Systematic Evaluation of Endothelin 1 Measurement Relative to Traditional and Modern Biomarkers for Clinical Assessment and Prognosis in Patients With Chronic Systolic Heart Failure: Serial Measurement and Multimarker Testing.

OBJECTIVES: To define the role of single or serial measurement of endothelin 1 (ET-1) for prognostication beyond traditional and modern markers of risk in heart failure (HF). METHODS: In total, 115 patients with chronic systolic HF were followed for 10 months. Clinical assessment and ET-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), highly sensitive troponin I (hsTnI), soluble ST2 (sST2), and galectin 3 were measured at each visit. RESULTS: Elevated ET-1 was associated with worse HF, lower right ventricular function, higher pulmonary pressure, and higher left atrial volume index despite similar left ventricular function. ET-1 correlated with angiotensin-converting enzyme inhibitor use. A model containing traditional risk factors, ET-1, NT-proBNP, hsTnI, and sST2 best predicted cardiovascular events, and ET-1 improved reclassification. In an adjusted time-integrated model, percent time spent with ET-1 of 5.90 pg/mL or less was predictive of fewer cardiovascular events (odds ratio, 0.75; 95% confidence interval, 0.62-0.91). ET-1 reduction over time was associated with a lower rate of cardiovascular events compared with increasing or stable ET-1 (24.4% vs 50.0%). CONCLUSIONS: ET-1 may be a unique predictor of HF prognosis, complementing other biomarkers in a multimarker profile. Serial measurement of ET-1 may provide additional prognostic information.

Lung ultrasound for the evaluation of pulmonary congestion in outpatients: a comparison with clinical assessment, natriuretic peptides, and echocardiography.

OBJECTIVES: The aim of this study was to define the performance of lung ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and echocardiography, to evaluate decompensation in patients with systolic heart failure (HF) in an outpatient clinic. BACKGROUND: Evaluation of pulmonary congestion in chronic HF is challenging. LUS has been recently proposed as a reliable tool for the semiquantification of extravascular lung water through assessment of B-lines. METHODS: This was a cohort study of patients with moderate to severe systolic HF. Receiver-operating characteristic (ROC) analyses were performed to compare LUS with a previously validated clinical congestion score (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e' ratio, chest x-ray, and 6-min walk test. RESULTS: Ninety-seven patients were enrolled. Decompensation was present in 57.7% of patients when estimated by CCS, 68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' ≥15. The number of B-lines was correlated to NT-proBNP (r = 0.72; p < 0.0001), E/e' (r = 0.68; p < 0.0001), and CCS (r = 0.43; p < 0.0001). In ROC analyses, considering as reference for decompensation a combined method (E/e' ≥ 15 and/or NT-proBNP >1,000 pg/ml), LUS yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing the best accuracy with a cutoff ≥ 15 B-lines (sensitivity 85%, specificity 83%). A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk test in different combinations as reference for decompensation also corroborated this cutoff and found a similar accuracy for LUS. CONCLUSIONS: In an HF outpatient clinic, B-lines were significantly correlated with more established parameters of decompensation. A B-line ≥15 cutoff could be considered for a quick and reliable assessment of decompensation in outpatients with HF.

Transthoracic bioimpedance and brain natriuretic peptide assessment for prognostic stratification of outpatients with chronic systolic heart failure.

BACKGROUND: In patients with chronic heart failure, physical evaluation and clinical judgment may be inadequate for prognostic stratification. HYPOTHESIS: Information obtained with simple bedside tests would be helpful in patient management. METHODS: We report on 142 outpatients with systolic heart failure seen at our heart failure unit from 2007 to 2010 (ages 69.4 ± 8.9 years; ejection fraction [EF] 30.6 ± 6.1%; 43% with implanted defibrillators and/or resynchronization devices). At their first visit, we assessed levels of brain natriuretic peptide (BNP) (pg/mL), evaluated transthoracic conductance (TFC) (1/kΩ) by transthoracic bioimpedance, and performed echocardiography. RESULTS: Four-year mortality was 21.2%. At multivariate analysis, surviving and deceased subjects did not differ regarding New York Heart Association, age, gender, heart failure etiology, or EF at index visit. Patients who died had higher BNP and TFC (BNP = 884 ± 119 pg/mL vs 334 ± 110 pg/mL; TFC = 50 ± 8/kΩ vs 37 ± 7/kΩ, both P < 0.001]. Patients with BNP < 450 pg/mL and TFC < 40/kΩ had a 2.1% 4-year mortality, compared to 46.5% mortality of patients having BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ. BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ showed high sensitivity (91%) and specificity (88%)in identifying patients who died at follow-up. CONCLUSIONS: The combined use of BNP and impedance cardiography during the first assessment of a patient in a heart failure unit identified those carrying a worse medium-term prognosis. This approach could help the subsequent management of patients, allowing better clinical and therapeutic strategies.

Simultaneous assessment of unprocessed ProBNP1-108 in addition to processed BNP32 improves identification of high-risk ambulatory patients with heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) is produced as a biologically inactive prohormone (proBNP(1-108)), processed, and released as an inactive amino acid N-terminal fragment (proBNP(1-76)) and a biologically active carboxyl-terminal fragment (proBNP(77-108) or BNP32). We hypothesized that simultaneous assessment of proBNP(1-108) and active BNP32, as an index of natriuretic peptide processing efficiency, would improve risk stratification in patients with chronic systolic heart failure. METHODS AND RESULTS: We quantified plasma proBNP(1-108) and BNP32 in 756 participants in the Penn Heart Failure Study, a prospective cohort of outpatients with predominantly systolic heart failure. Cox models were used to determine the association between biomarker level at the time of study entry and incident risk of adverse cardiovascular outcomes. A significant amount of unprocessed proBNP(1-108) circulates in patients with systolic heart failure (median, 271 pg/mL; interquartile range, 65 to 825). Higher levels of proBNP(1-108) were associated with an increased risk of all-cause death or cardiac transplantation (adjusted hazard ratio, 4.9; 95% CI, 2.5 to 9.7; P<0.001, comparing third versus first proBNP(1-108) tertile). ProBNP(1-108) provided additive information to BNP32 risk assessment, particularly in patients with BNP32 less than the median of 125 pg/mL (adjusted hazard ratio, 1.4; 95% CI, 1.2 to 1.8; P<0.001 per doubling of proBNP(1-108)). CONCLUSIONS: Circulating proBNP(1-108) is independently associated with an increased risk of adverse cardiovascular outcomes in ambulatory patients with chronic systolic heart failure. The combined assessment of BNP32 and proBNP(1-108) provides additional information in determining risk of adverse clinical outcomes, particularly in patients with low BNP32 values that might otherwise be reassuring to the clinician.

Clinical value of B-type natriuretic peptide for the assessment of left ventricular filling pressures in patients with systolic heart failure and inconclusive tissue Doppler indexes.

Invasive hemodynamic monitoring with Swan-Ganz catheterization to guide treatment decisions in heart failure may be hazardous and may lack prognostic value. We assessed the clinical utility of B-type natriuretic peptide (BNP) in estimating left ventricular filling pressures in patients with inconclusive tissue Doppler indexes. In this study, 50 patients with systolic heart failure and an early transmitral velocity to early diastolic mitral annular velocity ratio (E/Ea) between 8 and 15 were studied. Among them, 25 had been admitted for acutely decompensated heart failure (group A) and the remainder were clinically stable outpatients (group B). All patients underwent simultaneous invasive pulmonary capillary wedge pressure (PCWP) determination, BNP measurement, and echocardiography. In group A, BNP correlated with PCWP (r = 0.803, P < 0.001), deceleration time (DT, r = -0.602, p = 0.001), and end-systolic wall stress (SWS, r = 0.565, P = 0.003). In multivariate analysis, BNP was the only parameter independently associated with PCWP (P = 0.023). In group B, no correlation was found between BNP and PCWP or SWS, while DT correlated significantly with both PCWP (r = -0.817, P < 0.001) and BNP (r = -0.8, P < 0.001). We conclude that BNP may be a useful noninvasive tool for the assessment of left ventricular filling pressures in patients with acutely decompensated heart failure and inconclusive tissue Doppler indexes.