Diagnostic and prognostic value of the AST/ALT ratio in patients with sepsis and septic shock.

OBJECTIVE: The study investigates the diagnostic and prognostic value of the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in patients with sepsis and septic shock. Limited data regarding the prognostic value of the AST/ALT ratio in patients suffering from sepsis or septic shock is available. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from day of disease onset (day 1), day 2, 3, 5 and 7. First, the diagnostic value of the AST/ALT ratio was tested for septic shock compared to sepsis. Second, the prognostic value of the AST/ALT ratio was tested for 30-d all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. RESULTS: A total of 289 patients were included, of which 55% had sepsis and 45% septic shock. The overall rate of all-cause mortality at 30 d was 53%. With an area under the curve (AUC) of 0.651 on day 1 and 0.794 on day 7, the AST/ALT ratio revealed moderate but better diagnostic discrimination of septic shock compared to bilirubin. Furthermore, the AST/ALT ratio was able to discriminate 30-d all-cause mortality (AUC = 0.624; 95% CI 0.559 - 0.689; p = 0.001). Patients with an AST/ALT ratio above the median (>1.8) had higher rates of 30-d all-cause mortality compared to lower values (mortality rate 63 vs. 43%; log-rank p = 0.001), even after multivariable adjustment (HR = 1.703; 95% CI 1.182 - 2.453; p = 0.004) and propensity score matching. CONCLUSIONS: The AST/ALT was a reliable diagnostic tool for the diagnosis of septic shock as well as a reliable tool to predict 30-d all-cause mortality in patients suffering from sepsis and septic shock.

Diagnostic and prognostic role of platelets in patients with sepsis and septic shock.

Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable t-test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 106/ml. The presence of thrombocytopenia (i.e. <150 × 106/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057-1.878; p = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045-2.109; p = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567-2.026; p = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock.

What is the context? Despite improved treatment strategies in intensive care medicine, sepsis and septic shock represent one of the major causes of death at intensive care units worldwide.Although it is known that platelets are associated with prognosis, most studies included "critically illness" patients and were not restricted to patients admitted with sepsis or septic shock. Furthermore, studies focusing on patients with sepsis were predominantly published prior to the sepsis-3 criteria. Specifically, the course of the platelet count during ICU hospitalization needs further investigation.What is new? The present study suggests that the platelet count reflects a reliable tool for the diagnosis of septic shock during the first week of ICU hospitalization.Furthermore, platelet count and the platelet-to-white-blood-cell-ratio are predictive for 30-day all-cause mortality in the presence of sepsis or septic shock.Especially, a decrease in platelet count during the first 5 days of ICU hospitalizations was associated with an increased risk of 30-day all-cause mortality in patients with sepsis and septic shock, whereas the platelet recovery was not found to be associated with a worse prognosis.What is the impact? This study provides further evidence that the platelet count represents a reliable tool for the diagnosis of septic shock and furthermore predicts short-term prognosis in patients admitted with sepsis or septic shock during the first 10 days of ICU hospitalization.

The Neutrophil-to-Lymphocyte-Ratio as Diagnostic and Prognostic Tool in Sepsis and Septic Shock.

BACKGROUND: Studies investigating the diagnostic and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in sepsis or septic shock commonly included preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of the NLR in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 from the prospective "MARSS-registry" were included monocentrically. First, the diagnostic value of the NLR compared to established sepsis scores was tested for septic shock compared to sepsis. Second, the diagnostic value of the NLR with regard to positive blood cultures was tested. Thereafter, the prognostic value of the NLR was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier analyses, Cox proportional regression analyses as well as uni- and multivariate logistic regression models. RESULTS: A total of 104 patients were included, of which 60% were admitted with sepsis and 40% with septic shock. The overall rate of all-cause mortality at 30 days was 56%. With an area under the curve (AUC) of 0.492, the NLR was shown to have a poor diagnostic value with regard to the diagnosis of septic shock compared to sepsis. However, the NLR was shown to be a reliable parameter to discriminate between patients with negative and positive blood cultures when admitted with septic shock (AUC = 0.714). This was still evident after multivariable adjustment (OR = 1.025; 95% CI 1.000 - 1.050; p = 0.048). In contrast, the NLR revealed a poor prognostic accuracy (AUC = 0.507) with regard to 30-day all-cause mortality. Finally, a higher NLR was not associated with an increased risk of 30-day all-cause mortality (log rank p-value = 0.775). CONCLUSIONS: The NLR was a reliable diagnostic tool for the identification of patients with blood culture confirmed sepsis. Yet, the NLR was not a reliable parameter to discriminate between patients with sepsis and septic shock nor between 30-day survivors and non-survivors.

D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock.

BACKGROUND: Studies investigating the diagnostic and prognostic value of D-dimer levels and the disseminated intravascular coagulation (DIC) score in sepsis or septic shock commonly include preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of D-dimer levels and the DIC score in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock enrolled in the prospective and monocentric "MARSS" registry from 2019 to 2021 were included. First, the diagnostic value of D-dimer levels was compared to the DIC score to discriminate patients with septic shock from patients with sepsis without shock. Thereafter, the prognostic value of D-dimer levels and the DIC score was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier, as well as uni- and multivariable cox regression analyses. RESULTS: One hundred patients were included (n = 63 with sepsis and n = 37 with septic shock). The overall rate of all-cause mortality at 30 days was 51%. With an area under the curve (AUC) of 0.710 and 0.739, both D-dimer level and the DIC score revealed reliable diagnostic accuracy for the discrimination of septic shock. However, D-dimer levels and the DIC scores were shown to have poor to moderate prognostic accuracy (AUC 0.590 - 0.610) with regard to 30-day all-cause mortality. Specifically, very high D-dimer levels (i.e., > 30 mg/L) (HR = 2.648; 95% CI 1.147 - 6.112; p = 0.023) and a DIC scores ≥ 3 (HR = 2.095; 95% CI 1.095 - 4.009; p = 0.0258) were associated with highest risk of 30-day all-cause mortality. Finally, both higher D-dimer levels (HR = 1.032; 95% CI 1.005 - 1.060; p = 0.021) and DIC scores (HR = 1.313; 95% CI 1.106 - 1.559; p = 0.002) were associated with increased risk of 30-day all-cause mortality after multivariable adjustment. CONCLUSIONS: Both D-dimer levels and the DIC scores revealed reliable diagnostic accuracy for the discrimination of septic shock, but a poor to moderate prognostic value for the discrimination of 30-day all-cause mortality. Especially very high D-dimer levels (i.e., > 30 mg/L) and a DIC score ≥ 3 were associated with highest risk of 30-day all-cause mortality.

Diagnostic and Prognostic Performance of Plasma Albumin and Cholinesterase in Patients with Sepsis and Septic Shock.

OBJECTIVE: Despite improved risk stratification tools and identification of novel biomarkers for the diagnosis and prognosis in patients with sepsis, sepsis-related mortality has not significantly improved during the past years. This study investigates the diagnostic and prognostic role of the plasma albumin and cholinesterase (ChE) in patients with sepsis and septic shock. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included at one institution. Blood samples were obtained on the day of disease onset (day 1), and on days 2, 3, 5, and 7 thereafter. The diagnostic value of ChE for the diagnosis of a septic shock was compared to albumin and the prognostic value of the albumin and the ChE for 30-day all-cause mortality was tested. RESULTS: 239 patients were included with a median albumin level of 21.4 g/dL and a median ChE of 5004 U/L on admission. With an area under the curve (AUC) of 0.641-0.762 on days 3 and 5, the ChE was associated with moderate but better diagnostic discrimination between sepsis and septic shock than albumin. Furthermore, ChE was able to discriminate between 30-day non-survivors and survivors (range of AUC 0.612-0.686). Patients with a ChE below the median had higher rates of 30-days all-cause mortality in comparison to patients with a ChE above the median (65 vs. 42%, log rank p = 0.001; HR = 1.820; 95% CI = 1.273-2.601; p = 0.001), which was still demonstrated after multivariable adjustment. CONCLUSION: The level of ChE was associated with moderate diagnostic and prognostic accuracy in patients with sepsis and septic shock, whereas albumin was not.

Cardiac disease and prognosis associated with ventricular tachyarrhythmias in young adults and adults.

BACKGROUND: This study evaluates cardiac diseases and prognosis in young adults and adults presenting with ventricular tachyarrhythmias (VTA). METHODS: The present longitudinal, observational, registry-based, monocentric cohort study includes all consecutive patients 45 years old or younger presenting with VTA at admission from 2002 to 2016. Rates of coronary angiography, coronary artery disease (CAD) and need for percutaneous coronary intervention (PCI), cardiac diseases associated with VTA, and differences in long-term prognostic endpoints for young adults (20-34 years old) were analyzed and compared to those of adults (35-45 years old), for whom multivariable risk prediction models were developed. Kaplan-Meier analyses were performed according to age and type of VTA. RESULTS: A total of 259 consecutive patients were included in the study (36% young adults and 64% adults). At admission, 38% of young adults had VTA due to CAD that required PCI. Furthermore, VTA in young adults was commonly idiopathic (27%), or had underlying channelopathies (18%), primary cardiomyopathies (13%) or acute myocardial infarction (AMI, 11%). In adults, VTA was mostly associated with AMI (28%), though the rate of idiopathy was still high (20%). A total 41% of all patients received cardiopulmonary resuscitation (CPR), for whom AMI (STEMI 17%, NSTEMI 24%) was most frequently observed. Irrespective of the type of VTA, all-cause mortality was similar for young adults and adults. In young adults, left ventricular ejection fraction (LVEF) < 35% (HR = 33.590) was associated with increased long-term all-cause mortality. CONCLUSION: Despite high rates of idiopathic ventricular tachyarrhythmias, CAD and AMI are common causes of VTA and CPR in adults 45 years old and younger. Young adults and adults had comparable survival at index hospitalization and after 2.5 years irrespective of the type of VTA. Clinical trial registration clinicaltrials.gov identifier: NCT02982473.

Galectin-3 reflects the echocardiographic quantification of right ventricular failure.

Objectives. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Design. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm (n = 23); TAPSE 18-24 mm (n = 55); TAPSE ≤17 mm (n = 13); permitting the detailed statistical analysis of derived data. Results. Serum levels of gal-3 in all patients correlated with age (r = 0.36. p < .001), creatinine (r = 0.60, p < .001), NT-proBNP (r = 0.53, p < .001), RA area (r = 0.38, p < .001) and TAPSE (r = -0.3. p < .01). The distribution of echocardiographic indices according to TAPSE subgroups revealed an association between gal-3 and its ability to identify patients with right ventricular failure (RVF) as diagnosed by a TAPSE ≤17 mm (r = 0.04, p < .001). The multivariable logistic regression model with adjusted odds ratio showed the ability of gal-3 to identify RVF when adjusted to age and gender (adjusted odds ratio 3.60, 95% CI 1.055-12.282, p < .05). Conclusion. Gal-3 correlated with echocardiographic indices of RVF and could effectively diagnose these patients. The supplementary use of NT-proBNP strengthened the diagnostic capability of each biomarker. Trial Registration: The 'Cardiovascular Imaging and Biomarker Analyses' (CIBER Study), clinicaltrials.gov identifier: NCT03074253. Registered 3/8/2017. https://www.clinicaltrials.gov/ct2/show/NCT03074253.

Extravascular compared to Intravascular Femoral Closure is Associated with Less Bleeding and Similar MACE after Percutaneous Coronary Intervention.

Background: Various types of vascular closure devices (VCDs) are frequently utilized in patients undergoing percutaneous coronary intervention (PCI) in order to prevent arterial access site bleeding, which represents one of the most relevant complications associated with adverse clinical outcomes. This study aims to compare directly two mechanistically different types of femoral closure (FC) devices in patients undergoing PCI. Methods: This single-center, prospective, observational study includes consecutively patients either treated by the extravascular StarClose SE® (Abbott, Illinois, U.S.A.) or the intravascular AngioSeal™ FC (St. Jude Medical, Inc., St. Paul, MN, U.S.A.) after PCI. The primary endpoint was bleeding complications, the secondary endpoint was major adverse cardiac events (MACE) at 30 days of follow-up. Results: 200 patients in each group (StarClose SE® and AngioSeal™) were enrolled following PCI. The rates of overall and non-access site bleedings were significantly higher in the AngioSeal™ group (56%; 6%) compared to the StarClose SE® group (43.5%; 0.5%) (p = 0.012; 0.003). Additionally, complicated access site bleedings were also significantly higher in the AngioSeal™ group (p = 0.011). No significant differences of MACE were observed in both groups. However, there was a higher rate of unsuccessful implantation of the StarClose SE® (n=12, excluded from the study). Conclusions: In case of successful implantation, FC by the AngioSeal™ is associated with the higher rate of both access and non-access site bleedings, but similar rates of MACE at 30 days compared to the StarClose SE® device.

Prevalence of malignant arrhythmia and sudden cardiac death in takotsubo syndrome and its management.

Aims: Recent studies have highlighted that takotsubo syndrome (TTS) is associated with a poor clinical outcome. Our study was conducted to determine the short- and long-term prevalence, recurrence rate and impact of life-threatening arrhythmias (LTA) on the clinical outcome of TTS. Methods and results: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The patient groups, divided according to the presence (n = 13, 11.4%) or absence (n = 101, 88.6%) of LTAs, were followed-up over a period of 3 years so as to determine the clinical outcome. Our analyses suggest that patients comprising the LTA group suffered significantly more often from an acute cardiovascular event including cases of a newly diagnosed atrial fibrillation (38.4% vs. 2.9%), cardiogenic shock with use of inotropic agents (53.8% vs. 14.8%) and cardiopulmonary resuscitation (61.5% vs. 1%). The short-term recurrence rate of a LTA episode was 15.3%, while the long-term recurrence rate of any LTA was around 5%. Whereas, in-hospital mortality was significantly higher in TTS associated with LTAs, the overall survival rate over 3 years was similar. A multivariate Cox regression analysis suggested atrial fibrillation, EF ≤ 35%, cardiogenic shock, and glomerular filtration rate <60 mL/min. as independent predictors of adverse outcome. Conclusion: The short- as well as the long-term prevalence and recurrence of LTAs in TTS patients is high. The long-term mortality rates were similar to the TTS patients presenting without any LTAs. LTAs in TTS could be triggered by a concomitant atrial fibrillation.

Pentraxin-3 Predicts Short- and Mid-term Mortality in Patients with Sepsis and Septic Shock During Intensive Care Treatment.

BACKGROUND: The prognostic value of the acute phase protein Pentraxin 3 (PTX-3) is not well evaluated in patients with septic shock, which reveal an unacceptably high short- and long-term mortality. New Sepsis-3 definitions are not yet implemented in most biomarker studies. Therefore, this study assesses the prognostic value of PTX-3 for short- and mid-term mortality in patients with sepsis or septic shock, as defined by the latest definitions, treated at a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3, and 8. All-cause mortality was followed up to 30 days and at 6 months. RESULTS: On all three days, PTX-3 levels were able to discriminate non-survivors from survivors at 30 days and 6 months (AUC range: 0.59 - 0.70; 95% CI: 0.52 - 0.79; p ≤ 0.02). Highest PTX-3 levels within the fourth quartiles during the first week of ICU treatment were associated with an increased mortality rate at 30 days (OR = 7; 95% CI: 2.0 - 23.5; p ≤ 0.002) and at 6 months (OR = 5; 95% CI: 2.1 - 11.4; p ≤ 0.006). Additionally, the prognostic value of PTX-3 was proven for all patients as well as in subcohorts of patients with sepsis and septic shock, according to Sepsis-3 criteria, both in univariate and multivariate analyses for 30-day and 6-months all-cause mortality, especially predicting all-cause mortality in septic shock (HRs range: 1.0 - 2.9; 95% CI: 0.3 - 5.1; p ≤ 0.03). CONCLUSIONS: PTX-3 offers prognostic value for the prediction of short- and mid-term all-cause mortality in patients suffering from sepsis and septic shock according to the latest Sepsis-3 criteria.

Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines.

BACKGROUND: Left atrial appendage closure (LAAC) represents the interventional alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). The metabolism of acylcarnitines was shown to affect cardiovascular diseases. This study evaluates the influence of successful LAAC on the metabolism of acylcarnitines. METHODS: Patients undergoing successful LAAC were enrolled prospectively. Peripheral blood samples for metabolomics measurements were collected immediately before (i.e., index) and six months after LAAC (i.e., mid-term). A targeted metabolomics analysis based on electrospray ionization-liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. RESULTS: 44 patients with non-valvular AF (median CHA2DS2-VASc score 4, median HAS-BLED score 4) and successful LAAC were included. Significant changes in acylcarnitine levels were found in the total cohort, which were mainly attributed to patients with impaired left ventricular and renal function, elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) and diabetes mellitus. Adjusted multivariable regression models revealed significant changes of five metabolites over mid-term follow-up: C2, C14:1, C16, and C18:1 decreased significantly (each p < 0.05); short-chain C5 acylcarnitine plasma levels increased significantly (p < 0.05). CONCLUSION: This study demonstrates that successful LAAC affects the metabolism of acylcarnitines at mid-term follow-up. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02985463.

Impact of concomitant atrial fibrillation on the prognosis of Takotsubo cardiomyopathy.

AIMS: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. Supraventricular tachycardia is a well-known complication of TTC. This study was performed to determine the short- and long-term prognostic impact of atrial fibrillation associated with TTC patients. METHODS AND RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015. The patients were divided into two groups according to the presence (n = 21, 18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), all-cause mortality, rehospitalization due to heart failure, stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality, and long-term mortality were significantly higher in the atrial fibrillation group. Kaplan-Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 3 years in the atrial fibrillation group than that in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence interval, CI: 1.1-4.9, P < 0.05) and EF ≤ 35% (HR 2.0, 95% CI: 1.1-3.8, P < 0.05) were the only independent predictors of a primary endpoint. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTC patients suffering from atrial fibrillation compared with patients without atrial fibrillation.

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

BACKGROUND: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. RESULTS: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). CONCLUSION: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. TRIAL REGISTRATION: NCT01535534 . Registered 14.02.2012.

Arterial access-site complications after use of a vascular closure device related to puncture height.

BACKGROUND: To analyze differences of access-site complications related to the height of femoral arterial puncture and the use of a vascular closure device (VCD) following percutaneous coronary intervention (PCI). METHODS: A subgroup of the FERARI study being treated by femoral arterial access and valuable inguinal angiography before implantation of a VCD were included. Inguinal angiographies were systematically reviewed by two independent cardiologists to determine the correct height of femoral arterial puncture. Bleeding complications were documented within 30 days after PCI and were categorized according to BARC, TIMI, GUSTO and FERARI classifications. RESULTS: Femoral access point imaging was available in 95 patients compared to 105 patients without. The common femoral artery (CFA) was the most accessed artery in 41%, followed by the femoral arterial bifurcation (39%) and lower access sites distally from the femoral arterial bifurcation (low puncture: 20%). No differences were observed regarding indication of PCI, procedural data and anticoagulation therapies in relation to the heights of femoral arterial access (p > 0.05). Despite using VCD, arterial puncture at the CFA resulted in numerically highest numbers of overall bleedings (62%) compared to femoral arterial bifurcation (41%) (p = 0.059). 58% of bleedings occurred after arterial puncture below the femoral bifurcation (low puncture). Though no significant differences of bleedings regarding classifications of BARC, GUSTO, TIMI and FERARI as well as other vascular endpoints were observed regarding puncture height. CONCLUSIONS: The present analysis demonstrates no significant differences of bleeding complications in relation to the height of femoral arterial puncture and subsequent use of a VCD.

Galectin-3 Reflects Left Atrial Function being Assessed by Cardiac Magnetic Resonance Imaging.

BACKGROUND: This study aims to evaluate the association between galectin-3 and left atrial function (LAF) in patients undergoing cMRI. METHODS: Patients undergoing cMRI were prospectively enrolled. Right ventricular dysfunction (< 50%) was excluded. Blood samples for biomarker measurements of galectin-3 and NT-proBNP were collected at the time of cMRI examination. RESULTS: A total of 84 patients were included. Median LVEF was 59% (IQR 51 - 64%). Galectin-3 was inversely correlated with overall LAF within a multivariable linear regression model (Beta -0.27; T -2.54; p = 0.01). Galectin-3 increased significantly according to the different stages of impaired LAF (p = 0.003) and was able to discriminate both patients with impaired LAF < 55% (AUC = 0.70, p = 0.002) and LAF < 45% (AUC = 0.69, p = 0.004). In multivariable logistic regression models, galectin-3 was still associated with impaired LAF (LAF < 55%: OR = 2.64, p = 0.07; LAF < 45%: OR = 6.65, p = 0.007). CONCLUSIONS: This study demonstrates that galectin-3 is able to reflect LAF being assessed by cMRI.

Clinical outcomes of femoral closure compared to radial compression devices following percutaneous coronary intervention: the FERARI study.

This study aims to compare prospectively the differences of clinical outcomes being associated with a specific femoral closure (FC) compared to a radial compression (RC) device following percutaneous coronary interventions (PCI). This single-center, prospective observational study included consecutively 400 patients either treated by a specific FC (Angio-Seal™, St. Jude Medical, Inc., St. Paul, MN) or RC (TR Band®, Terumo Corporation, Tokyo, Japan) device following PCI. The primary outcome was to evaluate overall, access site and non-access site bleedings, the secondary outcome was major adverse cardiac events (MACE) occurring within 30 days of follow-up. 200 patients in each group (FC and RC group) were enrolled following PCI. The prevalence of overall bleedings was 56% in FC and 37% in RC group (p = 0.001). Access site bleedings were significantly higher in the FC (50%) compared to the RC (30%) group (p = 0.001). Most common type of access site bleeding consisted of hematomas (FC 45% vs. RC 27%, p = 0.001). Of these, intermediate and large hematomas were significantly higher in the FC group (p < 0.05). Surgical interventions following device-related bleedings were uncommon in both groups. No significant differences of MACE were observed in both treatment groups. Despite the use of a vascular closure device, the femoral arterial access is still associated with a higher rate of access site bleedings, consisting mostly of intermediate to large hematomas. No differences of MACE were found between FC versus RC following PCI at 30 days. TRIAL REGISTRY: ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02455661 ).

Ischemic biomarker heart-type fatty acid binding protein (hFABP) in acute heart failure - diagnostic and prognostic insights compared to NT-proBNP and troponin I.

BACKGROUND: To evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF). METHODS: 401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP. RESULTS: Additional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to "rule out" AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1-2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8-8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3-7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml. CONCLUSIONS: Combining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00143793 .

C-terminal agrin fragment (CAF) reflects renal function in patients suffering from severe sepsis or septic shock.

BACKGROUND: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT). METHODS: 61 patients suffering from severe sepsis or septic shock were included during the first 24 hours of ICU treatment and blood samples for biomarker measurements, i.e., CAF, creatinine, cystatin C, procalcitonin (PCT), interleukin 6, C reactive protein (CRP), and white blood cells (WBC) were collected on the first day of intensive care treatment. The number of RRT days and the incidence of AKI were documented. RESULTS: 13% of the patients (8/61) suffered from SIRS/sepsis, 20% (12/61) from severe sepsis, and 67% (41/61) from septic shock. Serum levels of CAF significantly correlated with creatinine (r = 0.623, p < 0.001) and cystatin C (r = 0.578, p < 0.001). Multiple linear regression analyses adjusting CAF for inflammatory parameters (i.e., WBC, CRP, interleukin 6, PCT), age, and gender showed a strong correlation between CAF and creatinine (r = 0.643, p < 0.001). Serum levels of CAF were significantly associated with the need of RRT (area under the curve (AUC) = 0.772, 95% CI: 0.641-0.903, p = 0.002) and the incidence of AKI (AUC = 0.721, 95% CI: 591-0.850, p = 0.004) as indicated by ROC analysis. CONCLUSIONS: In patients suffering from severe sepsis and septic shock, serum levels of CAF were significantly associated with kidney function and RRT and were not influenced by severe septic conditions.

Diagnostic and Long-Term Prognostic Value of Sensitive Troponin I in Symptomatic Patients Suspected of Acute Heart Failure.

BACKGROUND: To evaluate the diagnostic and prognostic value of sensitive troponin I (TnI) in patients with acute dyspnea and/or peripheral edema suspected of having acute heart failure (AHF). METHODS: This single centre prospective clinical study evaluates 372 patients presenting with acute dyspnea and/or peripheral edema to the emergency department (ED). Measurements of TnI and NT-proBNP were performed at the initial presentation in the ED. All patients were followed up to 5 years. The diagnostic value of TnI compared to NT-proBNP for AHF diagnosis as well as long-term prognostic values for all cause mortality and AHF related rehospitalization were evaluated. RESULTS: TnI plus NT-proBNP improved the diagnosis of AHF (improvement of accuracy (75%, 95% CI 71% - 79%), specificity (68%, 95% CI 62% - 74%), PPV (54%, 95% CI 47% - 62%), and NRI +0.15) compared to NT-proBNP alone (p = 0.0001). TnI levels showed independent prognostic value for all-cause mortality and AHF related rehospitalization after 1 and 5 years (range of AUCs 0.64 - 0.72; p = 0.03 or lower). Highest TnI levels of the 4th quartile revealed an up to 5.5 times higher risk of death within 1 and 5 years (range of HRs: 2.5 - 5.5; p = 0.0001). TnI added significantly to multivariable Cox prediction models even after adjusting for NT-proBNP, particularly in AHF patients (range of HRs: 2.1 - 2.7; p ≤ 0.05). CONCLUSIONS: TnI improves AHF diagnosis when combined with NT-proBNP. TnI identifies patients with high 1- and 5-year all-cause mortality and AHF-related rehospitalization risk and adds prognostic value to NT-proBNP.

Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment.

INTRODUCTION: The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment. METHODS: In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models. RESULTS: Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC. CONCLUSIONS: In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment. TRIAL REGISTRATION: ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.