Susan R. Isakson

Serial Sampling of ST2 Predicts 90-Day Mortality Following Destabilized Heart Failure

BACKGROUND To prospectively determine the prognostic utility of serial sampling of the interleukin-1 receptor family member, ST2, for predicting 90-day mortality in patients with heart failure (HF) admitted to a Veteran Affairs Medical Center. METHODS AND RESULTS A total 150 patients hospitalized with acutely destabilized HF were followed at the Veteran Affairs Healthcare System in San Diego, CA. Multiple cardiac-related parameters were measured including ST2, B-type natriuretic peptide (BNP), NT-proBNP, and blood urea nitrogen (BUN). Plasma samples were collected at 6 time points between admission and discharge. Biomarker concentrations were correlated to survival at 90 days. Uni- and multivariate analyses were used to identify prognostic variables. From admission to discharge, percent change in ST2 was strongly predictive of 90-day mortality: those patients whose ST2 values decreased by 15.5% or more during the study period had a 7% chance of death, whereas patients whose ST2 levels failed to decrease by 15.5% in this time interval had a 33% chance of dying. CONCLUSIONS Percent change in ST2 concentrations during acute HF treatment is predictive of 90-day mortality and was independent of BNP or NT-proBNP levels. ST2 may provide clinicians with an additional tool for guiding treatment in patients with acute destabilized HF.

Pro-B-Type Natriuretic Peptide Levels in Acute Decompensated Heart Failure

OBJECTIVES The present study sought to evaluate the clinical utility of pro-B-type natriuretic peptides (proBNP) in patients admitted with acute decompensated heart failure. BACKGROUND Plasma natriuretic peptides (BNP(1-)(32), N-terminal [NT]-proBNP(1-76)) have been demonstrated to assist in the diagnosis of patients with heart failure. However, the precursor to these polypeptides (proBNP(1-108)) circulates in plasma and may interfere with the measurement of currently used biomarkers. METHODS Plasma natriuretic peptides were assessed in 164 individuals (99% men) hospitalized with decompensated heart failure. The B-type natriuretic peptide (BNP), NT-proBNP, and proBNP levels at hospital admission and discharge were compared with the incidence of cardiac death and all-cause mortality within 90 days post-discharge. RESULTS Pro-B-type natriuretic peptides demonstrated a high degree of correlation with both BNP (R = 0.924, p < 0.001) and NT-proBNP (R = 0.802, p < 0.001) at admission. Further characterization of proBNP demonstrated little variation with changes in age, body mass index, creatinine, or systolic dysfunction. All 3 plasma natriuretic peptides were significantly elevated at admission in patients suffering a cardiac death or all-cause mortality (p < 0.05). Receiver-operating characteristic curves demonstrated that admission and discharge NT-proBNP (area under the curve [AUC] 0.788 and AUC 0.834) had superior prognostic power for all-cause mortality when compared with BNP (AUC 0.644, p < 0.01 and AUC 0.709, p < 0.01) and proBNP (AUC 0.653, p < 0.01 and AUC 0.666, p < 0.01) at the same time points. CONCLUSIONS Admission values of all natriuretic peptides can be used to predict cardiac death and all-cause mortality. A preliminary comparison suggests that discharge values of NT-proBNP have the greatest diagnostic yield for predicting these end points. Further studies should explore the synergistic prognostic potential of all natriuretic peptides.

Correlation and Prognostic Utility of B-Type Natriuretic Peptide and Its Amino-Terminal Fragment in Patients With Chronic Kidney Disease

This study compared the correlation and prognostic utility of B-type natriuretic peptide (BNP) and the N-terminal fragment of proBNP (NT-proBNP) in 171 outpatients with renal dysfunction. The NT-proBNP correlated well with BNP in all cases (r = 0.911; P pound .01), regardless of degree of renal impairment or type of left ventricular dysfunction. BNP and NT-proBNP concentrations (P < .005) and their ratios (P pound .01) increased as the glomerular filtration rate (GFR) declined, indicating a greater effect of GFR on NT-proBNP levels. Both natriuretic peptide levels were higher in patients with systolic dysfunction (P < .05) compared with patients with normal echocardiograms. In contrast, BNP and NT-proBNP levels were below the diagnostic cutoffs for congestive heart failure exacerbations in patients with normal heart function or diastolic dysfunction, with no statistical difference between these groups (P = .99). Both peptides are useful prognostic tools for predicting mortality and cardiac hospitalization in renal patients.

B-Type Natriuretic Peptide and Impedance Cardiography at the Time of Routine Echocardiography Predict Subsequent Heart Failure Events

BACKGROUND Detection of heart failure (HF) in stable outpatients can be difficult until an overt event occurs. This study sought to determine whether the combination of B-type natriuretic peptide (BNP) and impedance cardiography (ICG) could be used in a nonacute clinical setting to risk stratify and predict HF-related events in stable outpatients. METHODS AND RESULTS Patients undergoing routine outpatient echocardiography underwent ICG and BNP testing and were followed for one year for HF-related events (Emergency Department [ED] visit or hospitalization due to HF or all-cause death). A total of 524 patients were analyzed, resulting in 57 HF-related events; 16 ED visits, 17 hospitalizations, and 24 all-cause deaths. Using Cox regression analyses, BNP and systolic time ratio index (STRI) by ICG proved to be the strongest predictors of future HF-related events. Patients with a BNP >100 pg/ml and STRI >0.45 sec(-1) had a significantly lower event-free survival rate than those with a high BNP and low STRI (67% versus 89%, P=.001). In patients with LV dysfunction only, if both BNP and STRI values were high, the relative risk of a HF-related event increased by 12.5 (95 % C.I. 4.2-36.7), when compared with patients with a low BNP and low STRI (P<.001). CONCLUSIONS In a nonacute clinical setting, both BNP and ICG testing can provide unique predictive power of long-term HF-related events in a stable cohort of patients with and without LV dysfunction.

Natriuretic peptides: diagnostic tools and predictors of heart failure outcome

Congestive heart failure (CHF) is a progressive disease whose outcome largely depends on early, accurate and prompt diagnosis, accompanied by evidence-based treatment. The explosion of uptake of natriuretic peptides (NPs) in clinical practice belies an understanding of how peptides are used. The signal for NP release is the same signal that causes symptoms of CHF, such as increased wall stress. Thus, NPs can reliably add to the information a physician brings to the table as they attempt to diagnose the acutely dyspneic patient with CHF. Additionally, NPs have strong prognostic utility in the emergency room and the hospital. Monitoring of NPs during treatment for acute CHF may help manage the patient. In the future, it is possible that NPs will play a more prominent role in early detection of left ventricular dysfunction as well as guiding chronic CHF treatment.

Natriuretic peptides as prognosticators in congestive heart failure

Decompensated congestive heart failure (CHF) is a clinical syndrome often characterized by elevated left ventricular fi lling pressures (LVEDP). Therapy for decompensated CHF aims at normalizing fi lling pressures and thereby improves both symptoms and outcomes. However, therapy guided by direct measurements of fi lling pressure is not practical in most patients, focusing attention on non-invasive surrogate measures of LVEDP for tailoring of heart failure therapy.Natiruretic peptide levels (NP) are closely correlated with LVEDP, which is consistently elevated in decompensated heart failure. In the absence of acute mitral regurgitation and fl ash pulmonary edema, and in the presence of volume overload, NP levels are a useful indication of pulmonary capillary wedge pressure (PCWP). In a study by Kazenegra et al, patients admitted for decompensated CHF had BNP levels and hemodynamic measurements taken every 2 hours for the fi rst 24 hours and every four hours for the next 24-48 hours. PCWP showed a decrease from 33 to 25 mmHg over the fi rst 24 hours, while BNP levels decreased from 1472 to 670 pg/ml. However, no change in BNP was noted in patients with end-stage heart failure, even as wedge pressures dropped