Kopplungsuntersuchungen zur Identifizierung Atherosklerose assoziierter Genorte und Atherosklerose- modifizierender Faktoren in LDL-Rezeptor defizienten BALB/c und C57BL/6 Mäusen: Publikationsdissertation zur Erlangung des akademischen Grades Dr. med.an der Medizinischen Fakultätder Universität Leipzig

Atherosklerotisch bedingte Herz-Kreislauferkrankungen zählen weltweit zu den häufigsten Todesursachen. Die vorliegende Arbeit befasst sich in einem Mausmodell mit der Identifikation neuer Genorte, welche die Ausprägung der Atherosklerose und deren Kofaktoren beeinflussen. Zu diesem Zweck wurde eine Kopplungsuntersuchung in einer Kreuzung Atherosklerose-empfindlicher C57BL/6 und BALB/c Mäuse auf dem LDL-Rezeptor defizienten Hintergrund durchgeführt. Außer der Größe der atherosklerotischen Läsionen wurden 61 weitere Phänotypen bestimmt. Als Hauptergebnis konnte ein neuer Genlocus auf dem proximalen Chromosom 2 identifiziert werden, welcher einen Einfluss auf die Größe der atherosklerotischen Läsionen an der Aortenwurzel hat. Des Weiteren zeigte sich eine Co-Segregation von Lipoproteinen (Very-Low-Density Lipoprotein (VLDL) Cholesterin und High-Density Lipoprotein (HDL) Cholesterin mit diesem Locus sowie eine Korrelation dieser Lipide mit der Läsionsgrösse. Diese Ergebnisse deuten darauf hin, dass der Effekt des Chromosom 2 Lokus auf die Atherosklerose durch genetische Faktoren des Fettstoffwechsels bedingt ist. Weitere Experimente sind notwendig um den QTL weiter einzuengen und die verantwortlichen Gene zu identifizieren

Computed tomography for planning and postoperative imaging of transvenous mitral annuloplasty: first experience in an animal model

To investigate the use of computed tomography (CT) to measure the mitral valve annulus size before implantation of a percutaneous mitral valve annuloplasty device in an animal trial. Seven domestic pigs underwent CT before and after implantation of a Cardioband™ (a percutaneously implantable mitral valve annuloplasty device) with a second-generation 128-section dual-source CT machine. Implantation of the Cardioband™ was performed in a standard fashion according to a protocol. Animals were sacrificed afterwards and the hearts explanted. The Cardioband™ was found to be adequately implanted in all animals, with no anchor dehiscence and no damage of the circumflex artery (CX) or the coronary sinus (CS). The correct length of the band as chosen according to the length of the posterior mitral annulus measured in CT before implantation was confirmed in gross examination in all animals. The device did not result in a metal artifact-related degradation of image quality. The closest distance from the closest anchor to the CX was 2.1 ± 0.7 mm in diastole and 1.6 ± 0.5 mm systole. Mitral annulus distance to the CS was 6.4 ± 1.3 mm in diastole and 7.7 ± 1.1 mm in systole. CT visualization and measurement of the mitral valve annulus dimensions is feasible and can become the imaging method of choice for procedure planning of Cardioband™ implantations or other transcatheter mitral annuloplasty devices

Comprehensive assessment of frailty for elderly high-risk patients undergoing cardiac surgery

Objective: Cardiosurgical operative risk can be assessed using the logistic European system for cardiac operative risk evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) score. Factors other than medical diagnoses and laboratory values such as the ‘biological age' are not included in these scores. The aim of the study was to evaluate an additional assessment of frailty in routine cardiac surgical practice. Methods: ‘The comprehensive assessment of frailty' test was applied to 400 patients ≥74 years who were admitted to our centre between September 2008 and January 2010. For comparison, the STS score and the EuroSCORE were calculated. The primary end point was the correlation of Frailty score to 30-day mortality. A total of 206 female and 194 male patients were included. Results: Median Frailty score was 11 [7,15]. Median of logistic EuroSCORE was 8.5% [5.8%; 13.9%]. Median of STS score was 3.3% [2.1%; 5.1%]. There were low-to-moderate albeit significant correlations of Frailty score with STS score and EuroSCORE (p≪0.05). There was also a significant correlation between Frailty score and observed 30-day mortality (p≪0.05). Patients received isolated coronary artery bypass grafting (CABG) (n=90), isolated valve surgery (n=128), trans-catheter valve implantation (n=59) or combined procedures (n=123). Conclusions: The comprehensive assessment of frailty is an additional tool to evaluate elderly patients adequately before cardiac surgical interventions. The Frailty score combines characteristics of the Fried criteria [1], of patient phenotype, of his physical performance and laboratory results. Further analysis on a larger patient population is warranted. A combination of the new Frailty score and the traditional scoring systems may facilitate a more accurate risk scoring in elderly high-risk patients scheduled for conventional cardiac surgery or trans-catheter aortic valve replacemen

Hemodynamic Modeling of Biological Aortic Valve Replacement Using Preoperative Data Only

Objectives: Prediction of aortic hemodynamics after aortic valve replacement (AVR) could help optimize treatment planning and improve outcomes. This study aims to demonstrate an approach to predict postoperative maximum velocity, maximum pressure gradient, secondary flow degree (SFD), and normalized flow displacement (NFD) in patients receiving biological AVR. Methods: Virtual AVR was performed for 10 patients, who received actual AVR with a biological prosthesis. The virtual AVRs used only preoperative anatomical and 4D flow MRI data. Subsequently, computational fluid dynamics (CFD) simulations were performed and the abovementioned hemodynamic parameters compared between postoperative 4D flow MRI data and CFD results. Results: For maximum velocities and pressure gradients, postoperative 4D flow MRI data and CFD results were strongly correlated (R 2 = 0.75 and R-2 = 0.81) with low root mean square error (0.21 m/s and 3.8 mmHg). SFD and NFD were moderately and weakly correlated at R 2 = 0.44 and R 2 = 0.20, respectively. Flow visualization through streamlines indicates good qualitative agreement between 4D flow MRI data and CFD results in most cases. Conclusion: The approach presented here seems suitable to estimate postoperative maximum velocity and pressure gradient in patients receiving biological AVR, using only preoperative MRI data. The workflow can be performed in a reasonable time frame and offers a method to estimate postoperative valve prosthesis performance and to identify patients at risk of patient-prosthesis mismatch preoperatively. Novel parameters, such as SFD and NFD, appear to be more sensitive, and estimation seems harder. Further workflow optimization and validation of results seems warranted

Interactive editing of virtual chordae tendineae for the simulation of the mitral valve in a decision support system

Purpose: Decision support systems for mitral valve disease are an important step toward personalized surgery planning. A simulation of the mitral valve apparatus is required for decision support. Building a model of the chordae tendineae is an essential component of a mitral valve simulation. Due to image quality and artifacts, the chordae tendineae cannot be reliably detected in medical imaging. Methods: Using the position-based dynamics framework, we are able to realistically simulate the opening and closing of the mitral valve. Here, we present a heuristic method for building an initial chordae model needed for a successful simulation. In addition to the heuristic, we present an interactive editor to refine the chordae model and to further improve pathology reproduction as well as geometric approximation of the closed valve. Results: For evaluation, five mitral valves were reconstructed based on image sequences of patients scheduled for mitral valve surgery. We evaluated the approximation of the closed valves using either just the heuristic chordae model or a manually refined model. Using the manually refined models, prolapse was correctly reproduced in four of the five cases compared to two of the five cases when using the heuristic. In addition, using the editor improved the approximation in four cases. Conclusions: Our approach is suitable to create realistically parameterized mitral valve apparatus reconstructions for the simulation of normally and abnormally closing valves in a decision support system

Feasibility of the Engager™ aortic transcatheter valve system using a flexible over-the-wire design

OBJECTIVES The aim was to investigate the safety and feasibility of the redesigned Engager™ transcatheter aortic valve implantation (TAVI) system. METHODS Transapical aortic valve implantation with the Engager™ valve prosthesis was intended in 11 patients, and performed in 10. Endpoints were defined according to the valve academic research consortium recommendations for reporting outcomes of TAVI in clinical trials. RESULTS All 10 patients were implanted successfully. No devicerelated or delivery system complications like coronary obstruction or aortic dissection emerged. One patient (10%) died from non-device-related reasons at post-operative day 23 of multi-organ failure. The invasively measured peak-to-peak gradient after valve implantation was 7.1±3.5mmHg. In 90%, there was no or only trivial (≤grad I) aortic regurgitation due to paravalvular leakage. In 10% of the patients, aortic regurgitation grade I-II was observed. At 30-day follow up, the mean gradient was 15.6±4.9mmHg, and no more than a mild transvalvular and paravalvular aortic regurgitation was seen as assessed by transthoracic echocardiography. CONCLUSIONS Application of the Engager™ TAVI system is safe and feasible. Prosthesis deployment in an anatomically correct position was facilitated by the design of the valve prosthesis and was successful in all patients. No device or delivery-system-related complications emerged. Safety and feasibility endpoints were met. Good results concerning the aortic valve performance after implantation and at 30-day follow up were ascertained. These results encouraged the start of a European Pivotal trial including patients to dat

Cardiovalve in mitral valve position—Additional solution for valve replacement

We report on a 72 years old male patient with recurrent heart failure hospitalizations caused by severe mitral regurgitation due to severe restriction of the posterior mitral leaflet treated with the transfemoral mitral valve replacement (TMVR) system Cardiovalve. Immediate interventional success was obtained resulting in a quick mobilization and discharge

Off-pump surgery for the poor ventricle?

Severely decreased ejection-fraction is an established risk-factor for worse outcome after cardiac surgery. We compare outcomes of off-pump coronary artery bypass grafting (OPCAB) and on-pump CABG (ONCABG) in patients with severely compromised EF. From 2004 to 2009, 478 patients with a decreased EF ≤35% underwent myocardial-revascularization. Patients received either OPCAB (n=256) or ONCABG (n=222). Propensity score (PS), including 50 preoperative risk-factors, was used to balance characteristics between groups. PS adjusted logistic regression analysis was performed to assess mortality and major adverse cardiac and cerebrovascular events (MACCE). A composite endpoint for major non-cardiac complications such as respiratory failure, renal failure, rethoracotomy was applied. Complete revascularization (CR) was assumed when the number of distal anastomoses was larger than that of diseased vessels. There was no difference for mortality (2.3 vs. 4.1%; PS-adjusted odds ratio (PS-OR)=1.05; p=0.93) and MACCE (13.7 vs. 17.6%; PS-OR=1.22; p=0.50) including myocardial-infarction (1.4 vs. 4.9%; PS-OR=0.39; p=0.26), low cardiac output (2.3 vs. 4.7%; PS-OR=0.75; p=0.72) and stroke (2.3 vs. 2.7%; PS-OR=0.69; p=0.66). OPCAB patients presented with a trend to less frequent occurrence of the non-cardiac composite (12.1 vs. 22.1%; PS-OR=0.54; p=0.059) including renal dysfunction (PAOR=0.77; 95% CI 0.31-1.9; p=0.57), bleeding (PAOR=0.42; 95% CI 0.14-1.20; p=0.10) and respiratory failure (PAOR=0.39; 95% CI 0.05-3.29; p=0.39). The rate of complete revascularization was similar (92.2 vs. 92.8%; PS-OR=0.75; p=0.50). OPCAB in patients with severely decreased EF is safe and feasible. It may even benefit these patients in regard to non-cardiac complications and does not come at cost of less complete revascularizatio

Total arterial off-pump surgery provides excellent outcomes and does not compromise complete revascularization†

OBJECTIVES The combination of aortic ‘no-touch' off-pump surgery (OPCAB) and total arterial revascularization (TAR) can reduce peri-procedural morbidity and yields excellent long-term outcomes albeit at a reported risk of incomplete revascularization. The feasibility of OPCAB-TAR with specific regards to the complete revascularization (CR) in patients with multi-vessel disease was evaluated. METHODS From 2003 to 2010, 712 patients underwent TAR including 526 patients who had OPCAB-TAR and 186 patients who received on-pump TAR [(ONCAB grafting (ONCABG)-TAR)]. Of these, 52% (n=272; OPCAB) vs. 83% (n=155; ONCABG) had triple-vessel disease (TVD). To balance patient characteristics, a non-parsimonious, propensity score (PS) model was applied. Endpoints evaluated were mortality, stroke, major adverse cardiac and cerebrovascular events (MACCE). To evaluate CR, an ‘Index of CR' (ICOR) was calculated, defined as the number of distal anastomoses divided by the number of the diseased coronary vessels. CR was assumed when the following requirements were fulfilled: the number of distal anastomoses was equal to or higher than that of diseased vessels (ICOR≥1), and all affected coronary territories (left anterior descending, circumflex artery and/or right coronary artery) were grafted. RESULTS Mortality was comparable between groups, whereas OPCAB patients suffered from significantly decreased rates of MACCE [3.0 vs. 7.0%; propensity-adjusted odd ratio (PAOR)=0.24; confidence interval (CI) 95% 0.08-0.66; P=0.006] including a clear trend towards reduced stroke and myocardial infarction. In the subgroup with TVD, OPCAB patients presented with significantly reduced rates for MACCE (1.8 vs. 5.8%; PAOR=0.07; CI 95% 0.01-0.65; P=0.02), including a significantly lower rate for stroke. For all-comers, the number of diseased vessels was lower after OPCAB (2.36±0.73 vs. 2.87±0.39; P<0.001) and consequently, these patients received an overall lower number of distal anastomoses (2.42±1.15 vs. 3.06±0.98; P<0.001). Although the ICOR was slightly lower (1.04±0.37 vs. 1.07±0.37; P=0.02), CR was achieved more frequently in OPCAB patients (82.1 vs. 73.1%; P=0.01). In the subgroup with TVD, the number of distal anastomoses (2.99±1.14 vs. 3.10±0.98; P=0.19) and the ICOR (1.00±0.38 vs. 1.03±0.33; P=0.19) was comparable between groups. The frequency of CR was slightly higher (75 vs. 67.7%; P=0.11), and the proportion of complete in situ grafting was significantly higher after OPCAB (37.1 vs. 23.9%; P=0.005). CONCLUSIONS Aortic ‘no-touch' OPCAB-TAR leads to a significant reduction of MACCE. It does not compromise CR in patients with TVD and thus can be safely applied to these patient