Strong relationship between NT-proXNP levels and cardiac output following cardiac surgery in neonates and infants.

BACKGROUND: NT-proXNP, a new natriuretic peptide analyte, incorporates information about the concentrations of both N-terminal pro-atrial and pro-brain natriuretic peptides (NT-proANP, NT-proBNP). We aimed to investigate whether NT-proXNP is a reliable indicator of the cardiac index (CI) and the hemodynamic state in neonates and infants undergoing an open heart surgery. METHODS: We enrolled 26 children under the age of 1 year into this prospective study. All patients underwent an elective cardiac operation with cardiopulmonary bypass (CPB) to achieve complete biventricular repair. Peri-operative hemodynamic parameters were assessed by transpulmonary thermodilution and natriuretic peptide levels were recorded. RESULTS: The NT-proXNP level correlated significantly with the simultaneously measured NT-proANP level (r=0.60, P<0.001), but more strongly with the NT-proBNP level (r=0.89, P<0.001) and the arithmetic sum of both (r=0.88, P<0.001). NT-proXNP had a strong correlation with CI (r=-0.85, P<0.001), the stroke volume index (r=-0.80, P<0.001) and the global ejection fraction (r=-0.67, P<0.009) throughout the post-operative period. Conventionally measured parameters such as heart rate, mean arterial pressure and pulse-pressure product exhibited weaker correlations with CI than NT-proXNP. Among laboratory values, creatinine levels correlated significantly with CI (r=-0.77, P<0.001) and NT-proXNP (r=0.76, P<0.001) during the post-operative period. A post-operative NT-proXNP level of 3079 pmol/l was diagnostic for CI <3 l/min/m(2) with 89% sensitivity and 90% specificity (area under the curve: 0.91 +/- 0.05). CONCLUSION: NT-proXNP is a good marker of cardiac output following pediatric cardiac surgery and might be a useful tool in the recognition of a low output state.

Plasma N-terminal fragments of natriuretic peptides predict the risk of stroke and atrial fibrillation in men.

BACKGROUND: Risk stratification for cardiovascular outcomes is gaining importance in general population. Prognostic value of natriuretic peptides has been established in patients with heart failure. However, the prognostic significance of natriuretic peptides with respect to stroke is not well known in general populations. METHODS: Plasma natriuretic peptides were measured in a representative population-based sample of 958 men (age 46-65 years) from Eastern Finland. There were 46 cases of stroke, 74 of atrial fibrillation and 31 cases of ischaemic strokes during a follow-up of 9.6 years. RESULTS: The multivariable adjusted risk was 1.35-fold (95% CI 1.01 to 1.84, p = 0.049) for any stroke and 1.30-fold (95% CI 0.90 to 1.91, p = 0.0150) for ischaemic stroke for each log-transformed SD (0.240 pmol/l) increment in N-terminal fragment of proA-type natriuretic peptide. The respective risks were 1.36-fold (95% CI 1.05 to 1.76, p = 0.010) and 1.50-fold (95% CI 1.12 to 2.02, p = 0.007) for each log-transformed SD (0.237 pmol/l) increment in N-terminal fragment of proB-type natriuretic peptide. The multivariate adjusted risks for future atrial fibrillation were 1.71 (95% CI 1.32 to 2.22, p<0.001) and 1.68-fold (95% CI 1.38 to 2.07, p<0.001) for each log-transformed SD increment in N-terminal fragments of proA- and proB-type natriuretic peptides, respectively. CONCLUSIONS: N-terminal fragments of pro-atrial natriuretic peptide and pro-brain natriuretic peptide are new additional predictors of any stroke and atrial fibrillation. Natriuretic peptides provide prognostic information for stroke and atrial fibrillation and may help in identifying subjects at risk for stroke and atrial fibrillation.

Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction.

OBJECTIVE: To test our hypothesis that human fetal N-terminal peptide of proB-type natriuretic peptide (NT-proBNP) secretion is increased in proportion to the severity of fetal cardiovascular compromise in intrauterine growth restriction. METHODS: This prospective cross-sectional study consisted of 42 growth-restricted fetuses who underwent Doppler ultrasonographic examination of cardiovascular hemodynamics within 7 days before delivery. Group 1 fetuses (n = 13) had normal umbilical artery (UA) velocimetry. Group 2 fetuses (n = 15) had abnormal UA and normal ductus venosus (DV) velocimetry. In Group 3 fetuses (n = 14), both UA and DV velocimetries were abnormal. At delivery, an UA blood sample was obtained for assessment of NT-proBNP. Normal values for UA NT-proBNP were determined in 49 neonates (control group) with uncomplicated pregnancy and delivery. RESULTS: Group 3 fetuses demonstrated greater (P < 0.05) UA and descending aorta pulsatility indices (PIs) and greater DV, left hepatic vein (LHV) and inferior vena cava PIs for veins (PIVs) than fetuses in Groups 1 and 2. Weight-indexed cardiac outputs and ventricular ejection forces were similar among the groups. Group 3 fetuses had higher (P < 0.05) UA NT-proBNP concentration than fetuses in Groups 1 and 2. In the control group, the 95(th) percentile value of UA NT-proBNP was 518 pmol/L. In Group 3, 13/14 neonates demonstrated abnormal UA NT-proBNP levels. The corresponding incidences were 4/13 and 7/15 in Groups 1 and 2. Significant positive correlations were found between UA, DV and LHV PIVs and UA NT-proBNP concentrations. CONCLUSION: In human fetal growth restriction, increased cardiac afterload and pulsatility in DV blood velocity waveform pattern are associated with elevated UA NT-proBNP concentrations.

Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation.

OBJECTIVES: Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT). METHODS: Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion. RESULTS: Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline. CONCLUSIONS: Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.

Very acute cardiac toxicity during BEAC chemotherapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation.

Cardiotoxicity is potentially the most threatening nonhaematological side effect of high-dose CY. We prospectively evaluated the very acute cardiac effects of high-dose CY in 17 adult non-Hodgkin's lymphoma (NHL) patients receiving CY 1500 mg/m2/day as a part of BEAC high-dose therapy (HDT). Magnetic resonance imaging (MRI) and plasma natriuretic peptide (NT-proBNP, NT-proANP) measurements were performed prior to HDT (d-7) and just after completing HDT (d-2). After the high-dose CY left atrial end-systolic area increased from 15.2+/-1.2 to 18.5+/-1.4 cm2 (P=0.001), left ventricular end-diastolic volume from 136.1+/-12.3 to 156.6+/-11.1 cm3 (P=0.04) and left ventricular end-systolic volume from 67.4+/-7.8 to 75.3+/-7.1 cm3 (P=0.018). However, no significant change in left ventricular ejection fraction (LVEF) was observed. At the same time, plasma levels of NT-proBNP increased from 134.9+/-53.3 to 547.1+/-168.4 pmol/l (P=0.003) and NT-proANP from 481.1+/-105.5 to 1056.6+/-193.1 pmol/l (P=0.001), respectively. To conclude, high-dose CY results in very acute cardiac toxicity characterised by enlargement of the heart chambers in NHL patients previously treated with anthracyclines. This toxicity can be detected with increased concentrations of circulating natriuretic peptides but not with LVEF measurement.