Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study

Introduction

The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients.

Methods

We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography.

Results

Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (ρ = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (ρ = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90).

Conclusions

NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.     

Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis

Background

Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis.

Methods

Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2–21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected.

Results

According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4–884.2); CM 20.4 pg/ml (15.6–20.4); NM 19.5 pg/ml (13.8–50.7); p < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9–163.6) vs. 20 pg/ml (14–44.4); p = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95 % confidence interval 1.7–50; p = 0.011).

Conclusions

Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.     

Midregional pro-Adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study

Introduction

The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.

Methods

We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.

Results

MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).

Conclusions

MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.     

Direct comparison of serial B-type natriuretic peptide and NT-proBNP levels for prediction of short- and long-term outcome in acute decompensated heart failure

Introduction

Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome.

Methods

This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission.

Results

During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions.

Conclusions

BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP.

Trial registration

ClinicalTrials.gov identifier: NCT00514384.     

Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction

Background

Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI.

Methods

In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2?C6?days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery. Blood samples were drawn for biochemical determinations.

Results

From baseline to 6?months, there was a significant decrease in the levels of N-terminal probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) in the whole patient population (P?<?0.001 for all). However, no difference was observed between the BMC group (n?=?39) and the placebo group (n?=?39) in the change of the levels of NT-proANP (median ?54 vs. +112?pmol/L), NT-proBNP (?88 vs. ?115?pmol/L) or inflammatory markers IL-6 (?3.86 vs. ?5.61?pg/mL), hsCRP (?20.29 vs. ?22.36?mg/L) and tumor necrosis factor ?? (?0.12 vs. ?0.80?pg/mL) between baseline and 6?months.

Conclusion

Intracoronary BMC therapy does not appear to exert any significant effects on the secretion of natriuretic peptides or inflammatory biomarkers in STEMI patients.     

Usefulness of N-terminal pro-brain natriuretic peptide and C-reactive protein to predict ICU mortality in unselected medical ICU patients: a prospective, observational study

Introduction

The performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) to predict clinical outcomes in ICU patients is unimpressive. We aimed to assess the prognostic value of NT-proBNP, CRP or the combination of both in unselected medical ICU patients.

Methods

A total of 576 consecutive patients were screened for eligibility and followed up during the ICU stay. We collected each patient's baseline characteristics including the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, NT-proBNP and CRP levels. The primary outcome was ICU mortality. Potential predictors were analyzed for possible association with outcomes. We also evaluated the ability of NT-proBNP and CRP additive to APACHE-II score to predict ICU mortality by calculation of C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices.

Results

Multiple regression revealed that CRP, NT-proBNP, APACHE-II score and fasting plasma glucose independently predicted ICU mortality (all P < 0.01). The C-index with respect to prediction of ICU mortality of APACHE II score (0.82 ± 0.02; P < 0.01) was greater than that of NT-proBNP (0.71 ± 0.03; P < 0.01) or CRP (0.65 ± 0.03; P < 0.01) (all P < 0.01). As compared with APACHE-II score (0.82 ± 0.02; P < 0.01), combination of CRP (0.83 ± 0.02; P < 0.01) or NT-proBNP (0.83 ± 0.02; P < 0.01) or both (0.84 ± 0.02; P < 0.01) with APACHE-II score did not significantly increase C-index for predicting ICU mortality (all P > 0.05). However, addition of NT-proBNP to APACHE-II score gave IDI of 6.6% (P = 0.003) and NRI of 16.6% (P = 0.007), addition of CRP to APACHE-II score provided IDI of 5.6% (P = 0.026) and NRI of 12.1% (P = 0.023), and addition of both markers to APACHE-II score yielded IDI of 7.5% (P = 0.002) and NRI of 17.9% (P = 0.002). In the cardiac subgroup (N = 213), NT-proBNP but not CRP independently predicted ICU mortality and addition of NT-proBNP to APACHE-II score obviously increased predictive ability (IDI = 10.2%, P = 0.018; NRI = 18.5%, P = 0.028). In the non-cardiac group (N = 363), CRP rather than NT-proBNP was an independent predictor of ICU mortality.

Conclusions

In unselected medical ICU patients, NT-proBNP and CRP can serve as independent predictors of ICU mortality and addition of NT-proBNP or CRP or both to APACHE-II score significantly improves the ability to predict ICU mortality. NT-proBNP appears to be useful for predicting ICU outcomes in cardiac patients.     

Connective tissue growth factor (CTGF/CCN2): diagnostic and prognostic value in acute heart failure

Background

As a mediator of ECM homeostasis, connective tissue growth factor (CTGF) appears to be involved in adverse structural remodeling processes in the heart. However, the diagnostic and prognostic value of CTGF levels in acute heart failure (AHF) in addition to natriuretic peptide testing has not yet been evaluated.

Methods and results

A total of 212 patients presenting with acute dyspnea and/or peripheral edema to the Emergency Department were evaluated. CTGF and NT-proBNP plasma levels were measured at the initial presentation. All patients were followed up to 1 and 5 years. The first endpoint tested was the diagnostic non-inferiority of combined CTGF plus NT-proBNP compared to NT-proBNP alone for AHF diagnosis. Afterwards, the additional diagnostic value of CTGF plus NT-proBNP was tested. CTGF levels were higher in NYHA class III/IV and AHA/ACC class C/D patients compared to lower class patients (p = 0.04). Patients with HFREF revealed highest CTGF levels (median 93.3 pg/ml, IQR 18.2–972 pg/ml, n = 48) compared to patients with a normal heart function (i.e., without HFREF and HFPEF) (median 25.9, IQR <1–82.2 pg/ml, n = 37) (p < 0.05), followed by patients with HFPEF (median 82.2 pg/ml, IQR 11.5–447 pg/ml, n = 32) as assessed by echocardiography. Finally, CTGF levels were higher in patients with AHF (median 77.3 pg/ml, IQR 22.5–1012 pg/ml, n = 66) compared to those without (p = 0.002). CTGF plus NT-proBNP was non-inferior to NT-proBNP testing alone for AHF diagnosis (AUC difference 0.01, p > 0.05). CTGF plus NT-proBNP improved the diagnostic capacity for AHF (accuracy 82 %, specificity 83 %, positive predictive value 66 %, net reclassification improvement +0.11) compared to NT-proBNP alone (p = 0.0001). CTGF levels were not able to differentiate prognostic outcomes after 1 and 5 years.

Conclusions

Additional CTGF measurements might lead to a better discrimination of higher functional and structural heart failure stages and might identify patients of an increased risk for an acute cardiac decompensation.     

Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis

Introduction

In this study, we aimed to assess the association between acute kidney injury (AKI) and mortality in critically ill patients using an original competing risks approach.

Methods

Unselected patients admitted between 1997 and 2009 to 13 French medical or surgical intensive care units were included in this observational cohort study. AKI was defined according to the RIFLE criteria. The following data were recorded: baseline characteristics, daily serum creatinine level, daily Sequential Organ Failure Assessment (SOFA) score, vital status at hospital discharge and length of hospital stay. Patients were classified according to the maximum RIFLE class reached during their ICU stay. The association of AKI with hospital mortality with "discharge alive" considered as a competing event was assessed according to the Fine and Gray model.

Results

Of the 8,639 study patients, 32.9% had AKI, of whom 19.1% received renal replacement therapy. Patients with AKI had higher crude mortality rates and longer lengths of hospital stay than patients without AKI. In the Fine and Gray model, independent risk factors for hospital mortality were the RIFLE classes Risk (sub-hazard ratio (SHR) 1.58 and 95% confidence interval (95% CI) 1.32 to 1.88; P < 0.0001), Injury (SHR 3.99 and 95% CI 3.43 to 4.65; P < 0.0001) and Failure (SHR 4.12 and 95% CI 3.55 to 4.79; P < 0.0001); nonrenal SOFA score (SHR 1.19 per point and 95% CI 1.18 to 1.21; P < 0.0001); McCabe class 3 (SHR 2.71 and 95% CI 2.34 to 3.15; P < 0.0001); and respiratory failure (SHR 3.08 and 95% CI 1.36 to 7.01; P < 0.01).

Conclusions

By using a competing risks approach, we confirm in this study that AKI affecting critically ill patients is associated with increased in-hospital mortality.     

Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics

Introduction

Medication induced diabetes (MID) during induction therapy (MIDi) in patients with acute lymphoblastic leukemia (ALL) is not well characterized in children, with recent studies yielding conflicting results.

Purpose

The purpose of the study was to describe the prevalence of MIDi and risk factors for its development.

Methods

We retrospectively gathered demographic, disease course and treatment data on 363 patients aged 1 to 17.9?years diagnosed with ALL at a pediatric tertiary care hospital between 1998 and 2005. MIDi was defined as blood glucose ≥200?mg/dL (11.1?mmol/L) on at least 2 separate days during induction.

Results

Fifty-seven subjects (15.7%) developed MIDi during the study period. Patients ≥10?years were more likely to develop MIDi than those <10?years (odds ratio [OR] 9.6, 95% confidence interval [CI] 5.1–17.8). BMI percentile among those with MIDi (mean?±?SD 58.2?±?31.0) did not differ from those without MIDi (52.2?±?32.0, P?=?0.429). The presence of Trisomy 21 (OR 3.6, 95% CI 1.1–11.4, P?=?0.030) and CNS involvement at diagnosis (OR 3.8, 95% CI 1.4–10.1, P?=?0.009) were associated with an increased risk of MIDi. After adjustment for potential confounding variables, age ≥10?years and the presence of CNS disease at diagnosis remained significantly associated with MIDi.

Conclusions

Older age and CNS involvement at diagnosis increase the risk of MIDi. In contrast to previous studies, higher BMI was not associated with MIDi in our population.     

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction

Background

Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI.

Methods

We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12?h of symptom onset. Blood samples were taken on admission and at four time points within the first 24?h after PCI.

Results

In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249?pmol/L and normalized within 10?h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14?h from symptom onset at a maximum of 275?U/L, 5.75???g/L, and 4.16???g/L, respectively, and decreased more gradually.

Conclusions

Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.     

N-Terminal pro B-type natriuretic peptide testing for short-term prognosis in breathless older adults

Background

Amino-terminal pro–brain natriuretic peptide (NT-proBNP) is useful for the triage of patients with dyspnea. Our aim was to determine whether NT-proBNP levels could predict in-hospital outcome in breathless elderly patients.

Methods

At admission, NT-proBNP plasma concentrations were determined in 324 dyspneic patients aged 75 years and older. The association between NT-proBNP values and in-hospital mortality was assessed.

Results

Median NT-proBNP concentrations were not different in deceased patients (n = 43, 13%) compared to that of survivors (n = 281, 87%) (4354 vs 2499 pg/mL, respectively; P = .06). To predict in-hospital mortality, the optimum threshold of NT-proBNP was 3855 pg/mL, as defined by the receiver operating characteristic (ROC) curve, with a nonsignificant area under the ROC curve of 0.59. Mortality was significantly higher in patients (n = 139) with NT-proBNP levels 3855 pg/mL or higher (17.9% vs 9.7%, P = .045). After multivariate analysis, NT-proBNP level 3855 pg/mL or higher at admission was predictive of mortality (odds ratio, 2.41; 95% confidence interval, 1.02-5.68; P = .04).

Conclusion

NT-proBNP higher than 3855 pg/mL is associated with in-hospital mortality in patients aged 75 years and older admitted for dyspnea.     

One-year clinical outcomes with abciximab in acute myocardial infarction: results of the BRAVE-3 randomized trial

Purpose

In the Bavarian Reperfusion Alternatives Evaluation (BRAVE)-3 study upstream administration of abciximab additional to 600 mg clopidogrel loading did not reduce the infarct size in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions. The aim of this study was to investigate 1-year clinical outcomes in the BRAVE-3 study patients.

Methods

A total of 800 patients with acute STEMI within 24 h from symptom onset, all treated with 600 mg of clopidogrel were randomized in a double-blind fashion to receive either abciximab (n = 401) or placebo (n = 399) in the intensive care unit before being sent to the catheterization laboratory.

Results

The main outcome of interest of the present study, the composite of death, recurrent myocardial infarction, stroke or revascularization of the infarct-related artery (IRA) at 1 year, was 23.0% (92 patients) in the abciximab versus 25.7% (102 patients) in the placebo group [relative risk (RR) = 0.90, 95% confidence interval (CI) 0.67–1.20; P = 0.46]. The combined incidence of death, recurrent myocardial infarction or stroke was 9.3% in the abciximab group versus 6.0% in the placebo group (RR = 1.55, 95% CI 0.93–2.58; P = 0.09). There was a significant reduction of the IRA revascularization with abciximab compared to placebo (16.3 vs. 22.3%, RR = 0.71, 95% CI 0.52–0.98; P = 0.04).

Conclusion

In patients with STEMI, all receiving 600 mg clopidogrel, abciximab did not improve overall clinical outcomes at 1 year after primary coronary stenting.     

Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial

Purpose

We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES).

Methods

In post hoc analyses, we examined the associations between fluid assignment, hemostatic variables, bleeding events, transfusions, and death among 798 patients with severe sepsis randomized to fluid resuscitation with HES 130/0.42 versus Ringer’s acetate. We used Cox regression analysis adjusted for fluid assignment and baseline characteristics.

Results

Overall, 93 (23 %) patients assigned to HES versus 60 (15 %) patients assigned to Ringer’s acetate bled in the ICU (relative risk (RR) 1.55; 95 % CI 1.16–2.08; P = 0.003). Of these, 38 and 25 (RR 1.52; 95 % CI 0.94–2.48; P = 0.09), respectively, had severe bleeding (intracranial or concomitant transfusion with three units of red blood cells). Most patients bled in the first days after randomization when most trial fluid was given. The hazards ratios for occurrence of any bleeding and severe bleeding in patients treated with HES versus Ringer’s acetate were 1.70 (95 % CI 1.23–2.36; P = 0.001) and 1.55 (95 % CI 0.93–2.56; P = 0.09), respectively. The adjusted hazard ratios for death among patients with any bleeding and severe bleeding compared to those without bleeding were 1.36 (95 % CI 1.04–1.79; P = 0.03) and 1.74 (95 % CI 1.20–2.53; P = 0.004), respectively.

Conclusions

In post hoc analyses of patient with severe sepsis, treatment with HES increased the risk of bleeding which was associated with increased risk of death. HES-induced bleeding complications may negatively affect outcome in patients with severe sepsis.     

Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke

Introduction

Erythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.

Methods

In total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or serve as placebo (group 2). The circulating level of EPCs (double-stained markers: CD31/CD34 (E₁), CD62E/CD34 (E₂) and KDR/CD34 (E₃)) was determined using flow cytometry at 48 h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.

Results

Circulating EPC (E₁ to E₃) level at 48 h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48 h and on Day 7 after IS, EPC (E₁ to E₃) level did not differ between groups 1 and 2 (all P > 0.1). However, by Day 21, EPC (E₁ to E₃) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy (95% confidence interval (CI), 0.153 to 0.730; P = 0.006) and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) levels were significantly and independently predictive of a reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale ≥8, or death).

Conclusions

EPO therapy significantly improved circulating EPC level and 90-day MANE.

Trial registration number

ISRCTN: ISRCTN96340690     

Cardiometabolic biomarkers are predictors of readmission and death in patients hospitalized for acute dyspnea

Background

Acute dyspnea affects a large heterogeneous patient group with high mortality and readmission rates.

Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores)

Objectives and Background

Tissue factor (TF) contributes to thrombosis following plaque disruption in acute coronary syndromes (ACS). Aim of the study was to investigate the impact of plasma TF activity on prognosis in patients with ACS.

Methods and Results

One-hundred seventy-four patients with unstable Angina pectoris (uAP) and 112 patients with acute myocardial infarction (AMI) were included with a mean follow up time of 3.26 years. On admission, plasma TF activity was assessed. Patients were categorized into 2 groups: a high-TF activity group with TF >24 pmol/L and low TF activity group with TF ≤ 24 pmol/L. Fifteen cardiovascular deaths occurred in the uAP group and 16 in the AMI group. In AMI TF activity was 24,9 ± 2,78 pmol/l (mean ± SEM) in survivors and 40,9 ± 7,96 pmol/l in nonsurvivors (P = 0.024). In uAP no differences were observed (25.0 ± 8.04 pmol/L nonsurvivors vs. 25.7 ± 2.14 pmol/L survivors; P = 0.586). Kaplan-Meier estimates of survival at 3.26 years regarding TF activity in AMI were 81.3% and 92.2% with an hazard ratio of 3.02 (95% CI [1.05–8.79], P = 0.03). The Cox proportional hazards model adjusting for correlates of age and risk factors showed that plasma TF activity was an independent correlate of survival (hazard ratio 9.27, 95% CI [1.24–69.12], P = 0.03). In an additional group of patients with uAP and AMI, we identified circulating microparticles as the prevailing reservoir of plasma TF activity in acute coronary syndromes.

Conclusion

Systemic TF activity in AMI has an unfavorable prognostic value and as a marker for dysregulated coagulation may add to predict the atherothrombotic risk.     

Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors

Purpose

Insomnia is increasingly recognized as a major symptom outcome in breast cancer; however, little is known about its prevalence and risk factors among women receiving aromatase inhibitors (AIs), a standard treatment to increase disease-free survival among breast cancer patients.

Methods

A cross-sectional survey study was conducted among postmenopausal women with stage 0?CIII breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic of a large university hospital. The insomnia severity index (ISI) was used as the primary outcome. Multivariate logistic regression analyses were performed to evaluate risk factors.

Results

Among 413 participants, 130 (31.5?%) had subthreshold insomnia on the ISI, and 77 (18.64?%) exceeded the threshold for clinically significant insomnia. In a multivariate logistic regression model, clinically significant insomnia was independently associated with severe joint pain (adjusted odds ratio (AOR) 4.84, 95?% confidence interval (CI) 1.71?C13.69, P?=?0.003), mild/moderate hot flashes (AOR 2.28, 95?% CI 1.13?C4.60, P?=?0.02), severe hot flashes (AOR 2.29, 95?% CI 1.23?C6.81, P?=?0.015), anxiety (AOR 1.99, 95?% CI 1.08?C3.65, P?=?0.027), and depression (AOR 3.57, 95?% CI 1.48?C8.52, P?=?0.004). Age (>65 vs. <55?years; AOR 2.31; 95?% CI 1.11?C4.81; P?=?0.026) and time since breast cancer diagnosis (<2 vs. 2?C5?years; AOR 1.94; 95?% CI 1.02?C3.69; P?=?0.045) were also found to be significant risk factors. Clinical insomnia was more common among those who used medication for treating insomnia and pain.

Conclusions

Insomnia complaints exceed 50?% among AI users. Clinically significant insomnia is highly associated with joint pain, hot flashes, anxiety and depression, age, and time since diagnosis.     

Gender-specific predictors of early mortality after coronary artery bypass graft surgery

Background

Female gender is a risk factor for early mortality after coronary artery bypass graft surgery (CABG). Yet, the causes for this excess mortality in women have not been fully explained.

Objectives

To analyse gender differences in early mortality (30?days post surgery) after CABG and to identify variables explaining the association between female gender and excess mortality, taking into account preoperative clinical and psychosocial, surgical and postoperative risk factors.

Methods

A total of 1,559 consecutive patients admitted to the German Heart Institute Berlin (2005–2008) for CABG were included in this prospective study. A comprehensive set of prespecified preoperative, surgical and postoperative risk factors were examined for their ability to explain the gender difference in early mortality.

Results

Early mortality after CABG was higher in women than in men (6.9 vs. 2.4?%, HR 2.91, 95?% CI 1.70–4.96, P?P?P?P?=?0.01), respiratory insufficiency (9.4 vs. 5.3?%, P?=?0.006) and resuscitation (5.2 vs. 1.8?%, P?=?0.001). The combination of these factors explained 71?% of the gender difference in early mortality; age and physical functioning alone accounted for 61?%. Adjusting for these variables, HR for female gender was 1.36 (95?% CI 0.77–2.41, P?=?0.29).

Conclusions

Age, physical function and postoperative complications are key mediators of the overmortality of women after aortocoronary bypass surgery. Self-assessed physical functioning should be more seriously considered in preoperative risk assessment particularly in women.     

Right ventricular function in grown-up patients after correction of congenital right heart disease

Aims

We investigated whether a correlation exists between biomarkers of the neurohumoral system and clinical markers in grown-up patients with congenital heart disease (GUCH) and right ventricular function.

Methods and results

Prospective, cross-sectional, multicenter study of 104 GUCH patients (median) 16?years (range 6?C43?years) after corrective surgery with RV pressure and/or volume overload and 54 healthy controls. Clinical, functional, and laboratory parameters were assessed. Natriuretic peptide levels were significantly increased in GUCH patients (NTproBNP 101 vs. 25?pg/ml, p?<?0.001), but we observed no differences in norepinephrine, aldosterone, angiotensin II and Endothelin-1 levels. NTproBNP correlated significantly with clinical markers such as NYHA classification, prolonged QRS duration and reduced exercise capacity (VO₂ peak) (all p?<?0.001), as well as self-reported quality of life (p?<?0.001). MRI and echocardiography derived RV volumes were elevated and ejection fraction reduced in the patients (both p?<?0.001). Tissue Doppler parameter showed significantly restricted ventricular longitudinal systolic function (longitudinal tricuspid valve movement, 1.7 vs. 2.3?cm, p?<?0.001), suggesting stiffness and reduced RV compliance.

Conclusion

In conclusion, grown-up patients with congenital right heart disease NTproBNP correlates well with various clinical markers of RV failure, such as prolongation of QRS duration, exercise capacity, echocardiography and MRI parameters, and quality of life.     

Long-term clinical outcomes following sirolimus-eluting stent implantation in patients with acute myocardial infarction. A meta-analysis of randomized trials

Objectives

The aim of this study was to perform a meta-analysis of randomized trials, evaluating the long-term outcomes of sirolimus-eluting stents (SES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).

Background

Despite short-term outcomes of patients with STEMI undergoing primary percutaneous coronary intervention indicate a benefit of SES in terms of reintervention, several concerns remain on the long-term safety and efficacy of SES.

Methods

A systematic literature search of electronic resources, through October 2011, was performed using specific search terms. Included trials were randomized studies comparing SES to BMS in STEMI patients, with a follow-up ≥3?years.

Results

Seven trials were included, with a total of 2,364 patients. At a median follow-up of 3?years, SES significantly reduced the risk of target-vessel revascularization when compared with BMS [odds ratio (OR), 0.44; 95?% confidence interval (CI), 0.34–0.57; p?<?0.0001], without increasing the risk of mortality (OR 0.78; 95?% CI, 0.57–1.08; p?=?0.14), reinfarction (OR 0.91; 95?% CI, 0.61–1.35, p?=?0.64) and early to late stent thrombosis (OR 0.77; 95?% CI, 0.49–1.20; p?=?0.25). However after the first year, SES did not further reduce target-vessel revascularization (OR 1.06; 95?% CI, 0.64–1.74; p?=?0.83) and increased the risk of very late stent thrombosis (OR 2.81; 95?% CI, 1.33–5.92; p?=?0.007).

Conclusions

At long-term follow-up, SES compared to BMS use in STEMI patients reduces the risk of target-vessel revascularization, without increasing the risk of death and reinfarction. However, the strong SES efficacy is counterbalanced by a significant risk of very late stent thrombosis.