Rainer Leyh

Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells

Background— Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. Methods and Results— Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. Conclusions— TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

Evolving Strategies for Treatment of Acute Aortic Dissection Type A

Objective—To assess the outcome of 3 different surgical approaches for treatment of acute aortic dissection type A (AADA). Methods and Results—Between October 1990 and October 2003, we operated on 295 patients (pts) for AADA. Follow-up was complete for 257 pts (87%). Supracommissural replacement (SCR) of the ascending aorta was applied to 145 pts, 64 pts received a composite replacement (comp), and 48 pts were treated with the aorta valve-sparing (AVS) reimplantation technique. Pts in SCR were older compared with AVS and comp (P=0.002), gender (overall 65% male, P=0.143) and presence of Marfan syndrome (overall 5%, P=0.109) were comparable. Cannulation of the aorta was performed more often in AVS (58%) than in comp (19%) or SCR (22%; P<0.001). Mean operation time, extracorporeal circulation time, and aortic cross-clamp time differ significantly between groups (P<0.001, respectively). Stay in the intensive care unit (P=0.12) and time of hospitalization (P=0.32) were comparable. Overall perioperative mortality was 24% and did not show significant differences between groups (AVS 10.4% versus comp 28% versus SCR 26%; P=0.053). Incidence of neurological complications was similar between groups (P=0.95). Mean time of follow-up was shorter for AVS (19±20 months) compared with comp (48±48 months) and SCR (46±45 months). Survival at 5 years was comparable with 89% for AVS, 85% for comp, and 80% for SCR (P=0.61). Two patients from AVS (4.1%) required reoperation for failure of the reconstructed valve. Pts in comp required less aortic reoperations than pts in SCR (comp 6.3% versus SCR 22%; P=0.005). Conclusions—In acute aortic dissection type A, the reimplantation technique leads to results comparable to established techniques. Complete removal of diseased tissue, low incidence of reoperation, and lack of anticoagulation may favor this approach in selected patients.

Prevention of sternal dehiscence and infection in high-risk patients: a prospective randomized multicenter trial.

BACKGROUND One factor for the development of sternal wound infection (SWI) is bony instability after sternotomy. This study compares two surgical techniques with respect to the occurrence of SWI in patients with an increased risk. METHODS In this multicenter study, 815 consecutive patients with an increased risk for SWI were prospectively randomly assigned to a conventional osteosynthesis (transsternal or peristernal wiring; n = 440) or to an osteosynthesis with additional lateral reinforcement (Robicsek; n = 375). Primary endpoints were the rate of sternal dehiscence as well as the occurrence of superficial sternal wound infections and deep sternal wound infections. RESULTS Both groups were comparable concerning preoperative and intraoperative variables. The rate of sternal dehiscence, superficial sternal wound infections, and deep sternal wound infections (conventional technique 2.5%, 3.4%, 2.5%; and Robicsek 3.7%, 5.6%, 3.7%) did not differ between the groups. Logistic regression analysis found independent risk factors for the development of sternal dehiscence: body mass indes greater than 30 kg/m(2) (odds ratio [OR]: 2.9; p = 0.05), New York Heart Association class more than III (OR: 2.4; p = 0.07), impaired renal function (OR: 3.9; p = 0.01), peripheral arterial disease (OR: 3.6; p = 0.001), immunosuppressant state (OR: 3.3; p = 0.001), sternal closure performed by an assistant doctor (OR: 2.5, p = 0.004), postoperative bleeding (OR: 4.2; p = 0.03), transfusion of more than 5 red blood units (OR: 3.7, p = 0.01), reexploration for bleeding (OR: 6.9, p = 0.001), and postoperative delirium (OR: 3.5, p = 0.01). There was an inverse relation between the numbers of wires and DSWI in patients with conventional sternal closure (p = 0.008). CONCLUSIONS In patients with an increased risk for sternal instability and wound infection after cardiac surgery, sternal reinforcement according to the technique described by Robicsek did not reduce this complication.

Decade of Aortic Valve Sparing Reimplantation Are We Pushing the Limits Too Far

Background—This single center study assesses the outcome of aortic valve sparing reimplantation (AVS) in 284 consecutive patients who were operated on for various indications during the last 11 years. Methods and Results—From July, 1993, to July, 2004, 284 patients underwent AVS. Mean age was 53±16 (range 8 to 84) years. Of the 284 patients, 184 were male (64.8%) and 54 (19%) experienced Marfan’s syndrome. Acute aortic dissection Stanford type A was present in 53 patients (19%) and a bicuspid aortic valve was present in 17 patients (6%). Concomitant arch replacement was necessary in 120 patients (42%). Additional procedures were performed in 66 patients (23.2%). Mean follow-up time was 41±32 (range 0 to 130) months. The 30-day mortality was 3.2% overall, 11.3% in emergency patients, and 1.3% in elective patients. Mean bypass time was 174±48 (range 90 to 440) minutes and aortic cross clamp time was 132±33 (range 64 to 283) minutes. In patients undergoing arch replacement, circulatory arrest was 25±17 (range 7 to 99) minutes. Rethoracotomy for bleeding was required in 4.6% of patients. During follow-up, there were 20 (7.3%) late deaths. Reoperation of the reconstructed valve was required in 15 patients (5.3%); underlying reasons were endocarditis (n=4) and aortic insufficiency (n=11) requiring aortic valve replacement. Average grade of aortic insufficiency increased significantly from 0.23±0.46 postoperatively to 0.34±0.59 at latest evaluation (P=0.026). Two patients experienced a transient ischemic attack early postoperatively; no further thromboembolic complications were noticed. The majority of patients (96%) presented with a favorable exercise tolerance at last contact. Conclusions—The aortic valve reimplantation technique leads to excellent clinical outcome in patients with various pathologies. Lack of anticoagulation and favorable durability should encourage the extension of indications for this technique.

Prognostic Significance of Multiple Previous Percutaneous Coronary Interventions in Patients Undergoing Elective Coronary Artery Bypass Surgery

Background— A possible relationship between increased perioperative risk during coronary artery bypass grafting (CABG) and previous percutaneous coronary intervention (PCI) is debatable. We sought to determine the impact of previous PCI on patient outcome after elective CABG. Methods and Results— Between January 2000 and January 2005, 2626 consecutive patients undergoing first-time isolated elective CABG as the primary revascularization procedure (group 1) were evaluated for in-hospital mortality and major adverse cardiac events (MACEs) and were compared with 360 patients after single PCI (group 2) and with 289 patients after multiple PCI sessions (group 3) before elective CABG. Unadjusted univariate and risk-adjusted multivariate logistic-regression analysis revealed previous multiple PCIs to be strongly associated with in-hospital mortality (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.52 to 3.21; P<0.001) and MACEs (OR, 2.28; 95% CI, 1.38 to 3.59; P<0.001). To control for selection bias, a computed propensity-score matching based on 13 patient characteristics and preoperative risk factors was performed separately comparing group 1 versus 2 and group 1 versus 3. After propensity matching, conditional logistic-regression analysis confirmed previous multiple PCIs to be strongly associated with in-hospital mortality (OR, 3.01; 95% CI, 1.51 to 5.98; P<0.0017) and MACEs (OR, 2.31; 95% CI, 1.45 to 3.67; P<0.0004). Conclusions— In patients with a history of multiple PCI sessions, perioperative risk for in-hospital mortality and MACEs during subsequent elective CABG is increased.

Development of an integrated stent graft-dacron prosthesis for intended one-stage repair in complex thoracic aortic disease.

Complex thoracic aortic disease involving the ascending aorta, the aortic arch and the descending aorta still represents a challenge for the cardiothoracic surgeon. The classic approach for this pathology consists of a two-stage strategy, summing up to a mortality up to 40%, with a 5% mortality for the waiting period between both surgical stages [1–3]. One-stage repair can be performed, if required, via a clamshell thoracotomy, but is associated with major surgical trauma and perioperative morbidity as pulmonary or renal dysfunction, indicating that elderly patients probably are poor candidates for this strategy [4]. With the introduction of endovascular stenting in combination with classic aortic arch surgery an attractive treatment alternative has emerged for facilitated repair of complex aneurysmal disease in the thoracic aorta [5, 6]. Modifying this new technique using self-expanding descending aortic stent grafts and the classic ascending and aortic arch replacement techniques seems to be the logical consequence for intended one-stage repair, which was started by our group 06/2001 [7, 8]. Standard thoracic aortic stent graft devices (e.g., Medtronic Talent©, Minneapolis, MN, USA) are designed for retrograde aortic delivery, which demonstrate shortcomings for the antegrade use: their stiffness limits steerability, causing problems to pass the angle between the distal aortic arch and proximal descending aorta, resulting in significant friction to the inner aortic wall. This is worsened by the stiff outer plastic sheath which frequently shows kinking when curved > 45°. The most rigid zone is identified to be at the proximal border between stent graft and tip of the introducer and at the distal site between stent graft and the wire-reinforced inner pusher, limiting continuous and precise stent graft opening. At that point the already opened distal bare springs only allow for minor correction in proximal direction in case of displacement. A second significant problem is caused by the longitudinal wire (connecting bar), which is positioned along the outer curvature of the stent. This force provokes the stent to straighten up resulting in a significant protrusion of the proximal bare springs into the aortic wall. To overcome those shortcomings, a new integrated stent graft-Dacron prosthesis for antegrade delivery through the open aortic arch into the descending aorta in an “elephant trunk”-like manner was created. This “Essen I prosthesis” (E-vita open; Jotec®, Hechingen, Germany [Figure 1]) consists of a polyester fabric with an extremely flexible Nitinol wire skeleton, fixed on the outer aspect of the fabric with polypropylene sutures. To increase flexibility, a longitudinal wire is abandoned, and no open bar ends or reinforced circular springs are incorporated distally or proximally. At the proximal end, a woven crimped vascular Dacron prosthesis of 7 cm length is incorporated continuously to the stent graft prosthesis, allowing for direct replacement of the aortic arch without an additional anastomosis like in classic elephant trunk operations, by simply pulling back the invaginated Dacron prosthesis at its sewn suture sling into the arch position. Stent graft re1 Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital Essen, Germany, 2 Department of Cardiology, West German Heart Center Essen, University Hospital Essen, Germany.

Anticoagulation for prosthetic heart valves during pregnancy: is low-molecular-weight heparin an alternative?

We report on the treatment failure of low molecular weight heparin (LMWH) for anticoagulation in a pregnant woman that underwent artificial mitral valve replacement 10 years prior to her pregnancy. Until she became pregnant warfarin was administered for anticoagulation, but due to the often mentioned increased risk for warfarin-induced maternal and fetal complications, at gestational week 5 the anticoagulation regimen was switched to subcutaneous application of low molecular weight heparin. At gestational week 24 our patient developed acute life-threatening pulmonary edema and hemodynamic instability due to acute mitral valve thrombosis and underwent emergency valve re-replacement with a biological porcine valve. She recovered uneventfully and gave birth to a healthy child at gestational week 35. In addition to our case presentation we review the sparse evidence in the literature regarding anticoagulation in pregnant women with mechanical heart valves and discuss the rational of different anticoagulation regimens with regards to maternal and fetal outcome. Special consideration is directed towards LMWH administration as an alternative to oral anticoagulation during pregnancy in women with mechanical heart valves.

A multicentre evaluation of the autograft procedure for young patients undergoing aortic valve replacement: update on the German Ross Registry

OBJECTIVES Conventional aortic valve replacement (AVR) in young, active patients represents a suboptimal solution in terms of long-term survival, durability and quality of life. The aim of the present work is to present an update on the multicentre experience with the pulmonary autograft procedure in young, adult patients. METHODS Between 1990-2013, 1779 adult patients (1339 males; 44.7 ± 11.6 years) underwent the pulmonary autograft procedure in 8 centres. All patients underwent prospective clinical and echocardiographic examinations annually. The mean follow-up was 8.3 ± 5.1 years (range 0-24.3 years) with a total cumulative follow-up of 14 288 years and 662 patients having a follow-up of at least 10 years. RESULTS The early (30-day) mortality rate was 1.1% (n = 19). Late (>30 day) survival of the adult population was comparable with the age- and gender-matched general population (observed deaths: 101, expected deaths: 91; P = 0.29). Freedom from autograft reoperation at 5, 10 and 15 years was 96.8, 94.7 and 86.7%, respectively, whereas freedom from homograft reoperation was 97.6, 95.5 and 92.3%, respectively. The overall freedom from reoperation was 94.9, 91.1 and 82.7%, respectively. Longitudinal modelling of functional valve performance revealed a low (<5%) probability of a patient being in higher autograft regurgitation grades throughout the first decade. Similarly, excellent homograft function was observed throughout the first 15 years. CONCLUSION The autograft principle results in postoperative long-term survival comparable with that of the age- and gender-matched general population and reoperation rates within the 1%/patient-year boundaries and should be considered in young, active patients who want to avoid the shortcomings of conventional prostheses.

Impact of preoperative aortic root diameter on long-term aortic valve function after valve sparing aortic root reimplantation.

Background—Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. Methods and Results—From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43±26 months, group B 40±25 months, group C 23±19 months; group C versus group A, P =0.005; group C versus group B, P =0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P =ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98±2%, for group B 96±3%, and for group C 100±0% (P =ns). Freedom from reoperation for group A was 98±2%, for group B 96±3%, and for group C 88±8% (P =ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100±0%, for group B 88±8%, and for group C 94±5% (P =ns). During follow-up no thromboembolic or bleeding events were noticed. Conclusions—Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.

Sternal closure techniques and postoperative sternal wound complications in elderly patients

OBJECTIVE Postoperative sternal wound complications (PSWC) including deep sternal wound infection (DSWI) and sternal dehiscence (SD) cause significant morbidity and mortality. Elderly patients with several risk factors are particularly prone to suffer PSWC. METHODS We present (I) a subset of 86 patients, all aged > or =75 years out of 339 cardiac surgery patients prospectively randomised to receive either conventional sternal closure or a Robicsek type closure. Primary end-points were SD and DSWI; secondary end-points included a composite of clinical parameters; (II) we retrospectively assessed data of 54/5273 patients with mediastinitis regarding the influence of advanced age. In addition, we report an epidemiological overview of different sternal closure techniques. RESULTS (I) The Robicsek technique showed an impact on SD and DSWI, and several secondary end-points: ventilator support (p=0.03), postoperative blood loss (p=0.04), and chest pain >3 days (p=0.04). (II) A total of 54/5273 (1.02%) patients developed postoperative mediastinitis. Twelve out of 54 (22%) patients died within 6 months of the initial operation. Predictors of mortality were insulin-dependent diabetes mellitus (p=0.05), renal insufficiency (p=0.01), delayed sternal closure (p=0.05), ICU-stay >10 days (p=0.01), and methicillin-resistant Staphylococcus aureus (p=0.03) or fungal infection (p=0.02). CONCLUSIONS No statistical difference in sternal dehiscence or mediastinitis was found irrespective of whether the bilateral and longitudinal parasternal closure or the conventional peri/trans-sternal wiring technique was used, but there was an obvious, positive influence on sternal dehiscence, deep sternal wound infection, and clinical parameters. However, the study population is relatively small.