Burritt, Mary F.

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.

Purpose Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL. Patients and Methods Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 μg/L, and cTnI < 0.1 μg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively. Results Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI+NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively. Conclusion Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.

The authors evaluated the relationship between blood lactate accumulation and hemodynamics in a prospective controlled animal study. Seven healthy pigs were anesthetized and mechanically ventilated with a 0.6 fraction of inspired oxygen to achieve a normal PaCO 2 . Catheters for blood sampling, lactate infusion, and hemodynamic assessment were inserted into the femoral vein and femoral artery. Bolus infusions (466 µmol • kg — 1 over 1 minute) of a neutral solution of sodium lactate were given at 0, 30, 60, and 90 minutes. Each bolus was followed by continuous infusion of the same lactate solution (31.7 µmol • kg — 1 • min —1 after the first, with the rate doubled after each subsequent bolus). Arterial blood samples were drawn at baseline and at 30, 60, 90, and 120 minutes, with simultaneous hemodynamic assessment. Significant increases were seen in blood lactate (from 1.6 ± 0.4 mmol/L at baseline to 4.4 ± 0.8 at 30 minutes, 8.0 ± 1.0 at 60 minutes, and 14.4 ± 2.1 at 90 minutes), pH (from 7.40 ± 0.03 to 7.44 ± 0.05 at 30 minutes, 7.50 ± 0.05 at 60 minutes, and 7.56 ± 0.04 at 90 minutes), and HCO 3 — (from 28 ± 1.4 mmol/L to 30 ± 0.7 at 30 minutes, 34 ± 0.9 at 60 minutes, and 37 ± 1.2 at 90 minutes). PaCO 2 decreased significantly from 44 ± 3 torr at baseline to 40 ± 4.7 torr at 90 minutes. Blood pressure decreased after each lactate bolus, recovering within 2 minutes initially but not after later injections. Cardiac output, heart rate, and glucose increased significantly, mean arterial pressure and systemic vascular resistance decreased, and stroke volume did not change. Thus, the accumulation of blood lactate due to exogenous administration of a neutral solution of sodium lactate was associated with significant systemic vasodilation, increased cardiac output, increased heart rate, and metabolic alkalosis.

AbstractPrimary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.