caution is necessary when inserting chest tubes in patients where thorax imaging by X-ray or ultrasonic device does not provide a clear anatomical site. In order to minimise complications, a blunt puncturing procedure or Seldinger technique should be used and assisted by a Doppler ultrasonic device. Also early imaging by CT and Doppler ultrasonic technique should be attempted. This may reduce incidence of severe complications as in this case.