Article Figures & Data
Figures
- Fig. 1.
Patients with normal, transiently high, or persistently high Nt-proBNP. (A) Patients with normal (<125 pg/ml) Nt-proBNP at T1. This group of patients included a subgroup in which Nt-proBNP was normal throughout chemotherapy (B) and a subgroup that showed transient elevations during chemotherapy (C). (D) Patient with high (>125 pg/ml) Nt-proBNP at T1 (*P < 0.001 for Nt-proBNP at T1 vs. T0). In these last patients, Nt-proBNP gradually increased over the second half of chemotherapy (E). Values are shown in whisker plots with medians and ranges (A and D) or medians with ranges (B, C, and E). Shaded areas indicate the range of normality. Chemotherapy was expressed as the percentage of length to permit comparisons among oncologic regimens of different durations. Open symbols denote out-of-range levels that the investigators considered normal according to patients’ characteristics at T0 or T1. Out-of-range values at T0 normalized over the first two or three cycles of chemotherapy and were therefore included in the analyses.
- Fig. 2.
Nt-proBNP versus BMI in patients with normal, transiently high, or persistently high Nt-proBNP. Upper panels show that BMI at T1 correlated linearly with BMI at T0, and no significant difference occurred compared with the line of identity (dashed line). Lower panels show net changes of BMI from T0 to T1 versus net changes of Nt-proBNP. A borderline significant inverse correlation between BMI and Nt-proBNP was observed only for patients with normal Nt-proBNP. Shaded areas indicate 95% confidence interval of linear regressions.
- Fig. 3.
Time courses of myocardial relaxation versus Nt-proBNP. Upper panels show changes in myocardial relaxation from T0 to T1 (best-fitting curves). Arrows indicate the time when cardiac imaging was done during chemotherapy and the median cumulative anthracycline dose reached at that time. Bottom panels show time courses of Nt-proBNP from T0 to T1 (best-fitting curves). For patients with persistently high Nt-proBNP, the solid line indicates an anthracycline-based oncologic regimen, whereas the dashed line indicates a nonanthracycline regimen. Shaded areas indicate the range of normality of myocardial relaxation or Nt-proBNP. For best-fitting curves, the S.D. of residuals (Sy.x) was ≤2.0, making in-range values significantly different to out-of-range values.
- Fig. 4.
Time courses of LVEF and Nt-proBNP in patients with persistently high Nt-proBNP. (A) shows LVEF from T0 to T1. Arrows indicate the time when cardiac imaging was done during chemotherapy and the median cumulative anthracycline dose reached at that time. (B) Time course of Nt-proBNP from T0 to T1 (best-fitting curves). The shaded area indicates the range of normality of Nt-proBNP.
- Fig. 5.
Nt-proBNP levels and myocardial relaxation in 12 patients with persistently high Nt-proBNP at T1. Panel A shows individual Nt-proBNP levels in 12 patients with persistently high Nt-proBNP at T1. Panel B shows individual values of myocardial relaxation for the same 12 patients (columns and best-fitting curve). *Only patient who developed a persistently high Nt-proBNP and a concomitant impairment of myocardial relaxation. Shaded areas indicate ranges of normality for Nt-proBNP or myocardial relaxation.
- Fig. 6.
Hb loss and Δ bpm for patients with normal, transiently high, or persistently high Nt-proBNP. Upper panels show that at T1, Δ bpm correlated with Δ Hb for patients with normal or transiently high Nt-proBNP but not for patients with persistently high Nt-proBNP. Shaded areas indicate 95% confidence intervals of linear regression. Lower panels (best-fitting curves) show that theoretical Δ bpm was congruent with clinical Δ bpm for patients with normal or transiently high Nt-proBNP. For patients with persistently high Nt-proBNP, clinical Δ bpm deviated from and exceeded theoretical Δ bpm when Nt-proBNP increased above its range of normality. See also text for explanations.
- Fig. 7.
Effects of 5 weeks of ranolazine on myocardial relaxation, Nt-proBNP, and clinical versus theoretical Δ bpm in patients with impaired relaxation/Nt-proBNP <125 pg/ml or normal relaxation/persistently high Nt-proBNP. After 5 weeks on ranolazine (T5), patients with impaired relaxation/Nt-proBNP <125 pg/ml at T1 (normal or transiently high Nt-proBNP during chemotherapy, n = 6) showed improved myocardial relaxation, insignificant increases or decreases of Nt-proBNP, and a negative clinical Δ bpm that was congruent with theoretical Δ bpm attributable to Hb recovery from T1 to T5 (Δ Hb = 1.3 (−0.1 to 2.2) g/dl). For patients with normal relaxation/persistently high Nt-proBNP at T1 (n = 5), ranolazine did not change myocardial relaxation but diminished Nt-proBNP levels and caused clinical Δ bpm that exceeded theoretical Δ bpm due to Hb recovery (median Δ Hb = 1.1 (1.0–1.3) g/dl).
- Fig. 8.
Schematic representation of the mechanisms and consequences of BNP elevations in cancer patients. Cancer chemotherapy causes diastolic dysfunction (1), which represents a stimulus to BNP elevations (2). High BNP improves diastolic function (3) but causes also an undesired tachycardia (4).
Tables
Data were analyzed by two-tailed Mann-Whitney test, two-tailed square chi test or Fisher’s exact test, as appropriate.
a Doxorubicin (or epirubicin)/cyclophosphamide followed by docetaxel; epirubicin/cyclophosphamide/docetaxel; 5-fluorouracil/epirubicin/cyclophosphamide, with or without a subsequent docetaxel; rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone (for non-Hodgkin lymphoma).
b Folinate/5-fluorouracil/oxaliplatin; capecitabine/oxaliplatin.
c Expressed as doxorubicin myelotoxic equivalents.
d Grade 1 diastolic dysfunction at echocardiography.
e Nt-proBNP > 125 pg/ml.
- TABLE 2
Demographic and oncologic characteristics of patients with normal, transiently high, or persistently high Nt-proBNP
Data were analyzed by Kruskal-Wallis one-way analysis of variance with Dunn’s post-hoc test or two-tailed Chi-square test or Fisher’s exact test, as appropriate.
a Expressed as doxorubicin myelotoxic equivalents.
* P < 0.0001 vs. normal; **P < 0.0001 vs. transiently high.
- TABLE 3
Cardiovascular characteristics of patients with normal, transiently high, or persistently high levels of Nt-proBNP
Data were analyzed by Kruskall-Wallis one-way analysis of variance with Dunn’s post-hoc test or by Wilcoxon matched paired t test (for T0–T1 differences).
- TABLE 4
Hemoglobin (Hb) and heart rate (HR) in patients with normal, transiently highly, or persistently high Nt-proBNP
Data were analyzed by Kruskall Wallis one-way analysis of variance with Dunn’s post-hoc test or by two-tailed Chi-square test or Wilcoxon matched-paired t test (for T0–T1 differences).
In this issue
Chemotherapy, Diastolic Dysfunction, Natriuretic Peptide
