Twenty years' single-center experience with mechanical heart valves: a critical review of anticoagulation policy.

BACKGROUND AND AIM OF THE STUDY: Since January 1990, a variety of mechanical valves (St. Jude Medical, CarboMedics, ATS Medical) have been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of those mechanical valves, and to challenge the anticoagulation policy employed over the years. METHODS: Between January 1990 and December 2008, a total of 2,108 mechanical valves was inserted into 1,887 consecutive patients (1,346 aortic, 725 mitral, 27 tricuspid, 10 pulmonary). The mean age of the patients was 63 +/- 13.2 years, and the majority (61%) were males. Preoperatively, 71% the patients were in NYHA class > or = III (average 3.01). The most frequent comorbidities included: atrial fibrillation (n = 594), coronary disease (n = 567) and diabetes (n = 398). The follow up (99% complete) totaled 13,721 patient-years (pt-yr), and ranged from 12 to 241 months (average 84 months). RESULTS: In-hospital mortality was 5.2% (n = 98, 14 valve-related). Of the 629 late deaths, the majority were cardiac (n = 276). Survival (Kaplan-Meier estimation) was significantly better for aortic valve patients compared to mitral or multiple valve replacement (Mantel-Cox, p < 0.0001). The overall linearized incidences (as %/pt-yr) were: valve thrombosis 0.31, thromboembolism 1.08, and bleeding 0.91. However, as repeated events occurred in several patients, the hazard function was not constant. Multivariate analysis (Cox regression model) showed age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm (p = 0.001), concomitant coronary artery bypass grafting (p = 0.008) and higher International Normalized Ratio (INR) values (p = 0.013) as significant risk factors for death, with a trend for redo operations (p = 0.052). Multivariate analysis found variable INR, non-sinus rhythm and NYHA class > II as significant risk factors for thromboembolism, while long-acting coumadin and NYHA class > II were significant risk factors for bleeding. CONCLUSION: This 20-year experience demonstrated excellent clinical outcomes for patients with mechanical prostheses, with no valve structural failure and an acceptable incidence of adverse events. INR values between 2-2.5 for aortic valve patients, and 3-3.5 for mitral valve patients, yielded the fewest major adverse events.

O2 delivery and CO2 production during cardiopulmonary bypass as determinants of acute kidney injury: time for a goal-directed perfusion management?

INTRODUCTION: Acute kidney injury (AKI) is common after cardiac operations. There are different risk factors or determinants of AKI, and some are related to cardiopulmonary bypass (CPB). In this study, we explored the association between metabolic parameters (oxygen delivery (DO2) and carbon dioxide production (VCO2)) during CPB with postoperative AKI. METHODS: We conducted a retrospective analysis of prospectively collected data at two different institutions. The study population included 359 adult patients. The DO2 and VCO2 levels of each patient were monitored during CPB. Outcome variables were related to kidney function (peak postoperative serum creatinine increase and AKI stage 1 or 2). The experimental hypothesis was that nadir DO2 values and nadir DO2/VCO2 ratios during CPB would be independent predictors of AKI. Multivariable logistic regression models were built to detect the independent predictors of AKI and any kind of kidney function damage. RESULTS: A nadir DO2 level < 262 mL/minute/m2 and a nadir DO2/VCO2 ratio < 5.3 were independently associated with AKI within a model including EuroSCORE and CPB duration. Patients with nadir DO2 levels and nadir DO2/VCO2 ratios below the identified cutoff values during CPB had a significantly higher rate of AKI stage 2 (odds ratios 3.1 and 2.9, respectively). The negative predictive power of both variables exceeded 90%. The most accurate predictor of AKI stage 2 postoperative status was the nadir DO2 level. CONCLUSIONS: The nadir DO2 level during CPB is independently associated with postoperative AKI. The measurement of VCO2-related variables does not add accuracy to the AKI prediction. Since DO2 during CPB is a modifiable factor (through pump flow adjustments), this study generates the hypothesis that goal-directed perfusion management aimed at maintaining the DO2 level above the identified critical value might limit the incidence of postoperative AKI.

Evolution of vitamin D binding protein concentration in sera from cardiac surgery patients is determined by triglyceridemia.

BACKGROUND: Multiple human and animal studies have reviewed the (non-)actin scavenger functions of vitamin D binding protein (DBP). Recently, we demonstrated the partially lipid bound character of DBP. The purpose of the present study was to explore the link between actin, lipids and DBP in a cohort of patients undergoing cardiac surgery. METHODS: The interplay between DBP, actin and lipids was investigated in a cohort study of 35 Caucasian patients who underwent cardiac surgery. Total and actin-free DBP concentrations were assessed by immunonephelometry and ELISA. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase (-MB) and C-reactive protein (CRP) were measured using routine methods. Low-density lipoprotein cholesterol was calculated according to the Friedewald formula. The DBP phenotypes and the macromolecular bound DBP fractions were determined by polyacrylamide gel electrophoresis (PAGE) and confirmed by Western blotting. RESULTS: Using PAGE and Western blotting with an anti-human DBP polyclonal antibody, the actin-bound DBP complex was identified in serum. Following cardiac surgery, total serum DBP concentrations were characterized by a two phased course. This was paralleled by a similar pattern in serum total cholesterol, HDL-cholesterol and triglyceride concentrations. Good correlation was found between total and actin free serum DBP concentrations (r=0.69, p<0.0001). The serum actin free DBP/total DBP ratio remained stable throughout the study period. Although no significant correlation between cumulative CK-MB enzyme release and delta serum total DBP concentration was observed (p=NS), the latter value correlated significantly with delta serum triglyceride concentrations (r=0.37, p<0.05). CONCLUSIONS: The lipid bound character is an underestimated property of DBP in the extracellular actin-scavenger system.

Fifteen years' single-center experience with the ATS bileaflet valve.

BACKGROUND AND AIM OF THE STUDY: Since its introduction in May 1992, the bileaflet ATS Open Pivot valve has been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 15-year clinical results of these implanted ATS valves. METHODS: Between May 1992 and December 2005, a total of 1,160 ATS valves (749 aortic, 381 mitral, 21 tricuspid, nine pulmonary) was implanted in 1,047 consecutive patients (655 males, 392 females; mean age 62.1 +/- 12.4 years). Preoperatively, 75% of the patients were in NYHA class III or higher (mean 3.1). The most frequent comorbidities included atrial fibrillation (n = 381), coronary disease (n = 288) and diabetes (n = 172). RESULTS: The mean follow up was 78 months (range: 24-183 months); the total follow up was 6,887 patient-years (pt-yr) and was 99.8% complete. In-hospital mortality was 4% (n = 43; three valve-related). Survival (Kaplan-Meier) at five and 10 years was significantly better for aortic than for mitral valve patients (84% and 65% versus 75% and 41%, respectively) (Mantel-Cox, p < 0.001). A log rank analysis detected no statistical difference in the incidence of thromboembolism (p = 0.182) or bleeding (p = 0.375) between both groups. The overall linearized incidences were: thromboembolism 1.08%/pt-yr; bleeding 0.91%/pt-yr; endocarditis 0.22%/pt-yr; paravalvular leakage 0.33%/pt-yr; and valve thrombosis 0.21%/pt-yr. Multivariate analysis (Cox regression) indicated age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm (p = 0.001), concomitant CABG (p = 0.008) and higher INR values (p = 0.013) to be significant risk factors for death. CONCLUSION: This 15-year experience with the ATS bileaflet prosthesis showed excellent clinical outcomes for patients, with no structural failure and an acceptable incidence of adverse events.

Low target-INR anticoagulation is safe in selected aortic valve patients with the Medtronic Open Pivot mechanical prosthesis: long-term results of a propensity-matched comparison with standard anticoagulation.

OBJECTIVES: To investigate the long-term results of a low international normalized ratio (INR)-anticoagulation program in selected patients after aortic valve replacement (AVR) with the Medtronic Open Pivot mechanical heart valve (OPMHV). METHODS: From January 1993 to December 2012, 909 OPMHV valves were used for single AVR. Patients with preserved sinus rhythm and left ventricular function (Low-INR, n = 552), were managed to an INR of 1.5-2.5 and compared to patients (Standard-INR, n = 357) treated with standard anticoagulation (INR 2.5-3.5). Long-term outcome was analysed for survival and valve-related events, on propensity score matched pairs of 169 patients/group. RESULTS: Within a follow-up cumulating 3096 patient-years, 10- and 15-year survival was significantly better for Low-INR patients: 79% and 63% vs 63% and 34% ( P < 0.001). Multivariate analysis of late mortality identified older age [odds ratio (OR) = 1.05], chronic pulmonary disease (OR = 1.90) and coronary artery disease (OR = 1.57) as patient-related risk factors, and erratic INR (OR = 2.57) as anticoagulation-related factor. The linearized thromboembolic rate was 0.72%/patient-year in Low-INR patients, vs 0.87%/patient-year in Standard-INR patients ( P = 0.59), revealing INR variability as sole predictor (OR 3.54, 95% confidence interval (CI) 1.20-10.51, P = 0.022). The linearized bleeding incidence was respectively 0.61%/patient-year and 1.21%/patient-year for Low-INR and Standard-INR patients ( P = 0.04), retaining older age (OR 1.06, 95% CI 1.02-1.12, P = 0.009), hypertension (OR 2.06, 95% CI 1.00-4.25, P = 0.05) and erratic INR (OR 9.83, 95% CI 5.21-18.56, P < 0.001) as independent risk factors. CONCLUSIONS: This study demonstrated that application of an anticoagulation regimen, aiming a low INR, individualized to selected aortic OPMHV patients, is safe and effective over more than 20 years, without increasing the thromboembolic complication rate while lowering the haemorrhagic events. However, INR variability remains worrisome because of its deleterious effect on outcome.

Predicting ATS Open Pivot heart valve performance with computational fluid dynamics.

BACKGROUND AND AIM OF THE STUDY: In-vitro studies on the ATS heart valve have indicated that valve opening is less in an expanding conduit than in a straight conduit. METHODS: Bileaflet valve behavior was studied using a new computational fluid-structure interaction model. A three-dimensional model of the ATS valve was studied in two geometries, simulating the valve in a geometry with sudden expansion downstream of the valve, and in a straight conduit. Mitral and aortic flow patterns were simulated. RESULTS: The ATS valve in the expanding geometry showed opening to a maximum angle of 77.5 degrees; this was confirmed in previous clinical and in-vitro studies. The mean and maximum transvalvular Doppler pressure gradients were 1.1 and 4.3 mmHg, respectively. The maximum shear stress calculated on the leaflet was 25 Pa. Maximum opening of the valve was achieved in the straight conduit; with mean and maximum pressure gradients of 2.1 and 4.6 mmHg, respectively. The maximum shear stress calculated on the leaflet was 35 Pa. CONCLUSION: The results of this numerical study confirmed that valve hemodynamics and leaflet motion were dependent on the geometrical conditions of the valve: the presence of a diverging flow influenced the maximum opening angle of the valve leaflets. This model could be used to predict pressure gradients, effective orifice area, performance index and shear stress loading of mechanical heart valves, and in future will serve as a major research tool to characterize the hemodynamics of existing and new mechanical heart valves.

Stentless vs. stented aortic valve replacement: left ventricular mass regression.

The aim of this retrospective study was to evaluate the time-related regression of left ventricular hypertrophy after stentless vs. stented aortic valve replacement. From January 1992 to December 2002, 145 patients had a Toronto stentless porcine valve and 106 had a stented Carpentier-Edwards aortic valve replacement. Over a 10-year follow-up, survival was superior in the Toronto group vs. the Carpentier-Edwards group (84% vs. 74% at 4 years; 78% vs. 68% at 6 years; p < 0.001). A significant and constant reduction of peak and mean transvalvular gradients after valve replacement resulted in substantial regression of left ventricular mass index in both groups, which did not reach statistical significance. However, this phenomenon stopped at 3 years, and left ventricular mass index increased slowly after 5 years. Stentless and stented bioprostheses both showed good early and late clinical and hemodynamic outcomes, with the advantage of better midterm survival for stentless xenografts.

Aortic valve replacement with Toronto SPV in elderly patients: 10-year results.

A retrospective assessment of clinical and echocardiographic variables was performed in 145 patients who received a Toronto SPV aortic valve replacement. The majority (90%) of these elderly patients (mean age, 75.5 +/- 7.4 years) were preoperatively in New York Heart Association class III-IV. Operative mortality was 4.8%. Follow-up was complete up to 10 years and revealed few valve-related complications: thromboembolism (7), bleeding (4), and prosthesis dysfunction necessitating reoperation (3). Late mortality was cardiac-related in 11.7% and noncardiac-related in 17.2%. Actuarial survival was 83% at 5 years and 63% at 8 years. Echocardiography showed low transvalvular gradients (peak, 17.5 +/- 7.5 mm Hg; mean, 9.2 +/- 4.2 mm Hg) resulting in a significant reduction in left ventricular mass index during the first 3 years. Independent of the transprosthetic gradient, left ventricular mass index tended to increase again beyond the 5th year, which correlated positively with the presence of arterial hypertension in this older population. The Toronto SPV bioprosthesis offers an aortic valve substitute with excellent long-term hemodynamics, resulting in significant early left ventricular mass regression. Considering the limitations of this selected elderly population, the clinical outcome and survival up to 10 years are encouraging, with few observed valve-related events.

How to cope with a temporarily aborted transplant program: solutions for a prolonged waiting period.

BACKGROUND: Due to budgetary restrictions our university heart transplant program came to a standstill to be gradually restarted early 2011. Consequently waiting-times for transplantation increased dramatically beyond the usual 10-15 months. We reviewed the clinical results of this peculiar transplant program over the past 4 years. METHODS: Since March 2011 until February 2015, 65 patients (age 48±23 years) were listed for heart transplantation. Eight patients (11%) of whom three in high emergency were transplanted without any form of mechanical assistance. Fifty-one patients required a left ventricular assist device (LVAD) Heartware (Heartware Inc., Miami Lakes, FL, USA) as a bridge-to-transplant due to terminal heart failure. Merely 5 listed patients remain without assistance. RESULTS: One patient without assistance and 11 LVAD patients (22%) died on the waiting-list. Meanwhile 10 LVAD patients were transplanted after a 2-year waiting time (770±717 days). Four transplanted patients died of early graft failure none after LVAD explantation. Survival at 1 and 3 years was respectively 78 (72%) and 83 (78%) for transplanted and assisted patients (log-rank P=0.056). Cox multivariable regression analysis identified crash-to-burn patients (P=0.002) and waiting-times over 2 years (P=0.044) as risk factors for early death, while age above 60 (P=0.008) and ischemic aetiology (P=0.029) and pulmonary hypertension (P=0.092) were risk factors for survival. CONCLUSIONS: In times of donor shortage mechanical assistance proves very effective as bridge-to-transplant in patients for whom candidacy follows the standard inclusion procedures. In our settings, a steep increase in LVAD implantation served to salvage patients for whom transplantation became jeopardized due to an ever increasing waiting-time. Circulatory LVAD support could be considered as primary therapy in the future.

The initial experience with the ATS Medical mechanical cardiac valve prosthesis.

BACKGROUND: From May 1994 through October 2000, a total of 1,146 patients underwent valve replacement with the ATS Medical mechanical cardiac valve prosthesis under a study protocol approved by international ethics committees (non-United States participants) or under a United States Food and Drug Administration-approved Investigational Device Exemption study. The study took place at 19 domestic and three international centers. METHODS: As required by the Food and Drug Administration's Heart Valve Guidance Document, only isolated implants were included in the study (double-valve implants were excluded), with operative and follow-up data collected from each center. RESULTS: Aortic valve replacement (AVR) was conducted in 801 patients (309 with coronary bypass) and mitral valve replacement (MVR) in 345 patients (78 with coronary bypass). Overall operative (< or = 30 days post implant) mortality was 2.1% (17 AVR = 2.1%, 7 MVR = 2.0%), 7 of which (AVR = 4, MVR = 3) were valve related. In 2,086 patient-years (1,459 AVR patient-years, 627 MVR patient-years) of follow-up, there were an additional 50 patient deaths of these, 18 were valve related, 9 due to anticoagulant related bleeding, 5 sudden/unexplained, and 1 each after stroke, thrombosis, prosthetic valve endocarditis, and thromboembolism. Late (>30 days post implant) valve-related complications included: transient and chronic thromboembolism (27 AVR (linearized rate 1.85%/patient-year) and 20 MVR (3.19%/patient-year), of which 11/47 (0.53%/patient-year) had chronic deficits, thrombosis (1 AVR = 0.07%/patient-year and 4 MVR = 0.64%/patient-year), paravalvular leak (10 AVR = 0.69%/patient-year and 8 MVR = 1.28%/patient-year), anticoagulant related hemorrhage (34 AVR = 2.33%/patient-year and 8 MVR = 1.28%/patient-year), prosthetic valve endocarditis (3 AVR = 0.21%/patient-year and 2 MVR = 0.32%/patient-year), and structural valve failure or dysfunction (0%). Echocardiographic gradients were proportional to valve size and did not significantly change over the follow-up period. CONCLUSIONS: This study documented the ATS Medical mechanical cardiac valve prosthesis to be a valuable addition to the surgeon's armamentarium in the treatment of cardiac valvular disease.

Bovine glue (BioGlue) is catabolized by enzymatic reaction in the vascular dog model.

PURPOSE: The aim of the study is to explore the feasibility, patency, and histologic changes of a sutureless vascular anastomotic technique using biological glue as sole fixation method. DESCRIPTION: Eight mongrel dogs (+/-15 kg) underwent direct reanastomosis of their transsected iliac arteries. Both ends were placed on a 5-mm balloon and the anastomosis was secured with biological glue (BioGlue, Cryolife, Kennesaw, GA). No intravascular suture material was used. All survivors were angiographically controlled for patency after 6 weeks and 3 months. Then the animals were euthanized and tissues were obtained for histologic and pathologic examination by light and electron microscopy. EVALUATION: All procedures were successful except for 1 animal that died of uncontrollable bleeding at the anastomotic site. All first-time angiographically controlled grafts except three were patent. One animal showed manifest signs of fungal infection. Histology detected early granulocyte infiltration with an important enzymatic reaction adjacent to the surface of glue. Later on, the glue gradually regressed to disappear completely. Fibroblastic neointimal lining was noticed in most of the anastomoses, with some marked differences in the endothelium compared with normal. CONCLUSIONS: Good permeability (57%) was observed in this new sutureless anastomotic technique in the canine model. In contrast to previous reported studies we noticed a clear enzymatic breakdown of the glue before total disappearance. It is not yet known to what extend use of the bovine glue was responsible for this phenomenon.

Lower-intensity anticoagulation for mechanical heart valves: a new concept with the ATS bileaflet aortic valve.

BACKGROUND AND AIM OF THE STUDY: The design of the bileaflet ATS mechanical valve incorporates an open pivot at the hinge mechanism. Total washout of blood at the pivot area seen using three-dimensional computational fluid dynamics modeling may make the valve less vulnerable for clot formation in patients without major thromboembolic risk factors. METHODS: Between January 1993 and June 1999, the ATS valve was implanted in the aortic position in 286 consecutive patients. Patients were allocated prospectively to two groups: group 1 comprised patients in regular sinus rhythm with good left ventricular (LV) function (n = 144); group 2 included patients in non-sinus rhythm and/or with large hypocontractile left ventricles (n = 142). The anticoagulation regime in group 1 was to achieve an INR of 1.5-2.5, rather than to maintain INR strictly at 2.5-3.5 for mechanical valves (as in group 2). RESULTS: Follow up was 99% complete and ranged from 50 to 120 months. Survival (Kaplan-Meier) was respectively 95% and 90% and 90% and 83% at 2 and 5 years in favor of group 1 (p = 0.0055). Multivariate analysis selected advanced age, poor LV function and 'erratic' INR as risk factors for death. Log rank analysis failed to detect any statistical difference in thromboembolism. Bleeding occurred more frequently in group 2 (p = 0.018); independent risk factors for bleeding were the presence of aspirin (p = 0.0164) and advanced age (p = 0.02). CONCLUSION: The excellent group 1 data and outcome encouraged continuation of the low-intensity anticoagulation regime, and should be regarded as a new concept for the treatment of mechanical valve patients.

Twenty-year single-center experience with the medtronic open pivot mechanical heart valve.

BACKGROUND: Since May 1992 the Medtronic Open Pivot mechanical heart valve has been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of the valve. METHODS: Between May 1992 and December 2011 a total of 1,520 valves was inserted into 1,382 consecutive patients (1,012 aortic, 473 mitral, 26 tricuspid, 9 pulmonary). The mean age of the patients was 61±13.2 years. Preoperatively, 65% of the patients were in New York Heart Association (NYHA) class III or greater. Frequent comorbidities included atrial fibrillation (n=419), coronary disease (n=357), and diabetes (n=255). The 99% complete follow-up totaled 10,527 patient-years (range 12 to 244 months). RESULTS: Ninety-day mortality was 5.2% (n=73, 8 valve related). Of the 550 total deaths, 240 were cardiac and 56 valve related. Multivariate analysis selected age, NYHA III or greater, concomitant coronary revascularization, and respiratory insufficiency as risk factors for death. Renal failure was considered a risk factor in the aortic and atrial fibrillation in the mitral subgroup. Erratic international normalized ratio (INR), NYHA class III or greater, and non-sinus rhythm were risk factors for thromboembolism; likewise redo operations in the aortic subgroup. Erratic INR and age were risk factors for bleeding as were over-coagulation and coronary revascularization in the aortic subgroup and redo operations and renal failure in mitral patients. CONCLUSIONS: This 20-year experience demonstrated excellent clinical outcomes with no structural valve failure. Odds ratio defined aortic patients as the lowest risk for adverse events. By contrast atrial fibrillation and elderly age, in combination with instable anticoagulation, yielded the worst long-term results.

Sutureless replacement of aortic valves with St Jude Medical mechanical valve prostheses and Nitinol attachment rings: feasibility in long-term (90-day) pig experiments.

OBJECTIVE: Nitinol attachment rings (devices) used to attach mechanical aortic valve prostheses suturelessly were studied in long-term (90 days) pig experiments. METHODS: The aortic valve was removed and replaced by a device around a St Jude Medical mechanical valve prosthesis in 10 surviving pigs. Supravalvular angiography was done at the end of the operation. No coumarin derivates were given. RESULTS: No or minimal aortic regurgitation was confirmed in all surviving pigs at the end of the operation. Total follow-up was 846 days. In 4 pigs, follow-up was shorter than 90 days (28-75 days); the other 6 pigs did reach 90 days' survival or more. Repeat angiography in 4 pigs at the end of follow-up confirmed the unchanged position of the device at the aortic annulus, without aortic regurgitation. At autopsy, in all pigs the devices proved to be well grown in at the annulus, covered with endothelium, and sometimes tissue overgrowth related to not using coumarin derivates. There was no case of para-device leakage, migration, or embolization. No damage to surrounding anatomic structures or prosthetic valves was found. CONCLUSIONS: Nitinol attachment rings can be used to replace the aortic valve suturelessly with St Jude Medical mechanical aortic valve prostheses, without para-device leakage, migration, or damage to the surrounding tissues, in long-term pig experiments during a follow-up of 90 days or more. Refraining from anticoagulation in pigs with mechanical valve prostheses can lead to tissue overgrowth of the valve prosthesis. Further studies are needed to determine long-term feasibility of this method in human beings.

Extracorporeal bubbles: a word of caution.

OBJECTIVES: Gaseous microemboli (GME) are a cause of neurocognitive deficit postcardiac surgery with cardiopulmonary bypass. However, the measurement of microbubbles during cardiopulmonary bypass is not easy, because blood is an opaque fluid and contains microparticles. Recently, two new microbubble counters, the Gampt BC200 and the emboli detection and classification (EDAC) quantifier, were developed for use during cardiac surgery. The accuracy of both devices was validated against industrial standards. METHODS: A clear blood analogue (30%/70% glycerol-water) was pumped, by means of a rollerpump out of a partially filled arterial line screen filter with a nominal pore size of 20 microm. Downstream the pump, all test sensors and an optical cuvette, were inserted in a vertically mounted 3/8 inch tubing. Measurements were taken at flows of 405, 1080, 3000 and 6000 ml/min. Backlight shadowgraphy and optical counting were used as industrial reference techniques for measuring size and counts. RESULTS: On average the EDAC quantifier underestimates average bubble diameter by 35+/-1%, 13+/-8%, 71+/-7% and 33+/-4% at 405, 1080, 3000 and 6000 ml/min, respectively. The Gampt BC200 has good sizing agreement at 1080 ml/min (+5+/-17%) and 3000 ml/min (+33+/-6%) but overestimates average diameter by 220+/-40% and 295+/-49% at 405 and 6000 ml/min, respectively. Both devices only partially count the number of microbubbles at higher flows. At 3 l/min the EDAC counts 38%, the Gampt 18% of total counts and at 6 l/min both the EDAC and Gampt only count 3% of total counts. CONCLUSIONS: Both the EDAC and Gampt can be used in a clinical setting for monitoring basal GME production. However, both devices have some major limitations when used for studying 'worst case' scenarios. One should take great caution when correlating measured data with neurocognitive outcome. Finally, results obtained by one device in a first study cannot be compared nor exchanged with results from the other device in a second study.

Autologous glue: part of the sticky mystery unraveled.

OBJECTIVE: The aim of the study was to evaluate the safety and efficacy of an autologous surgical tissue adhesive. METHODS: Autologous glue was made out of canine concentrated plasma proteins mixed with 7.5% glutaraldehyde. Tensile strength and cytotoxicity of the autologous glue were tested. In a dog model, 8 transectioned iliac arteries were reanastomosed by using the animal's glue as the sole fixation method. After 120 days, all animals were angiographically controlled for patency and killed for histologic and immunohistochemical examination of the anastomosis. RESULTS: The autologous glue showed sufficient tensile strength (557 +/- 135 N/mm2). The elasticity of the glue is influenced by variations of concentrations in both proteins and glutaraldehyde. Glutaraldehyde remained cytotoxic, even at low concentrations of 2.5%. All operative procedures were successful. Angiographs performed before animal death showed all but 1 vessel to be patent and showed manifest compression signs in 3 anastomoses. Histological examination revealed only a foreign-body reaction adjacent to the surface of the glue. The autologous glue does not trigger any immune response on immunochemistry. Because fibroblastic neo-endothelial lining was near to normal, potential glutaraldehyde leaching does not seem too harmful for the vascular juncture in the dog model. CONCLUSIONS: Autologous glutaraldehyde glue has been used successfully as a vascular adhesive. In contrast to our previous studies with heterologous glue, we did not find a fierce acute inflammatory reaction indicating immune triggering. Nevertheless, glutaraldehyde remains a cytotoxic cross-linker. It is yet not known whether autologous glutaraldehyde glue can be used safely in clinical practice.

Fast sutureless implantation of mechanical aortic valve prostheses using Nitinol attachment rings: Feasibility in acute pig experiments.

OBJECTIVE: There is a need for fast sutureless implantation of valve prostheses with a better outcome than that of current valved stents. METHODS: The suture ring of a St Jude mechanical valve prosthesis (St Jude Medical, Minneapolis, Minn) was replaced by a proprietary non-stent-based attachment ring made of Nitinol memory metal (Endosmart, Stutensee, Germany) and covered with textile. In acute pig experiments, the aortic valve was removed and the device was introduced in a temporary stretched shape and activated by removing constrainers and heating to reach its final attachment shape. RESULTS: The devices could be actuated within seconds. Echocardiography showed normal prosthetic valve and heart function. No paradevice leakage was demonstrated by supravalvular angiography. At autopsy, no abnormalities were found in the surrounding structures or valve prostheses. Pulling tests showed the strong adhesive power of Nitinol attachment rings withstanding up to 5 kg of pulling force. CONCLUSION: Nitinol memory metal attachment rings, covered with textile, around suture ring-denuded St Jude mechanical aortic valve prostheses enabled fast and strong sutureless implantation in acute pig experiments. Further studies in chronic animal models and humans are needed to determine long-term safety.

Hydrodynamic evaluation of kangaroo aortic valve matrices for tissue valve engineering.

We evaluated the hydrodynamic performance of kangaroo aortic valve matrices (KMs) (19, 21, and 23 mm), as potential scaffolds in tissue valve engineering using a pulsatile left heart model at low and high cardiac outputs (COs) and heart rates (HRs) of 60 and 90 beats/min. Data were measured in two samples of each type, pooled in two CO levels (2.1 +/- 0.7 and 4.2 +/- 0.6 L/min; mean +/- standard errors on the mean), and analyzed using analysis of variance with CO level, HR, and valve type as fixed factors and compared to similar porcine matrices (PMs). Transvalvular pressure gradient (DeltaP) was a function of HR (P < 0.001) and CO (P < 0.001) but not of valve type (P = 0.39). DeltaP was consistently lower in KMs but not significantly different from PMs. The effective orifice area and performance index of kangaroo matrices was statistically larger for all sizes at both COs and HRs.

Lower anticoagulation for mechanical heart valves: experience with the ATS bileaflet valve.

BACKGROUND: The design of the bileaflet ATS (ATS Medical Inc., Minneapolis, USA) mechanical valve incorporates an open pivot at the hinge mechanism. Total washout of the blood at the pivot area was observed using 3-D computational fluid dynamics modelling. This phenomenon could make the valve less vulnerable to clot formation in patients without major thromboembolic risk factors. METHODS: From January 1993 to June 1999, 286 consecutive patients had the ATS valve inserted in the aortic position. Patients were divided into two groups. Group 1 comprised all patients in regular sinus rhythm with good left ventricular function (144 patients). Group 2 included patients in non-sinus rhythm and/or with large hypocontractile left ventricles (142 patients). The anticoagulation regime in group 1 was used to obtain an international normalised ratio (INR) between 1.5 and 2.5. This contrasts with our regular aim to maintain the INR strictly between 2.5 and 3.5 for all mechanical valves, as achieved in group 2. RESULTS: The follow-up period (99% completeness) ranged from 18 to 84 months. Survival (Kaplan-Meier) was 97 and 98% and 92 and 81% at 1 and 5 years in group 1 and group 2, respectively (P = 0.12). Log rank analysis failed to detect a statistical difference in thromboembolism or bleeding between both groups (P > 0.05). However, trends were in favour of group 1. Univariate analysis selected poor ventricular function and an 'erratic' INR value (P = 0.002) as risk factors for death. The sole independent risk factor for bleeding was the use of aspirin (P = 0.025). CONCLUSIONS: The excellent group 1 data and outcome encouraged us to continue our low intensive anticoagulation regime and perhaps should be regarded as a new concept for treatment of selected mechanical valve patients.