Steffen Pfeiffer

Minimally invasive aortic valve replacement with Perceval S sutureless valve: early outcomes and one-year survival from two European centers.

OBJECTIVE The aim of our study was to evaluate the early outcomes and 1-year survival of patients undergoing minimally invasive aortic valve replacement with the Perceval S sutureless valve for severe aortic stenosis. METHODS From March 2010 to March 2013, 281 high-risk patients underwent minimally invasive aortic valve replacement with the Perceval S sutureless valve through either right anterior minithoracotomy (n = 164) or upper ministernotomy (n = 117) at 2 cardiac centers. RESULTS The overall in-hospital mortality was 0.7% (2 patients). The overall median cardiopulmonary bypass and crossclamp time was 81 minutes (interquartile range, 68-98) and 48 minutes (interquartile range, 37-60), respectively. Postoperative stroke occurred in 5 patients (1.8%). The incidence of paravalvular leak greater than 1 of 4 and atrioventricular block requiring pacemaker implantation was 1.8% (5 patients) and 4.2% (12 patients), respectively. No migration occurred, and the mean postoperative gradient was 13 ± 4 mm Hg. At a median follow-up of 8 months (interquartile range, 4-14), the overall survival was 90%. CONCLUSIONS Minimally invasive aortic valve replacement with the Perceval S sutureless valve in high-risk patients is a safe and reproducible procedure associated with excellent hemodynamic results, postoperative outcomes, and 1-year survival.

The Perceval S Aortic Valve Has the Potential of Shortening Surgical Time: Does It Also Result in Improved Outcome?

BACKGROUND Sutureless aortic valve prostheses have the potential of shortening surgical time. However, whether shorter operative times may also result in improved patient outcomes remains to be established. METHODS One hundred patients underwent minimally invasive isolated aortic valve replacement. Of these, 50 patients received a Perceval (Sorin Group, Saluggia, Italy) bioprosthesis (group P) and 50 patients received a non-Perceval valve (group NP). RESULTS The group P patients were older (77.5 ± 5.3 versus 71.7 ± 10 years, p = 0.001) and at higher risk (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE] 9.9 ± 6.5 versus 4.3 ± 1, p = 0.001) than group NP patients. One implant failure occurred in group P (p = 0.5), and conversion to full sternotomy was necessary in 1 patient from each group. Aortic cross-clamp and cardiopulmonary bypass times were 39.4% and 34% shorter in group P (both p < 0.001). Within 30 days, a total of 5 patients died (2 in group P and 3 in group NP, p = 0.5). No significant differences were observed between groups in postoperative arrhythmias and need for pacemaker implantation (p = 0.3 and p = 0.5, respectively). Despite the higher surgical risk, group P patients less frequently required blood transfusion (1.1 ± 1.1 units versus 2.3 ± 2.8 units, p = 0.007), and had a shorter intensive care unit stay (1.9 ± 0.7 versus 2.8 ± 1.9 days, p = 0.002) and a shorter intubation time (9.2 ± 3.6 hours versus 15 ± 13.8 hours, p = 0.01). Group NP patients had a mean prosthesis size significantly smaller than for group P (23 ± 2 mm versus 23.9 ± 1.1 mm, p = 0.01). The Perceval valve provided comparable hemodynamic performance to that of non-Perceval valves (mean gradient 8.4 ± 6 mm Hg versus 10 ± 4.9 mm Hg, p = 0.24). CONCLUSIONS Sutureless implantation of the Perceval valve is associated with shorter cross-clamp and cardiopulmonary bypass times, resulting in improved clinical outcome. In addition, it compares favorably with conventional valves in terms of mortality and outcome variables.

Humoral Immunity to Vimentin Is Associated with Cardiac Allograft Injury in Nonhuman Primates

Immunity to autologous protein has not previously been described following nonhuman primate cardiac transplant. Native hearts and cardiac allografts from cynomolgus monkeys were assessed by immunohistology for vimentin, a highly conserved intermediate filament protein. IgM and IgG to vimentin were measured in serial sera from untreated (n = 4) or cyclosporine (CsA)‐treated (n = 8, 2 with ATG) cardiac allograft recipients, and in groups treated with anti‐CD154 antibody with (n = 6) or without ATG (n = 28). IgM or IgG reactive with vimentin was elaborated within 30 days with unmodified acute rejection (3/4) or in CsA‐treated animals (5/6). CD154 blockade did not prevent anti‐vimentin IgM (14/28) but tended to delay the IgG response during therapy (anti‐CD154: 8/28, p = 0.10 vs. CsA; anti‐CD154+ATG: 2/6). CAV and alloantibody were seen in 25 of 26 animals with grafts surviving over 30 days, including seven animals without increasing anti‐vimentin antibody. Anti‐vimentin antibodies and vascular complement deposition were found in rejected hearts. Acute and chronic alloimmunity disrupt modulation of autoreactivity to vimentin through pathways, which are resistant to CsA, but may be partially regulated by CD154.

Better Short-Term Outcome by Using Sutureless Valves: A Propensity-Matched Score Analysis

BACKGROUND Sutureless aortic valve prostheses have the potential of shortening ischemic time. However, whether shorter operative times may also result in improved patient outcomes and have an effect on hospital costs remains to be established. METHODS From March 2010 to April 2013, 566 patients underwent aortic valve replacement with bioprostheses; of these, 166 received a sutureless valve, and 400 received a stented valve. Redo and associated procedures were included. A propensity-score analysis was used to create two groups (sutureless and stented) with 82 matched pairs with comparable preoperative characteristics. Hospital outcome, follow-up, and health care resource consumption were compared. RESULTS There were 3 hospital deaths in the stented group and 2 in the sutureless group (p=0.65). Aortic cross-clamp, cardiopulmonary bypass, and operation times were significantly shorter in the sutureless group (p<0.001). Patients in the sutureless group required blood transfusion less frequently (1.2±1.3 vs 2.5±3.7 units, p=0.005), with a similar need for reexploration for bleeding (2 vs 5, p=0.221). The sutureless group had a shorter intensive care unit stay (2.0±1.2 vs 2.8±1.3 days, p<0.001), hospital stay (10.9±2.7 vs 12.4±4.4 days, p=0.001) and intubation time (9.5±4.6 vs 16.6±6.4 hours, p<0.001), and a lower incidence of postoperative atrial fibrillation (p=0.015), pleura effusions (p=0.024), and respiratory insufficiency (p=0.016). Pacemaker implantation and occurrence of neurologic events were similar between groups (p>0.05). A lower rate of postoperative complications resulted in reduced resource consumption in the sutureless group for diagnostics (€2,153 vs €1,387), operating room (€5,879 vs €5,527), and hospital stay (€9,873 vs €6,584), with a total cost saving of approximately 25% (€17,905 vs €13,498). CONCLUSIONS A shorter procedural time in the sutureless group is associated with better clinical outcomes and reduced hospital costs.

Sutureless, rapid deployment valves and stented bioprosthesis in aortic valve replacement: recommendations of an International Expert Consensus Panel.

OBJECTIVES After a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves. METHODS Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts. RESULTS Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19-27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves. CONCLUSION The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.

Co-stimulation blockade targeting CD154 and CD28/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft

Abstract:  Background:  The induced antibodies against Galα1,3Gal (Gal) and non‐Gal epitopes may contribute to delayed xenograft rejection (DXR). We asked whether blockade of the CD40/CD154 and CD28/B7 co‐stimulatory pathways modulates the baboon elicited antibody response to pig Gal and non‐Gal antigens.

Alloimmunity in Primate Heart Recipients with Cd154 Blockade: Evidence for Alternative Costimulation Mechanisms

Background. CD154 mediates key facets of humoral and cellular immunity to alloantigens, and is tolerogenic to influenza antigens in primates. Barriers to CD154-based tolerance induction for primate cardiac allografts have not previously been defined. Methods. Heterotopic cardiac allograft outcomes in cynomolgus monkeys treated with a CD154 inhibitor, IDEC-131 (n=27), were compared to no treatment (n=4) or cyclosporine A (n=6). Results. CD154 blockade significantly prolonged median allograft survival, from 6.2 (range 6, 7, n=4) days in untreated controls, to 39 (8,112, n=16) days with intensive monotherapy and 93 (>25, 386; n=3) days with added antithymocyte globulin (ATG), but did not yield tolerance. Alloantibody production was delayed but not prevented by IDEC-131 alone or with ATG, and was exacerbated by infusion of donor bone marrow (n=8). Expression of ICOS was prominent in graft infiltrating lymphocytes, and preceded elaboration of antidonor antibody and vasculopathy. Conclusion. CD154 monotherapy modulates primate cardiac alloimmunity, but does not readily induce tolerance. Targeting alternative costimulation pathways, including ICOS, may facilitate tolerance induction based on CD154 blockade.

Sutureless aortic valve replacement with Perceval bioprosthesis: are there predicting factors for postoperative pacemaker implantation?

OBJECTIVES Aortic valve replacement (AVR) with sutureless bioprostheses has become an alternative to conventional AVR for patients with intermediate to high operative risk. However, this technique is associated with an increased risk of postoperative conduction disorders. METHODS We analysed 258 patients who underwent AVR with the Perceval prosthesis from July 2010 to September 2014 at our centre. Electrocardiography were obtained at baseline to record preoperatively the presence of conduction disorders. Preoperative risk factors, intraoperative procedures and complications (61 variables) were compared between patients with permanent pacemaker (PPM group) and without (no-PPM group) need for postoperative PPM implantation. RESULTS One hundred and sixty-nine patients underwent isolated AVR with the Perceval bioprosthesis, 89 patients had associated surgery and 23 patients underwent redo operations. The mean age was 77.7 ± 5 years, 139 patients were female (46%) and the mean logistic EuroSCORE was 13.2 ± 11%. At baseline, 8 patients had already an implanted pacemaker. Postoperatively, 27 patients (10.5%) required new PPM implantation due to complete atrioventricular block. On univariate analysis, age (PPM vs no-PPM group: 80 ± 5 vs 77 ± 5 years, P = 0.009) and preoperative presence of right bundle branch block (RBBB) [overall n = 20 (7.8%); PPM vs no-PPM group: 9 vs 11 (33 vs 4.8%); P < 0.001] were identified as independent predictors of postoperative conduction disorders, but only pre-existing RBBB persisted on multivariate analysis (odds ratio 11.3-C-statistic 0.74, error estimate 0.064, confidence interval 0.672-0.801; P = 0.0002). Among patients undergoing sutureless AVR, the rate of PPM implantation was high. CONCLUSIONS The analysis of the data collected made it possible to identify preoperatively a subset of patients undergoing sutureless AVR at higher risk of postoperative atrioventricular block. Additional surgical precautions should be implemented to prevent the occurrence of conduction disorders after sutureless AVR.

Perceval S aortic valve implantation in mini-invasive surgery: the simple sutureless solution

The Perceval S bioprosthesis (21 and 23 mm) was approved for clinical use in December 2010 and it is now routinely used. This bioprosthesis is suggested for the treatment of patients undergoing minimally-invasive surgery for reasons of safety and reduction in implantation time. Here we describe the use of the Perceval bioprosthesis in patients undergoing minimally invasive cardiac surgery.

Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory genes

Abstract:  Background:  Hyperacute rejection (HAR) and early graft failure (EGF) have been described in a minority of pig‐to‐baboon heart transplants using organs transgenic for human complement regulatory proteins (hCRP). Here we investigate the role of coagulation cascade activation in the pathogenesis of HAR and EGF in a consecutive series where a high incidence of these outcomes was observed.