Thenral Socrates

Yale University, New Haven, Connecticut, United States

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Publications (35)

  • [Show abstract] [Hide abstract] ABSTRACT: The pathophysiology and key determinants of lower extremity edema in patients with acute heart failure are poorly investigated. We prospectively enrolled 279 unselected patients presenting to the Emergency Department with acute heart failure. Lower extremity edema was quantified at predefined locations. Left ventricular ejection fraction, central venous pressure quantifying right ventricular failure, biomarkers to quantify hemodynamic cardiac stress (B-type natriuretic peptide), and the activity of the arginine-vasopressin system (copeptin) also were recorded. Lower extremity edema was present in 218 (78%) patients and limited to the ankle in 22%, reaching the lower leg in 40%, reaching the upper leg in 11%, and was generalized (anasarca) in 3% of patients. Patients in the 4 strata according to the presence and extent of lower leg edema had comparable systolic blood pressure, left ventricular ejection fraction, central venous pressure, and B-type natriuretic peptide levels, as well as copeptin and glomerular filtration rate (P=NS for all). The duration of dyspnea preceding the presentation was longer in patients with more extensive edema (P=.006), while serum sodium (P=.02) and serum albumin (P=.03) was lower. Central venous pressure, hemodynamic cardiac stress, left ventricular ejection fraction, and the activity of the arginine-vasopressin system do not seem to be key determinants of the presence or extent of lower extremity edema in acute heart failure.
    Article · Aug 2012 · The American journal of medicine
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    [Show abstract] [Hide abstract] ABSTRACT: The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.
    Full-text available · Article · May 2012 · Clinical Science
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives. The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B-type natriuretic peptide (BNP) levels. Design. A randomized controlled trial. Setting. Twenty-nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. Subjects. A total of 323 consecutive patients presenting with dyspnoea. Interventions. Assignment in a 1:1 ratio to a diagnostic strategy including point-of-care measurement of BNP (n=163) or standard assessment without BNP (n=160). The total medical cost at 3months was the primary end-point. Secondary end-points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. Results. Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3months [median $1655, interquartile range (IQR), 850-3331 vs. $1541, IQR 859-2827; P=0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work-up (33% vs. 45%; P=0.02) and accelerated the initiation of the appropriate treatment (13days vs. 25days; P=0.01). The area under the receiver-operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81-0.93). Conclusions. The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end-points including diagnostic certainty and time to initiation of appropriate treatment. © 2012 The Association for the Publication of the Journal of Internal Medicine.
    Article · May 2012 · Journal of Internal Medicine
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    Tobias Breidthardt · Thenral Socrates · Beatrice Drexler · [...] · Christian Mueller
    [Show abstract] [Hide abstract] ABSTRACT: The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P<0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P<0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P=0.04) in multivariable regression analysis. Plasma NGAL levels do not adequately predict AKI in patients with AHF.
    Full-text available · Article · Jan 2012 · Critical care (London, England)
  • [Show abstract] [Hide abstract] ABSTRACT: The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need. We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604-1525] pg/mL versus 800 [427-1317] pg/mL; P<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010-0.306] μg/L versus 0.018 [0.010-0.060] μg/L [P<0.001]; 0.024 [0.008-0.106] μg/L versus 0.016 [0.004-0.044 ] μg/L [P=0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54-0.63], 0.61 [95% CI, 0.57-0.66], and 0.59 [95% CI,0.54-0.65], respectively). These findings were confirmed in the validation cohort. At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.
    Article · Jan 2012 · Circulation Heart Failure
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    Sascha Kopic · Maximilian E H Wagner · Christoph Griessenauer · [...] · John P Geibel
    [Show abstract] [Hide abstract] ABSTRACT: The vacuolar-type H-ATPase (V-ATPase) plays an important role in the active acidification of intracellular organelles. In certain specialized cells, such as the renal intercalated cell, apical V-ATPase can also function as a proton secretion pathway. In the parietal cells of the stomach, it has been thought that acid secretion is controlled solely via the H,K-ATPase. However, recent observations suggest that functional V-ATPase is necessary for acid secretion to take place. This study aimed to investigate and characterize the role of V-ATPase in parietal cell proton transport. Individual rat gastric glands were incubated with the pH-sensitive dye (BCECF) to monitor changes in intracellular pH in real time. Parietal cell V-ATPase activity was measured by quantifying the rate of intracellular alkalinization (ΔpH/minute) following an acid load, while excluding the contribution of non-V-ATPase proton transport mechanisms through pharmacological inhibition or ion substitution. Expression of V-ATPase was confirmed by immunohistochemistry. We observed concanamycin A-sensitive V-ATPase activity in rat parietal cells following intracellular acidification and H,K-ATPase inhibition. Furthermore, V-ATPase-mediated proton transport could be abolished by inhibiting trafficking mechanisms with paclitaxel and by stimulating H,K-ATPase with acid secretagogues. Our results propose that parietal cells contain a functional V-ATPase that can be mobilized using a microtubule network. V-ATPase may function as an auxiliary acid secretion or proton-buffering pathway in parietal cells, which is inactive during H,K-ATPase activity. Our findings may have important implications for patients experiencing acid breakthrough under proton pump inhibitor therapy.
    Full-text available · Article · Nov 2011 · Pflügers Archiv - European Journal of Physiology
  • [Show abstract] [Hide abstract] ABSTRACT: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 μg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 μg L(-1) ) and increased (≥0.028 μg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 μg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 μg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.
    Article · Oct 2011 · Journal of Internal Medicine
  • Nisha Arenja · Tobias Breidthardt · Thenral Socrates · [...] · Christian Mueller
    [Show abstract] [Hide abstract] ABSTRACT: Simple tools for risk stratification of patients with acute heart failure (AHF) are an unmet clinical need, particularly regarding long-term mortality. We prospectively enrolled 610 consecutive patients presenting to the emergency department with AHF. The diagnosis of AHF was adjudicated by two independent cardiologists. The classification and regression tree (CART) analysis was used to develop a simple risk algorithm. This was internally validated by cross-validation. One-year follow-up was complete in all patients (100%). A total of 201 patients (33%) died within 360 days. The CART analysis identified blood urea nitrogen (BUN) and age as the best single predictors of 1-year mortality and patients were categorised to three risk groups: high risk group (BUN >27.5 mg/dl and age >86 years), intermediate risk group (BUN >27.5 mg/dl and age ≤ 86 years) and low risk group (BUN ≤ 27.5 mg/dl). The Kaplan-Meier curves showed a significant increase in mortality in the high risk group compared with the lower risk groups (log-rank test p <0.001). The hazard ratio regarding 1-year mortality between patients identified as low and high risk was 2.0 (95% confidence interval, 1.7-2.4), with statistically significant differences between all risk groups (p <0.001). The likelihood-based 95%-confidence set for the age- and the urea-threshold is contained in the rectangular set defined by 25 mg/dl ≤ urea threshold ≤30.6 mg/dl and 76 years ≤ age threshold ≤96 years. These results suggest that AHF patients at low, intermediate and high risk for death within 360 days can be easily identified using patient's demographics and laboratory data obtained at presentation. Application of this simple risk stratification algorithm may help to improve the management of these patients.
    Article · Oct 2011 · Schweizerische medizinische Wochenschrift
  • Article · Aug 2011 · Journal of Cardiac Failure
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    Tobias Breidthardt · Stefan Kalbermatter · Thenral Socrates · [...] · Denes Kiss
    [Show abstract] [Hide abstract] ABSTRACT: Cardiac disease is the major cause of death in patients undergoing chronic haemodialysis. Recent studies have found that B-type natriuretic peptide (BNP) levels accurately reflect the cardiovascular burden of dialysis patients. However, the prognostic potential of BNP measurements in dialysis patients remains unknown. The study included 113 chronic dialysis patients who were prospectively followed up. Levels of BNP were measured at baseline and every 6 months thereafter. The potential of baseline BNP and annual BNP changes to predict all-cause and cardiac mortality were assessed as endpoints. Median follow-up was 735 (354-1459) days; 35 (31%) patients died, 17 (15%) of them from cardiac causes. Baseline BNP levels were similar among survivors and non-survivors, and failed to predict all-cause and cardiac death. Cardiac death was preceded by a marked increase in BNP levels. In survivors BNP levels remained stable [median change: +175% (+20-+384%) vs. -14% (-35-+35%) over the 18 months preceding either death or the end of follow-up, P< 0.001]. Hence, annual BNP changes adequately predicted all-cause and cardiac death in the subsequent year {AUC(all-cause) = 0.70 [SD 0.05, 95% CI (0.60-0.81)]; AUC(cardiac) = 0.82 [SD 0.04, 95%CI (0.73-0.90)]}. A BNP increase of 40% provided the best cut-off level. Cox regression analysis confirmed that annual increases over 40% were associated with a seven-fold increased risk for all-cause and cardiac death. Annual BNP increases above 40% predicted all-cause and cardiac death in the subsequent year. Hence, serially measuring BNP levels may present a novel tool for risk stratification and treatment guidance of end-stage renal disease patients on chronic dialysis.
    Full-text available · Article · May 2011 · European Journal of Heart Failure
  • Tobias Breidthardt · Thenral Socrates · Markus Noveanu · [...] · Christian Mueller
    [Show abstract] [Hide abstract] ABSTRACT: We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.
    Article · Mar 2011 · The American journal of cardiology
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    [Show abstract] [Hide abstract] ABSTRACT: Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome. 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. 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. 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. identifier: NCT00514384.
    Full-text available · Article · Jan 2011 · Critical care (London, England)
  • Nisha Arenja · Thenral Socrates · Christian Mueller
    Chapter · Jan 2011
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    Philipp Kirchhoff · Thenral Socrates · Shafik Sidani · [...] · John P Geibel
    [Show abstract] [Hide abstract] ABSTRACT: The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy. Intracellular pH was measured with 2',7'-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescein in both human and rat gastric glands following an acid load±a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI). We demonstrate that exposure to ZnCl(2) immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl(2) raised intragastric pH for over 3  h, including a fast onset of effect. Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.
    Full-text available · Article · Jan 2011 · The American Journal of Gastroenterology
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    [Show abstract] [Hide abstract] ABSTRACT: To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department. Central venous pressure was determined non-invasively using compression sonography in 140 patients with AHF at presentation. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥ 0.3 mg/dL during hospitalization. In the study cohort [age 77 ± 12 years, B-type natriuretic peptide 1862 ± 1564 pg/mL, left ventricular ejection fraction 40 ± 15%, estimated glomerular filtration rate (eGFR) 58 ± 28 mL/min, and CVP 13.2 ± 6.9 cmH(2)O], 51 patients (36%) developed WRF. No significant association between CVP at presentation or discharge and concomitant eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed. However, in patients with systolic blood pressure (SBP) <110 mmHg and concomitant high CVP (>15 cmH(2)O), eGFR was significantly lower at presentation and discharge (29 ± 17 vs. 47 ± 19 mL/min/1.73 m(2), P = 0.039 and 26 ± 10 vs. 53 ± 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at presentation and at discharge did not differ between patients with or without in-hospital WRF (12.6 ± 7.2 vs. 13.5 ± 6.7 cmH(2)O, P = 0.503 and 7.4 ± 6.5 vs. 7.7 ± 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively). However, patients with CVP in the lowest tertile (<10 cmH(2)O) at presentation were more likely to develop WRF within the first 24 h than patients with CVP in the highest tertile (>15 cmH(2)O) (18 vs. 4%, P = 0.046). In AHF, combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may also be associated with short-term WRF. The pathophysiology of WRF and the role of CVP seem to be more complex than previously thought.
    Full-text available · Article · Nov 2010 · European Journal of Heart Failure
  • D Staub · T Zeller · D Trenk · [...] · C Mueller
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA). In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA. BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml(-1) (interquartile range (IQR) 35-250) and decreased significantly within 1 day of PTRA to 62 pg ml(-1) (IQR 24-182) (p < 0.001), remaining at 75 pg ml(-1) (IQR 31-190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46-0.67). Pre-intervention BNP >50 pg ml(-1) was seen in 79% of patients with BP improvement compared with 56% in patients without improvement (p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml(-1) was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2-13.2). BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml(-1) may be helpful to identify patients in whom PTRA will improve BP.
    Article · Nov 2010 · European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery
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    Thenral Socrates · Christopher DeFilippi · Tobias Reichlin · [...] · Christian Mueller
    [Show abstract] [Hide abstract] ABSTRACT: The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP. Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL⁻¹, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL⁻¹) significantly predicted 1-year mortality (HR 2.3, P < 0.001). In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.
    Full-text available · Article · Nov 2010 · Journal of Internal Medicine
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    H Uthoff · D Staub · T Socrates · [...] · B Frauchiger
    [Show abstract] [Hide abstract] ABSTRACT: The predictive value of PROCAM, FRAMINGHAM, SCORE and SMART-score to estimate the cardiovascular risk in patients with overt atherosclerosis had never been assessed. 96 consecutive patients with clinically evident atherosclerosis (coronary, cerebrovascular, peripheral artery and renovascular disease) were enrolled in this preliminary observational study. At baseline, medical history and blood chemistry were obtained. Sonographic measurement of the intima-media thickness (IMT) in the common carotid artery was performed and risk estimations according to the above listed risk scores were calculated. During a 6 year follow-up the occurrence of cardiovascular death, acute coronary syndrome and stroke was assessed. Mean (±SD) risk-scores were 10.9±2.5, range 6-17 (SMART); 18.9±18.2%; range 0.2-94.1% (PROCAM); 21.4±13.1%, range 4-56% (FRAMINGHAM); and 4.8±3.9%, range 0.4-15.3% (SCORE). Mean IMT was 0.84±0.14 mm, range 0.51-1.20 mm. All scores correlate significantly with each other (r>0.321; p<0.01), but only SMART-score correlated significantly with baseline IMT(r=0.372; p<0.001). Within the median follow-up of 73 months, a cardiovascular endpoint was observed in 36 (42%) patients. The AUC (95% confidence interval) for SMART-risk-score predicting a cardiovascular event was 0.67 (0.54-0.77; p<0.02); for PROCAM 0.60 (0.47-0.73; p=n.s.); for FRAMINGHAM 0.56 (0.43-0.69; p=n.s.); and for SCORE 0.60 (0.46-0.73; p=n.s.). Cox regression analysis showed a relative risk for a cardiovascular event per additional SMART score point of 1.15 (95% CI 1.01-1.30 p=0.03). PROCAM-, FRAMINGHAM- and SCORE-risk score seem to be barely useful in a secondary prevention setting. In patients with overt atherosclerosis, the cardiovascular risk seems to be better assessed by means of the SMART score.
    Full-text available · Article · Nov 2010 · VASA.: Zeitschrift für Gefässkrankheiten. Journal for vascular diseases
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    [Show abstract] [Hide abstract] ABSTRACT: 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 Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. We conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea. Copeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk. Copeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.
    Full-text available · Article · Nov 2010 · Critical care (London, England)
  • Conference Paper · Sep 2010