Impact of history of heart failure on diagnostic and prognostic value of BNP: results from the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study.

OBJECTIVES: This study aimed to examine the influence of history of heart failure (HF) on circulating levels, diagnostic accuracy and prognostic value of B-type natriuretic peptide (BNP) in patients presenting with all cause dyspnea at the emergency department. BACKGROUND: BNP has been shown to be very helpful in diagnosis and prognosis of HF. Due to chronically elevated cardiac filling pressures, patients with a history of HF might have higher BNP levels and therefore diagnostic and prognostic properties of BNP may be affected. METHODS: We analyzed circulating levels, diagnostic accuracy and prognostic value of BNP in 388 patients without a previous history of HF and compared these to data to 64 patients with a history of HF included in the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) Study. RESULTS: Baseline BNP levels were higher in patients with a history of HF (median 814 pg/ml [353-1300 pg/ml] vs. 216 pg/ml [45-801 pg/ml], p<0.001). Diagnostic accuracy of BNP to identify HF was comparable in patients with (AUC=0.804; 95% CI 0.628-0.980) and in patients without history of HF (AUC=0.883; 95% CI 0.848-0.919, p=0.389). Prognostic ability of BNP to predict one-year mortality was lower in overall patients with history of HF (AUC=0.458; 95%CI 0.294-0.622) compared to patients without history of HF (AUC=0.710; 95% CI 0.653-0.768, p<0.05). CONCLUSIONS: In patients with history of HF, BNP levels retain diagnostic accuracy. Ability to predict one-year mortality was decreased in unselected patients, but not in patients with acute HF-induced dyspnea.

Diagnostic and prognostic value of uric acid in patients with acute dyspnea.

BACKGROUND: Uric acid was shown to predict outcome in patients with stable chronic heart failure. Its impact in patients admitted in the Emergency Department with acute dyspnea, however, remains unknown. METHODS: We prospectively investigated the diagnostic and prognostic value of uric acid in 743 unselected patients presenting to the Emergency Department with acute dyspnea. RESULTS: Uric acid at admission was higher in patients with acute decompensated heart failure (51% of the cohort) as compared with patients with noncardiac causes of dyspnea (median, 447 micromol/L vs 340 micromol/L, P <.001). The area under the receiver operating characteristic curve for the accuracy to detect acute decompensated heart failure was inferior for uric acid (0.70) than for B-type natriuretic peptide (area under the receiver operating characteristic curve 0.91, P <.001). Patients in the highest uric acid tertile more often required admission to the hospital (92% vs 74% in the first tertile, P <.001) and had higher in-hospital mortality (13% vs 4% in the first tertile, P <.001). Cumulative 24-month mortality rates were 28% in the first, 31% in the second, and 50% in the third tertile (P <.001). After adjustment in multivariable Cox proportional hazard analysis, uric acid predicted 24-month mortality independently of B-type natriuretic peptide (P=.003). CONCLUSIONS: Our study first shows that uric acid, measured at Emergency Department admission or hospital discharge, is a powerful predictor of long-term outcome in dyspneic patients.

B-type natriuretic peptide-guided management and outcome in patients with obesity and dyspnea--results from the BASEL study.

BACKGROUND: Obesity may reduce diagnostic accuracy of B-type natriuretic peptide (BNP) and affect long-term outcome. METHODS: This study evaluated patients included in the BASEL study (N = 452). We compared BNP levels in patients with (n = 86) and without (n = 366) obesity (body mass index <30 and >30 kg/m(2)) and determined sensitivities and specificities of BNP in both patient groups by receiver-operating characteristic analysis. Impact of BNP measurements on patient management and outcome in obesity, as well as 360-day mortality, was assessed. RESULTS: The BNP levels were lower in obese patients (172 pg/mL [interquartile range 31-515] vs 306 [interquartile range 75-1,040]). The optimal BNP cut-point to detect heart failure was 182 pg/mL in obese patients and 298 pg/mL nonobese patients. Obese patients had lower in-hospital mortality (3.5% vs 8.5%, P = .045) and 360-day mortality (15% vs 30%, P = .001). In obese patients, the determination of BNP levels reduced time to initiation of the appropriate treatment (96 +/- 98 vs 176 +/- 230, P < .05) without impacting other end points. CONCLUSIONS: Adjustment of BNP values in the assessment of obese patients presenting with acute dyspnea seems necessary to improve diagnostic accuracy and patient management. Obese patients had half the short- and long-term mortality of nonobese patients, independent of their final discharge diagnosis.

Incremental value of copeptin for rapid rule out of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). BACKGROUND: The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. METHODS: In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. RESULTS: The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T < or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. CONCLUSIONS: The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).

The use of B-type natriuretic peptide in the management of patients with atrial fibrillation and dyspnea.

The utility of B-type natriuretic peptide (BNP) testing in patients with atrial fibrillation (AF) is poorly defined. We analyzed patients (n=452) included in the BNP for Acute Shortness of Breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with or without the use of BNP. Ninety-nine patients presented with AF (n=48 BNP group; n=51 control group). Although comparable with respect to gender and cardiopulmonary comorbidity, patients with AF were older and more often had heart failure as the cause of dyspnea. In addition, patients with AF had higher in-hospital mortality (13% versus 6%, P=0.012). The use of BNP significantly reduced time to discharge (BNP group median 8 days [1-16] versus 12 days [IQR 4-21] control group; P=0.046) in patients with AF. Initial total treatment costs (median) were $4239 [769-7422] in the BNP group and $5940 [4024-10848] in the control group (P=0.041). These benefits were maintained after 90 days: patients in the BNP group had spent fewer days in hospital (10 days [2-21] versus 15 days [IQR 9-27]; P=0.022) and induced lower total treatment costs ($4790 [1260-9387] versus $7179 [4311-13173]; P=0.016). In conclusion, the use of BNP seems to improve the management of patients with AF presenting with dyspnea.

Percutaneous coronary intervention versus coronary artery bypass grafting as primary revascularization in patients with acute coronary syndrome.

New European Society of Cardiology/American College of Cardiology guidelines classify patients with acute coronary syndrome and increased cardiac troponins as non-ST-segment elevation myocardial infarction (NSTEMI) who would have been classified as unstable angina pectoris (UAP) using the older World Health Organization (WHO) definition. The optimal revascularization strategy in these patients is poorly defined. This prospective cohort study included 1,024 consecutive patients with acute coronary syndrome classified as UAP, NSTEMI according to the WHO definition (WHO NSTEMI), and NSTEMI additionally identified by the novel European Society of Cardiology/American College of Cardiology definition (additional NSTEMI). All patients underwent coronary angiography within 24 hours and were treated with immediate percutaneous coronary intervention (PCI) or early coronary artery bypass grafting (CABG). The primary end point was all-cause mortality during follow-up of 36 months. Patients with additional NSTEMI showed excessive cumulative 3-year mortality if undergoing CABG (hazard ratio 5.9, 95% confidence interval 2.7 to 13.1, p <0.001). In patients with UAP or WHO NSTEMI, mortality was similar in the CABG and PCI groups. In conclusion, in the absence of randomized trials specifically including patients with additional NSTEMI, the excessive mortality observed with CABG in this cohort study suggested that PCI may be the preferable revascularization strategy in this subgroup.

Impact of body temperature on in-hospital and long-term mortality in patients with acute heart failure.

OBJECTIVES: Body temperature (BT) was shown to have impact on outcome in several medical conditions. This study investigated the prognostic impact of BT in patients with acute heart failure (HF). DESIGN AND PATIENTS: The B-type natriuretic peptide for Acute Shortness of breath EvaLuation (BASEL) study prospectively enrolled 452 consecutive patients presenting with acute dyspnoea to the emergency department. Among these, 170 patients had a final discharge diagnosis of acute HF and a documented BT on presentation. The primary endpoint was cardiovascular mortality during long-term follow-up. Morbidity was documented as secondary endpoint. RESULTS: BT on presentation was 37.2 degrees C (SD 0.9) and ranged from 34.8-40.4 degrees C. Patients were divided into quartiles of BT. Initial morbidity as reflected by intensive care unit admission rate was significantly higher among patients in the highest quartile (38% versus 13% in the first quartile, p <0.05). Length of stay in hospital was significantly increased by 2.7 days per one degree rise in BT. A total of 64 cardiovascular deaths occurred (38%). Kaplan-Meier analysis showed no apparent difference in long-term cardiovascular mortality among quartiles of BT. Cardiovascular mortality rate was 47% in the first (<36.6 degrees C), 26% in the second (36.7-37.2 degrees C), 44% in the third (37.3-37.8 degrees C) and 35% in the fourth quartile ( 37.9 degrees C; P = 0.31) at 720 days. In addition, Cox regression analysis adjusted for age and sex showed no association between BT and either in-hospital (HR 0.59, 95% CI 0.26-1.35; P = 0.21) or long-term cardiovascular mortality (HR 0.91, 95% CI 0.67-1.24; P = 0.55). CONCLUSION: In patients with acute HF, BT on presentation is not associated with in-hospital or long-term cardiovascular mortality, but is associated with short-term morbidity. However, it is important to stress that our findings relate to central BT and do not negate the undisputed value of assessing peripheral BT, which reflects peripheral hypoperfusion.

New definition of myocardial infarction: impact on long-term mortality.

BACKGROUND: The use of cardiac troponin allows the identification of additional patients developing myocardial necrosis during an acute coronary syndrome. Novel guidelines of European and American cardiac societies recommend labeling these events as myocardial infarction. Our study evaluated the long-term mortality in the group of patients with non-ST segment elevation myocardial infarction not meeting the older World Health Organization (WHO) criteria (creatine phosphokinase) but additionally identified by the novel definition of myocardial infarction. METHODS: This cohort study included 1024 consecutive patients with non-ST segment elevation acute coronary syndrome classified into "unstable angina," myocardial infarction according to the WHO definition ("WHO criteria"), and myocardial infarction additionally identified by the novel definition ("additional criteria"). All patients were treated with an early invasive strategy. The primary end point was all-cause mortality during follow-up of up to 36 months. RESULTS: During long-term follow-up (median 16 months, interquartile range 6-29 months), 67 deaths occurred. Kaplan-Meier analysis showed cumulative 3-year mortality rates of 5.6% in patients with "unstable angina," 9.1% in patients identified by "WHO criteria," and 17.5% in patients identified by "additional criteria" (P <.001). Cox regression analysis confirmed the "additional criteria" as a significant predictor of mortality (hazard ratio 3.1; 95% confidence interval, 1.9-5.0; P <.001). CONCLUSIONS: The new definition of myocardial infarction based on cardiac troponin testing identifies a high-risk group of additional patients with acute coronary syndrome that is, therefore, appropriately classified as myocardial infarction. In fact, long-term mortality in "additional criteria" patients is higher than in "WHO criteria" patients.

Multimarker strategy for risk prediction in patients presenting with acute dyspnea to the emergency department.

BACKGROUND: Multimarker approaches improve risk prediction in patients presenting with acute coronary syndrome. We hypothesized that simultaneous assessment of B-type natriuretic peptide (BNP), cardiac troponin I (cTNI) and C-reactive protein (CRP) enables clinicians to better predict risk among patients with acute dyspnea presenting to the emergency department. METHODS AND RESULTS: In this post-hoc analysis of the B-Type natriuretic peptide for Acute Shortness of Breath Evaluation (BASEL) study, above biomarkers were available in 305 patients. Death occurred in 123 (40%) patients within 24 months of follow-up. Using prospectively defined cut-off points (BNP>100 pg/mL; cTNI>0.8 microg/L; CRP>5 mg/L) and categorizing patients by the number of elevated cardiac biomarkers, the 24 months risk of death increased in proportion to the number of cardiac biomarkers elevated (p<0.001 for trend). Elevated biomarkers significantly predicted increased risk of death at 24 months of follow-up in univariate Cox models (BNP: RR 4.78, 95%CI: 2.51-9.14; p<0.001; cTNI: RR: 2.29, 95%CI: 1.61-3.26, p<0.001; CRP: RR 1.98, 95%CI: 1.28-3.08; p=0.002). Multivariable Cox regression analysis revealed that elevated levels of BNP (p<0.001) and TNI levels (p<0.002) indicated increased risk of death during long-term follow-up, while only a statistical trend was seen for elevated CRP (p=0.09). Comparably, risk of death or rehospitalization significantly increased with the number of elevated biomarkers. CONCLUSIONS: Our findings suggest that a simple multimarker approach with simultaneous assessment of BNP, and cTNI demonstrates potential to assist clinicians in predicting risk of death and/or rehospitalization in patients presenting with acute dyspnea in the emergency department.

Medical and economic long-term effects of B-type natriuretic peptide testing in patients with acute dyspnea.

BACKGROUND: The objective of this prospective study was to assess the medical and economic long-term effects of using B-type natriuretic peptide (BNP) concentrations in the management of patients with acute dyspnea. METHODS: We performed follow-up analysis of the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation, a randomized study including 452 patients who presented to the emergency department with acute dyspnea. Participants were randomly assigned to a diagnostic strategy involving the rapid measurement of BNP concentrations (n = 225) or standard assessment (n = 227). Mortality was assessed at 720 days, morbidity and economic data at 360 days. RESULTS: BNP testing induced several important changes in initial patient management, including a reduction in the initial hospital admission rate, the use of intensive care, and initial time to discharge. At 720 days, 172 deaths had occurred. Cumulative all-cause 720-day mortality was not different between the BNP group (37%) and the control group (36%, P = 0.6). Morbidity as reflected by days spent in-hospital at 360 days was significantly lower in the BNP group [median 12 days ([interquartile range 2-28 days)] compared with the control group [median 16 (7-32)] days, P = 0.025]. Functional status was similar in both groups. Economic outcome as quantified by total treatment cost at 360 days was significantly improved in the BNP group (mean 10,144 dollars vs 12,748 dollars in the control group, P = 0.008). CONCLUSIONS: Rapid BNP testing in patients with acute dyspnea has no effect on long-term mortality. However, morbidity as quantified by days spent in-hospital and economic outcome are still improved at 360 days.

QRS and QTc interval prolongation in the prediction of long-term mortality of patients with acute destabilised heart failure.

OBJECTIVES: To quantify the prognostic utility of QRS and QTc interval prolongation in patients presenting with acute destabilised heart failure (ADHF) to the emergency department (ED). DESIGN: Prospective cohort study among patients enrolled in the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study. QRS and QT intervals were measured in 173 consecutive patients with ADHF. QT interval was corrected using the Bazett formula. The primary end point was all-cause mortality during the 720-day follow-up. RESULTS: QRS interval was prolonged (> or =120 ms) in 27% of patients, and QTc interval was prolonged (> or =440 ms) in 72% of patients. Baseline demographic and clinical characteristics were comparable in patients with normal and prolonged QRS or QTc intervals. A total of 78 patients died during follow-up. Interestingly, the 720-day mortality was similar in patients with prolonged and normal QTc (44% vs 42%, p = 0.546), but was significantly higher in patients with prolonged QRS interval than in those with normal QRS (59% vs 37%, p = 0.004). In Cox proportional hazards analysis, prolonged QRS interval was associated with a nearly twofold increase in mortality (HR 1.94, 95% CI 1.22 to 3.07; p = 0.005). This association persisted after adjustment for variables routinely available in the ED. CONCLUSIONS: Prolonged QRS interval, but not prolonged QTc interval, is associated with increased long-term mortality in patients with ADHF.