A total artificial heart (TAH) is typically used to bridge the time to heart transplantation. A device designed by Robert Jarvik has been improved through the years and under the name of Syncardia™ this has been the most successful commercially available TAH so far. Since 2008 the Carmat™ heart has been under development in Europe. The Scandinavian Real Heart™ is based on a unique physiological concept where the atrio-ventricular valve plane is of utmost importance in the pumping function of the heart. It consists of two identical parts driven separately by independent motors and in this first animal study we have used one part as a left ventricular assist device. This new concept makes the device flexible as it may be used not only as a TAH but also as a separate pump for left or right ventricular assist.

OBJECTIVE: To describe the dynamics of copeptin in open cardiac surgery during the perioperative course.

DESIGN: Prospective cohort study.

SETTING: Single tertiary hospital.

PARTICIPANTS: Twenty patients scheduled for open cardiac surgery procedures with cardiopulmonary bypass (CPB).

INTERVENTIONS: No intervention.

MEASUREMENTS AND MAIN RESULTS: Copeptin concentrations were measured pre-, peri-, and postoperatively until day 6 after surgery. Patients were analyzed as a whole cohort (n = 20) and in a restricted "normal cohort" consisting of patients with normal preoperative copeptin concentration (<10 pmol/L) and perioperative uneventful course (n = 11). In the whole cohort, preoperative copeptin concentration was 7.0 pmol/L (interquartile range: 3.1-11 pmol/L). All patients had an early rise of copeptin, with 80% having peak copeptin concentration at weaning from CPB or upon arrival in the intensive care unit. Patients in the "normal cohort" had copeptin concentration at weaning from CPB of 194 pmol/L (98-275), postoperative day 1, 27 pmol/L (18-31); and day 3, 8.9 pmol/L (6.3-12).

CONCLUSIONS: Regardless of cardiac surgical procedure and perioperative course, all patients had an early significant rise of copeptin concentrations, generally peaking at weaning from CBP or upon arrival in the intensive care unit. Among patients with normal copeptin concentration preoperatively and uneventful course, the postoperative copeptin concentrations decreased to normal values within 3-to-4 days after cardiac surgery. Furthermore, the restricted "normal cohort" generally tended to display lower levels of copeptin concentration postoperatively. Further studies may evaluate whether copeptin can be a tool in identifying risk patients in cardiac surgery.

Objectives: To describe the dynamics of N-terminal pro-B-type natriuretic peptide (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1-year mortality.

Methods: At preoperative evaluation, we prospectively included 462 patients accepted for aortic valve intervention. The median time to surgical aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6-month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation and aortic stenosis with and without coronary artery bypass were also analysed.

Results: NT-proBNP remained stable in all subgroups during the preoperative waiting period, but displayed a substantial transient early postoperative increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative days 1 and 3 revealed significant discriminatory power with regard to 1-year mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had higher levels of NT-proBNP both preoperatively and at the 6-month follow-up compared with the SAVR group.

Conclusions: The dynamic profile of NT-proBNP differed between patients undergoing TAVI and SAVR. NT-proBNP in the perioperative course was associated with increased risk of 1-year mortality in SAVR but not in TAVI.

BACKGROUND:

Postoperative heart failure remains the major cause of death after cardiac surgery. As N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor for postoperative heart failure, the aim was to evaluate if preoperative NT-proBNP could provide additional prognostic information to the recently launched EuroSCORE II.

METHODS:

A total of 365 patients with acute coronary syndrome (ACS) undergoing isolated coronary artery bypass graft (CABG) surgery were studied prospectively. Preoperative NT-proBNP and EuroSCORE II were evaluated with regard to severe circulatory failure after operation according to prespecified criteria. To assess what clinical outcomes are indicated by NT-proBNP levels in different risk categories, the patients were stratified according to EuroSCORE II. Based on receiver operating characteristics analysis, these cohorts were assessed with regard to preoperative NT-proBNP below or above 1028 ng litre(-1). The follow-up time averaged 4.4 (0.7) yr.

RESULTS:

Preoperative NT-proBNP≥1028 ng litre(-1) [odds ratio (OR) 9.9, 95% confidence interval (CI) 1.01-98.9; P=0.049] and EuroSCORE II (OR 1.24, 95% CI 1.06-1.46; P=0.008) independently predicted severe circulatory failure after operation. In intermediate-risk patients (EuroSCORE II 2.0-10.0), NT-proBNP≥1028 ng litre(-1) was associated with a higher incidence of severe circulatory failure (6.6% vs 0%; P=0.007), renal failure (14.8% vs 5.4%; P=0.03), stroke (6.6% vs 0.7%; P=0.03), longer intensive care unit stay [37 (35) vs 27 (38) h; P=0.002], and worse long-term survival.

CONCLUSIONS:

Combining EuroSCORE II and preoperative NT-proBNP appears to improve risk prediction with regard to severe circulatory failure after isolated CABG for ACS. NT-proBNP may be particularly useful in patients at intermediate risk according to EuroSCORE II.

Postoperative heart failure or low cardiac output syndrome is the major cause for morbidity and mortality in cardiac surgery. Unfortunately commonly used methods to assess hemodynamic state and heart failure are not well documented with regard to outcome. The aim for this dissertation was to study the predictive values of postoperative Mixed Venous Oxygen saturation (SvO2) and preoperative NT-proBNP for outcomes related to postoperative heart failure.

SvO2 was studied retrospectively in two cohorts of patients, one cohort operated with isolated Aortic Valve Replacement (AVR) for aortic stenosis, (n=396) and one operated with isolated Coronary Artery Bypass Grafting (CABG), (n=2755). SvO2 measured early after surgery, on admission to the intensive care unit (ICU), predicted postoperative morbidity and mortality. Our results suggest that, on admission to ICU SvO2 < 55 - 60% after AVR and SvO2 < 60% after CABG merits increased attention.

Preoperative NT-proBNP was studied in a cohort of patients with acute coronary syndrome (ACS) undergoing CABG with or without concomitant procedure. These patients (n=383) were included prospectively and evaluated with regard to mortality and severe circulatory failure postoperatively by an end-points committee blinded to NT-proBNP results. Preoperative NT-proBNP ≥ 1028 ng/L independently predicted increased risk for severe circulatory failure postoperatively in patients with ACS undergoing isolated CABG. Preoperative NT-proBNP provided additional prognostic information to EuroSCORE II in this cohort, particularly in patients at intermediate risk. Preoperative NT-proBNP appears to be markedly higher in patients having CABG with concomitant procedures than in patients undergoing isolated CABG. Further studies are warranted to identify preoperative NTproBNP risk thresholds for different heart conditions and surgery-specific cohorts.

In conclusion this dissertation shows that:

• Postoperative SvO2 on admission to ICU is a prognostic marker for morbidity and mortality after AVR and CABG.
• Preoperative NT-proBNP ≥ 1028 ng/L independently predicts severe circulatory failure postoperatively in patients undergoing isolated CABG and provides additional prognostic information to EuroSCORE II.
• The high negative predictive value of the identified cutoff levels for preoperative NTproBNP and postoperative SvO2 could be useful for pre and postoperative decisionmaking.

Objectives. The predictive value of preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated in patients with acute coronary syndrome undergoing coronary artery bypass grafting (CABG). Design. As a substudy to a clinical trial 383 patients with acute coronary syndrome undergoing CABG were studied. 17 patients had a concomitant procedure. NT-proBNP was measured immediately preoperatively and evaluated with regard to in-hospital mortality, and severe circulatory failure postoperatively according to prespecified criteria. Follow-up was 3.2 +/- 0.9 years. Results. In patients with isolated CABG, receiver operating characteristics (ROC) analysis showed an area under the curve (AUC) of 0.82 for in-hospital mortality and 0.87 for severe circulatory failure respectively with a best cut-off for preoperative NT-proBNP of 1028 ng/L. This cut-off level independently predicted severe circulatory failure. Patients with NT-proBNP andlt; 1028 ng/L had significantly better long-term survival (p = 0.004). Preoperative NT-proBNP was higher in patients with concomitant procedure than isolated CABG (2146 +/- 1858 v 887 +/- 1635 ng/L; p = 0.0005). In patients with concomitant procedure ROC analysis showed an AUC of 0.93 for severe circulatory failure with a best cut-off for preoperative NT-proBNP of 3145 ng/L. Conclusions. Preoperative NT-proBNP predicted in-hospital mortality, severe circulatory failure postoperatively and long-term survival in patients undergoing surgery for acute coronary syndrome but a higher threshold was found in patients having concomitant procedures.