Carcinoid Heart Valve Disease: Transcatheter Pulmonary Valve-In-Valve Implantation in Failing Biological Xenografts.

BACKGROUND AND AIM OF THE STUDY: Carcinoid heart valve disease (CHVD) occurs as the cardiac manifestation of carcinoid syndrome (also known as Hedinger's syndrome), which develops secondary to neuroendocrine tumor activity. CHVD almost exclusively affects right-sided heart valves, since circulating serotonin is metabolized by pulmonary endothelial cells, thus sparing left-sided valves. Replacement of the tricuspid and pulmonary valve is a well-established and feasible therapeutic option for these patients. Whether biological valve substitutes are subject to a continuous degenerative process is not entirely clear at present due to the rarity of the disease and inconclusive findings in the current literature. METHODS: Herein are presented the details of two patients suffering from advanced CHVD who had undergone previous combined tricuspid valve replacement (TVR) and pulmonary valve replacement (PVR) using biological xenografts, and had subsequently been readmitted with failure of the pulmonary valve substitute. RESULTS: Due to the increased risk for repeat surgical valve replacement, the patients were treated by percutaneous stent implantation into the pulmonary artery, followed by the implantation of a balloon- expandable transcatheter heart valve (THV). The procedures were feasible and safe through the intact TVR. CONCLUSION: This strategy resulted in a favorable acute outcome in both patients, with adequate valve function and no PVL as documented by TTE, although the transvalvular gradients were elevated in both cases. The patients had an uneventful postoperative course and were discharged home in timely fashion. Whether the residual elevated transvalvular gradients following the valve-in-valve procedures, or an early degeneration of the implanted bioprostheses, will have a negative impact on the patients' further course will become clear in the future.

Gender effects on health care costs in cardiovascular medicine-a black box?

INTRODUCTION: Gender differences were documented for several diseases. This might influence treatment costs for the insurance companies as well as reimbursement of the health care facilities. This manuscript deals with the possible economic implications of gender-related differences in cardiovascular medicine. METHODS: A systematical review of the literature reporting the impact of gender on health care costs with special focus on cardiovascular medicine. RESULTS: Women cause higher health care costs during their lifetime, but large part of the difference compared with men is caused by pregnancy and birth, not by diseases. However, after subtracting the costs for pregnancy and birth, there still remains a difference with higher costs for women, although the origin of this disparity is not definitely clear up to date. In cardiovascular medicine, especially the risk factor metabolic syndrome including diabetes had a higher prevalence in women and was shown to have a greater impact on cardiovascular disease compared with men. This concerned both costs and outcome. But in contrast to this, women experienced poorer preventive treatment of their metabolic syndrome, especially with regards to lipid levels. This influenced the costs of hospital treatment as well as the prognosis, for example, following coronary bypass grafting. COMMENTS: The higher influence of several risk factors on cardiovascular disease in women should lead to improved preventive strategies in female patients. Further research is necessary to give more evidence for gender-related differences within the impact of several risk factors on treatment costs. This could then also influence reimbursement strategies taking these gender disparities into account.

Post-mortem computed tomography (PMCT) and PMCT-angiography after cardiac surgery. Possibilities and limits.

BACKGROUND: PMCT is a well-known tool of the forensic pathologist. It is employed worldwide. PMCT-angiography offers additional insights. This paper intends to demonstrate possibilities of both methods after cardiac surgery. MATERIAL AND METHODS: Exemplary cases with typical findings were selected from our own collection. PMCT was performed as whole body CT (1mm slice, pitch 1.5, 130kV, 180-130mAs, 16 slice MDCT). In PMCT-angiography, contrast material (1.2 litres) is injected into the arteries (arterial phase, also documented with a whole body CT). Thereafter, contrast material is injected into the veins (venous phase, also documented with a whole body CT). The final CT is obtained after circulation has been provoked with a special pump (circulatory phase). RESULTS: PMCT visualised pseudoarthrosis and fractures of the sternum, implanted valves (TAVI) encroaching the ostia of the coronary arteries, bleeding and pericardial tamponade. PMCT-angiography showed the sources of the bleeding, vascular stenosis and obstruction and modified vascular supply. With respect to the postoperative care, malposition of tubes, drainages and complication of punctures could be seen. CONCLUSION: PMCT and PMCT-angiography can visualise complications and the cause of death. Such knowledge may allow for prevention of suffering and death. It may also aid in improving valve design and implantation procedures.

Post-mortem computed tomography (PMCT) and PMCT-angiography after transvascular cardiac interventions.

BACKGROUND AND PURPOSE: During the last years, Post Mortem Computed Tomography (PMCT) has become an integral part of the autopsy. PMCT-angiography may augment PMCT. Both exams have proven their value in visualizing complications after heart surgery. Therefore, they should also show complications after transvascular interventions. This assumption initiated our project: to evaluate the possibilities of PMCT and PMCT-angiography after transvascular cardiac interventions. MATERIAL AND METHODS: In our archives of characteristic and typical PMCT findings, we searched for observations on preceding transvascular cardiac interventions. Additionally, we reviewed our PMCT-angiographies (N = 140). RESULTS: After transvascular cardiac interventions, PMCT and PMCT-angiography visualized bleeding, its amount and its origin, cardiac tamponade, free and covered perforations, transvascular implanted valves and their position, catheters and pacemakers with fractures, abnormal loops and bending. Bubbles in the coronary vessels (indicating air embolism) become visible. CONCLUSION: After transvascular cardiac interventions, PMCT and PMCT-angiography show complications and causes of death. They prove a correct interventional approach and also guide autopsy. In isolated cases, they may even replace autopsy.

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution.

BACKGROUND: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)-based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. METHODS: Since 1999, 12 HTx recipients (10 men; 58 +/- 3.6 yr of age; 8.7 +/- 4.2 yr after HTx) with CNI-based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2-4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. RESULTS: After a mean follow-up of 20 +/- 16 months, CreaCl improved significantly: pre-conversion vs. post-conversion: 32.8 +/- 12.2 mg/dL vs. 42.8 +/- 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. CONCLUSIONS: Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.

Early Outcome of Bilateral Versus Single Internal Mammary Artery Grafting in the Elderly.

BACKGROUND: Bilateral internal mammary artery (BIMA) grafting is increasingly used in elderly patients without evidence of its risks or benefits compared with single internal mammary artery (SIMA) grafting. METHODS: In all, 2,899 patients aged 70 years or older (855 [29.5%] underwent BIMA grafting) operated on from January 2015 to December 2016 and included in the prospective multicenter Outcome After Coronary Artery Bypass Grafting (E-CABG) study were considered in this analysis. RESULTS: One-to-one propensity matching resulted in 804 pairs with similar preoperative risk profile. Propensity score matched analysis showed that BIMA grafting was associated with a nonstatistically significant increased risk of inhospital death (2.7% versus 1.6%, p = 0.117). The BIMA grafting cohort had a significantly increased risk of any sternal wound infection (7.7% versus 5.1%, p = 0.031) as well as higher risk of deep sternal wound infection/mediastinitis (4.0% versus 2.2%, p = 0.048). The BIMA grafting cohort required more frequently extracorporeal membrane oxygenation (1.0% versus 0.1%, p = 0.02), and the intensive care unit stay (mean 3.6 versus 2.6 days, p < 0.001) and inhospital stay (mean 11.3 versus 10.0 days, p < 0.001) were significantly longer compared with the SIMA grafting cohort. Test for interaction showed that urgent operation in patients undergoing BIMA grafting was associated with higher risk of inhospital death (5.6% versus 1.3%, p = 0.009). CONCLUSIONS: Bilateral internal mammary artery grafting in elderly patients seems to be associated with a worse early outcome compared with SIMA grafting, particularly in patients undergoing urgent operation. Until more conclusive results are gathered, BIMA grafting should be reserved only for elderly patients with stable coronary artery disease, without significant baseline comorbidities and with long life expectancy.

The impact of minor blood transfusion on the outcome after coronary artery bypass grafting.

PURPOSE: To investigate the impact of minor perioperative bleeding requiring transfusion of 1-2 red blood cell (RBC) units on the outcome after coronary artery bypass grafting (CABG). METHODS: Sixteen cardiac surgical centers contributed to the prospective European CABG registry (E-CABG). 1014 patients receiving 1-2 RBC units during or after isolated CABG were compared to 2264 patients not receiving RBCs. RESULTS: In 827 propensity score matched pairs, transfusion of 1-2 RBC units did not affect the risk of in-hospital/30-day death (p=0.523) or stroke (p=0.804). However, RBC transfusion was associated with an increased risk of acute kidney injury (p=0.008), sternal wound infection (p=0.001), postoperative use of antibiotics (p=0.001), prolonged use of inotropes (p<0.0001), use of intra-aortic balloon pump (p=0.012), length of intensive care unit stay (p<0.0001) and length of in-hospital stay (p<0.0001). Matched paired analysis excluding pre- and postoperative critical hemodynamic conditions showed that RBC transfusion was associated with an increased risk of major complications except in-hospital/30-day death. CONCLUSION: Minor perioperative bleeding and subsequent transfusion of 1-2 RBC units did not affect the risk of early death, but increased the risk of other major adverse events. Minimizing perioperative bleeding and prevention of even low-volume RBC transfusion may improve the outcome after CABG.

Venoarterial extracorporeal membrane oxygenation after coronary artery bypass grafting: Results of a multicenter study.

BACKGROUND: The evidence of the benefits of using venoarterial extracorporeal membrane oxygenation (VA-ECMO) after coronary artery bypass grafting (CABG) is scarce. METHODS: We analyzed the outcomes of patients who received VA-ECMO therapy due to cardiac or respiratory failure after isolated CABG in 12 centers between 2005 and 2016. Patients treated preoperatively with ECMO were excluded from this study. RESULTS: VA-ECMO was employed in 148 patients after CABG for median of 5.0days (mean, 6.4, SD 5.6days). In-hospital mortality was 64.2%. Pooled in-hospital mortality was 65.9% without significant heterogeneity between the centers (I2 8.6%). The proportion of VA-ECMO in each center did not affect in-hospital mortality (p=0.861). No patients underwent heart transplantation and six patients received a left ventricular assist device. Logistic regression showed that creatinine clearance (p=0.004, OR 0.98, 95% CI 0.97-0.99), pulmonary disease (p=0.018, OR 4.42, 95% CI 1.29-15.15) and pre-VA-ECMO blood lactate (p=0.015, OR 1.10, 95% CI 1.02-1.18) were independent baseline predictors of in-hospital mortality. One-, 2-, and 3-year survival was 31.0%, 27.9%, and 26.1%, respectively. CONCLUSIONS: One third of patients with need for VA-ECMO after CABG survive to discharge. In view of the burden of resources associated with VA-ECMO treatment and the limited number of patients surviving to discharge, further studies are needed to identify patients who may benefit the most from this treatment.

Post-mortem computed tomography and post-mortem computed tomography angiography following transcatheter aortic valve implantation†.

OBJECTIVES: At present, transcatheter aortic valve implantation (TAVI) is widely used. As with any interventional treatment, however, TAVI may also be accompanied by complications and may result in periprocedural mortality. This study aims to evaluate such complications and causes of death after TAVI. METHODS: The study included 32 deceased (59.4% female, n = 19, median age: 82 years) patients with TAVI, since 2008, in whom post-mortem computed tomography (PMCT) and PMCT angiography were performed with the intention of identifying complications. RESULTS: Altogether, we registered bleeding (28.1%, 9/32), perforation and rupture (25%, 8/32), cerebral infarction (18.8%, 6/32), injury of the conduction system (3.1%, 1/32), insufficiency of the aortic (12.5%, 4/32) and the mitral valve (9.4%, 3/32) and of valve-in-valve procedures (9.4%, 3/32). Furthermore, there were findings due to cardiopulmonary resuscitation and intensive care. PMCT and PMCT angiography has advantages over autopsy. The demonstration of bleeding vessels, ruptures, the position of the implanted aortic valve and its effects on the mitral valve and its suspensions were more easily accessible by computed tomography-imaging display than by customary autopsy photo-documentation. CONCLUSIONS: After TAVI, PMCT and PMCT angiography successfully demonstrated the complications leading to death. PMCT and PMCT angiography contribute to the post-mortem analysis of causes of periprocedural death.

Preoperative Ticagrelor administration leads to a higher risk of bleeding during and after coronary bypass surgery in a case-matched analysis.

OBJECTIVES: To evaluate the effect of Ticagrelor on intra- and postoperative bleeding complications in patients undergoing coronary bypass surgery. METHODS: For this study, patients who underwent on-pump or off-pump coronary bypass surgery with preoperative acetylsalicylic acid (ASA) and Ticagrelor administration, between January 2014 and December 2014, were included. In the matched control group, continued dual antiplatelet therapy (DAPT) consisted of Clopidogrel and ASA. A total of 28 consecutive patients (24 males; 73 ± 6.6 years) with preoperative Ticagrelor intake underwent elective (n = 22), urgent (n = 2) or emergency (n = 4) cardiac bypass surgery. The postoperative blood loss, red blood cell units given and intra- and postoperative bleeding complications were documented. To evaluate the effect of Ticagrelor treatment on bleeding during and after coronary bypass surgery in a non-randomized study, we used a case-matched analysis. RESULTS: Baseline parameters showed no important differences between the study group and the control group regarding the matching variables, left ventricular function, preoperative clinical status and risk stratification. The preoperative laboratory analysis showed no important differences regarding coagulation and blood cell count parameters. Overall blood loss was significantly higher in the study group with a mean loss of 1028.8 ± 735.5 ml (P = 0.0002). Accordingly, units of red blood cells administered were also significantly higher in the study group (P = 0.0002). In the Ticagrelor group, there were six rethoracotomies due to postoperative bleeding with a blood loss of more than 1200 ml in the first 3 h. With no rethoracotomies in the Clopidogrel group, this also showed statistical significance for the postoperative course (P = 0.02). There were no differences found regarding ICU stay and ventilation time. Comparing the mean hospital stay, the study group presented a significantly longer stay than the control group (P = 0.001). CONCLUSIONS: Recent studies about bleeding complications in patients with Ticagrelor intake undergoing CABG in a real-life scenario presented inconsistent data. We were able to show in a case-matched analysis that Ticagrelor administration leads to significantly higher blood loss, more red blood cell units transfused and a higher rate of rethoracotomies. The data also present a longer hospital stay to the disadvantage of the study group. Consequently, Ticagrelor intake before CABG procedures should be avoided or at least discontinued 3 days before cardiac surgery.

Safety of Preoperative Use of Ticagrelor With or Without Aspirin Compared With Aspirin Alone in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting.

Importance: The optimal timing of discontinuation of ticagrelor before cardiac surgery is controversial. Objective: To evaluate the safety of preoperative use of ticagrelor with or without aspirin in patients with acute coronary syndromes (ACS) undergoing isolated coronary artery bypass grafting (CABG) compared with aspirin alone. Design, Setting, and Participants: This prospective, multicenter clinical trial was performed at 15 European centers of cardiac surgery. Participants were patients with ACS undergoing isolated CABG from the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry between January and September 2015. Exposures: Before surgery, patients received ticagrelor with or without aspirin or aspirin alone. Main Outcomes and Measures: Severe bleeding as defined by the Universal Definition of Perioperative Bleeding (UDPB) and E-CABG bleeding classification criteria. A propensity score-matched analysis was performed to adjust for differences in baseline and operative covariates. Results: Of 2482 patients from the E-CABG registry, the study cohort included 786 (31.7%) consecutive patients with ACS (mean [SD] age, 67.1 [9.3] years; range, 32-88 years), and 132 (16.8%) were female. One-to-one propensity score matching provided 215 pairs, whose baseline and operative covariates had a standardized difference of less than 10%. Preoperative use of ticagrelor was associated with a similar risk of bleeding according to the UDPB and E-CABG bleeding classifications, but the incidence of platelet transfusion was higher in the ticagrelor group (13.5% [29 of 215] vs 6.0% [13 of 215]). Compared with those receiving aspirin alone, continuing ticagrelor up to the time of surgery or discontinuing its use less than 2 days before surgery was associated with a higher risk of platelet transfusion (22.7% [5 of 22] vs 6.4% [12 of 187]) and E-CABG bleeding grades 2 and 3 (18.2% [4 of 22] vs 5.9% [11 of 187]) and tended to have an increased risk of UDPB grades 3 and 4 (22.7% [5 of 22] vs 9.6% [18 of 187]). Among patients in whom antiplatelet drug use was discontinued at least 2 days before surgery, the incidence of platelet transfusion was 12.4% (24 of 193) in the ticagrelor group and 3.6% (1 of 28) in the aspirin-alone group. Conclusions and Relevance: In propensity score-matched analyses among patients with ACS undergoing CABG, the use of preoperative ticagrelor with or without aspirin compared with aspirin alone was associated with more platelet transfusion but similar degree of bleeding; in patients receiving ticagrelor 1 day before or up until surgery, there was an increased rate of severe bleeding.

Bleeding, transfusion and the risk of stroke after coronary surgery: A prospective cohort study of 2357 patients.

INTRODUCTION: This study was planned to investigate the impact of severe bleeding and blood transfusion on the development of stroke after coronary surgery. METHODS: This cohort study includes 2357 patients undergoing isolated CABG from the prospective European Coronary Artery Bypass Grafting (E-CABG) registry. Severity of bleeding was categorized according to the Universal Definition of Perioperative Bleeding (UDPB), E-CABG and PLATO definitions. RESULTS: Thirty patients (1.3%) suffered postoperative stroke. The amount of transfused red blood cell (RBC) (OR 1.10, 95%CI 1.03-1.18), preoperative use of unfractioned heparin (OR 4.49, 95%CI 1.91-10.60), emergency operation (OR 3.97, 95%CI 1.47-10.74), diseased ascending aorta (OR 4.62, 95%CI 1.37-15.65) and use of cardiopulmonary bypass (p = 0.043, OR 4.85, 95%CI 1.05-22.36) were independent predictors of postoperative stroke. Adjusted analysis showed that UDPB classes 3-4 (crude rate: 3.6% vs. 1.0%; adjusted OR 2.66, 95%CI 1.05-6.73), E-CABG bleeding grades 2-3 (crudes rate: 6.3% vs. 0.9%; adjusted OR 5.91, 95%CI 2.43-14.36), and PLATO life-threatening bleeding (crude rate: 2.5% vs. 0.6%, adjusted OR 3.70, 95%CI 1.59-8.64) were associated with an increased risk of stroke compared with no or moderate bleeding. CONCLUSIONS: Bleeding and blood transfusion are associated with an increased risk of stroke after CABG, which is highest in patients with severe bleeding.

Mechanical circulatory support in pediatric patients with the MEDOS assist device.

Mechanical circulatory support is successfully applied to patients with low cardiac output. The MEDOS-System provides pulsatile ventricular assistance for patients of all age groups, including neonates. We report our experience with seven consecutive pediatric patients with the MEDOS-VAD. The indication was bridge to transplantation in all patients. Mean age was 7.3 +/- 6.5 years (range 0.75-16.9 years) and mean weight was 26.3 +/- 21.7 kg (range 5.9-60 kg). Perioperative survival was 100%; complications occurred in six patients (86%; two cerebral embolism/bleeding, two rethoracotomy, two exchange of pump chamber due to thrombus formation after 4 and 9 days). Mean duration of support was 20.4 +/- 10.8 days (range 6-38 days). Bilirubin decreased from 3.5 +/- 2.6 mg/d to 2.1 +/- 1.2 mg/d. Hospital mortality was three of seven patients who did not receive an organ offer in time. All patients who underwent subsequent heart transplantation (four of seven patients; 57%) were discharged from the hospital. Mechanical circulatory support with the MEDOS-System can be performed successfully in pediatric patients of any age. Secondary organ functions improve under this pulsatile circulatory assistance. Hemorrhage and thromboembolic events are the most frequent complications.

Failing stentless Bioprostheses in patients with carcinoid heart valve disease.

BACKGROUND: Carcinoid tumor with consecutive endocardial fibroelastosis of the right heart, known as carcinoid heart valve disease (CHVD) or Hedinger's syndrome, is accompanied by combined right-sided valvular dysfunction with regurgitation and stenosis of the affected valves. Cardiac surgery with replacement of the tricuspid and/or pulmonary valve is an established therapeutic option for patients with Hedinger's syndrome. Little is known about the long term outcome and the choice of prosthesis for the pulmonal position is still a matter of debate. METHODS: The authors report three cases of pulmonary valve replacement with stentless bioprostheses (Medtronic Freestyle, Medtronic PLC, Minneapolis, MN, USA) due to severe pulmonary valve degeneration in consequence of Hedinger's syndrome. RESULTS: All patients presented with re-stenosis of the pulmonal valve conduit at the height of the anastomoses in a premature fashion. Due to the increased risk for repeat surgical valve replacement, two patients were treated by transcatheter heart valves. CONCLUSION: We do not recommend the replacement of the pulmonary valve with stentless bioprostheses in patients with CHVD. These valves presented with an extreme premature degeneration and consecutive re-stenosis and heart failure.

Improved results after heart-lung transplantation: a 17-year experience.

OBJECTIVE: In selected patients with severe end-stage combined cardiopulmonary diseases, heart-lung transplantation (HLTx) remains the only therapeutical option for improving survival and quality of life. PATIENTS AND METHODS: Since 1983, 51 HLTx were done at our institution. Mean patient age was 27+/-12 years with a mean donor age of 25+/-11 years. Indications for HLTx were primary pulmonary hypertension (PPH) in 49% of patients, congenital heart disease in 39%, cystic fibrosis in 6%, and repeat-HLTx in 6%. Eleven patients were younger than 14 years. Among these pediatric patients, the indications were PPH in 55% of patients, pulmonary atresia with severe pulmonary artery hypoplasia in 27%, and cystic fibrosis and cardiomyopathy with fixed pulmonary hypertension in 9% of patients each. Two patients had additional liver transplantation because of chronic aggressive virus hepatitis. For organ preservation, Euro-Collins solution (lung perfusion) and cardioplegic solution according to Bretschneider (heart perfusion) were used until 1994. The University of Wisconsin solution replaced Bretschneider's solution in 1994. Since 1996, Perfadex, a low-potassium dextran-based preservation solution, replaced Euro-Collins. All transplantations were done through a median sternotomy until 1994. Thereafter, a transverse thoracotomy was used in patients with suspected adhesions. Until 1995, cyclosporine A, azathioprine, and prednisolone were used for immunosuppression. Since then, tacrolimus replaced cyclosporine A. RESULTS: From 1983 until 1993, perioperative mortality was 35% (6/19). From 1994 on perioperative mortality decreased to 12.5% (4/32). Early mortality was caused by graft failure (n=5), severe bleeding (n=2), multi-organ failure (n=2), and acute rejection (n=1). Cumulative survival rates were 81% after 30 days, 63% after 1 year, and 54% after 5 years, respectively. Since 1994, cumulative survival rates were markedly improved to 87% after 30 days, 81% after 6 months, and 78% after 1 year. There was no death during the first postoperative year among the 11 pediatric patients. Late death was mainly caused by obliterative bronchiolitis (OB; 76%); two patients died because of multi-organ failure or septic complications, respectively, and one patient died within the first postoperative year because of aspergillosis. CONCLUSION: Changes in organ preservation management, surgical techniques, and immunosuppressive therapy significantly improved the short- and mid-term results after HLTx. Long-term results can only be improved in cases of successful prevention and treatment of OB.

Development of an artificial vessel lined with human vascular cells.

OBJECTIVES: Thrombogenity of small-diameter vascular prostheses might be reduced by complete coverage of the luminal surface with vascular cells. We investigated cell seeding on polyurethane vascular prostheses. METHODS: Thirty polyurethane vascular prostheses were divided into 3 groups of 10 each: group A, diameter of 20 mm and gamma-sterilized; group B, diameter of 4 mm and gamma-sterilized; and group C, diameter of 4 mm and ethylene oxide sterilized. Human smooth muscle cells, fibroblasts, and endothelial cells were isolated from saphenous vein segments and expanded in culture. Five polyurethane vascular prostheses of each group were seeded with endothelial cells alone (mean, 4.8 +/- 1.2 x 10(6) cells), and the remaining 5 polyurethane vascular prostheses were preseeded with a mixed culture of fibroblasts and smooth muscle cells (mean, 7.7 +/- 2.3 x 10(6) cells), followed by endothelial cell seeding (mean, 4.4 +/- 0.9 x 10(6) cells). Seven days after cell seeding, the polyurethane vascular prostheses were perfused under a pulsatile flow (80 pulses/min, 140/80 mm Hg, and 120 mL/min) for 2 hours. Specimens were taken after each seeding procedure both before and after perfusion and then examined both with a scanning electron microscope and immunohistochemically. RESULTS: Isolated endothelial cell seeding revealed better initial adhesion in groups A and B than in group C (63% vs 33%). After 7 days, the cells had covered approximately 80% of the luminal surface in groups A and B, whereas group C cells rounded up and lost adhesion. After perfusion testing of group A and B prostheses, only 10% of the surface was still covered with endothelial cells. Preseeding with the mixed culture again revealed a better initial adhesion in groups A and B compared with that in group C (76% vs 41%). In groups A and B endothelial cell seeding (adhesion, 72%) resulted in a confluent endothelial cell layer. The results of immunohistochemical staining were positive for collagen IV, laminin, CD31, and Factor VIII. In group C only isolated cells were found after each seeding procedure, which rounded up and vanished during the next days. Perfusion testing of group A and B prostheses revealed that the confluent cell layer remained stable, with only small defects (<10% of the surface). The cells stained positivively for endothelial nitric oxide synthase. CONCLUSION: Seeding of a mixed culture out of fibroblasts and smooth muscle cells resulted in improved endothelial cell adhesion and resistance to shear stress. This outcome was caused by an increased synthesis of extracellular matrix proteins. Cell attachment was better on gamma-sterilized polyurethane vascular prostheses compared with on those undergoing ethylene oxide sterilization.

Preseeding with autologous fibroblasts improves endothelialization of glutaraldehyde-fixed porcine aortic valves.

OBJECTIVE: This study represents the development of a treatment and seeding procedure to improve endothelial cellular adhesion on glutaraldehyde-fixed valves. METHODS: Porcine aortic valves were fixed with 0.2% glutaraldehyde. Wall pieces of these valves had either no additional treatment (n = 4), incubation in M199 Earle (1x), with sodium carbonate at 2.2 g/L without l-glutamine for 24 hours (n = 4), or additional pretreatment with 5%, 10%, or 15% citric acid (three groups, n = 4 each). Thereafter the pieces were washed and buffered to a physiologic pH. This was followed by seeding of human endothelial cells (5 x 10(6) cells). On the basis of the results of these pilot tests, complete glutaraldehyde-fixed aortic roots treated with 10% citric acid were subjected to cell seeding. The valves were seeded with endothelial cells (4.3 x 10(6) cells) either alone (n = 4) or in combination with preseeding of autologous fibroblasts (2.4 x 10(7) cells, n = 4). After each seeding procedure specimens of the free wall of the grafts were taken. In addition, one leaflet was taken for histologic examination after endothelial cell seeding, after 7 days, and after 21 days. Finally, two commercially available stentless aortic valve prostheses (Freestyle; Medtronic, Inc, Minneapolis, Minn) were treated with 10% citric acid and seeded with human fibroblasts and endothelial cells. Specimen were taken according to the glutaraldehyde-fixed aortic roots. Specimen of all experiments were examined with scanning electron microscopy. Frozen sections were stained immunohistochemically for collagen IV, factor VIII, and CD31. RESULTS: On untreated glutaraldehyde-fixed aortic wall pieces, only poor adhesion (24%) was seen. No viable cells were found after 1 week. Cellular adhesion was best on aortic wall pieces pretreated with 10% citric acid. After 7 days, the cells formed a confluent layer. Endothelial cell seeding on citric acid-treated complete aortic valves showed 45% adhesion, but no confluent layer was found after 1 week. Preseeding of these valves with autologous fibroblasts resulted in an endothelial cellular adhesion of 76% and a confluent endothelial cell layer after 7 days. The layer remained stable for at least 21 days. Results of staining for collagen IV, factor VIII, and CD31 were positive on the luminal side of these valves, indicating the synthesis of matrix proteins and viability of the cells. Pretreatment of commercially available porcine valves with 10% citric acid and preseeding with autologous fibroblasts followed by endothelial cell seeding resulted in an adhesion of 78%. The cells formed a confluent cell layer after 7 days. CONCLUSIONS: Pretreatment of glutaraldehyde-fixed porcine aortic valves with citric acid established a surface more suitable for cellular attachment. Preseeding these valves with autologous fibroblasts resulted in a confluent endothelial cell layer on the luminal surface. Flow tests and animal experiments are necessary for further assessment of durability and shear stress resistance.

Homografts: a review.

Since their introduction into clinical practice in 1965 homografts have become established in clinical routine. The storing and sterilization procedures have been improved over time. Long-term results showed that homografts had a superior durability compared to xenogenic biological prostheses. Approximately 40% were still in place 20 years after implantation in aortic position. Their low rate of thromboembolic events made a life-time anticoagulative therapy unnecessary and their hemodynamics were superior to all other heart valve prostheses. There exist two implantation techniques, subcoronary or mini-root, both technically more demanding compared with implantation of stented valve prostheses. When using the subcoronary technique, the valve is suspended into the aortic root leaving the coronary arteries untouched. The success of this technique, however, depends on the relation of the recipients aortic root and the implanted valve. The mini-root technique requires reimplantation of the coronary arteries but left the morphology of the valve and its root unchanged. Especially in patients with endocarditis, the mini-root technique offered the advantage of allowing for excision of all affected tissue with subsequent replacement by the homograft. The Ross-procedure uses the patient's own pulmonary valve as aortic valve substitute with implantation of a homograft in pulmonary position. This proved to be advantageous in children, since in these patients the degeneration of an aortic homograft was faster compared to an older population. This was explained by the recipient's immunologic response to the graft which was more pronounced in younger patients. The advantages of homografts with regards to hemodynamics and thromboembolic risk make them a good alternative to mechanical prostheses in younger, active patients. In very young patients, a Ross-procedure was shown to be superior to aortic homografts due to slower degeneration of the autograft. The decision to use a homograft must be made individually according to the patients demands.

Minimally invasive heart valve surgery: already established in clinical routine?

Cardiac valve replacement with the need for open heart surgery still has the highest morbidity and mortality rates among routine cardiac surgery, with the exception of aortic aneurysm repair and surgery for congenital heart defects. Reducing invasiveness is a desirable goal, and different strategies and approaches have been used to achieve this with valve repair or replacement less invasive. Despite the good results reported with minimally invasive techniques, time on extracorporal circulation is always longer compared with the conventional procedures. Since these techniques do not reduce real invasiveness but rather improve the cosmetic results, minimal-access surgery would be a better nomenclature. With the exception of patients at a high risk for sternal infections or redo heart operations, a reduction in postoperative morbidity by the avoidance of a median sternotomy is not yet definitely proven. Meanwhile, most surgeons comply with the demand for minimally invasive surgery posed by patients by reducing the length of the incision in aortic valve replacement and by using a right anterolateral approach with a limited incision for mitral valve operations. However, the use of endoscopic or robotic devices is limited to a few centers, and has not yet found its way into clinical routine. Nonetheless, minimally invasive or minimal-access surgery is now established in many centers, and patients should always be informed of these techniques. When this information is provided objectively and patient selection is carried out accurately, these alternative approaches can help to improve postoperative convalescence.

Is there an advantage in using homografts in patients with acute infective endocarditis of the aortic valve?

BACKGROUND AND AIM OF THE STUDY: Acute infective endocarditis is a surgical challenge, particularly when paravalvular abscesses and annular destruction are present. The choice of a homograft or mechanical valve prosthesis is an important issue in these patients. The study aim was to compare the outcome with homografts and mechanical valves in patients with acute infective endocarditis. METHODS: A total of 77 patients (mean age 49+/-9 years) operated on for acute endocarditis of the aortic valve was included in the study and analyzed retrospectively. The causative bacterium was isolated from blood cultures in 71 cases. Preoperatively, 21 patients required artificial ventilation and 24 had inotropic support due to hemodynamic instability. Aortic homografts were implanted in 43 patients, and mechanical valve prostheses in 34. The two patient groups were similar in terms of gender, age and preoperative inotropic support. In total, 31 patients (44%) had paravalvular abscesses, and a homograft was used significantly more often (77%, p <0.05) in these cases. Follow up examinations (clinical examination, ECG and transthoracic echocardiography) were performed six months postoperatively and continued on an annual basis. Endocarditis relapse was defined as persisting infection, whereas re-endocarditis indicated a new infection after an interval of at least six months. RESULTS: Perioperative mortality was 11.5% (5/43) in homograft patients. In the 38 survivors, follow up was complete and averaged 5.0+/-1.2 years. One patient had an endocarditis relapse three months after surgery. Re-endocarditis occurred in three patients after two or three years. One other patient had pseudoaneurysm formation without a need for intervention, and one had repeat aortic valve replacement due to dysfunction of the graft after four years. The other 33 patients had an uneventful follow up. Echocardiography revealed aortic insufficiency grade 1 in 12 cases (36%), with no progression during follow up. Perioperative mortality in mechanicat valve patients was 20.5% (n = 7) (p <0.05 versus homograft), and in those with paravalvular abscess, perioperative mortality was even higher than in homograft patients (4/7, 57.1% versus 3/24, 12.5%; p <0.05). When considering only patients without paravalvular abscess, there was no significant difference between groups (10.5% versus 12.5%). Three relapses occurred in mechanical valve patients (10.3%), but no endocarditis recurred during follow up. One late death (3.7%) occurred due to bleeding complicating long-term anticoagulation. CONCLUSION: The study results do not permit a general recommendation to be made for homograft use in patients with acute endocarditis. In cases with paravalvular abscesses, however, there was a trend towards improved outcome in the homograft group.