Miller, Wayne L.

Background— Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years. Methods and Results— A cohort of 190 New York Heart Association class III–IV heart failure patients was prospectively enrolled from June 2001 to January 2004. Primary end points were death, cardiac transplantation, or hospitalization. At study enrollment cTnT was <0.01 ng/mL in 87 (45.8%) patients, 0.01 to 0.03 ng/mL in 50 (26.3%) patients, and >0.03 ng/mL in 53 (27.9%) patients. An increase in cTnT above normal (<0.01 ng/mL) carried a 3.4-fold increased risk ( P =0.019). Further increases (≥20%) from an elevated level worsened the overall risk (hazard ratio, 5.09; P <0.001). BNP was elevated (>95th percentile for age and gender normal population) in 122 (64.2%) patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but, once elevated, further changes in BNP (increases or decreases) remained associated with the same risk (hazard ratio, 5.09; P <0.001). Combined elevations of cTnT (>0.03 ng/mL) and BNP defined the highest risk group (hazard ratio, 8.58; P <0.001). Conclusions— Elevations of cTnT or BNP from normal detected at any time during clinical follow-up in ambulatory patients with chronic heart failure are highly associated with an increased risk of events. Further increases in cTnT contribute to additional risk. Combined elevations of cTnT and BNP contribute the highest risk. The ability to monitor changes by serial measurements adds substantially to the assessment of risk in this patient population.

Abstract Background: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion. Methods: NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A reduction in NT-proBNP was defined as a decrease from baseline during infusion (“infusion responders”) of &gt;3 SD of the variability of the assay measurement (∼20%). Patients with decreases &gt;20% in both NT-pro BNP and BNP at 6 h post infusion were designated “biochemical responders”. Results: Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h post infusion (P &lt;0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were infusion responders with a &gt;20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with &gt;20% decreases from baseline postinfusion for both NT-proBNP and BNP. Conclusions: In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.

Abstract Background Digitalis has a long history in the treatment of heart failure but its effects on cardiac hemodynamics and neurohormonal modulation are not well characterized. Aims The purpose of this study was to evaluate the relationship between atrial natriuretic peptide (ANP) and the hemodynamic responses to acute digitalis administration in patients with normal and impaired left ventricular function (LVD). Methods and Results Thirty patients were enrolled in the study, 20 with LVD (LVEF-22±8%) and 10 control subjects (LVEF-77±10%). Hemodynamics and plasma ANP concentrations were measured supine and with leg elevation before and after digitalis. In patients with normal ventricular function, the hemodynamic stress of leg elevation in the pre-digitalis state resulted in significant (P&lt;0.05) increases in PAWP and MPAP. Digitalis administration in the supine position produced reductions in heart rate, PAWP, MPAP and CI; SVR was increased. In LVD patients leg elevation further increased PAWP, RAP and MPAP. Digitalis in the supine position, however, reduced RAP, MPAP and PAWP and increased CI. These improved hemodynamics were preserved during the stress of leg elevation. Leg elevation following digitalis resulted in increased ANP concentrations despite decreased cardiac filling pressures. Conclusions Acute digitalis administration results in hemodynamic improvement in LVD patients which may in part result from digitalis stimulated release of myocardial ANP under conditions of hemodynamic stress.