Midterm results after aortic valve neocuspidization.

Objectives: Aortic valve neocuspidization with autologous pericardium is gaining increasing attention as a surgical treatment option for aortic valve disease. However, little is known about midterm durability and valve-related events. Methods: Patients undergoing aortic valve neocuspidization between 2016 and 2021 were included. Transthoracic echocardiography was performed before the operation, at discharge, and annually thereafter. Data were analyzed for incidences of structural valve deterioration, bioprosthetic valve failure, survival, freedom from reoperation, and hemodynamic performance. Results: A total of 162 patients underwent aortic valve neocuspidization (mean age, 52.6 ± 16.6 years; range, 13-78 years); 114 (70.4%) were male. A total of 132 patients presented with a bicuspid aortic valve (81.5%) and 126 patients presented with aortic valve stenosis (77.8%). Concomitant procedures were performed in 63 patients (38.9%). Mean follow-up was 3.5 ± 1.2 years. At discharge, peak and mean pressure gradients were 15.6 ± 7.2 mm Hg and 8.4 ± 3.7 mm Hg, respectively, with a mean effective orifice area of 2.4 ± 0.8 cm2. After 5 years, peak and mean pressure gradients were 14.5 ± 4.6 mm Hg and 7.5 ± 2.2 mm Hg, respectively, with a mean effective orifice area of 2.3 ± 0.8 cm2. At 5 years, cumulative incidences of moderate and severe structural valve deterioration and bioprosthetic valve failure were 9.82% ± 3.87%, 6.96% ± 3.71%, and 12.1% ± 4.12%, respectively. Survival was 97.3% ± 1.4%, and freedom from reoperation was 91.3% ± 2.4%. Conclusions: Aortic valve neocuspidization accomplishes low pressure gradients early after initial surgery and during follow-up. Survival in this young patient population is excellent. The main reason for reoperation is endocarditis, and rates for structural valve degeneration are low.

The Burden of Obesity in Cardiac Surgery: A 14 years' Follow-Up of 14.754 Patients.

Aims: The prevalence of obesity is rapidly increasing during the past decades. While previous research has focused on the early outcome after cardiac surgery or specific complications, the current study covers the whole burden of obesity in the field of cardiac surgery over short term and long term. Endpoints of the study were all-cause mortality, perioperative outcome, and wound-healing disorders (WHDs). Methods: 14.754 consecutive patients who underwent cardiac surgery over a 14 years' time period were analyzed. BMI classifications were used according to the WHO definition. Results: Mean survival was 11.95 years ± 0.1; CI 95% [12.04-12.14]. After adjustment for clinical baseline characteristics, obesity classes' I-III (obesity) did not affect 30-day mortality or all-cause mortality during the whole observational period. After adjustment for known risk factors, the risk for WHDs doubled at least in obesity patients as follows: obesity I (OR = 2.06; CI 95% [1.7-2.5]; p < 0.0001), obesity II (OR = 2.5; CI 95% [1.83-3.41]; p < 0.0001), and obesity III (OR = 4.12; CI 95% [2.52-6.74]; p < 0.0001). The same applies to the risk for sternal reconstruction that is substantially elevated in obesity I (OR = 2.23; CI 95% [1.75-2.83]; p < 0.0001), obesity II (OR = 2.81; CI 95% [1.91-4.13]; p < 0.0001), and obesity III (OR = 2.31; CI 95% [1.08-4.97]; p=0.03). No significant correlation could be found between obesity and major adverse events in the perioperative course like renal failure, ventilation >24 h, re-exploration, or cerebrovascular events. Conclusions: Cardiac surgery is safe in obesity as short- and long-term mortality are not increased, and major adverse events during the perioperative course are similar to control patients. The burden of obesity lies in substantially increased rates of wound-healing disorders and sternal reconstructions.

Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial).

INTRODUCTION: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies. METHODS AND ANALYSIS: This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites. ETHICS AND DISSEMINATION: The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT05126303.

Aortic valve neocuspidization using autologous pericardium compared to surgical aortic valve replacement.

INTRODUCTION: Aortic valve neocuspidization (AVNeo) for trileaflet aortic valve reconstruction using autologous pericardium (Ozaki procedure) depicts an encouraging new technique for the surgical treatment of aortic valve pathologies. The current study analyzes the early hemodynamic outcome of AVneo compared with surgical aortic valve replacement (SAVR) using the Abbott/St. Jude Trifecta aortic valve biological prostheses. METHODS: All patients who underwent either AVNeo or SAVR between March 2017 and April 2020 were included. Exclusion criteria were emergency cases, endocarditis, redo- or additional root procedures. Main endpoints were differences between the two groups in terms of the effective orifice area (EOA) and the effective orifice area index (EOAI) at discharge. RESULTS: During the study period, 105 AVNeo patients and 458 SAVR patients met the inclusion criteria. EOA was significantly higher in the AVNeo group (2.4 cm2 ± 0.8 vs. 2.1 cm2 /m2 ± 0.6 in the SAVR group, respectively; p < .001). Multiple regression analysis, including AVNeo, annulus size, bicuspid valve, preoperative stenosis, left ventricular ejection fraction (LVEF), and diastolic diameter (LVEDD) found two factors, which favor larger EOA: Annulus size (p < .0001) and AVneo (p = .005). EOAI was significantly higher in the AVNeo group (1.23 ± 0.4 vs. 1.02 cm2 /m2 ± 0.3, respectively; p < .001). Multiple regression analysis for EOAI showed effects for AVneo (p = .005) and bicuspid valve (p = .029). Mean pressure gradients (MPG) were lower in the AVNeo group than in the SAVR group (AVNeo: MPG = 8.0 mmHg ± 3.6 vs. SAVR: MPG = 8.3 mmHg ± 3.6), but this finding did not reach statistical significance (p = .091). CONCLUSIONS: AVNeo shows significantly larger EOA and EOAI compared to SAVR using the Abbott/St. Jude Trifecta aortic valve biological prostheses.

Cav1.3 calcium channels are full-range linear amplifiers of firing frequencies in lateral DA SN neurons.

The low-threshold L-type calcium channel Cav1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Cav1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Cav1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson's disease.

Surgical Aortic Valve Replacement-Age-Dependent Choice of Prosthesis Type.

BACKGROUND: Recently, the use of surgically implanted aortic bioprostheses has been favoured in younger patients. We aimed to analyse the long-term survival and postoperative MACCE (Major Adverse Cardiovascular and Cerebral Event) rates in patients after isolated aortic valve replacement. METHODS: We conducted a single-centre observational retrospective study, including all consecutive patients with isolated aortic valve replacement. 1:1 propensity score matching of the preoperative baseline characteristics was performed. RESULTS: A total of 2172 patients were enrolled in the study. After propensity score matching the study included 428 patients: 214 biological vs. 214 mechanical prostheses, divided into two subgroups: group A < 60 years and group B > 60 years. The mean follow-up time was 7.6 ± 3.9 years. Estimated survival was 97 ± 1.9% and 89 ± 3.4% at 10 years for biological and mechanical prosthesis, respectively in group A (p = 0.06). In group B the survival at 10 years was 79.1 ± 5.8% and 69.8 ± 4.4% for biological and mechanical prosthesis, respectively (p = 0.83). In group A, patients with a bioprosthesis exhibited a tendency for higher cumulative incidence MACCE rates compared to patients with a mechanical prosthesis, p = 0.83 (bio 7.3 ± 5.3% vs. mech 4.6 ± 2.2% at 10 years). In group B, patients with a mechanical prosthesis showed a tendency for higher cumulative incidence MACCE rates compared to patients with bioprosthesis, p = 0.86 (bio 4.3 ± 3.1% vs. mech 9.1 ± 3.1% at 10 years). CONCLUSIONS: Long-term survival after surgical aortic valve replacement is similar in patients with a biological and mechanical prosthesis, independent of the patients' age. Moreover, younger patients (<60 years) with bioprosthesis showed a survival benefit, compared to patients with mechanical prosthesis in this age group.

Excellent Hemodynamic Performance After Aortic Valve Neocuspidization Using Autologous Pericardium.

BACKGROUND: Aortic valve neocuspidization (AVNeo) for trileaflet aortic valve reconstruction using autologous pericardium (Ozaki procedure) offers an alternative treatment modality to overcome drawbacks of conventional prosthetic aortic valve replacement. METHODS: Between October 2016 and April 2019, 103 patients underwent surgery. Mean follow-up was 426 ± 270 days. Aortic stenosis was the leading diagnosis in 80 patients (77.7%) and aortic regurgitation in 23 (22.3%), respectively. Mean age was 54.0 ± 16.4 years (range, 13.8-78.5). A bicuspid valve was found in 81 patients (78.6%). Transthoracic echocardiography was performed at discharge and at 6 to 12 months after surgery. During AVNeo surgery valve sizing for an Abbott/St Jude Trifecta bioprosthesis (virtually implanted Trifecta bioprosthesis; St Jude Medical, St Paul, MN) was performed to compare pressure gradients and effective orifice area with published data. RESULTS: Trileaflet aortic valve reconstruction was achieved in all patients. In 38 patients neocommissures were created (36.9%). Mean cross-clamp time was 135 ± 20 minutes. Four patients underwent reoperation; the overall freedom from reoperation was 96.1%. Echocardiographic 6- to 12-months follow-up after surgery was available in 93.8% of patients and did not show any change in hemodynamic parameters compared with discharge. Comparison between AVNeo and virtually implanted Trifecta Bioprosthesis revealed a significantly lower mean pressure gradient (8.5 ± 3.7 mm Hg vs 10.2 ± 2.0 mm Hg, P < .001) and higher mean effective orifice area (2.2 ± 0.7 cm2 vs 2.1 ± 0.4 cm2, P = .037) for AVNeo. CONCLUSIONS: AVNeo shows low reoperation rates after surgery within the first 2 years. The hemodynamic performance is excellent, and the effective orifice area and mean pressure gradient remain stable within the first year.

Different Rates of Bioprosthetic Aortic Valve Failure With Perimount™ and Trifecta™ Bioprostheses.

OBJECTIVES: The use of bioprostheses in surgical aortic valve replacement (SAVR) has increased in younger patients. Comparative analysis of different types of bioprostheses is lacking. We aimed to compare two proprietary bioprostheses with different designs, i.e., internally and externally mounted leaflets, focusing on the long-term durability and survival. METHODS: We conducted a large single-center retrospective analysis of all consecutive patients who underwent SAVR with either Perimount™ or Trifecta™ bioprostheses between 2001 and 2019. The patient groups were further subdivided by age <65 and >65. Endpoints of the study were all-cause mortality and reoperation due to bioprosthetic valve failure (BVF). RESULTS: Selection criteria resulted in a total sample of 5,053 patients; 2,630 received a Perimount prosthesis (internally mounted leaflets) and 2,423 received a Trifecta prosthesis (externally mounted leaflets). The mean age at surgery was similar (69 ± 11 y, PM, and 68 ± 10 y, TF, p = 0.9), as was estimated survival at 8 years (76.1 ± 1.3%, PM, and 63.7 ± 1.9% TF; p=0.133). Patients in the Trifecta group had a significantly higher cumulative reoperation rate at 8 years compared to those in the Perimount group (16.9 ± 1.9% vs. 3.8 ± 0.4%; p < 0.01). This difference persisted across age groups (<65 y, 13.3% TF vs. 8.6% PM; >65 y, 12% TF vs. 7% PM). CONCLUSION: Bioprostheses for SAVR with externally mounted leaflets (Trifecta) showed significantly higher long-term reoperation rates compared to those with internally mounted leaflets (Perimount), regardless of the patient's age at SAVR. Survival was similar with both bioprostheses.

Comparison of outcomes following isolated repair of tricuspid versus bicuspid aortic valves.

BACKGROUND: Aortic valve repair (AV-repair) is an alternative treatment option for patients with aortic regurgitation (AR), but durability is still reason for concern, especially for bicuspid aortic valves (BAV). We retrospectively evaluated mid-term results after AV-repair in patients with BAV or tricuspid aortic valves (TAV), including reoperation rates, recurrence of regurgitation, and survival. METHODS: Patients undergoing AV-repair between November 2004 and March 2016 without procedures involving the aortic root were included. Echocardiographic examinations were performed before and after the operation and at follow-up. Repair techniques were recorded and evaluated. RESULTS: Of 150 patients, 89 (59.3%) had TAV and 61 (40.7%) BAV. AR ≥ moderate was found in 66 patients with TAV (74.2%) and 49 with BAV (80.3%). At discharge, 74 TAV-patients had ≤ mild AR (84.4%), 11 (12.4%) moderate. 57 patients (93.4%) with BAV had ≤ mild AR, 1 (1.6%) moderate and 2 (3.3%) severe. Mean follow-up was 4.4±2.7 years with ≤ mild AR in 56 TAV patients (73.7%) and moderate in 18 (20.2%). In patients with BAV, 43 (76.8%) had ≤ mild AR and 4 (6.6%) moderate. Survival in patients with TAV was significantly decreased compared to BAV (P=0.033), but reoperation-rates did not differ significantly (P=0.651). CONCLUSIONS: AV-repair is a safe and feasible option in patients with AR and can achieve similar results in patients with TAV and BAV. The complexity of the repair technique predicts repair failure.

Functional and Degenerative Mitral Regurgitation: One Ring Fits All?

BACKGROUND: Three-dimensional saddle-shaped annuloplasty rings have been shown to create a larger surface of leaflet coaptation in mitral valve repair (MVR) for functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) which may increase repair durability. For the first time, this study reports mid-term results after MVR for DMR and FMR using a rigid three-dimensional ring (Profile 3D, Medtronic). METHODS: Between June 2009 and June 2012, 369 patients with DMR (n = 326) or FMR (n = 43) underwent MVR (mean age 62.3 ± 12.6 years). A total of 205 patients (55.6%) underwent isolated MVR and 164 patients (44.4%) a combined procedure. Follow-up examinations were performed in 94.9% (mean 4.9 ± 0.9 years). Echocardiographic assessment was complete in 93.2% (mean 4.3 ± 1.2 years). RESULTS: The 30-day mortality was 1.5% (5/326) for DMR (1.5% for isolated and 1.6% for combined procedures) and 9.3% (4/43) for FMR (0% for isolated and 10.5% for combined procedures). Survival at 6 years was 92.1 ± 1.9% for DMR (92.9 ± 2.6% for isolated and 90.7 ± 2.7% for combined procedures) and 66.4 ± 7.9% for FMR (80.0 ± 17.9% for isolated and 63.7 ± 8.9% for combined procedures). Cumulative risk for mitral valve-related reoperation at 6 years was 0% for FMR and 7.1 ± 1.5% for DMR. At echocardiographic follow-up, one patient presented with mitral regurgitation (MR) more than moderate. The only predictor of recurrent MR after MVR for DMR was residual mild MR at discharge. CONCLUSION: Repair of FMR with the three-dimensional Profile 3D annuloplasty ring shows excellent mid-term results with regard to recurrence of MR. In cases of DMR, the results are conforming to the current literature.

Apolipoprotein E genotype, TNF-α 308G/A and risk for cardiac surgery associated-acute kidney injury in Caucasians.

OBJECTIVES: Acute kidney injury following cardiac surgery depicts a severe clinical problem that is strongly associated with adverse short- and long-term outcome. We analyzed two common genetic polymorphisms that have previously been linked to renal failure and inflammation, and have been supposed to be associated with cardiac surgery associated-acute kidney injury (CSA-AKI). METHODS: A total of 1415 consecutive patients who underwent elective cardiac surgery with CPB at our institution were prospectively enrolled. Patients were genotyped for Apolipoprotein E (ApoE E2,E3,E4) (rs429358 and rs7412) and TNF-α-308 G > A (rs1800629). RESULTS: Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between ApoE (E2,E3,E4) and TNF-α-308 G > A genotypes and the RIFLE criteria could be detected. Several multiple linear regression analyses for postoperative creatinine increase revealed highly significant associations for aortic cross clamp time (p < 0.001), CPB-time (p < 0.001), norepinephrine (p < 0.001), left ventricular function (p = 0.004) and blood transfusion (p < 0.001). No associations were found for ApoE (E2,E3,E4) and TNF-α-308 G > A genotypes or baseline creatinine. When the sample size is 1415, the multiple linear regression test of R(2 )= 0 for seven covariates assuming normal distribution will have at least 99% power with significance level 0.05 to detect an R(2) of 0.108 or 0.107 as observed in the data. CONCLUSIONS: ApoE (E2,E3,E4) polymorphism and the TNF-α-308 G > A polymorphism are not associated with renal injury after CPB.

COMT-Val158Met-polymorphism is not a risk factor for acute kidney injury after cardiac surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) depicts a major complication after cardiac surgery using cardiopulmonary bypass (CPB). OBJECTIVE: CSA-AKI has clearly been linked to increased perioperative morbidity and mortality. Dysregulations of vasomotor tone are assumed to be causal for CSA-AKI. While catechol-O-methyltransferase (COMT) is involved in metabolizing catecholamines, a single-nucleotide polymorphism (SNP) in the COMT gene leads to different enzyme activities according to genotype. Pilot studies found associations between those COMT genotypes and CSA-AKI. METHODS: We prospectively included 1741 patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB). Patients were genotyped for COMT-Val158Met-(G/A) polymorphism (rs4680). RESULTS: Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between COMT genotypes and the RIFLE criteria could be detected. A multiple linear regression analysis for postoperative creatinine increase revealed highly significant associations for aortic cross-clamp time (P < 0.001), CPB time (P < 0.001), norepinephrine (P < 0.001), and age (P < 0.001). No associations were found for COMT genotypes or baseline creatinine. With an R (2) = 0.39 and a sample size of 1741, the observed power of the regression analysis was >99%. CONCLUSIONS: Based on our results, we can rule out an association between the COMT-Val158Met-(G/A) polymorphism and the appearance of CSA-AKI.

Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial.

OBJECTIVES: We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND: Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS: A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS: Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS: Treatment of brain-dead donors with dopamine of 4 µg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Tumor necrosis factor-α -863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery.

OBJECTIVE: Cardiac surgery using cardiopulmonary bypass (CPB) initiates an inflammatory response that shows a wide inter-individual range and determines postoperative morbidity. Previous research suggests that genetic diversity contributes to individual susceptibility to perioperative trauma and stress. Nevertheless, the genetic triggering of the tumor necrosis factor-alpha (TNF-α) release remains unclear. We tested two genetic single-nucleotide polymorphisms (SNPs) from the promoter region of the TNF-α gene for associations with perioperative TNF-α level after CPB. METHODS: We prospectively included 122 patients, who underwent elective coronary artery bypass grafting (CABG). Patients were genotyped for TNF-α -863 C/A (rs1800630) and TNF-α -308 G/A (rs1800629). Plasma level of TNF-α was obtained preoperatively, at the end of CPB, 6h postoperatively, and on the first postoperative day (POD). RESULTS: Demographic characteristics and operative data revealed no significant differences between the different genotypes. Multiple linear regression analyses revealed significant associations for the TNF-α 863 C/A polymorphism: the major -863 CC variant was associated with higher TNF-α level preoperatively (p = 0.003), after CPB (p = 0.005), and 6h postoperatively (p = 0.010), independently from CPB time, left ventricle (LV) function and age. Contrarily, the AA allele had lower TNF-α level preoperatively (p = 0.008), after surgery (p = 0.024) and 6h postoperatively (p = 0.001). For the TNF-α 308 G/A polymorphism, only few significant associations could be observed: -308 GG carriers were associated with lower TNF-α level immediately after CPB (p = 0.020), whereas 308 AA carriers were significantly associated with elevated TNF-α level preoperatively (p = 0.032) and immediately after CPB (p = 0.05). No heterozygote variant of both SNPs revealed any significant associations with perioperative TNF-α level. CONCLUSIONS: The current study suggests that the major -863 CC variant determines elevated TNF-α level preoperatively and throughout the postoperative course after CPB.

Enhanced thrombin generation after cardiopulmonary bypass surgery.

BACKGROUND: Thrombin generation has a key role in the pathophysiology of hemostasis. Research has focused on the intraoperative course of hemostasis, while little is known about postoperative hemostatic activation. Thrombin generation assays quantify the potential for thrombin generation ex vivo and may be useful for determining hypercoagulability. The thrombin dynamics test (TDT) assesses the initial kinetics of thrombin formation. We hypothesized that there would be an increase in thrombin generation as well as thrombin capacity after cardiac surgery. METHODS: Two hundred twenty patients undergoing primary coronary artery bypass grafting or aortic valve replacement (AVR) surgery were prospectively enrolled. Patients undergoing AVR received warfarin beginning on the second postoperative day. In addition to prothrombin fragment (F(1+2)), TDT, d-dimer, and troponin T were assessed. Blood samples were obtained preoperatively, at the end of the operation, 4 hours postoperatively, and the morning of postoperative days (PODs) 1, 3, and 5. The primary end point was the change of thrombin dynamics on POD 1. RESULTS: In all patients, F(1+2) peaked at the end of the operation and remained significantly elevated until POD 5. Compared with baseline and after an initial decrease, TDT was found to be significantly elevated on POD 1. After coronary artery bypass graft, TDT remained significantly elevated, whereas in AVR patients with warfarin treatment, TDT was significantly reduced on PODs 3 and 5. CONCLUSIONS: After cardiac surgery, thrombin generation continues, accompanied by a high thrombin-generating capacity and elevated fibrinogen levels. This constellation suggests a marked procoagulopathic state in the postoperative period with the potential to aggravate the risk of thromboembolic complications. Warfarin treatment after AVR significantly reduced thrombin-generating capacity.

Impact of the indexed effective orifice area on mid-term cardiac-related mortality after aortic valve replacement.

BACKGROUND: There has been ongoing controversy as to whether prosthesis-patient mismatch (PPM, defined as indexed effective orifice area (EOAI) <0.85 m(2)/cm(2)) influences mortality after aortic valve replacement (AVR). In most studies, PPM is anticipated by reference tables based on mean EOAs as opposed to individual assessment. These reference values may not reflect the actual in vivo EOAI and hence, the presence or absence of PPM may be based on false assumptions. OBJECTIVE: To assess the impact of small prosthesis EOA on survival after aortic valve replacement AVR. METHODS: 645 patients had undergone an AVR between 2000 and 2007 entered the study. All patients underwent transthoracic echocardiography for determination of the actual EOAI within 6 months postoperatively. In order to predict time from surgery to death a proportional hazards model for competing risks (cardiac death vs death from other causes) was used. EOAI was entered as a continuous variable. RESULTS: PPM occurred in 40% of the patients. After a median follow-up of 2.35 years, 92.1% of the patients were alive. The final Cox regression model showed a significantly increased risk for cardiac death among patients with a smaller EOAI (HR=0.32, p=0.022). The effect of EOAI on the 2-5 year mortality risk was demonstrated by risk plots. CONCLUSIONS: In contrast to previous studies these EOAI values were obtained through postoperative echocardiography, substantially improving the accuracy of measurement, and the EOAI was modelled as a continuous variable. There was a significantly improved survival for larger EOAIs following AVR. Strategies to avoid PPM should become paramount during AVR.

Impact of preoperative positron emission tomography in patients with severely impaired LV-function undergoing surgical revascularization.

In patients with ischemic cardiomyopathy, coronary artery bypass grafting (CABG) offers an important therapeutic option but is still associated with high perioperative mortality. Although previous studies suggest a benefit from revascularization for patients with defined viability by a non-invasive technique, the role of viability assessment to determine suitability for revascularization in patients with ischemic cardiomyopathy has not yet been defined. This study evaluates the hypothesis that the use of PET imaging in the decision-making process for CABG will improve postoperative patient survival. We reviewed 476 patients with ischemic cardiomyopathy (LV ejection fraction 70 (P = 0.016). Preoperative assessment of myocardial viability via PET identifies patients, who will benefit most from CABG.

Tranexamic acid and aprotinin in primary cardiac operations: an analysis of 220 cardiac surgical patients treated with tranexamic acid or aprotinin.

BACKGROUND: Antifibrinolytics are widely used in cardiac surgery to reduce bleeding. Allogeneic blood transfusion, even in primary cardiac operations with low blood loss, is still high. In the present study we evaluated the impact of tranexamic acid compared to aprotinin on the transfusion incidence in cardiac surgical patients with low risk of bleeding. METHODS: This prospective, randomized, double-blind study included 220 patients undergoing primary coronary artery revascularization (coronary artery bypass grafting [CABG]) or aortic valve replacement (AVR). Randomized in blocks of 20, patients received either tranexamic acid (approximately 6 g) or full-dose aprotinin (approximately 5-6 x 10(6) Kallikrein Inhibiting Units). Transfusion was guided by a strict transfusion algorithm. Molecular markers of hemostasis were determined to assess differences in the mode of action of the two drugs. Primary end-points were the incidence of allogeneic red cell transfusion and 24-h postoperative blood loss. Data were analyzed according to the intention-to-treat principle and compared using the chi(2) and Mann-Whitney U-test. RESULTS: Two-hundred-twenty patients were enrolled (CABG: 134, AVR: 86). In the aprotinin Group 47% of patients received allogeneic blood during the hospital stay as compared to 61% in the tranexamic acid group (P = 0.036). Aprotinin conferred a 23% reduction in allogeneic transfusion risk (RR 0.77, 95% CI 0.53-0.88). Overall, no significant difference in postoperative bleeding was observed, although 24-h blood loss was reduced in aprotinin-treated CABG patients (500, 350-750 mL vs 650, 475-875 mL (median, 25th-75th percentile); P = 0.039). Despite the lower transfusion rate, the hemoglobin concentration on the first postoperative day was higher in the aprotinin group (11.3, 9.9-12.1 vs 10.6, 9.9-11.6 mg/dL; P = 0.023). The fibrinolytic activity at the end of operation determined by D-Dimer was comparable in both groups. (0.15, 0.11-0.17 mg/L [aprotinin] versus 0.18, 0.12-0.24 mg/L [tranexamic acid]). The activated partial thromboplastin time was prolonged up to 4 h postoperatively in the aprotinin group, while the heparin requirement was reduced: 19% of the patients in the aprotinin group and 45% in the tranexamic acid group received at least one additional bolus heparin during cardiopulmonary bypass (P < 0.001). Troponin T levels postoperatively and on postoperative day 1 were significantly higher in the tranexamic acid group (P = 0.017). No differences in renal, cardiac, or mortality outcomes were observed. CONCLUSION: Considering the rate of transfusion of red blood cells, tranexamic acid was slightly inferior in patients undergoing CABG, but there was no difference in patients receiving AVR. Tranexamic acid seems to be less effective in operations with increased bleeding such as CABG. Clinical benefit depends on specific patient and institution characteristics (ClinicalTrials.gov NCT00396760).

Partial median "I" sternotomy: minimally invasive alternate approach for aortic valve replacement.

Minimally invasive aortic valve replacement using the inversed L-like partial upper sternotomy has evolved during the last 10 years. It is performed with excellent results with regard to sternal stability and cosmesis. However, the lateral incision may result in sternal overriding, instability, or fracture. We present an alternate minimally invasive approach to aortic valve replacement. We performed a partial median "I" sternotomy in 30 consecutive patients: After a 6- to 8-cm skin incision, the sternum was incised from the jugulum downward to the corpus, ending at the level of the fourth or fifth intercostal space. No lateral incision of the sternum was performed. The access to the heart and aorta was excellent. During the postoperative course and during follow-up, clinical examination revealed sternal stability and normal wound healing in all patients. These results show that the partial median I sternotomy can be performed safely and provides excellent clinical and cosmetic results.