Glutamate infusion associated with reduced rises of p-Copeptin after coronary surgery: Substudy of GLUTAMICS II.

BACKGROUND: Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG. METHODS: A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0 and underwent CABG ± valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10-20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke ≤24 h and mortality ≤30 days were safety outcomes. RESULTS: We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality ≤30 days (0% vs. 2.1%; p = .50) and stroke ≤24 h (0% vs. 3.2%; p = .25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 ± 66 vs. 115 ± 102 pmol/L; p = .02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p = .02) and POD 3 (p = .02). CONCLUSIONS: Glutamate did not reduce rises of p-Copeptin significantly after moderate to high-risk CABG. However, glutamate was associated with reduced rises of p-Copeptin among patients without diabetes. These results agree with previous observations suggesting that glutamate mitigates myocardial dysfunction after CABG in patients without diabetes. Given the exploratory nature of these findings, they need to be confirmed in future studies.

Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II): A randomized controlled trial.

BACKGROUND: Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG. METHODS AND FINDINGS: A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation. CONCLUSIONS: Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824. European Union Drug Regulating Authorities Clinical Trials Database (Eudra CT number 2011-006241-15).

The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery: a randomized study.

BACKGROUND: Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP. METHODS: Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M L-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP. RESULTS: Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995-6260] vs. 6745 [3455-12,687] ng•L-1, p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426-7423] vs. 8430 [5370-14,100] ng•L-1, p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19-26] vs. 25 [22-46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170-500] vs. 560 [210-910] ng•L-1, p = 0.025). CONCLUSIONS: Post hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings. Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1.

Better platelet function, less fibrinolysis and less hemolysis in re-transfused residual pump blood with the Ringer's chase technique - a randomized pilot study.

INTRODUCTION: Residual pump blood from the cardiopulmonary bypass (CPB) circuit is often collected into an infusion bag (IB) and re-transfused. An alternative is to chase the residual blood into the circulation through the arterial cannula with Ringer's acetate. Our aim was to assess possible differences in hemostatic blood quality between these two techniques. METHODS: Forty adult patients undergoing elective coronary artery bypass graft surgery with CPB were randomized to receive the residual pump blood by either an IB or through the Ringer's chase (RC) technique. Platelet activation and function (impedance aggregometry), coagulation and hemolysis variables were assessed in the re-transfused blood and in the patients before, during and after surgery. Results are presented as median (25-75 quartiles). RESULTS: Total hemoglobin and platelet levels in the re-transfused blood were comparable with the two methods, as were soluble platelet activation markers P-selectin and soluble glycoprotein VI (GPVI). Platelet aggregation (U) in the IB blood was significantly lower compared to the RC blood, with the agonists adenosine diphosphate (ADP) 24 (10-32) vs 46 (33-65), p<0.01, thrombin receptor activating peptide (TRAP) 50 (29-73) vs 69 (51-92), p=0.04 and collagen 24 (17-28) vs 34 (26-59), p<0.01. The IB blood had higher amounts of free hemoglobin (mg/L) (1086 (891-1717) vs 591(517-646), p<0.01) and D-dimer 0.60 (0.33-0.98) vs 0.3 (0.3-0.48), p<0.01. Other coagulation variables showed no difference between the groups. CONCLUSIONS: The handling of blood after CPB increases hemolysis, impairs platelet function and activates coagulation and fibrinolysis. The RC technique preserved the blood better than the commonly used IB technique.

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study.

AIMS: Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients. METHODS AND RESULTS: All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012-13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72-120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53-1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72-120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04-2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56-0.92), P = 0.012]. CONCLUSION: The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.

Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass.

OBJECTIVES: Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but may affect platelet aggregation. We assessed changes in platelet function in relation to protamine administration. DESIGN: Platelet aggregation was analyzed by impedance aggregometry before and after protamine administration in 25 adult cardiac surgery patients. Aggregation was also studied after in vitro addition of heparin and protamine. The activators adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used. RESULTS: Platelet aggregation was reduced by approximately 50% after in vivo protamine administration; ADP 640 ± 230 (AU*min, mean ± SD) to 250 ± 160, TRAP 939 ± 293 to 472 ± 260, AA 307 ± 238 to 159 ± 143 and COL 1022 ± 350 to 506 ± 238 (all p < 0.001). Aggregation was also reduced after in vitro addition of protamine alone with activators ADP from 518 ± 173 to 384 ± 157 AU*min p < 0.001, and AA 449 ± 311 to 340 ± 285 (p < 0.01) and protamine combined with heparin (1:1 ratio) with activators ADP to 349 ± 160 and AA to 308 ± 260 (both p < 0.001); and COL from 586 ± 180 to 455 ± 172 (p < 0.05). CONCLUSIONS: Protamine given after CPB markedly reduces platelet aggregation. Protamine added in vitro also reduces platelet aggregation, by itself or in combination with heparin.

Post hoc analysis of the glutamics-trial: intravenous glutamate infusion and use of inotropic drugs after cabg.

BACKGROUND: Intravenous glutamate reduced the risk of developing severe circulatory failure after isolated coronary artery bypass graft surgery (CABG) for acute coronary syndrome (ACS) in a double-blind randomised clinical trial (GLUTAMICS-ClinicalTrials.gov Identifier: NCT00489827 ). Here our aim was to study if glutamate was associated with reduced the use of inotropes. METHODS: Post-hoc analysis of 824 patients undergoing isolated CABG for ACS in the GLUTAMICS-trial. ICU-records were retrospectively scrutinised including hourly registration of inotropic drug infusion, dosage and total duration during the operation and postoperatively. RESULTS: ICU-records were found for 171 out of 177 patients who received inotropes perioperatively. Only one fourth of the patients treated with inotropes fulfilled study criteria for postoperative heart failure at weaning from cardiopulmonary bypass (CPB) or later in the ICU. Inotropes were mainly given preemptively to facilitate weaning from CPB or to treat postoperative circulatory instability (bleeding, hypovolaemia). Except for a significantly lower use of epinephrine there were only trends towards lower need of other inotropes overall in the glutamate group. In patients treated with inotropes (glutamate n = 17; placebo n = 13) who fulfilled study criteria for left ventricular failure at weaning from CPB the average duration of inotropic treatment (34 ± 20 v 80 ± 77 h; p = 0.014) and the number of inotropes used (1.35 ± 0.6 v 1.85 ± 0.7; p = 0.047) were lower in the glutamate group. CONCLUSIONS: Intravenous glutamate was associated with a minor influence on inotrope use overall in patients undergoing CABG for ACS whereas a considerable and significant reduction was observed in patients with heart failure at weaning from CPB.

Association of Glutamate Infusion With Risk of Acute Kidney Injury After Coronary Artery Bypass Surgery: A Pooled Analysis of 2 Randomized Clinical Trials.

Importance: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality, and measures to prevent AKI have had limited success. Glutamate has been reported to enhance natural postischemic recovery of the heart, but not among animals and humans with diabetes. Objective: To summarize pooled results from the GLUTAMICS (Glutamate for Metabolic Intervention in Coronary Surgery) trials regarding the effect of glutamate on postoperative AKI among patients without diabetes undergoing coronary artery bypass graft (CABG) surgery. Design, Setting, and Participants: Data on a total of 791 patients without diabetes from 2 prospective, randomized, double-blind multicenter trials performed at 5 cardiac surgery centers in Sweden between October 4, 2005, and November 12, 2009, and between November 15, 2015, and September 30, 2020, were pooled. Patients had acute coronary syndrome, left ventricular ejection fraction of 0.30 or less, or a European System for Cardiac Risk Evaluation II score of 3.0 or more and underwent CABG with or without additional valve procedure. Statistical analysis was performed from May to November 2023. Interventions: Intravenous infusion of 0.125-M l-glutamic acid or saline at 1.65 mL/kg/h for 2 hours during reperfusion, after which the infusion rate was halved and an additional 50 mL was given. Main Outcomes and Measures: The primary end point was AKI, defined as postoperative increase of plasma creatinine of 50% or more, corresponding to the Risk stage or higher in the Risk, Injury, Failure, Loss, and End-Stage kidney disease (RIFLE) criteria. Results: A total of 791 patients without diabetes (391 who received glutamate [mean (SD) age, 69.3 (9.1) years; 62 women (15.9%)] and 400 controls [mean (SD) age, 69.6 (9.5) years; 73 women (18.3%)]) were randomized. Baseline data did not differ between groups. Glutamate was associated with a significantly lower risk of AKI (relative risk, 0.49 [95% CI, 0.29-0.83]). Dialysis was required for 2 patients in the glutamate group and 5 patients in the control group. In multivariable analysis, glutamate remained significantly associated with a protective effect against AKI (odds ratio, 0.47 [95% CI, 0.26-0.86]). In the glutamate and control groups, the rate of postoperative mortality at 30 days or less was 0.5% (2 of 391) vs 1.0% (4 of 400), and the rate of stroke at 24 hours or less was 0.8% (3 of 391) vs 1.8% (7 of 400). Conclusions and Relevance: In this pooled analysis of 2 randomized clinical trials, infusion of glutamate was associated with a markedly lower risk of AKI after CABG among patients without diabetes. The findings are exploratory and need to be confirmed in prospective trials. Trial Registration: ClinicalTrials.gov Identifiers: NCT00489827 and NCT02592824.

Glutamate Infusion Reduces Myocardial Dysfunction after Coronary Artery Bypass Grafting According to NT-proBNP: Summary of 2 Randomized Controlled Trials (GLUTAmate for Metabolic Intervention in Coronary Surgery [GLUTAMICS I-II]).

BACKGROUND: Glutamate is reported to enhance the recovery of oxidative metabolism and contractile function of the heart after ischemia. The effect appears to be blunted in diabetic hearts. Elevated plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction. In the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) II trial, the proportion of patients with diabetes had nearly doubled to 47% compared with the cohort used for sample size estimation, and a significant effect on the postoperative rise in NT-proBNP was only observed in patients without diabetes. OBJECTIVE: We aimed to summarize the pooled NT-proBNP results from both GLUTAMICS trials and address the impact of diabetes. METHODS: Data from 2 prospective, randomized, double-blind multicenter trials with similar inclusion criteria and endpoints were pooled. Patients underwent a coronary artery bypass grafting (CABG) ± valve procedure and had a left-ventricular ejection fraction of ≤0.30 or a European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) of ≥3.0 with at least 1 cardiac risk factor. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was started 10-20 min before reperfusion and continued for 150 min. The primary endpoint was the difference between preoperative and day 3 postoperative NT-proBNP levels. RESULTS: A total of 451 patients, 224 receiving glutamate and 227 controls, fulfilled the inclusion criteria. Glutamate was associated with a reduced primary endpoint (5344 ± 5104 ng/L and 6662 ± 5606 ng/L in glutamate and control groups, respectively; P = 0.01). Postoperative mortality at ≤30 d was 0.9% and 3.5% (P = 0.11), whereas stroke at ≤24 h was 0.4% and 2.6% in glutamate and control groups, respectively (P = 0.12). No adverse events related to glutamate were observed. A significant interaction regarding the primary endpoint was only detected between glutamate and insulin-treated diabetes groups (P = 0.04). Among patients without insulin-treated diabetes, the primary endpoint was 5047 ± 4705 ng/L and 7001 ± 5830 ng/L in the glutamate and control groups, respectively (P = 0.001). CONCLUSIONS: Infusion of glutamate reduced the postoperative rise in NT-proBNP after CABG in medium- to high-risk patients. A significantly blunted effect was observed only in insulin-treated patients with diabetes. CLINICAL TRIAL DETAILS: This trial was registered at www. CLINICALTRIALS: gov as NCT02592824.

Evaluation of left ventricular diastolic function in patients operated for aortic stenosis.

BACKGROUND: Left ventricular diastolic dysfunction is common in patients with aortic valve stenosis (AS) and reportedly affects prognosis after surgical aortic valve replacement (SAVR). Here we investigated whether and how diastolic function (assessed following the most recent guidelines) was affected by SAVR, and whether preoperative diastolic function affected postoperative outcome. We also examined whether long-term mortality was associated with preoperative NT-proBNP and postoperative heart failure (PHF). METHODS: We performed a prospective observational study of 273 patients with AS who underwent AVR with or without concomitant coronary artery bypass surgery. Of these patients, 247 were eligible for assessment of left ventricular (LV) filling pressure. Preoperatively and at the 6-month postoperative follow-up, we measured N-terminal pro-B type natriuretic peptide (NT-proBNP) in serum and assessed diastolic function with Doppler echocardiography. PHF was diagnosed using prespecified criteria. Multivariable logistic regression was performed to explore variables associated with high LV filling pressure. Cox regression was performed to explore variables associated with mortality, accounting for timeto-event. RESULTS: At the time of surgery, 22% (n = 54) of patients had diastolic dysfunction expressed as high LV filling pressure. Of these 54 patients, 27 (50%) showed postoperative diastolic function improvement. Among the 193 patients with preoperative low LV filling pressure, 24 (12%) showed postoperative diastolic function deterioration. Increased long-term mortality was associated with PHF and high preoperative NT-proBNP, but not with preoperative or postoperative diastolic dysfunction. Cox regression revealed the following independent risk factors for long-term mortality: diabetes, renal dysfunction, preoperative NT-proBNP>960 ng/L, age, and male gender. CONCLUSIONS: Surgery for aortic stenosis improved diastolic function in patients with high LV filling pressure in 50% of the patients. Our results could not confirm the previously suggested role of diastolic dysfunction as a marker for poor long-term survival after SAVR. Our findings showed that both PHF and high preoperative NT-proBNP were associated with long-term mortality.

The combined impact of postoperative heart failure and EuroSCORE on long-term outcome after surgery for aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Although the EuroSCORE was developed for predicting operative mortality after cardiac surgery, it has also been shown to predict long-term mortality. It has been reported that postoperative heart failure (PHF) in association with surgery, albeit comparatively benign in the short term, has a profound impact on five-year survival after surgery for aortic stenosis (AS). The study aim was to determine the combined impact of EuroSCORE and PHF on long-term survival after isolated aortic valve replacement (AVR) for AS. METHODS: A total of 397 patients (48% females; average age 70 +/- 10 years) who underwent AVR for AS at the authors' institution between 1995 and 2000 was studied. The cohort was subdivided according to the additive EuroSCORE into a high-risk group (EuroSCORE >7) and a low-risk group (EuroSCORE < or = 7), and further analyzed in relation to PHF. RESULTS: The average follow up was 8.1 years (range: 5.2-11.2 years). Forty-five patients (11%) were treated for procedure-associated PHF. Patients with or without PHF and a high-risk EuroSCORE had crude five-year survivals of 57% and 64%, respectively (p = 0.6), whereas those with or without PHF but with a low-risk EuroSCORE had crude five-year survivals of 58% and 89%, respectively (p = 0.0003). CONCLUSION: Both PHF and a high EuroSCORE were associated with poor long-term survival. The role of PHF per se for the long-term prognosis was illustrated by the fact that the negative impact on long-term survival was almost as profound in patients of the low-risk group as of the high-risk group.

Functional impairment after treatment with pectoral muscle flaps because of deep sternal wound infection.

OBJECTIVE: Pectoral muscle flaps (PMF) are effective in terminating protracted sternal wound infections (SWI) but long-term outcome remains uncertain. Therefore, the aim of this study was to evaluate long-term outcome in patients treated with PMF. DESIGN: Thirty-four of 263 patients revised because of deep SWI from 1991--2005 were treated with PMF. Of the 21 patients alive, 11 had left-sided, two right-sided and eight bilateral procedures. Sternal debridement without closure of the sternum was done in 17 patients. Nineteen of 21 patients responded to a questionnaire. RESULTS: At follow-up on average 5.9 years (range 1.9--14.8 years) after surgery 63% (12/19) experienced unstable chest. Two thirds (12/18) reported problems carrying a grocery bag and 37% (7/19) had problems putting on a coat. Reduction of power and mobility was more common in the right arm and shoulder even in patients with left-sided PMF. Thirty-two percent (6/19) would have preferred alternative treatment if possible to avoid sternal instability even if healing had been substantially delayed. CONCLUSIONS: Surgery with PMF and sternal debridement was associated with long-term disability, which appeared to be significant in one third of the patients. The function of the right arm and shoulder was affected more often despite the majority of procedures being left-sided suggesting that loss of skeletal continuity of the chest wall is more disabling than loss of pectoral muscle function.

Utility of NT-proBNP as an objective marker of postoperative heart failure after coronary artery bypass surgery: a prospective observational study.

BACKGROUND: Postoperative heart failure (PHF) is the main cause for mortality after cardiac surgery but unbiased evaluation of PHF is difficult. We investigated the utility of postoperative NT-proBNP as an objective marker of PHF after coronary artery bypass surgery (CABG). METHODS: Prospective study on 382 patients undergoing isolated CABG for acute coronary syndrome. NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A blinded Endpoints Committee used prespecified criteria for PHF. Use of circulatory support was scrutinized. RESULTS: After adjusting for confounders PHF was associated with 1.46 times higher NT-proBNP on POD1 (p = 0.002), 1.54 times higher on POD3 (p < 0.0001). In severe PHF, NT-proBNP was 2.18 times higher on POD1 (p = 0.001) and 1.81 times higher on POD3 (p = 0.019). Postoperative change of NT-proBNP was independently associated with PHF (OR 5.12, 95% CI 1.86-14.10, p = 0.002). The use of inotropes and ICU resources increased with incremental quartiles of postoperative NT-proBNP. CONCLUSIONS: Postoperative NT-proBNP can serve as an objective marker of the severity of postoperative myocardial dysfunction. Due to overlap in individuals, NT-proBNP is useful mainly for comparisons at cohort level. As such, it provides a tool for study purposes when an unbiased assessment of prevention or treatment of PHF is desirable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00489827 https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=2&rank=1 .

A metabolic protective strategy could improve long-term survival in patients with LV-dysfunction undergoing CABG.

OBJECTIVE: Adverse outcome after CABG is closely related to postoperative heart failure precipitated by ischemia and myocardial infarction. Restrictive use of inotropes is therefore desirable. Patients with preoperative left ventricular dysfunction are a high-risk group in this respect. To reduce myocardial oxygen expenditure we evolved a metabolic strategy for perioperative care. DESIGN: Observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. The metabolic strategy implied physiological measures to minimize myocardial oxygen expenditure including restrictive use of inotropes and specific measures such as extended CPB and metabolic support to facilitate myocardial recovery. Hemodynamic state was primarily assessed by mixed venous oxygen saturation (SvO(2)). Follow-up averaged 9.7+/-1.4 years. RESULTS: LVEF was 0.30+/-0.05 (range 0.20-0.37) and 3.5+/-1.3 vessels were bypassed. Inotropes were used in 6.7% for weaning from CPB. Increase of s-creatinine by > or =50% compared to preoperative values was observed in 2.9%. Logistic EuroSCORE was 8.3% whereas observed 30-day mortality was 1.0%. Crude 5-year survival was 89.4%. CONCLUSIONS: The metabolic strategy allowed restrictive use of inotropes and was associated with encouraging long-term survival. Renal function was well preserved suggesting that SvO(2) served as an adequate marker of circulation. Randomized trials with metabolic support are warranted.

NT-proBNP and postoperative heart failure in surgery for aortic stenosis.

Objective: Postoperative heart failure (PHF) after aortic valve replacement (AVR) for aortic stenosis (AS) may initially appear mild and transient but has serious long-term consequences. Methods to assess PHF are not well documented. We studied the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and PHF after AVR for AS. Methods: This is a prospective, observational, longitudinal study of 203 patients undergoing elective first-time AVR for AS. Plasma NT-proBNP was assessed at preoperative evaluation, the day before surgery, and the first (POD1) and third postoperative morning. A clinical endpoints committee, blinded to NT-proBNP results, used prespecified haemodynamic criteria to diagnose PHF. The mean follow-up was 8.6±1.1 years. Results: No patient with PHF (n=18) died within 30 days after surgery, but PHF was associated with poor long-term survival (HR 3.01, 95% CI 1.45 to 6.21, p=0.003). NT-proBNP was significantly higher in patients with PHF only on POD1 (6415 (3145-11 220) vs 2445 (1540-3855) ng/L, p<0.0001). NT-proBNP POD1 provided good discrimination of PHF (area under the curve=0.82, 95% CI 0.72 to 0.91, p<0.0001; best cut-off 5290 ng/L: sensitivity 63%, specificity 85%). NT-proBNP POD1 ≥5290 ng/L identified which patients with PHF carried a risk of poor long-term survival, and PHF with NT-proBNP POD1 ≥ 5290 ng/L emerged as a risk factor for long-term mortality in the multivariable Cox regression (HR 6.20, 95% CI 2.72 to 14.1, p<0.0001). Conclusions: The serious long-term consequences associated with PHF after AVR for AS were confirmed. NT-proBNP level on POD1 aids in the assessment of PHF and identifies patients at particular risk of poor long-term survival.

Rise and fall of NT-proBNP in aortic valve intervention.

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.

Impact of underlying heart disease per se on the utility of preoperative NT-proBNP in adult cardiac surgery.

OBJECTIVE: The primary aim was to investigate the role of underlying heart disease on preoperative NT-proBNP levels in patients admitted for adult cardiac surgery, after adjusting for the known confounders age, gender, obesity and renal function. The second aim was to investigate the predictive value of preoperative NT-proBNP with regard to severe postoperative heart failure (SPHF) and postoperative mortality. METHODS: A retrospective cohort study based on preoperative NT-proBNP measurements in an unselected cohort including all patients undergoing first time surgery for coronary artery disease (CAD; n = 2226), aortic stenosis (AS; n = 406) or mitral regurgitation (MR; n = 346) from April 2010 to August 2016 in the southeast region of Sweden (n = 2978). Concomitant procedures were not included, with the exception of Maze or tricuspid valve procedures. RESULTS: Preoperative NT-proBNP was 1.67 times (p<0.0001) and 1.41 times (p<0.0001) higher in patients with AS or MR respectively, than in patients with CAD after adjusting for confounders. NT-proBNP demonstrated significant discrimination with regard to SPHF in CAD (AUC = 0.79, 95%CI 0.73-0.85, p<0.0001), MR (AUC = 0.80, 95%CI 0.72-0.87, p<0.0001) and AS (AUC = 0.66, 95%CI 0.51-0.81, p = 0.047). In CAD patients NT-proBNP demonstrated significant discrimination with regard to postoperative 30-day or in-hospital mortality (AUC = 0.78; 95%CI 0.71-0.85, p<0.0001). The number of deaths was too few in the AS and MR group to permit analysis. Elevated NT-proBNP emerged as an independent risk factor for SPHF, and postoperative mortality in CAD. CONCLUSIONS: Patients with AS or MR have higher preoperative NT-proBNP than CAD patients even after adjusting for confounders. The predictive value of NT-proBNP with regard to SPHF was confirmed in CAD and MR patients but was less convincing in AS patients.

Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?

BACKGROUND & AIMS: Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described. METHODS: Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques. RESULTS: Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial-venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups. CONCLUSION: The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.

Psychoeducational support to post cardiac surgery heart failure patients and their partners--a randomised pilot study.

OBJECTIVES: Postoperative heart failure is a serious complication that changes the lives of both the person who is critically ill and family in many ways. The purpose of this study was to evaluate the effects of an intervention in postoperative heart failure patient-partner dyads regarding health, symptoms of depression and perceived control. RESEARCH METHODOLOGY/DESIGN: Pilot study with a randomised controlled design evaluating psychosocial support and education from an interdisciplinary team. SETTING: Patients with postoperative heart failure and their partners. MAIN OUTCOME MEASURES: SF-36, Beck Depression Inventory, Perceived Control at baseline, 3 and 12 months. RESULTS: A total of 42 patient-partner completed baseline assessment. Partners in the intervention group increased health in the role emotional and mental health dimensions and patients increased health in vitality, social function and mental health dimensions compared with the control group. Patients' perceived control improved significantly in the intervention group over time. CONCLUSION: Psychoeducational support to post cardiac surgery heart failure dyads improved health in both patients and partners at short term follow-up and improved patients' perceived control at both short and long-term follow-up. Psychoeducational support appears to be a promising intervention but the results need to be confirmed in larger studies.