Is 300 Seconds ACT Safe and Efficient during MiECC Procedures?

INTRODUCTION: The recommended minimum activated clotting time (ACT) level for cardiopulmonary bypass (CPB) of 480 seconds originated from investigations with bubble oxygenators and uncoated extracorporeal circulation (ECC) systems. Modern minimal invasive ECC (MiECC) systems are completely closed circuits containing a membrane oxygenator and a tip-to-tip surface coating. We hypothesized that surface coating and the "closed-loop" design allow the MiECC to safely run with lower ACT levels and that an ACT level of 300 seconds can be safely applied without thromboembolic complications. The aim of this study was to investigate the potential risks during application of reduced heparin levels in patients undergoing coronary surgery. METHODS: In this study, 68 patients undergoing coronary artery bypass grafting with MiECC were randomized to either the study group with an ACT target of 300 seconds or the control group with an ACT of 450 seconds. All other factors of MiECC remained unchanged. RESULTS: The study group received significantly less heparin and protamine (heparin [international units] median [min-max], Red_AC: 32,800 [23,000-51,500] vs. Full_AC: 50,000 [35,000-65,000] p < 0.001; protamine [international units], Red_AC: 18,000 [10,000-35,000] vs. Full_AC: 30,000 [20,000-45,000] p < 0.001). The ACT in the study group was significantly lower at the start of MiECC (mean ± standard deviation: study group 400 ± 112 vs. control group 633 ± 177; p < 0.0001). Before termination of CPB the ACT levels were: study group 344 ± 60 versus control group 506 ± 80. In both groups, the values of the endogenous thrombin potential (ETP) decreased simultaneously. None of the study participants experienced thromboembolic complications. CONCLUSION: Since no evidence of increased thrombin formation (ETP) was found from a laboratory standpoint, we concluded that the use of MiECC with a reduced anticoagulation strategy seems possible. This alternative anticoagulation strategy leads to significant reduction in dosages of both heparin and protamine. We can confidently move forward with investigating this anticoagulation concept. However, to establish clinical safety of ACT below 300 seconds, we need larger clinical studies.

Shed-blood-separation and cell-saver: an integral Part of MiECC? Shed-blood-separation and its influence on the perioperative inflammatory response during coronary revascularization with minimal invasive extracorporeal circulation systems - a randomized controlled trial.

OBJECTIVE: The postoperative systemic inflammatory response after cardiopulmonary bypass (CPB) is still an undesirable side-effect after cardiac surgery. It is most likely caused by blood contact with foreign surfaces and by the surgical trauma itself. However, the recirculation of activated shed mediastinal blood is another main cause of blood cell activation and cytokine release. Minimal invasive extracorporeal circulation (MiECC) comprises a completely closed circuit, coated surfaces and the separation of suction blood. We hypothesized that MiECC, with separated cell saved blood, would induce less of a systemic inflammatory response than MiECC with no cell-saver. The aim of this study was, therefore, to investigate the impact of cell washing shed blood from the operating field versus direct return to the ECC on the biomarkers for systemic inflammation. MATERIAL AND METHODS: In the study, patients with MiECC and cell-saver were compared with the control group, patients with MiECC and direct re-transfusion of the drawn blood shed from the surgical field. RESULTS: High amounts of TNF-α (+ 120% compared to serum blood) were found in the shed blood itself, but a significant reduction was demonstrated with the use of a cell-saver (TNF-α ng/l post-ECC 10 min: 9.5±3.5 vs. 19.7±14.5, p<0.0001). The values for procalcitonin were not significantly increased in the control group (6h: 1.07±3.4 vs. 2.15±9.55, p=0.19) and lower for C-reactive protein (CRP) (24h: 147.1±64.0 vs.134.4±52.4 p=0.28). CONCLUSION: The use of a cell-saver and the processing of shed blood as an integral part of MiECC significantly reduces the systemic cytokine load. We, therefore, recommend the integration of cell-saving devices in MiECC to reduce the perioperative inflammatory response.

ACCURACY OF NONINVASIVE ANESTHETIC MONITORING IN THE ANESTHETIZED GIRAFFE (GIRAFFA CAMELOPARDALIS).

This study evaluated the accuracy of pulse oximetry, capnography, and oscillometric blood pressure during general anesthesia in giraffes (Giraffa camelopardalis). Thirty-two giraffes anesthetized for physiologic experiments were instrumented with a pulse oximeter transmittance probe positioned on the tongue and a capnograph sampling line placed at the oral end of the endotracheal tube. A human size 10 blood pressure cuff was placed around the base of the tail, and an indwelling arterial catheter in the auricular artery continuously measured blood pressure. Giraffes were intermittently ventilated using a Hudson demand valve throughout the procedures. Arterial blood for blood gas analysis was collected at multiple time points. Relationships between oxygen saturation as determined by pulse oximetry and arterial oxygen saturation, between arterial carbon dioxide partial pressure and end-tidal carbon dioxide, and between oscillometric pressure and invasive arterial blood pressure were assessed, and the accuracy of pulse oximetry, capnography, and oscillometric blood pressure monitoring evaluated using Bland-Altman analysis. All three noninvasive methods provided relatively poor estimates of the reference values. Receiver operating characteristic curve fitting was used to determine cut-off values for hypoxia, hypocapnia, hypercapnia, and hypotension for dichotomous decision-making. Applying these cut-off values, there was reasonable sensitivity for detection of hypocapnia, hypercapnia, and hypotension, but not for hypoxemia. Noninvasive anesthetic monitoring should be interpreted with caution in giraffes and, ideally, invasive monitoring should be employed.

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output.

Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation.

OBJECTIVES: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. DESIGN: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight pigs died and seven were excluded due to mediastinal infection (n = 2) or failure to produce MR (n = 5). Thus, 28 pigs were included and were divided into three groups: controls (n = 12), mild MR (mMR; n = 10), and moderate to severe MR (sMR; n = 6). The change in LV internal diameter in diastole (LVIDd) from baseline to follow-up was significantly higher in the sMR group compared to that of the control group (P = 0.0017). Furthermore, LV weight was significantly increased in the mMR (P = 0.047) and the sMR (P = 0.0087) groups compared to that of the control group. CONCLUSIONS: A new model for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs.

Entire Mitral Valve Reconstruction Using Porcine Extracellular Matrix: Adding a Ring Annuloplasty.

PURPOSE: This study investigated the implications of inserting a flexible annuloplasty ring after reconstructing the entire mitral valve in a porcine model using a previously investigated tube graft design made of 2-ply small intestinal submucosa extracellular matrix (CorMatrix®). METHODS: An acute model with eight 80-kg pigs, each acting as its own control, was used. The entire mitral valve was reconstructed with a 2-ply small intestinal submucosa extracellular matrix tube graft (CorMatrix®). Subsequently, a Simulus® flexible ring was inserted. The characterization was based on mitral annular geometry and valvular dynamics with sonomicrometry and echocardiography. RESULTS: After adding the ring annuloplasty, the in-plane annular dynamics were more constant throughout the cardiac cycle compared to the reconstruction alone. However, the commissure-commissure distance was statistically significantly decreased [35.0 ± 3.4 mm vs. 27.4 ± 1.9 mm, P < 0.001, diff = - 7.6 mm, 95% CI, - 9.8 to (-5.4) mm] after ring insertion, changing the physiological annular D-shape into a circular shape which created folds at the coaptation zone resulting in a central regurgitant jet on color Doppler. CONCLUSION: We successfully reconstructed the entire mitral valve using 2-ply small intestinal submucosal extracellular matrix (CorMatrix®) combined with a flexible annuloplasty. The annuloplasty reduced the unphysiological systolic widening previously found with this reconstructive technique. However, the Simulus flex ring changed the physiological annular D-shape into a circular shape and hindered a correct unfolding of the leaflets. Thus, we do not recommend a flexible ring in conjunction with this reconstructive technique; further investigations are needed to discover a more suitable remodelling annuloplasty.

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.

BACKGROUND: Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS: We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS: Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION: Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING: UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

Surgical relocation of the papillary muscles in functional ischemic mitral regurgitation: what are the forces of the relocation stitches acting on the myocardium?

BACKGROUND AND AIM OF THE STUDY: In patients with chronic functional ischemic mitral regurgitation (FIMR), papillary muscle relocation has the potential to induce reverse left ventricular remodeling. However, in order to optimize function and durability, the forces imposed on the left ventricular myocardium by papillary muscle relocation should be assessed. METHODS: Eight pigs with FIMR were subjected to down-sized ring annuloplasty in combination with relocation of the anterior (5 mm) and posterior (15 mm) papillary muscles towards the respective trigone. Papillary muscle relocation was obtained by a 2-0 expanded polytetrafluoroethylene stitch fixed to the trigone, exteriorized through the myocardium overlying the papillary muscle, and fixed to an epicardial disc. Tension in these stitches was measured at a systolic blood pressure > 80 mmHg using a custom-made sliding caliper with a strain gauge mounted in line. This allowed assessment of the cyclic change from minimal diastolic to maximum systolic papillary muscle relocation stitch tension. RESULTS: Maximum cyclic change in the posterior papillary muscle (PPM) stitch tension was 1.1 N at 15 mm relocation. In comparison, the anterior papillary muscle (APM) tension was increased to a maximum of 1.4 N with only 5 mm relocation. Surprisingly, during each step of isolated PPM relocation, the APM stitch tension increased concomitantly, but in contrast APM relocation did not influence the magnitude of PPM stitch tension. There was no statistically significant difference between cyclic changes in APM and PPM stitch tension at any step of relocation. CONCLUSION: Papillary muscle relocation using stitches attached between epicardial discs and respective trigones induced a cyclic change in papillary muscle relocation stitch tension of 1.1-1.4 N. These values were in the range of normal tension in the mitral valve apparatus, and equivalent to only 19-24% of the total papillary muscle forces. Therefore, this technique does not appear to induce a non-physiologically high cyclic load on the mitral valve complex.

Evaluation of aortic wall strength in human immunodeficiency virus associated thoracic ascending aortic aneurysm: a pilot study.

Background: Human immunodeficiency virus (HIV) associated aortopathy is associated with considerable morbidity and mortality. The pathophysiology of aortic wall strength in HIV thoracic aortic aneurysm has not been studied. Methods: The patients with HIV associated thoracic ascending aortic aneurysm (TAAA) were enrolled in the study and underwent surgery as part of their routine management. We compared collagen quantity in aneurysmal and non-aneurysmal aortic tissue in TAAA with regards to hydroxyproline concentration as a surrogate measure for collagen content and sent aneurysmal aorta for routine clinical histological assessment. This data was analysed to identify potential relations between aortic aneurysm formation and the collagen content of the aortic wall. Results: The study included 12 patients with HIV aortopathy (9 females, median age 49 years). In total 33 tissue samples were investigated (14 aneurysmal, 13 non-aneurysmal aortic tissue and 6 aortic leaflets). There was no difference in hydroxyproline concentration of aneurysmal aortic tissue and seemingly normal tissue [19.40 (15.19-22.98) vs. 20.85 (15.55-25.83) µg/mg; P=0.82]. No difference was noted in hydroxyproline concentration among aneurysmal, seemingly normal aortic tissue and aortic valve leaflets [19.40 (15.19-22.98) vs. 20.85 (15.55-25.83) vs. 19.09 (13.94-22.00) µg/mg; P=0.86]. Histology showed fragmentation of elastin fibres in 50% of the cases. Conclusions: No difference in collagen concentration in the aneurysmal and non-aneurysmal aortic tissue was noted. However, most of the aneurysmal tissue had fragmentation of elastin fibres.

Aortic root distensibility after subcoronary stentless valve implantation.

BACKGROUND AND AIM OF THE STUDY: The preservation of aortic root dynamics is considered important for the durability of aortic valve bioprostheses. Stentless heart valves are believed to support physiologic biomechanics. To date, dynamic analysis has been limited to the full root prosthesis, and exclusively in the radial direction. The study aim was to investigate and compare the radial and longitudinal aortic root distensibilities of subcoronary stentless valves, and of stented and native pig valves. METHODS: Stented pericardial (Mitroflow) or stentless (Solo, Toronto SPV) valve prostheses, or native porcine valves, were investigated in 32 pigs. Postoperatively, 12 sonomicrometry crystals were placed on the aortic root in order to measure aortic root distensibility, in both radial and longitudinal directions. RESULTS: Sonomicrometry data were obtained from 23 pigs (72%). At the annular level, the native and Solo valves were significantly more distensible in a radial direction than the Mitroflow valve (p = 0.04). However, at the level of the sinotubular junction (STJ), commissures and aorta, the native valve was significantly more distensible than all of the artificial valves (p = 0.006, p = 0.006, and p = 0.02, respectively). The Solo valve exhibited less longitudinal distensibility than the Toronto SPV and Mitroflow valves. The Toronto SPV initiated a radial expansion at the STJ significantly later in the cardiac cycle than did both the Solo and native valves (p = 0.03), but showed no difference compared to the Mitroflow valve. Longitudinal expansion between the annulus and the STJ started significantly earlier for the Solo valve than for both the Toronto SPV (p = 0.03) and Mitroflow (p = 0.02) valves. CONCLUSION: The Solo valve proved to be superior in maintaining annular distensibility immediately following implantation when compared to the Mitroflow valve. The Solo valve did not, however, preserve longitudinal distensibility as well as the other investigated valves. Finally, the Solo valve appeared to provide a more physiologic aortic root expansion pattern than its prosthetic counterparts.

Mitral Annular Forces and Their Potential Impact on Annuloplasty Ring Selection.

Objectives: To provide an overview that describes the characteristics of a mitral annuloplasty device when treating patients with a specific type of mitral regurgitation according to Carpentier's classification of mitral regurgitation. Methods: Starting with the key search term "mitral valve annuloplasty," a literature search was performed utilising PubMed, Google Scholar, and Web of Science to identify relevant studies. A systematic approach was used to assess all publications. Results: Mitral annuloplasty rings are traditionally categorised by their mechanical compliance in rigid-, semi-rigid-, and flexible rings. There is a direct correlation between remodelling capabilities and rigidity. Thus, a rigid annuloplasty ring will have the highest remodelling capability, while a flexible ring will have the lowest. Rigid- and semi-rigid rings can furthermore be divided into flat and saddled-shaped rings. Saddle-shaped rings are generally preferred over flat rings since they decrease annular and leaflet stress accumulation and provide superior leaflet coaptation. Finally, mitral annuloplasty rings can either be complete or partial. Conclusions: A downsized rigid- or semi-rigid ring is advantageous when higher remodelling capabilities are required to correct dilation of the mitral annulus, as seen in type I, type IIIa, and type IIIb mitral regurgitation. In type II mitral regurgitation, a normosized flexible ring might be sufficient and allow for a more physiological repair since there is no annular dilatation, which diminishes the need for remodelling capabilities. However, mitral annuloplasty ring selection should always be based on the specific morphology in each patient.

Annular and subvalvular dynamics after extracellular matrix mitral tube graft implantation in pigs.

OBJECTIVES: Entire mitral valve reconstruction with an extracellular matrix tube graft is a potential candidate to overcome the current limitations of mechanical and bioprosthetic valves. However, clinical data have raised concern with respect to patch failure. The aim of our study was to evaluate the impact of extracellular matrix mitral tube graft implantation on mitral annular and subvalvular regional dynamics in pigs. METHODS: A modified tube graft design made of 2-ply extracellular matrix was used (CorMatrix®; Cardiovascular Inc., Alpharetta, GA, USA). The reconstructions were performed in an acute 80-kg porcine model (N = 8), where each pig acted as its own control. Haemodynamics were assessed with Mikro-Tip pressure catheters and mitral annular and subvalvular geometry and dynamics with sonomicrometry. RESULTS: Catheter-based peak left atrial pressure and pressure difference across the mitral and aortic valves in the reconstructions were comparable to the values seen in the native mitral valves. Also comparable were maximum mitral annular area (755 ± 100 mm2), maximum septal-lateral distance (29.7 ± 1.7 mm), maximum commissure-commissure distance (35.0 ± 3.4 mm), end-systolic annular height-to-commissural width ratio (10.2 ± 1.0%) and end-diastolic interpapillary muscle distance (27.7 ± 3.3 mm). Systolic expansion of the mitral annulus was, however, observed after reconstruction. CONCLUSIONS: The reconstructed mitral valves were fully functional without regurgitation, obstruction or stenosis. The reconstructed mitral annular and subvalvular geometry and subvalvular dynamics were found in the same range to those in the native mitral valve. A regional annular ballooning effect occurred that might predispose to patch failure. However, the greatest risk was found at the papillary muscle attachments.

Impact of papillary muscle relocation as adjunct procedure to mitral ring annuloplasty in functional ischemic mitral regurgitation.

BACKGROUND: The optimal surgical treatment in functional ischemic mitral regurgitation (FIMR) remains controversial. Recently, a posterior papillary muscle relocation (PMR) technique as adjunct procedure to ring annuloplasty has been proposed to prevent recurrent FIMR. In the present study, we used 3D cardiac MRI to assess the impact of relocating both papillary muscles as adjunct procedure to downsized ring annuloplasty on mitral leaflet coaptation geometry in FIMR pigs. METHODS AND RESULTS: Eleven FIMR pigs were randomized to downsized ring annuloplasty (RA; n=6) or RA combined with PMR (RA+PMR, n=5). In the RA+PMR group, a 2-0 Gore-Tex suture was attached to each trigone, exteriorized through the corresponding papillary muscle, mounted on an epicardial pad, and tightened to relocate the myocardium adjacent to the anterior and posterior papillary muscles 5 and 15 mm, respectively. Using 3D MRI, the impact from these interventions on leaflet geometry was assessed. The distance from the posterior papillary muscle to the anterior trigone was reduced significantly more (median values) in the RA+PMR compared with RA animals at end-diastole (-7.9% versus 3.8%, P<0.01) and end-systole (-9.7% versus 2.5%, P=0.02). Accordingly, lateral tethering of the coaptation point (median values) was reduced significantly more in RA+PMR compared with RA animals (-42.8% versus -29.1%, P<0.01). CONCLUSIONS: Adding papillary muscle relocation to downsized ring annuloplasty reduced lateral leaflet tethering in a porcine experimental model of FIMR. Therefore, this technique holds promise for reducing persistent and recurrent FIMR in patients.

Does down-sized ring annuloplasty induce papillary muscle relocation in ischemic mitral regurgitation?

BACKGROUND AND AIM OF THE STUDY: Down-sized ring annuloplasty has been shown to induce left ventricular remodeling in patients with functional ischemic mitral regurgitation (FIMR). To determine if this remodeling comprised papillary muscle (PM) relocation, a chronic FIMR porcine model was used to assess the impact on three-dimensional (3D) PM positioning, by implanting a down-sized rigid ring annuloplasty. METHODS: Six out of ten FIMR pigs that underwent a down-sized mitral ring annuloplasty (CE Classic size 26-28) survived for six weeks postoperatively. 3D cardiac magnetic resonance imaging was carried out at one week preoperatively, and repeated at one and six weeks postoperatively, to assess the direct distances (in mm) from the anterior papillary muscle (APM) and posterior papillary muscle (PPM) to each trigone. Three reference planes were also constructed to determine APM and PPM displacement in the lateral, anterioposterior, and apical directions. RESULTS: Relative to the preoperative situation, at one week postoperatively a reduced displacement of the APM was observed in an anterior direction (from 18.8 to 16.2 mm; p < 0.05) and from the posterior trigone (from 40.5 to 37.4 mm; p < 0.05) at end-diastole. Relative to one week postoperatively, at six weeks postoperatively a reduced PPM displacement was observed from the anterior trigone (43.0 versus 42.0 mm; p < 0.05) at end-systole. Relative to the preoperative situation, no overall tendency of surgically induced PM relocation was observed at one or six weeks postoperatively. CONCLUSION: A down-sized ring annuloplasty did not induce an overall pattern of PM relocation in pigs with chronic FIMR.

Leaflet opening and closing dynamics of stentless bioprostheses.

BACKGROUND AND AIM OF THE STUDY: Stiffening of the aortic root may entail asynchronous aortic leaflet movement, and result in enhanced flexion-stress in specific areas of the cusps. As stentless prostheses are more flexible than their stented counterparts, they are more likely to exhibit physiologic leaflet movements. The study aim was to compare leaflet movement dynamics in stented versus non-stented aortic valves implanted in pigs. METHODS: Aortic bioprostheses were implanted surgically into adult pigs as follows: stented Mitroflow (n = 6), stentless Solo (n = 5), and stentless Toronto SPV (n = 4). In five control animals, the native aortic valve leaflets were untouched. Postoperatively, the aortic valve was displayed by epicardial echocardiography. M-mode display of the non-coronary leaflet was applied to assess rapid valve-opening velocity (V(open)) and rapid valve-closing velocity (V(close)). RESULTS: The mean V(open) values were 29.2, 25.5, 37.8, and 31.9 cm/s, respectively, for the native, Toronto SPV, Solo, and Mitroflow valves. The mean V(close) values were 23.2, 21.9, 34.1, and 34.3 cm/s, respectively. A comparison of V(open) values showed no statistically significant difference between the valves. The Mitroflow and Solo valves yielded significantly higher V(close) values than the native and Toronto SPV valves. The Toronto SPV exhibited marked systolic leaflet folding. CONCLUSION: The stent of a bioprosthetic valve does not appear to affect leaflet velocities when compared to the stentless bioprosthetic valve. The Solo and Mitroflow valves closed more abruptly than the porcine native aortic valve; however, the Toronto SPV valve displayed diverging systolic leaflet movement patterns.

In-vivo blood velocity and velocity gradient profiles downstream of stented and stentless aortic heart valves.

BACKGROUND AND AIM OF THE STUDY: Abnormal flow conditions across aortic bioprosthetic valves may result in degenerative processes. Thus, it is important to implant biological valve prostheses with velocity profiles similar to those of native valves. The study aim was to compare blood velocity and velocity gradient profiles downstream of stented and stentless aortic valves implanted in pigs, and in native porcine valves. METHODS: Stented valve prostheses (Mitroflow, n = 7) or stentless valve prostheses (Solo, n = 5 or Toronto SPV, n = 7) were implanted into pigs; the native valve was retained in eight animals. After weaning the animals from cardiopulmonary bypass, cardiac magnetic resonance imaging was performed to determine the blood velocities and velocity gradient profiles. RESULTS: The native valves had a significantly lower peak velocity (92 +/- 26 cm/s) than the artificial valves (Solo: 247 +/- 107 cm/s; Toronto: 252 +/- 41 cm/s; Mitroflow: 229 +/- 18 cm/s). The native valves exhibited a flat velocity profile during systole, whereas the Solo valve, and especially the Toronto SPV valve, displayed more parabola-shaped velocity profiles; velocity profiles downstream of the Mitroflow valve exhibited a flat shape. The native valves had a lower mean velocity gradient at peak systole (p < 0.0001). The velocity gradient percentage above mean was lowest for the native valve (0.14 +/- 0.11; p < 0.0001), while the Mitroflow valve had a percentage of 0.57 +/- 0.09, which was lower than the Solo valve (0.69 +/- 0.12; p = 0.074), and significantly lower than the Toronto valve (0.70 +/- 0.08; p = 0.015). All valves displayed high velocity gradients adjacent to the aortic wall; in particular, the Toronto SPV which also had high velocity gradients at the center of the vessel. CONCLUSION: All of the artificial valves tested had a significantly higher mean velocity gradient and peak velocity than the native valves. However, the Mitroflow had a mean velocity and a velocity gradient percentage lower than the two stentless valves. The Solo and Mitroflow valves displayed velocity profiles most like native valves, while the Toronto valve had a more irregular asymmetric velocity profile.

Recellularization of decellularized mitral heart valves in juvenile pigs.

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde-preserved bioprosthetic heart valves are non-viable and have a limited durability because of calcification, tissue wear, and inflammation, especially in children. Decellularized porcine heart valves, when treated with deoxycholic acid (DOA), have exhibited complete recellularization and an absence of calcification when implanted into the pulmonary position in juvenile sheep. The study aim was to determine the degree of recellularization and calcification in DOA-treated heart valve prostheses in the mitral position in juvenile pigs. METHODS: A mitral heart valve prosthesis was implanted into each of 17 pigs, and subsequently explanted and fixed in formaldehyde after between five and 26 weeks. A gross pathologic assessment, high-resolution X-ray imaging and histological examination were then performed on each valve. RESULTS: Eight pigs survived the observational period. Five valves had only a slight fibrin deposition and calcification foci within the fibrin deposits. Three valves had severe thrombotic material deposits with disseminated calcification and valve stenosis, and one valve had infective endocarditis. A myofibroblast-like cell ingrowth was observed at different locations of the valve housing in all explanted heart valves, but ingrowth in the basal part of the cusp matrix was limited. In four valve prostheses, endothelial cells covered up to 10% of the cusp surface after six months. Inflammatory cells were observed in large numbers in those valves showing endocarditis and severe thrombosis, but in only limited numbers in the other valves. CONCLUSION: All valves showed the deposition of fibrin and platelet material, in three cases to a severe degree. A limited ingrowth of both endothelial and myofibroblast-like cells was observed in five valves in which calcification was limited to a few commissural foci. The non-endothelialized surface of the decellularized valves makes them very susceptible to platelet and fibrin deposition; however, slow revitalization seems possible.

Comparison between TachoComb and TachoSil for surgical hemostasis in arterial bleeding: an animal experimental study.

BACKGROUND: TachoComb has frequently been used for the treatment of both venous and arterial bleeding. However, anaphylactic reactions have been reported after repeated use of hemostatic agents containing aprotinin such as TachoComb. Because aprotinin is also associated with risk of renal failure, manufacturing of a new product--TachoSil--which lacks aprotinin seems a logic evolvement. Furthermore, thrombin on the TachoSil material has been changed from bovine in TachoComb to human origin. These changes in the biochemical composition could lead to changes in the hemostatic performance. Therefore, we aimed to disclose any difference in hemostatic efficacy of the two products. METHODS: Twelve 70-kg pigs had controlled insults to the thoracic aorta with and without heparin administration. The iatrogenic lesion was randomly covered with either TachoComb or TachoSil and the time to hemostasis was measured. RESULTS: Time to hemostasis when using TachoSil compared with TachoComb was increased 14% (-13% to 48%) with heparin and 10% (-26% to 66%) without heparin (mean +/- 95% confidence interval; p > 0.05 in both). Time to hemostasis with heparin administration increased significantly in both treatments: TachoComb 80% (26%-156%) (p = 0.001) and TachoSil 75% (18%-158%) (p = 0.005). CONCLUSION: We found neither statistical nor clinical evidence that TachoComb should have better hemostatic properties than does TachoSil in arterial bleeding. Both TachoSil and TachoComb can be used with heparin administration, but significant prolongation of the time to hemostasis is to be expected for both products. TachoSil should be preferred to TachoComb due to the potential lower risk of side effects when using the former.

Mitral Valve Posterior Leaflet Reconstruction Using Extracellular Matrix: In Vitro Evaluation.

PURPOSE: To investigate the anatomical and functional effects of complete surgical reconstruction of the posterior mitral leaflet and associated chordae tendineae with a patch made of 2-ply small intestinal submucosal extracellular matrix in vitro. METHODS: Seven explanted mitral valves with intact subvalvular apparatus from 80-kg pigs were evaluated in a left heart simulator and served as their own controls. After testing the native valve, the mitral posterior leaflet and associated chordae tendineae were excised and reconstructed by using the 2-ply small intestinal submucosa extracellular matrix patch. The characterization of the reconstruction was based on geometric data from digital images, papillary muscle force, annular tethering force and leaflet pressure force. RESULTS: The reconstructed valves were fully functional without regurgitation, tearing or rupture during incrementally increased pressure from 0 to 120 mmHg. The leaflet areas were preserved after reconstruction, with a normal configuration of the coaptation line. However, the coaptation midpoint moved posteriorly after reconstruction (A2: 15.8 ± 1.4 vs. 18.9 ± 1.5 mm, p = 0.002, diff = 3.1 mm, 95% CI 1.3 to 4.8 mm). The anterior papillary muscle force increased significantly (3.9 vs. 4.6 N, p = 0.029, diff = 0.7 N, 95% CI 0.1 to 1.4 N at 120mmHg) after reconstruction. The posterior papillary muscle force, leaflet pressure force and annular pressure force did not change significantly. CONCLUSIONS: In this in vitro model, mitral valve anatomy and function were comparable between the native mitral valve and our new surgical technique for complete reconstruction of the posterior mitral leaflet and associated chordae tendineae. These promising results warrant further in vivo evaluation.

Annular Dynamics and Leaflet Geometry in Patch Reconstruction of the Posterior Mitral Leaflet After Adding a Flexible Annuloplasty Ring.

PURPOSE: Patch reconstruction of the posterior mitral leaflet using small intestinal submucosa extracellular matrix has been successfully performed in a porcine study. The patch reconstruction, however, resulted in non-physiological systolic widening of the mitral annulus, suggesting the need for an annuloplasty ring. The objective was to characterize the impact on annular dynamics and leaflet geometry of adding a flexible annuloplasty ring to the posterior mitral leaflet patch reconstruction. METHODS: Measurements were performed in an acute 80-kg porcine model, with seven pigs acting as their own controls. The posterior mitral leaflet was reconstructed with a 2-ply small intestinal submucosa extracellular matrix patch (CorMatrix®). Additionally, a Simulus® Flexible Annuloplasty Ring (Medtronic Inc., Minneapolis, MN, USA) was inserted. Mitral annular dynamics were evaluated using sonomicrometry, and leaflet geometry was described using echocardiography. RESULTS: The annuloplasty ring reduced mitral annular dimensions and restricted cyclic changes in mitral annular area (126 ± 19 vs. 30 ± 13 mm2, p < 0.001), septal-lateral and commisure-commisure distances. Ring annuloplasty prevented systolic widening in the mitral annulus after posterior mitral leaflet reconstruction. The annular saddle shape and leaflet coaptation length (8.7 ± 2.3 vs. 9.7 ± 1.3 mm, p = 0.221) were comparable before and after ring insertion. CONCLUSIONS: The flexible annuloplasty ring resulted in a downsized annulus with restriction of cyclic annular changes in the reconstructed mitral valve. Ring insertion preserved the annular saddle shape and coaptation length. The ring annuloplasty counteracted the non-physiological annular dynamics, and this may improve durability of the posterior mitral leaflet patch reconstruction.