Type II Minimal-Invasive Extracorporeal Circuit for Aortic Valve Replacement: A Randomized Controlled Trial.

Extracorporeal circulation triggers systemic inflammatory response and coagulation disorders which may lead to unfavorable clinical outcome. A type II minimally-invasive extracorporeal circuit (MiECC) is a closed system with markedly reduced artificial surface as compared to conventional extracorporeal circuits (CECC). The aim of this study was to investigate and compare inflammatory responses, complement activation and selected clinical end-points in isolated surgical aortic valve replacement (SAVR) performed with a type II MiECC circuit or a CECC. Fifty patients were prospectively randomized to MiECC or CECC perfusion regimen. Complement activation (sC5b-9), inflammation (IL-6, TNF-α, sCD40-ligand) and activation of the coagulation system (D-dimer, TAT-complex) were determined before operation, at 2 hours and 24 hours after surgery. Clinical end-points included perfusion time, transfusion of allogeneic blood products, postoperative bleeding, sepsis, new onset of atrial fibrillation, stroke and in-hospital mortality. Patient characteristics and baseline plasma markers were similar in both groups. Levels for sC5b-9, TNF-α, sCD40 ligand, TAT-complex and D-dimers were not significantly different between MiECC and CECC at 2 hours and 24 hours after surgery. The IL-6 plasma concentration was lower in the CECC group at 24 hours (P = 0.026, vs. MiECC). Comparisons of the baseline level to values at 2 hours and 24 hours, adjusted for the type of oxygenator and hemoglobin, showed a significantly lower sC5b-9 in MiECC at 2 hours (P = 0.013), but no difference at 24 hours (P=0.990). Compared with CECC, MiECC patients had a shorter perfusion time (P = 0.037) and less transfusion requirements (P = 0.04). In this selected cohort of SAVR patients, the type II MiECC was not inferior to CECC in terms of inflammatory response and complement activation. Thus, MiECC might be an alternative perfusion strategy to conventional.

Mortality and neurologic injury after surgical repair with hypothermic circulatory arrest in acute and chronic proximal thoracic aortic pathology: effect of age on outcome.

BACKGROUND: The goal of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology. METHODS AND RESULTS: A university center audit was done of 523 consecutive patients (median age, 64 years; interquartile range, 56-71 years) between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients) was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2% (P<0.001). Neurological injury was observed in 16.9% of patients with acute type A aortic dissection (chronic ascending aortic aneurysms, 7.9%; P=0.002). Multivariable regression analysis revealed hypothermic circulatory arrest >40 minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60-11.06; P=0.004) and redo surgery (OR, 3.44; 95% CI, 1.11-10.64; P=0.03) but not age (OR, 1.98; 95% CI, 0.73-5.38; P=0.18) as independent predictor of mortality. Emergency surgery (OR, 3.27; 95% CI, 1.31-8.15; P=0.01) and extracardiac arteriopathy (OR, 2.38; 95% CI, 1.26-4.50; P=0.008) but not age (OR, 1.80; 95% CI, 0.93-3.48; P=0.08) were independent predictors of neurological injury. CONCLUSIONS: Age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality, whereas emergency surgery and extracardiac arteriopathy predict neurological injury.

Aortic arch morphometry in living humans.

Anatomical features of the aortic arch such as its steepness, the take-off angles and the distances between its supra-aortic branches can influence the feasibility and difficulty of interventional and/or surgical maneuvers. These anatomical characteristics were assessed by means of 3D multiplanar reconstruction of thoracic angio-computed tomography scans of 92 living patients (79 males, 13 females, mean age 69.4 ± 9.9 years) carried out for various indications (gross pathology of the thoracic aorta excluded). There was a significant variation of all measured parameters between the subjects - a standard aortic arch (i.e. with all measured parameters within 2 SD) does not seem to exist. There were no significant differences between genders but some of the parameters correlated significantly to age.

Heart valve sound of various mechanical composite grafts, and the impact on patients' quality of life.

BACKGROUND AND AIM OF THE STUDY: The closing sounds of mechanical heart valves can be disturbing for patients and their closest relatives. Although some investigations into mechanical heart valve sounds have been performed, the particularities of the valve sound when it is attached to a vascular prosthesis to replace the aortic root and the ascending aorta has not been studied to date. The study aim was to compare the closing sounds of three various mechanical composite graft prostheses, and to analyze the impact of such sounds on the patients' quality of life. METHODS: Thirty patients who had undergone aortic root replacement were prospectively randomized into three groups, receiving either a Sorin, St. Jude Medical (SJM) or ATS mechanical composite graft. Valve sounds were recorded with microphones, and sound pressures at peak measured at three months after operation. Patients were interviewed at three and six months after surgery to assess subjective disturbance, using both an analog scale from 1 to 10 and a more detailed questionnaire. RESULTS: Sound pressures at peak tended to be lower for the ATS than for the SJM and Sorin composite grafts (44.4 +/- 3.1 dB versus 47.8 +/- 3.1 dB and 46.6 +/- 6.0 dB; p = NS). The overall subjective disturbance with ATS valves scored significantly lower than the SJM and Sorin composite grafts (2.5 +/- 1.6 versus 4.1 +/- 1.7 and 4.6 +/- 2.2; p<0.05 after three months; and 2.6 +/- 1.2 versus 4.4 +/- 2.3 and 4.4 +/- 3.3; p<0.05 after six months). Scores for disturbance during daily activities, sleep disturbance and audibility to relatives were lowest for the ATS composite grafts. CONCLUSION: The sound pressure of ATS composite grafts was slightly (p = NS) lower than that of SJM and Sorin composite grafts. Patients who received an ATS composite graft were significantly less disturbed by the valve noise than those with SJM and Sorin composite grafts.

Transapical implantation of a novel self-expanding sutureless aortic valve prosthesis.

BACKGROUND AND AIM OF THE STUDY: To date, transapical aortic valve implantation has required a balloon-expandable stented valve prosthesis. More recently, a novel self-expanding sutureless stented bovine pericardial prosthesis has been developed which allows rapid aortic valve replacement via an open transaortic approach in humans. The aim of this animal study was to develop a reliable protocol to facilitate the transapical implantation of this self-expanding valve in a porcine model. METHODS: Off-pump transapical aortic valve implantation was performed through a left mini-thoracotomy using a bovine pericardial valve mounted on a self-expandable nitinol stent of size 21 mm and 23 mm in 11 pigs (average weight 60 kg). The crimped valve was introduced through the left ventricular apex using a flexible and steerable delivery sheath, using a three-step technique. Biplane fluoroscopy and transesophageal echocardiography were simultaneously used for guidance. Successful adjustment of alignment along three axes prior to deployment of the valve was accomplished in each animal. Deployments were performed during a period of rapid pacing. RESULTS: All valves were successfully deployed and functioned normally following transapical removal of the delivery system. Paravalvular leak was documented in one case (9.1%) due to prosthetic misalignment. There was no evidence of valve migration. Correct anatomic seating was confirmed during post-procedure necropsy. CONCLUSION: Successful transapical implantation of a novel self-expandable bovine pericardial valve was accomplished in 11 animals, without cardiopulmonary bypass. A flexible, steerable delivery system with a three-step release mechanism allowed precise positioning of the valve with a low rate of paravalvular leakage, and excellent device stability.

An uncommon cause of coronary artery ostial obstruction: papillary fibroelastoma.

Cardiac papillary fibroelastoma is a benign tumor that mainly affects cardiac valves. The tumor has the potential to cause angina and myocardial infarction due to embolization of tumor fragments. We describe a rare case of right coronary artery ostial obstruction by a 12 x 19 mm sized papillary fibroelastoma located in the sinus of Valsalva. The report underlies the importance of echocardiography in diagnosis and intraoperative treatment of this type of cardiac mass.

Temporary neurological dysfunction after surgery of the thoracic aorta: a predictor of poor outcome and impaired quality of life.

BACKGROUND: Transient neurological dysfunction (TND) consists of postoperative confusion, delirium and agitation. It is underestimated after surgery on the thoracic aorta and its influence on long-term quality of life (QoL) has not yet been studied. This study aimed to assess the influence of TND on short- and long-term outcome following surgery of the ascending aorta and proximal arch. METHODS: Nine hundred and seven patients undergoing surgery of the ascending aorta and the proximal aortic arch at our institution were included. Two hundred and ninety patients (31.9%) underwent surgery because of acute aortic dissection type A (AADA) and 617 patients because of aortic aneurysm. In 547 patients (60.3%) the distal anastomosis was performed using deep hypothermic circulatory arrest (DHCA). TND was defined as a Glasgow coma scale (GCS) value <13. All surviving patients had a clinical follow up and QoL was assessed with an SF-36 questionnaire. RESULTS: Overall in-hospital mortality was 8.3%. TND occurred in 89 patients (9.8%). As compared to patients without TND, those who suffered from TND were older (66.4 vs 59.9 years, p<0.01) underwent more frequently emergent procedures (53% vs 32%, p<0.05) and surgery under DHCA (84.3% vs 57.7%, p<0.05). However, duration of DHCA and extent of surgery did not influence the incidence of TND. In-hospital mortality in the group of patients with TND compared to the group without TND was similar (12.0% vs 11.4%; p=ns). Patients with TND suffered more frequently from coronary artery disease (28% vs 20.8%, p=ns) and were more frequently admitted in a compromised haemodynamic condition (23.6% vs 9.9%, p<0.05). Postoperative course revealed more pulmonary complications such as prolonged mechanical ventilation. Additional to their transient neurological dysfunction, significantly more patients had strokes with permanent neurological loss of function (14.6% vs 4.8%, p<0.05) compared to the patients without TND. ICU and hospital stay were significantly prolonged in TND patients (18+/-13 days vs 12+/-7 days, p<0.05). Over a mean follow-up interval of 27+/-14 months, patients with TND showed a significantly impaired QoL. CONCLUSION: The neurological outcome following surgery of the ascending aorta and proximal aortic arch is of paramount importance. The impact of TND on short- and long-term outcome is underestimated and negatively affects the short- and long-term outcome.

The Shelhigh No-React bovine internal mammary artery: a questionable alternative conduit in coronary bypass surgery?

BACKGROUND: Increasing age and comorbidities among patients undergoing coronary artery bypass surgery (CABG) stimulates the exhaustive research for alternative grafts. No-React treatment should render the tissue resistant against degeneration and reduce early inflammatory response. The aim of the present study was an invasive assessment of the patency of No-React bovine internal mammary artery (NRIMA grafts) used as bypass conduit in CABG surgery. PATIENTS AND METHODS: Nineteen NRIMA grafts were used in 17 patients (2.9%) out of a total of 572 patients undergoing CABG surgery within a 12-month period. All intraoperative data were assessed and in-hospital outcome was analysed. Follow-up examination was performed 7.0+/-4.0 months after initial surgery, including clinical status and coronary angiography to assess patency of the NRIMA grafts. RESULTS: Average perioperative flow of all NRIMA grafts was 71+/-60 ml/min. One patient died in hospital due to a multi-organ failure. Four patients refused invasive assessment. Follow-up was complete in 12 patients with overall 13 NRIMA grafts. Nine NRIMA grafts (69.2%) were used for the right coronary system, two NRIMA grafts (15.4%) on the LAD and two on the circumflex artery. Graft patency was 23.1% and was independent of the intraoperative flow measurement. CONCLUSIONS: NRIMA grafts show a very low patency and cannot be recommended as coronary bypass graft conduits. Patency was independent of the perioperative flow, assessed by Doppler ultrasound. Because of this unsatisfying observation, this type of graft should be utilised as a last resource conduit and used only to revascularise less important target vessels, such as the end branches of the right coronary artery.

Aprotinin in cardiac surgery: a different point of view.

Aprotinin is widely used in cardiac surgery to reduce postoperative bleeding and the need for blood transfusion. Controversy exists regarding the influence of aprotinin on renal function and its effect on the incidence of perioperative myocardial infarction (MI) and cerebrovascular incidents (CVI). In the present study, we analyzed the incidence of these adverse events in patients who underwent coronary artery bypass grafting (CABG) surgery under full-dose aprotinin and compared the data with those recently reported by Mangano et al [2006]. For 751 consecutive patients undergoing CABG surgery under full-dose aprotinin (>4 million kalikrein-inhibitor units) we analyzed in-hospital data on renal dysfunction or failure, MI (defined as creatine kinase-myocardial band > 60 iU/L), and CVI (defined as persistent or transient neurological symptoms and/or positive computed tomographic scan). Average age was 67.0 +/- 9.9 years, and patient pre- and perioperative characteristics were similar to those in the Society of Thoracic Surgeons database. The mortality (2.8%) and incidence of renal failure (5.2%) ranged within the reported results. The incidence rates of MI (8% versus 16%; P < .01) and CVI (2% versus 6%; P < .01) however, were significantly lower than those reported by Mangano et al. Thus the data of our single center experience do not confirm the recently reported negative effect of full-dose aprotinin on the incidence of MI and CVI. Therefore, aprotinin may still remain a valid option to reduce postoperative bleeding, especially because of the increased use of aggressive fibrinolytic therapy following percutaneous transluminal coronary angioplasty.

Minimized cardiopulmonary bypass combined with a smart suction device: the future of cardiopulmonary bypass?

OBJECTIVE: The standard heart-lung machine is a major trigger of systemic inflammatory response and the morbidity attributed to conventional extracorporeal circulation (CECC) is still significant. Reduction of blood-artificial surface contact and reduction of priming volume are principal aims in minimized extracorporeal circulation (MECC) cardiopulmonary bypass systems. The aim of this paper is to give an overview of the literature and to present our experience with the MECC-smart suction system. METHODS AND RESULTS: At our institution, 1799 patients underwent isolated coronary artery bypass grafting (CABG) surgery, 1372 with a MECC-smart suction system and 427 with CECC. All in-hospital data were assessed and the results were compared between the 2 groups. Patient characteristics and the distribution of EuroSCORE risk profile in our collective were similar between both groups. Average age in the MECC collective was 67.5 +/- 11.4 years and average EuroSCORE was 5.0 +/- 1.5. Average number of distal anastomoses was similar to the average number encountered in patients undergoing CABG surgery with CECC (3.3 +/- 1.0 for MECC versus 3.2 +/- 1.1 for CECC; P = ns). Myocardial protection is superior in MECC patients with lower postoperative maximal cTnI values (11.0 +/- 10.8 micromol/L for MECC versus 24.7 +/- 25.3 micromol/L for CECC; P < .05). Postoperative recovery was faster in patients operated on with the MECC-smart suction system and discharge from the hospital was earlier than for CECC patients (7.4 +/- 1.9 days for MECC versus 8.8 +/- 3.8 days for CECC; P < .05). CONCLUSIONS: The MECC-smart suction system is a safe perfusion technique for CABG surgery. In patients operated on with this system, the clinical outcome seems to be better than in patients operated on with CECC. This promising and less damaging perfusion technology has the potential to replace CECC systems in CABG surgery.

Large area of the false lumen favors secondary dilatation of the aorta after acute type A aortic dissection.

BACKGROUND: Since 1994 patients with acute aortic dissection type A (AADA) are followed-up in our outpatient clinic. Early diagnosis of secondary dilatation of the diseased aorta is crucial to reduce late mortality in these patients. Aim of the present study is to asses the impact of a large volume in the false lumen of the diseased downstream aorta on secondary dilatation. METHODS AND RESULTS: 134 patients of 264 patients who underwent surgery for AADA (between January 1994 and June 2003) are followed-up at our outpatient clinic since 1994. 84 patients (62.7%) fulfilled the inclusion criteria. Areas of the true and the false lumens of the aorta were analyzed and a logistic regression was calculated at 5 levels of the aorta for each patient. Patients were divided in 3 groups: group 1 included 34 patients (40.5%) without progression, group 2 had 34 patients (40.5%) with slight progression, and group 3 had 16 patients (19.0%) with important progression, requiring surgery in all patients. In 87.5% of the patients the area of the original lumen was <0% in group 3, compared with 11.8% in group 2 and 8.8% in group 1 in relation to the total area of the aorta 6 months after surgery (P<0.001). CONCLUSIONS: A large false lumen, with an area of the true lumen <30% 6 months after surgery, is the strongest predictor for secondary dilatation of the diseased downstream aorta.

Improved assessment of graft function by echocardiography in cynomolgus monkey recipients of hDAF-transgenic pig cardiac xenografts.

BACKGROUND: The current practice of evaluating heterotopic heart xenografts by palpation allows only detection of severe graft dysfunction, which indicates terminal graft failure. Therefore, we evaluated whether echocardiography is a better method of detecting early graft dysfunction as a marker of rejection in abdominal pig heart xenografts in cynomolgus monkeys. METHODS: Six cynomolgus monkeys received heterotopic heart transplants from pig donors transgenic for human decay-accelerating factor (hDAF). Induction therapy consisted of either cyclophosphamide or rabbit anti-thymocyte globulin. Maintenance therapy consisted of cyclosporine or tacrolimus, steroids, and sodium mycophenolate or mycophenolate mofetil, GAS914 (alphaGal oligosaccharide containing glycoconjugate), and for some animals TP10 (soluble complement receptor type 1). Echocardiography was performed immediately after transplantation and 3 times a week after surgery. We scored contractility and measured left ventricular wall thickness. Impaired contractility or increased wall thickness were considered graft dysfunction and were treated with pulse steroids. Palpation score was recorded daily. We also obtained myocardial biopsy specimens. RESULTS: Palpation score remained at 4 out of 4 in all animals until 2 to 5 days before final graft failure, whereas echocardiography detected several episodes of impaired graft function, either decreased left ventricular contractility or increased left ventricular wall thickness before graft failure. Treatment with pulse steroids improved graft function only during early episodes of graft impairment. Final graft failure was steroid resistant and caused by severe vascular rejection. CONCLUSIONS: Echocardiography is a better method of assessing graft dysfunction than is palpation. Therefore, echocardiography may detect early rejection episodes of heterotopic heart xenografts in non-human primates.

Experimental stenting of the posterior mitral leaflet to correct prolapse in mitral valve insufficiency.

OBJECTIVE: This study investigated the use of a new concept of mitral valve reconstruction using a novel device to stent the posterior mitral leaflet in combination with semicircular annuloplasty. Modern mitral valve repair is an accepted modality and a routine procedure for treatment of degenerative mitral valve insufficiency. One of the most common mechanisms of mitral valve insufficiency is leaflet prolapse. In the majority of cases the posterior leaflet is dysfunctional and therapeutic reconstruction of the PII flail leaflet segment involves quadrangular resection which is usually combined to mitral annulo-plasty with a ring. A new time-saving concept of mitral valve reconstruction by stenting the posterior mitral leaflet in combination with semicircular annuloplasty is presented. METHODS: The new mitral valve reconstruction device (Shelhigh MitroFast, Shelhigh, Inc., Union, NJ, USA) was implanted in four adult sheep. It is constructed as an annuloplasty ring in combination with a posterior leaflet stent. The device has the shape of a closed posterior leaflet and forms a "buttress" against which the anterior leaflet can coapt. RESULTS: Every implantation of a MitroFast device could be performed in less than 30 minutes. After implantation of the device, all animals could be successfully weaned from CPB. Invasively measured left atrial pressure was below 12 mm Hg in all animals. After chest closure, transoesophageal echocardiography revealed a competent mitral valve in all animals, without any inflow restriction in three animals, and suspected mild stenosis in one animal. CONCLUSIONS: In this experimental model, implantation of the newly designed annuloplasty ring with stenting the posterior mitral leaflet avoids extensive and time-consuming reconstructive surgery on a flail posterior leaflet. Implantation of the device resulted in favorable short-term hemodynamic effects. Implantation technique of the device is simple, the potential for minimal invasive implantation of a conceptual similar device will be further investigated.

Treatment with humanized monoclonal antibodies against CD80 and CD86 combined with sirolimus prolongs renal allograft survival in cynomolgus monkeys.

BACKGROUND: Co-stimulatory blockade has been shown to prolong allograft survival in different transplant models. We investigated the effect of combining humanized anti-CD80 and anti-CD86 monoclonal antibodies (mAb) with sirolimus in cynomolgus monkey renal transplant recipients. METHODS: After renal transplantation, groups of four animals were treated daily with sirolimus, sirolimus and nine weekly doses of mAb, two weekly doses of mAb, or sirolimus and two weekly doses of mAb. RESULTS: Survival was significantly better in monkeys treated with the combination of sirolimus and mAb when compared with treatment with either agent alone (P=0.0067 by log-rank analysis). When combined with sirolimus, nine weekly doses of mAb did not result in an additional survival benefit compared with only two mAb doses (P=0.74). None of the treatment regimens used in this study resulted in development of transplantation tolerance. CONCLUSIONS: Sirolimus can be successfully combined with humanized mAb against CD80 and CD86. Induction with a short course of mAb is effective in prolonging allograft survival in combination with sirolimus.

In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates.

BACKGROUND: ISA(TX)247 is a novel calcineurin inhibitor that has shown more potency than cyclosporine in vitro. This is the first in vivo study of the effects of ISA(TX)247 on lymphocyte functions in non-human primates. METHODS: Groups of cynomolgus monkeys were treated orally twice daily for 7 days, each dose consisting of 25 mg/kg cyclosporine (n = 5), 25 mg/kg ISA(TX)247 (n = 6) or 50 mg/kg ISA(TX)247 (n = 6). Levels of cyclosporine and ISA(TX)247 in whole blood were measured by liquid chromatography/mass spectrometry. After mitogen stimulation, lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation and by flow cytometry (expression of proliferating cell nuclear antigen in cells in S/G(2)M phase). Flow cytometry was also used to assess production of intracellular cytokines by T cells (interleukin-2, interferon-gamma, tumor necrosis factor-alpha) and expression of T-cell surface activation antigens (CD25, CD71, CD11a, CD95, CD154). RESULTS: Trough (C(14 hr)) and peak (C(3 hr)) drug levels, as well as area under the concentration-time curve, were significantly higher for cyclosporine than ISA(TX)247 (370 ng/ml vs 70 ng/ml, 877 ng/ml vs 303 ng/ml and 6,262 ng. h/ml vs 1,979 ng. h/ml, respectively). On Day 7 at C(14 hr), lymphocyte proliferation had been suppressed by approximately 50% in all groups compared with proliferation before treatment. Three hours after dosing, lymphocyte proliferation was inhibited significantly more by ISA(TX)247 (approximately 80%, with no differences between the two ISA(TX)247 dose levels) than by cyclosporine (65% inhibition). Similar differences between the immunosuppressive effects of ISA(TX)247 and cyclosporine were found for inhibition of expression of T-cell surface activation antigens. Despite lower ISA(TX)247 exposures compared with cyclosporine, the cyclosporine treatment only rarely suppressed cytokine production more than treatment with ISA(TX)247. CONCLUSIONS: In non-human primates, ISA(TX)247 produces a greater or similar inhibition of lymphocyte proliferation, expression of T-cell activation surface antigens, and cytokine production when compared with cyclosporine, despite ISA(TX)247's lower blood levels and total exposure. We conclude that ISA(TX)247 suppresses diverse T-cell functions more potently than cyclosporine in non-human primates in vivo.

Effects of the malononitrilamide FK778 on immune functions in vitro in whole blood from non-human primates and healthy human volunteers.

BACKGROUND: FK778, a malononitrilamide analog of leflunomide, is currently being investigated for use in clinical transplantation. METHODS: Whole blood from cynomolgus monkeys (n=4) and healthy human volunteers (n=4) was incubated with different concentrations of FK778 and stimulated with mitogens in culture medium. Lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation and by flow-cytometric analysis of expression of proliferating cell nuclear antigen on cells in S/G(2)M phase. Flow cytometry was also used to assess expression of T and B lymphocyte activation surface antigens and production of intracellular cytokines by T cells. RESULTS: Not only lymphocyte proliferation, but also expression of various T cell surface antigens (CD25, CD11a, CD95, CD154) was suppressed by FK778. Fifty percent effective concentration values for the different immune functions were lower in human blood than in blood from cynomolgus monkeys. CONCLUSIONS: FK778 inhibits multiple immune functions. Their flow cytometric evaluation can be used to assess the effects of the drug in vivo.

Ten-year comparison of pericardial tissue valves versus mechanical prostheses for aortic valve replacement in patients younger than 60 years of age.

OBJECTIVE: Aortic valve replacement using a tissue valve is controversial for patients younger than 60 years old. The long-term survival in this age group, the expected event rates during long-term follow-up, and valve-related complications are not clearly determined. METHODS: From January 2000 to December 2009, overall survival, valve-related events, and echocardiographic outcomes were analyzed in all patients younger than 60 years of age, who underwent biologic aortic valve replacement. Patients who received a Perimount Carpentier-Edwards pericardial tissue valve (n = 103) were selected and compared with a propensity matched group of 103 patients who received aortic valve replacement using a mechanical bileaflet valve. The mean follow-up was 33 ± 24 months (range, 2-120), and the mean age at implantation was 50.6 ± 8.8 years (bioprosthesis, 55 ± 8.9 years; mechanical valve, 50 ± 8.6 years; P = .03). RESULTS: Survival was significantly reduced in patients after biologic aortic valve replacement (90.3% vs 98%; P = .038). Freedom from all valve-related complications (bioprosthesis, 54.5%; mechanical valve, 51.6%; P = NS) and freedom from reoperation (bioprostheses, 100%; mechanical valve, 98%; P = NS) were comparable in both groups. The average transvalvular mean (11.2 ± 4.2 mm Hg vs 10.5 ± 6.0 mm Hg, P = .05) and peak (19.9 ± 6.7 mm Hg vs 16.7 ± 8.0 mm Hg, P = .03) gradients were greater after biologic aortic valve replacement. Regression of the left ventricular mass index was more pronounced after mechanical valve replacement (118.5 ± 24.9 g/m(2) vs 126.5 ± 38.5 g/m(2); P = NS). The echocardiographic patient-prosthesis mismatch was greater at follow-up after biological aortic valve replacement (0.876 ± 0.2 cm(2)/m(2) vs 1.11 ± 0.4 cm(2)/m(2); P = .01). Oral anticoagulation was a protective factor for survival among the bioprosthetic valve patients (P = .024). CONCLUSIONS: In the present limited cohort of patients younger than 60 years old, biologic aortic valve replacement was associated with reduced mid-term survival compared with survival after mechanical aortic valve replacement. Despite similar valve-related event rates in both groups, the better hemodynamic performance of the mechanical valves and/or protective effect of oral anticoagulation seemed to improve the outcome. The transcatheter valve-in-valve intervention as potential treatment of tissue valve degeneration should not be considered the sole bailout strategy for younger patients because no evidence is available that this would improve the outcome.

Autotransfusion system or integrated automatic suction device in minimized extracorporeal circulation: influence on coagulation and inflammatory response.

OBJECTIVE: To measure surrogate markers of coagulation activation as well as of the systemic inflammatory response in patients undergoing primary elective coronary artery bypass grafting (CABG) using either the so-called Smart suction device or a continuous autotransfusion system (C.A.T.S.®). METHODS: Fifty-eight patients being operated with a miniaturized circuit (minimal extracorporeal circuit, MECC) were prospectively randomized to using a so-called Smart suction device or a routine continuous autotransfusion system (C.A.T.S.®) for collection of mediastinal shed blood. The coagulation response was measured by thrombin-antithrombin complex (TAT) and D-dimer. The inflammatory response was measured by Interleukin 6 (IL-6) and complement factor 3a (C3a) at three different time points, before surgery, 2h after surgery, as well as 18 h after surgery. RESULTS: No serious adverse cardiovascular event was observed. Serum levels of TAT significantly differed between both groups 2h after surgery (Smart suction 16.12 ± 13.51 µg l⁻¹ vs C.A.T.S® 9.83 ± 7.81 µg l⁻¹, p = 0.040) and returned to baseline values after 18 h in both groups. Serum levels of D-dimer showed a corresponding pattern with a peak 2h after surgery (Smart suction 1115 ± 1231 ng ml⁻¹ vs C.A.T.S.® 507 ± 604 ng ml⁻¹, p = 0.025). IL-6 levels also significantly differed between both groups 2h after surgery (Smart suction 186 ± 306 pg ml⁻¹ vs C.A.T.S.® 82 ± 71 pg ml⁻¹, p = 0.072). No significant changes in serum levels of C3a over time could be observed. CONCLUSIONS: Despite no differences in the clinical course of patients with either Smart suction or C.A.T.S.® being observed, surrogate markers of coagulation and inflammation seem to be less pronounced in patients where cardiotomy blood is not being directly reinfused. As such, C.A.T.S.® should be preferred in routine CABG, as long as no extensive volume substitution is anticipated.

Antegrade cerebral protection in thoracic aortic surgery: lessons from the past decade.

OBJECTIVE: Prolonged deep hypothermic circulatory arrest (DHCA) adversely affects outcome and quality of life in thoracic aortic surgery. Several techniques of antegrade cerebral perfusion are routinely used: bilateral selective antegrade cerebral protection (SACP) by introducing catheters in the innominate and left carotid artery, unilateral perfusion through the right axillary antegrade cerebral perfusion (RAACP) or a combination of right axillary perfusion with an additional catheter in the left carotid artery (RAACCP), resulting also in bilateral perfusion. The aim of the present study was to analyse the impact of the different approaches on the quality of life (QoL). METHODS: The data of 292 patients who underwent surgery of the thoracic aorta using DHCA at our hospital between January 2004 and December 2007 have been analysed and a follow-up was performed focussing on QoL, assessed with the Short Form-36 Health Survey Questionnaire (SF-36). Results were analysed according to the type of cerebral perfusion and the duration of DHCA. RESULTS: Patients' characteristics were similar in all groups. Of the total, 3.4% patients underwent DHCA (average 8.3+/-6.4 min) without ACP, 45.9% underwent SACP (average DHCA of 15.6+/-7.1 min), 40.4% had RAACP (average DHCA of 28.1+/-11.6 min) and 9.4% bilateral perfusion (RAACCP) (average DHCA of 43.1+/-16.7 min). The average follow-up was 23.2+/-15.1 months. QoL was preserved in all groups. For DHCA above 40 min, bilateral ACP provides superior midterm QoL than unilateral RAACP (average SF-36 95.1+/-44.4 vs 87.6+/-31.3; p=0.072). CONCLUSIONS: When midterm QoL is assessed, bilateral SACP provides the best cerebral protection for prolonged DHCA (>40 min).