Soluble urokinase plasminogen activator receptor and survival in elective cardiac surgery.

BACKGROUND: The study investigated the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing cardiac surgery and calculated a simplified biomarker score comprising suPAR, N-terminal pro B-type natriuretic peptide (NT-proBNP) and age. METHODS AND RESULTS: Biomarkers were assessed in a cohort of 478 patients undergoing elective cardiac surgery. After a median follow-up of 4.2 years, a total of 72 (15.1%) patients died. SuPAR, NT-proBNP and age were independent prognosticators of mortality in a multivariable Cox regression model after adjustment for EuroScoreII. We then calculated a simplified biomarker score comprising age, suPAR and NT-proBNP, which had a superior prognostic value compared to EuroScoreII (Harrel's C of 0.76 vs. 0.72; P for difference = 0.02). Besides long-term mortality, the biomarker score had an excellent performance predicting one-year mortality and hospitalization due to heart failure. CONCLUSION: The biomarker suPAR and NT-proBNP were strongly and independently associated with mortality in patients undergoing cardiac surgery. A simplified biomarker score comprising only three variables (age, suPAR and NT-proBNP) performed better than the established EuroScoreII with respect to intermediate and long-term outcome as well as hospitalization due to heart failure. As such, integration of established and upcoming biomarkers in clinical practice may provide improved decision support in cardiac surgery.

The Prognostic Impact of Anti-thrombotic Treatment Strategies After Biological Aortic Valve Replacement.

PURPOSE: Optimal antithrombotic therapy in patients who underwent surgical biological aortic valve replacement (AVR) represents an issue of ongoing discussion. Additionally, the prognostic impact of anti-thrombotic treatment strategies after biological AVR and real-life data on anticoagulation strategies (AC) of patients presenting with short-term postoperative atrial fibrillation (POAF) has not clearly been investigated so far. Therefore, this study aimed to investigate the impact of therapeutic AC after biological AVR on patient outcome and whether the presence of POAF affects decision making on anti-thrombotic management. METHODS: Within this prospective observational study, 200 individuals that underwent biological AVR surgery were enrolled. Participants were followed prospectively until the primary study endpoint was reached. Multivariate logistic regression analysis was performed to elucidate the effect of therapeutic AC on outcome. RESULTS: Overall, 106 individuals received therapeutic AC at the time of discharge. The fraction of patients presenting with POAF was balanced between individuals receiving AC and the non-AC subgroup (p = 0.617). After a median follow-up time of 1418 days, 31 (15.5%) individuals died, referring to 15 (13.9%) POAF-free patients and 16 (17.4%) with POAF. We observed a strong inverse association of therapeutic AC and cardiovascular mortality, which remained stable after adjustment for potential confounders showing a HR of 0.437 (95% CI 0.202-0.943; p = 0.035), while bleeding risk was comparable (p = 0.680). CONCLUSION: Within this investigation, therapeutic AC showed a strong and independent inverse association with long-term mortality in patients that underwent biological AVR. Although POAF is associated with thromboembolic adverse events, the development of this arrhythmia did not affect decision-making of the anti-thrombotic management.

Perioperative Risk Factors for Intensive Care Unit Readmissions and Mortality After Cardiac Surgery.

OBJECTIVE: The aim of this study was to identify perioperative risk factors associated with intensive care unit readmission and in-hospital death after cardiac surgery. DESIGN: Retrospective analysis using a multivariate regression model to identify independent risk factors for intensive care unit [ICU] readmission and in-hospital mortality. SETTING: The study was carried out in a single tertiary-care hospital. PARTICIPANTS: This was an analysis of 2,789 adult patients. INTERVENTIONS: All patients underwent cardiac surgery and were admitted to the intensive care unit perioperatively at the General Hospital Vienna. MEASUREMENTS AND MAIN RESULTS: Among the 2,789 patients included in the analysis, 167 (6%) were readmitted to the intensive care unit during the same hospital stay. Preoperative risk factors associated with ICU readmission included end-stage renal failure (odds ratio [OR] 2.80, 95% CI: 1.126-6.964), arrhythmia (OR 1.59, 95% CI: 1.019-2.480), chronic obstructive pulmonary disease (OR 1.51, 95% CI: 1.018-2.237), age >80 (OR 2.55, 95% CI: 1.189-5.466), and European System for Cardiac Operative Risk Evaluation II >8 (OR 1.40, 95% CI: 1.013-1.940). Readmitted patients were more likely to die than nonreadmitted patients (OR 5.3, 95% CI: 3.284-8.558). In-hospital mortality in readmitted patients was 19.2%, whereas that in the nonreadmitted study population was 5.1%. CONCLUSION: Preoperative risk assessment is crucial for identifying cardiac surgery patients at risk of ICU readmission and in-hospital death. The potentially modifiable risk factors pinpointed by this study call for the optimization of care before surgery and after ICU discharge.

The impact of volume substitution on post-operative atrial fibrillation.

BACKGROUND: Post-operative atrial fibrillation (POAF) represents a common complication after cardiac valve or coronary artery bypass surgery. While strain of atrial tissue is known to induce atrial fibrillating impulses, less attention has been paid to potentially strain-promoting values during the peri- and post-operative period. This study aimed to determine the association of peri- and post-operative volume substitution with markers of cardiac strain and subsequently the impact on POAF development and promotion. RESULTS: A total of 123 (45.4%) individuals were found to develop POAF. Fluid balance within the first 24 hours after surgery was significantly higher in patients developing POAF as compared to non-POAF individuals (+1129.6 mL [POAF] vs +544.9 mL [non-POAF], P = .044). Post-operative fluid balance showed a direct and significant correlation with post-operative N-terminal pro-brain natriuretic peptide (NT-ProBNP) values (r = .287; P = .002). Of note, the amount of substituted volume significantly proved to be a strong and independent predictor for POAF with an adjusted odds ratio per one litre of 1.44 (95% CI: 1.09-1.31; P = .009). In addition, we observed that low pre-operative haemoglobin levels at admission were associated with a higher need of intraoperative transfusions and volume-demand. CONCLUSION: Substitution of larger transfusion volumes presents a strong and independent predictor for the development of POAF. Via the observed distinct association with NT-proBNP values, it can reasonably be assumed that post-operative atrial fibrillating impulses are triggered via increased global cardiac strain. Optimized pre-operative management of pre-existing anaemia should be considered prior surgical intervention in terms of a personalized patient care.

Initial Postoperative Hemoglobin Values Are Independently Associated With One-Year Mortality in Patients Undergoing Double-Lung Transplantation Requiring Intraoperative Transfusion.

OBJECTIVE: To evaluate the association of postoperative hemoglobin values and mortality in patients undergoing double- lung transplantation with intraoperative transfusion. DESIGN: Retrospective cohort study. SETTING: University hospital. PARTICIPANTS: Adult patients who underwent double-lung transplantation at the authors' institution, with intraoperative transfusion of packed red blood cells between 2009 and 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraoperative transfusion requirements and general characteristics of 554 patients were collected. A generalized additive model, controlling for postoperative hemoglobin levels, number of transfused units of packed red blood cells, perioperative change in hemoglobin levels, disease leading to lung transplantation, and postoperative extracorporeal membrane oxygenation, was created to predict one-year mortality. A postoperative hemoglobin level of 11.3 g/dL was calculated as an optimal cutoff point. The patients were stratified according to this level. The end -point was all-cause one-year mortality after double-lung transplantation, assessed using the Kaplan-Meier analysis with log-rank test. All-cause mortality of the 554 patients was 17%. Postoperatively, 171 patients (31%) were categorized as being below the cutoff point. Improved survival was observed in the group with higher postoperative hemoglobin values (p = 0.002). CONCLUSION: Lower postoperative hemoglobin levels in double-lung transplantation recipients were associated with increased mortality during the first year after surgery. Confirmation of these findings in additional investigations could alter patient blood management for double-lung transplantation.

Risk factors for early bleeding complications after lung transplantation - a retrospective cohort study.

Risk factors for early bleeding complications after lung transplantation are not well described. Our aim was to evaluate coagulation test results and the use of extracorporeal membrane oxygenation as risk factors for bleeding after lung transplantation. We analyzed a single-center cohort of bilateral lung transplants between January 2009 and August 2015. Predictors of severe postoperative bleeding (bleeding requiring reoperation within 48 h of transplantation) were assessed using multivariable logistic regression. The effect of bleeding on survival was assessed using a Cox proportional-hazards model. Twenty-nine (4.5%) of 641 patients experienced severe postoperative bleeding. Postoperative fibrinogen levels (OR = 0.99, 95% CI 0.98-0.995, P = 0.001; per mg/dl increase) and pre- and postoperative use of extracorporeal membrane oxygenation (OR = 14.41% 95% CI 5.4-40.19, P < 0.001 and OR = 4.25, 95% CI 1.0-11.09, P = 0.002, respectively) were associated with an increased risk of severe postoperative bleeding. Severe postoperative bleeding was associated with decreased survival within 60 days after transplantation (adjusted HR = 5.73, 95% CI 2.52-13.02, P < 0.001). Low postoperative fibrinogen levels, and pre- and postoperative use of extracorporeal membrane oxygenation were risk factors for bleeding after lung transplantation.

Sublingual functional capillary rarefaction in chronic heart failure.

BACKGROUND AND OBJECTIVE: Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls. METHODS: Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age-matched subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR). RESULTS: Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = -.38) or estimated glomerular filtration rate (r = -.34) in CHF patients. CONCLUSION: CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.

Urinary Output Predicts Survival in Patients Undergoing Extracorporeal Membrane Oxygenation Following Cardiovascular Surgery.

OBJECTIVES: Extracorporeal membrane oxygenation represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, survival remains poor and accurate risk stratification challenging. Therefore, we evaluated the predictive value of urinary output within 24 hours after extracorporeal membrane oxygenation initiation on mortality in patients undergoing venoarterial extracorporeal membrane oxygenation support following cardiovascular surgery and aimed to improve established risk prediction models. DESIGN: Single-center, observational registry. SETTING: University-affiliated tertiary care center. PATIENTS: We included 205 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following cardiovascular surgery at a university-affiliated tertiary-care center into our single-centre registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a median follow-up time of 35 months (interquartile range, 19-69), 64% of patients died. Twenty-four-hour urinary output was the strongest predictor of outcome among renal function variables with an adjusted hazard ratio per 1 SD of 0.55 (95% CI, 0.40-0.76; p < 0.001) for 30-day mortality and of 0.65 (95% CI, 0.53-0.86; p = 0.002) for 2-year long-term mortality. Most remarkably, 24-hour urinary output showed additional prognostic value beyond that achievable with the simplified acute physiology score-3 and sequential organ failure assessment score indicated by improvements in the category-free net reclassification index for 30-day mortality (simplified acute physiology score-3: 36%, p = 0.015; sequential organ failure assessment score: 36%, p = 0.02), as well as for 2-year mortality (simplified acute physiology score-3: 33%, p = 0.02; sequential organ failure assessment score: 43%, p = 0.005). CONCLUSIONS: We identified 24-hour urinary output as a strong and easily available predictor of mortality in patients undergoing extracorporeal membrane oxygenation therapy following cardiovascular surgery. Implementation of 24-hour urinary output leads to a substantial improvement of established risk prediction models in this vulnerable patient population. These results are particularly compelling because measurement of urinary output is inexpensive and routinely performed in all critical care units.

Prognostic Impact of Persistent Thrombocytopenia During Extracorporeal Membrane Oxygenation: A Retrospective Analysis of Prospectively Collected Data From a Cohort of Patients With Left Ventricular Dysfunction After Cardiac Surgery.

OBJECTIVE: The prognostic impact of thrombocytopenia in patients supported by extracorporeal membrane oxygenation after cardiac surgery is uncertain. We investigated whether thrombocytopenia is independently predictive of poor outcome and describe the incidence and time course of thrombocytopenia in extracorporeal membrane oxygenation patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Cardiosurgical ICU at a tertiary referral center. PATIENTS: Three hundred adult patients supported with venoarterial extracorporeal membrane oxygenation for more than 24 hours because of refractory cardiogenic shock after heart surgery between January 2001 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-way analysis of variance was used to compare the time course of platelet count changes between survivors and nonsurvivors. Using multiple Cox regression with time-dependent covariates, we investigated the impact of platelet count on 90-day mortality. In nonsurvivors, the daily incidence of moderate (< 100 - 50 × 10/L), severe (49 - 20 × 10/L), and very severe (< 20 × 10/L) thrombocytopenia was 50%, 54%, and 7%, respectively. Platelet count had a biphasic temporal pattern with an initial decrease until day 4-5 after the initiation of extracorporeal membrane oxygenation. Although a significant recovery of the platelet count was observed in survivors, a recovery did not occur in nonsurvivors (p = 0.0001). After adjusting for suspected confounders, moderate, severe, and very severe thrombocytopenia were independently associated with 90-day mortality. The highest risk was associated with severe (hazard ratio, 5.9 [2.7-12.6]; p < 0.0001) and very severe thrombocytopenia (hazard ratio, 25.9 [10.7-62.9], p < 0.0001). CONCLUSION: Thrombocytopenia is an independent risk factor for poor outcome in extracorporeal membrane oxygenation patients after cardiac surgery, with persistent severe thrombocytopenia likely reflecting a high degree of physiologic imbalance.

Liver function predicts survival in patients undergoing extracorporeal membrane oxygenation following cardiovascular surgery.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, despite significant advances in ECMO techniques and management, prognosis remains poor and accurate risk stratification challenging. We therefore evaluated the predictive value of liver function variables on all-cause mortality in patients undergoing venoarterial ECMO support after cardiovascular surgery. METHODS: We included into our single-center registry a total of 240 patients undergoing venoarterial ECMO therapy following cardiovascular surgery at a university-affiliated tertiary care center. RESULTS: The median follow-up was 37 months (interquartile range 19-67 months), and a total of 156 patients (65%) died. Alkaline phosphatase and total bilirubin were the strongest predictors for 30-day mortality, with adjusted hazard ratios (HRs) per 1-standard deviation increase of 1.36 (95% confidence interval [CI] 1.10-1.68; P = 0.004) and 1.22 (95% CI 1.07-1.40; P = 0.004), respectively. The observed associations persisted for long-term mortality, with adjusted HRs of 1.27 (95% CI 1.03-1.56; P = 0.023) for alkaline phosphatase and 1.22 (95% CI 1.07-1.39; P = 0.003) for total bilirubin. CONCLUSIONS: The present study demonstrates that elevated values of alkaline phosphatase and total bilirubin are sensitive parameters for predicting the short-term and long-term outcomes of ECMO patients.

Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon.

OBJECTIVES: Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect. DESIGN: Prospective ex-vivo investigation. SETTING: University hospital. PARTICIPANTS: Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon. INTERVENTIONS: Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments. MEASUREMENTS AND MAIN RESULTS: Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01). CONCLUSIONS: Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.

Serological features of antibodies to protamine inducing thrombocytopenia and thrombosis.

BACKGROUND: A significant proportion of patients undergoing cardiopulmonary bypass develop anti-protamine antibodies, with or without the association of thromboembolic events. METHODS: We extensively investigated the serological features of protamine antibodies, which developed in six patients who were clinically suspected to have heparin-induced thrombocytopenia (HIT). Three patients had thrombotic events. Sera were tested by four different commercially available immunoassays, a heparin-platelet aggregation test, and for their binding properties to heparin, platelet factor 4 (PF4), complex heparin-PF4, protamine, and protamine complex with heparin. Sera from four patients were also tested for the capability to induce platelet activation and the formation of platelet-monocyte heterotypic aggregates. RESULTS: The ELISA assay Zymutest HIA was strongly positive in all cases, the HPIA Asserachrome was borderline, and the gel centrifugation test PaDGIA was positive in two tested patients. Platelet aggregation tests were negative. Using a variation of the Zymutest HIA we demonstrate that IgG antibodies bound only to protamine or protamine complex with heparin, but not to heparin or PF4 only. Sera-induced platelet P-selectin expression and the formation of platelet-monocyte aggregates. Blood samples from one patient proofed positive concomitantly with the thromboembolic event. However, serological characteristics did not differ between antibodies associated with thromboembolic events from those without. CONCLUSIONS: These data show that protamine-induced antibodies are specific and may induce platelet activation, which explains their association with thromboembolic events.

Serum butyrylcholinesterase predicts survival after extracorporeal membrane oxygenation after cardiovascular surgery.

INTRODUCTION: Risk stratification in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery remains challenging, because data on specific outcome predictors are limited. Serum butyrylcholinesterase demonstrated a strong inverse association with all-cause and cardiovascular mortality in non-critically ill patients. We therefore evaluated the predictive value of preoperative serum butyrylcholinesterase levels in patients undergoing venoarterial ECMO support after cardiovascular surgery. METHODS: We prospectively included 191 patients undergoing venoarterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care center in our registry. RESULTS: All-cause and cardiovascular mortality were defined as primary study end points. During a median follow-up time of 51 months (IQR, 34 to 71) corresponding to 4,197 overall months of follow-up, 65% of patients died. Cox proportional hazard regression analysis revealed a significant and independent inverse association between higher butyrylcholinesterase levels and all-cause mortality with an adjusted hazard ratio (HR) of 0.44 (95% CI, 0.25 to 0.78; P = 0.005), as well as cardiovascular mortality, with an adjusted HR of 0.38 (95% CI, 0.21 to 0.70; P = 0.002), comparing the third with the first tertile. Survival rates were higher in patients within the third tertile of butyrylcholinesterase compared with patients within the first tertile at 30 days (68% versus 44%) as well as at 6 years (47% versus 21%). CONCLUSIONS: The current study revealed serum butyrylcholinesterase as a strong and independent inverse predictor of all-cause and cardiovascular mortality in patients undergoing venoarterial ECMO therapy after cardiovascular surgery. These findings advance the limited knowledge on risk stratification in patients undergoing ECMO support and represent a valuable addition for a comprehensive decision making before ECMO implantation.

Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Soluble ST2 is associated with postoperative atrial fibrillation after cardiac surgery in postmenopausal women.

BACKGROUND: Postoperative atrial fibrillation (POAF) represents the most common complication following cardiac surgery. Approximately one-third of patients experiencing POAF transition to atrial fibrillation within a year, challenging the notion of POAF as merely a transient event. Soluble ST2 (sST2) is an established biomarker regarding fibrosis and myocardial stretch, however, its role in predicting the onset of POAF remains unclear. METHODS: Preoperative sST2 levels have been assessed in 496 individuals with no prior history of AF who underwent elective cardiac surgery, including valve, coronary artery bypass graft surgery, or a combined procedure. RESULTS: The average age was 70 years, and 29.4 % were female. Overall, 42.3 % developed POAF. sST2 levels were found to be significantly higher in patients with POAF. Interestingly, sST2 was only predictive of POAF in females with an adjusted OR of 1.894 (95 %CI:1.103-3.253; p = 0.021) and not males (OR:1.091; 95 %CI:0.849-1.402; p = 0.495). Furthermore, within a linear regression model it was observed that for every 1 ng/mL increase in sST2 levels, the average POAF duration extended by 39.5 min (95 %CI:15.8-63.4 min; p = 0.001). CONCLUSION: sST2 predicts the onset of POAF in women but not men undergoing cardiac surgery. Furthermore, sST2 levels were associated with the subsequent burden of POAF. Thus, assessment of sST2 in addition to clinical risk factors could improve risk stratification for development of POAF following elective cardiac surgery.

Relationship of Fibroblast Growth Factor 23 With Hospitalization for Heart Failure and Cardiovascular Outcomes in Patients Undergoing Cardiac Surgery.

Background Fibroblast growth factor 23 (FGF-23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF-23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF-23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF-23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF-23 modeled as a continuous variable (adjusted hazard ratio for a 1-unit increase in standardized log-transformed biomarker, 1.82 [95% CI, 1.34-2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF-23 to N-terminal pro-B-type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34-0.81]; P<0.001; integrated discrimination increment, 0.03 [95% CI, 0.01-0.05]; P<0.001). Conclusions FGF-23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of high-risk patients.

Hemodynamic and Rhythmologic Effects of Push-Dose Landiolol in Critical Care-A Retrospective Cross-Sectional Study.

BACKGROUND: The highly ß1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. METHODS: We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring. RESULTS: Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130-150) vs. 105 (100-125) bpm, p < 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO2 after the bolus application did not differ significantly. No serious adverse events were seen. CONCLUSIONS: Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted.

Increased serum levels of HSP27 as a marker for incipient chronic obstructive pulmonary disease in young smokers.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is amongst the leading causes of morbidity and mortality, no biomarkers for its early detection are known. We have recently demonstrated that COPD is accompanied by elevated serum heat shock protein (HSP) 27 levels as compared to a control population. OBJECTIVES: In an open prospective study, we investigated whether elevated HSP27 levels are associated with the early radiological signs of COPD, i.e., air trapping (AT), emphysema (E) and impaired lung function. METHODS: In total, 120 apparently healthy smokers underwent lung function testing and serum sampling. Serum levels of HSP27, phospho-HSP27, CXCR2 chemokines and proteins related to inflammation, tissue remodeling and apoptosis were evaluated by ELISA. Of these 120 subjects, 94 voluntarily underwent a high-resolution computed tomography scan. RESULTS: AT or AT and E were detected in 57.45%. Subjects with AT and E (n = 23) showed significantly higher HSP27 levels than those without any pathology [i.e., nothing abnormal detected (NAD)] (4,618 +/- 1,677 vs. 3,282 +/- 1,607 pg/ml; p = 0.0081). In a univariate logistic regression model including NAD and AT and E, the area under the curve of HSP27 in the receiver-operating-characteristic curve was 0.724, (0.594­0.854, 95% CI; p = 0.0033). Interestingly, proinflammatory IL-8 was elevated in those subjects with evidence of AT and E compared to those with AT and NAD. Lung function did not correlate with increased HSP27 levels or pathological radiological findings. CONCLUSIONS: HSP27 serum levels correlated with the early radiological signs of COPD, whereas lung function did not match with radiological findings or HSP27 serum levels. Serum HSP27 levels may serve as a potential marker to identify the early signs of COPD independent of lung function in young smokers.

The impact of left atrial mechanics on adverse events and clinical outcome after cardiac surgery.

OBJECTIVES: Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery that is associated with unfavourable clinical outcome. Identifying patients at risk for POAF is crucial but challenging. This study aimed to investigate the prognostic potential of speckle-tracking echocardiography on POAF and fatal adverse events from a long-term perspective. METHODS: A total of 124 patients undergoing elective cardiac surgery were prospectively enrolled and underwent preoperative speckle-tracking echocardiography. Patients were followed prospectively for the occurrence of POAF within the entire hospitalization and reaching the secondary end points cardiovascular and all-cause mortality. RESULTS: Within the study population 43.5% (n = 53) of enrolled individuals developed POAF. After a median follow-up of 3.9 years, 25 (20.2%) patients died. We observed that patients presenting with POAF had lower global peak atrial longitudinal strain (PALS) values compared to the non-POAF arm {POAF: 14.8% [95% confidence interval (CI): 10.9-17.8] vs non-POAF: 19.4% [95% CI: 14.8-23.5], P < 0.001}. Moreover, global PALS was a strong and independent predictor for POAF [adjusted odds ratio per 1 standard deviation: 0.37 (95% CI: 0.22-0.65), P < 0.001] and independently associated with mortality [adjusted hazard ratio per 1 standard deviation: 0.63 (95% CI: 0.40-0.99), P = 0.048]. Classification and Regression Tree analysis revealed a cut-off value of <17% global PALS as high risk for both POAF and mortality. CONCLUSIONS: Global PALS is associated with the development of POAF following surgery in an unselected patient population undergoing CABG and/or valve surgery. Since patients with global PALS <17% face a poor long-term prognosis, routine assessment of global PALS needs to be considered in terms of proper secondary prevention in the era of personalized medicine.