Dominik Wiedemann

Quality of Life Improvement after Robotically Assisted Coronary Artery Bypass Grafting

Objectives: Coronary artery bypass grafting (CABG) is associated with long rehabilitation periods and slow quality of life (QOL) improvement. Totally endoscopic coronary artery bypass grafting (TECAB) can be performed using robotic technology and remote access perfusion. The aim of this study was to evaluate whether TECAB leads to accelerated QOL improvement as compared to standard CABG. Methods: We included 120 patients who had received robotically assisted CABG, 56 of whom were operated on using standard sternotomy. These patients were compared to 55 patients who underwent the TECAB procedure and to 9 TECAB patients who required conversion to conventional sternotomy. QOL evaluation was performed before the operation and 1, 3 and 6 months after the procedure using the SF-36 health survey and a standardized questionnaire. Results: All quality of life aspects improved significantly in all study patients. At 3 months, TECAB patients showed significantly better QOL scores related to bodily pain and physical health. Hospital stay and time to restoration of daily activities were significantly shorter. Converted patients experienced similar courses to sternotomy patients in terms of QOL. Conclusions: TECAB using robotic technology leads to improved physical health, shorter hospital stay and a more rapid restoration of daily activities. Conversion from TECAB to sternotomy does not lead to QOL impairment as compared to primary sternotomy.

The Angiogenic Factor Secretoneurin Induces Coronary Angiogenesis in a Model of Myocardial Infarction by Stimulation of Vascular Endothelial Growth Factor Signaling in Endothelial Cells

Background—Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells. Methods and Results—In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein. Conclusions—Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.

Effectiveness and Safety of Total Endoscopic Left Internal Mammary Artery Bypass Graft to the Left Anterior Descending Artery

Totally endoscopic coronary artery bypass grafting (CABG) has become a feasible option using robotic technology and remote access perfusion techniques. The aim of this study was to determine the progression of the procedures performance in the currently largest single-center series of arrested-heart totally endoscopic CABG. From 2001 to 2007, arrested-heart totally endoscopic CABG was performed in 100 patients (median age 59 years, range 46 to 70; 81 men, 19 women). All patients received left internal mammary artery grafts to the left anterior descending artery using the da Vinci Surgical System. Remote-access femoral perfusion and aortic balloon endo-occlusion were used in all patients. The series was divided into 4 phases: phase 1 (patients 1 to 25), phase 2 (patients 26 to 50), phase 3 (patients 51 to 75), and phase 4 (patients 76 to 100). The conversion rates to larger thoracic incisions were 7 of 25 (28%) in phase 1, 2 of 25 (8%) in phase 2, 1 of 25 (4%) in phase 3, and 1 of 25 (4%) in phase 4 (p = 0.018). Operative times and hospital stays decreased significantly with each subsequent phase, and clinical outcome showed corresponding improvements. There was no perioperative mortality. For the whole patient series, 5-year postoperative survival, freedom from angina, and freedom from major adverse cardiac and cerebral events were 100%, 91%, and 89%, respectively. In conclusion, after an initial steep learning curve, completely endoscopic left internal mammary artery-to-left anterior descending CABG can be performed safely, with low conversion rates. The learning curve for operative times and improvements in clinical outcome continued even at 100 procedures.

Effect of cerebral protection strategy on outcome of patients with Stanford type A aortic dissection

OBJECTIVE The aim of the present study was to assess the efficacy and mid- to long-term results of different cerebral protection techniques in the treatment of acute type A aortic dissection. METHODS Between April 1987 and January 2011, 329 patients (220 male patients; median age, 60 years; range, 16-87) with type A aortic dissection underwent replacement of the ascending aorta or aortic arch with an open distal anastomosis. Either hypothermic circulatory arrest alone at 18 °C (n = 116; 35%) or combined with retrograde cerebral perfusion (n = 122; 37%) or antegrade cerebral perfusion at 25 °C (n = 91; 28%) was used. RESULTS The median circulatory arrest time was 30 minutes (range, 12-92). The overall 30-day mortality was 19% (62 of 329). The 30-day mortality stratified by group was 26% (30 patients) in the hypothermic circulatory arrest group, 16% in the retrograde cerebral perfusion group (20 patients), and 13% (12 patients) in the antegrade cerebral perfusion group (P = .047). Permanent neurologic dysfunction occurred in 53 patients (16%), with statistically significant differences among the 3 groups (23% for hypothermic circulatory arrest, 12% for retrograde cerebral perfusion, and 12% for antegrade cerebral perfusion; P = .033). Univariate analysis showed a significant effect of the brain protection strategy on 30-day mortality and neurologic outcome. Multivariate analysis revealed preoperative hemodynamic instability, preoperative resuscitation, age, and operative year as independent predictors of 30-day mortality. Regarding permanent neurologic dysfunction, the multivariate analysis could not identify any independent predictors. Kaplan-Meier analyses revealed statistically significant differences among the 3 groups with a 1-, 3-, and 5-year survival rate of 84%, 79%, and 77% with antegrade cerebral perfusion, 75%, 72%, and 66% with retrograde cerebral perfusion, and 66%, 62%, and 60% with hypothermic circulatory arrest alone. CONCLUSIONS Patients in the antegrade cerebral perfusion group had the best short- and long-term survival rates. However, during the study period, several significant improvements in the treatment of patients with type A aortic dissection were achieved; therefore, independent predictors of mortality and permanent neurologic dysfunction were difficult to identify.

Training Surgeons to Perform Robotically Assisted Totally Endoscopic Coronary Surgery

BACKGROUND Robotic totally endoscopic coronary bypass (TECAB) surgery was developed during the past decade, and younger surgeons need to be trained in this new modality. This study assessed the learning curves and independent TECAB performance of 2 junior surgeons undergoing TECAB training. METHODS Two surgeons in training performed portions of 44 of 239 robotic TECAB operations, including left (LIMA) and right interior mammary artery (RIMA) harvesting, lipectomy, pericardiotomy, and IMA to left anterior descending coronary artery (LAD) anastomotic suturing. RESULTS The procedure portions performed faster by the senior surgeon vs trainees were, in minutes (range), lipectomy, 5 (2 to 18) vs 10 (5 to 21; p < 0.001); pericardiotomy, 5 (1 to 21) vs 7 (3 to 16; p = 0.001); RIMA takedown, 35 (25 to 48) vs 49 (40 to 55; p = 0.034); and LIMA to LAD anastomosis, 26 (12 to 100) vs 34 (24 to 67; p = 0.043). After assuming senior roles in the robotic cardiac surgery program, the 2 trained surgeons performed 14 TECABs (LIMA to LAD) without the senior surgeon. Lipectomy took 5 (3 to 8) minutes; pericardiotomy, 5 (2 to 10) minutes; LIMA takedown, 43 (27 to 70) minutes; LIMA to LAD anastomosis, 24 (15 to 60) minutes, cardiopulmonary bypass time, 73 (40 to 126) minutes; and aortic endo-occlusion time, 53 (0 to 83) minutes. No hospital deaths occurred. CONCLUSIONS TECAB can be well taught with a stepwise training program involving portions of the procedure performed by trainees. With such an approach, independent performance after training can be within adequate time limits and yields seemingly acceptable results.

Predictors, causes, and consequences of conversions in robotically enhanced totally endoscopic coronary artery bypass graft surgery.

BACKGROUND Totally endoscopic coronary artery bypass graft surgery (TECAB), using the da Vinci telemanipulator, has become a reproducible operation at dedicated centers. As in every endoscopic operation, conversion is an important and probably inevitable issue. METHODS We performed robotic TECAB in 326 patients (age, 60 years; range, 31 to 90 years); 242 were single-vessel and 84 were multivessel TECAB. RESULTS Forty-six of 326 patients (14%) were converted to a larger incision (minithoracotomy, n = 5; sternotomy, n = 41). Left internal mammary artery injury (n = 7), epicardial injury (n = 4), balloon endoocclusion problems (n = 7), and anastomotic problems (n = 18) were common reasons for conversions. Conversion rate was significantly less for single-vessel versus multivessel TECABs (10% versus 25%; p = 0.001). Non-learning-curve case (7% versus 21%; p < 0.001) and transthoracic assistance (11% versus 22%; p = 0.018) were associated with lower conversion rates. In multivariate analysis, learning-curve case was the only independent predictor of conversion (p = 0.005). Conversion translated into increased packed red blood cell transfusion in the operating room (3 versus 0 units; p < 0.001), longer ventilation time (14 versus 8 hours; p < 0.001), and intensive care unit stay (45 versus 20 hours; p = 0.001). Hospital mortality was 0.6% in this series, with 1 patient in the conversion group (2.2%) and 1 patient in the nonconverted group (0.4%; not significant). Five-year survival was 98% in nonconverted patients and 88% in converted patients (p = 0.018). There was no difference in freedom from angina or freedom from major adverse cardiac and cerebral events. CONCLUSIONS Conversion in TECAB is primarily learning curve-dependent and associated with increased morbidity, but does not significantly affect hospital mortality. Both nonconverted and converted patients show good long-term survival, which is comparable to patients undergoing open sternotomy coronary artery bypass grafting. Long-term freedom from angina or freedom from major adverse cardiac and cerebral events is not influenced by conversion.

Surgical problems and complex procedures: Issues for operative time in robotic totally endoscopic coronary artery bypass grafting

OBJECTIVE Robotically assisted totally endoscopic coronary artery bypass grafting (TECAB) is a viable option for closed chest coronary surgery, but it requires learning curves and longer operative times. This study evaluated the effect of extended operation times on the outcome of patients undergoing TECAB. METHODS From 2001 to 2009, 325 patients underwent TECAB with the da Vinci telemanipulation system. Correlations between operative times and preoperative, intraoperative, and early postoperative parameters were investigated. Receiver operating characteristic analysis was used to define the threshold of the procedure duration above which intensive care unit stay and ventilation time were prolonged. Demographic data, intraoperative and postoperative parameters, and survival data were compared. RESULTS Patients with prolonged operative times more often underwent multivessel revascularization (P < .001) and beating-heart TECAB (P =.023). Other preoperative parameters were not associated with longer operative times. Incidences of technical difficulties and conversions (P < .001) were higher among patients with longer operative times. Prolonged intensive care unit stay, mechanical ventilation, hospital stay, and with requirement of blood products were associated with longer operative times. Receiver operating characteristic analysis showed operative times >445 minutes and >478 minutes to predict prolonged (>48 hours) intensive care unit stay and mechanical ventilation, respectively. Patients with procedures >478 minutes had longer hospital stays and higher perioperative morbidity and mortality. Kaplan-Meier analysis revealed decreased survival among patients with operative times >478 minutes. CONCLUSIONS Multivessel revascularization and conversions lead to prolonged operative times in totally endoscopic coronary artery bypass grafting. Longer operative times significantly influence early postoperative and midterm outcomes.

Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts

Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease.

The elderly patient and cardiac surgery - a mini-review.

Introduction: Due to the increase in average life expectancy and the higher incidence of cardiovascular disease with advancing age, more elderly patients present for cardiac surgery nowadays. Advances in pre- and postoperative care mean that more elderly patients can be operated on safely and with a satisfactory outcome. Currently, coronary artery bypass surgery, aortic and mitral valve surgery and surgery of the ascending aorta are performed in elderly patients. Objective: In this review, we summarize the outcome of elderly patients undergoing various cardiac surgical procedures and give future perspectives for the treatment of elderly patients with cardiac surgery. Methods: A PubMed search for the period from 1980 to February 2009 was conducted with the following key words: ‘elderly patient’, ‘cardiac surgery’, ‘CABG aortic surgery’, ‘mitral valve surgery’ and ‘endocarditis’. Additional information concerning population demographics was obtained from the World Health Organization homepage. Results: More and more cardiac surgical procedures are offered to elderly patients. The short- and long-term survival rates of elderly patients are comparable to those of younger patients. Nevertheless, the risk for these patients is only acceptable in the absence of comorbidities. In particular, renal dysfunction, cerebrovascular disease and a poor clinical state are associated with a worse outcome in elderly patients. Conclusion: The data available show that most cardiac surgical procedures can be performed in elderly patients with a satisfactory outcome. Careful patient selection, flawless surgery, meticulous hemostasis, perfect anesthesia and myoacardial protection are basic requirements for the success of cardiac surgery in elderly patients.

Influence of preoperative serum N-terminal pro-brain type natriuretic peptide on the postoperative outcome and survival rates of coronary artery bypass patients

BACKGROUND: The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP) is an established biomarker for cardiac failure. OBJECTIVE: To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG). METHODS: In 819 patients undergoing isolated CABG surgery preoperative serum NT-proBNP levels were measured. NT-proBNP was correlated with various postoperative outcome parameters and survival rate after a median follow-up time of 18 (0.5–44) months. Risk factors of mortality were identified using χ2, Mann–Whitney test, and Cox regression. RESULTS: NT-proBNP levels >430 ng/ml and >502 ng/ml predicted hospital and overall mortality (p<0.05), with an incidence of 1.6% and 4%, respectively. Kaplan–Meier analysis revealed decreased survival rates in patients with NT-proBNP >502 ng/ml (p = 0.001). Age, preoperative serum creatinine, diabetes, chronic obstructive pulmonary disease, low left ventricular ejection fraction and BNP levels >502 ng/ml were isolated as risk factors for overall mortality. Multivariate Cox regression analysis, including the known factors influencing NT-proBNP levels, identified NT-proBNP as an independent risk factor for mortality (OR = 3.079 (CI = 1.149-8.247), p = 0.025). Preoperative NT-proBNP levels >502 ng/ml were associated with increased ventilation time (p = 0.005), longer intensive care unit stay (p = 0.001), higher incidence of postoperative hemofiltration (p = 0.001), use of intra-aortic balloon pump (p<0.001), and postoperative atrial fibrillation (p = 0.031) CONCLUSION: Preoperative NT-proBNP levels >502 ng/ml predict mid-term mortality after isolated CABG and are associated with significantly higher hospital mortality and perioperative complications.