atrial-natriuretic-factor and Lymphoma--Non-Hodgkin

There are three distinct types of doxorubicin-induced cardiotoxicity (acute, chronic, and late-onset). Although previous studies with animal models suggest that angiotensin II plays a key role in the process of the doxorubicin-induced cardiotoxicity, there has been no such observation in humans. This randomized study investigated whether valsartan, a new class of angiotensin II receptor blocker (ARB), can inhibit acute cardiotoxicity after doxorubicin-based chemotherapy.. Forty consecutive patients with untreated non-Hodgkin lymphoma who were scheduled to undergo standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) (mean age, 56 yrs; range, 24-70 yrs) were randomized with minimization methods to receive CHOP with or without 80 mg/day of valsartan. Acute cardiotoxicity was comprehensively evaluated with neurohumoral, echocardiographic, and electrocardiographic markers before and on Days 3, 5, and 7 after the initiation of CHOP.. CHOP induced transient increases in the left ventricular end-diastolic diameter in an echocardiogram, the QTc interval and QTc dispersion in an electrocardiogram, and in the plasma brain and atrial natriuretic peptides. All these changes returned to nearly normal levels within a week after CHOP (P < 0.001). Notably, valsartan significantly prevented all these changes except for the elevation in atrial natriuretic peptide (P < 0.05). No significant change was observed in blood pressure or heart rate between the valsartan and control groups.. The results indicate that angiotensin II may play an essential role in acute CHOP-induced cardiotoxicity in humans. Future long-term studies are necessary to judge whether ARBs have a potential to prevent the chronic or late-onset types of doxorubicin-induced cardiotoxicity.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Biomarkers; Cyclophosphamide; Doxorubicin; Female; Hemodynamics; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Prednisone; Tetrazoles; Valine; Valsartan; Vincristine

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Autonomic Nervous System; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart Rate; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Prednisone; Prospective Studies; Radionuclide Ventriculography; Stroke Volume; Ventricular Dysfunction, Left; Vincristine

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).. 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.. 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.. 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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Atrial Natriuretic Factor; Biomarkers; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Gated Blood-Pool Imaging; Heart; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Postoperative Period; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Stroke Volume; Systole; Transplantation, Autologous; Ventricular Dysfunction, Left

To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO).. Prospective study.. University hospital.. Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2).. The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2).. Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels.. The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Topics: Adult; Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Diastole; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Natriuretic Peptide, Brain; Prospective Studies; Protein Precursors; Systole; Ventricular Dysfunction, Left

Thirty adult patients with non-Hodgkin's lymphoma who were planned to receive up to 8-10 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) to a cumulative doxorubicin dose of 400-500 mg/m2 were studied to evaluate the value of serial plasma atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP) and brain natriuretic peptide (BNP) measurements in the early detection of doxorubicin-induced left ventricular dysfunction. Plasma levels of natriuretic peptides were measured before every treatment course and 4 wk after the last one. Cardiac function was monitored with serial radionuclide ventriculography. Twenty-eight patients were evaluable for cardiotoxicity. Clinical heart failure developed in 2 patients (7%). Left ventricular ejection fraction (LVEF) decreased from 58.0+/-1.3% to 49.6+/-1.7% (p <0.001). Plasma levels of ANP increased from 16.4+/-1.3 pmol/l to 22.7+/-2.4 pmol/l (p= 0.002), NT-proANP from 288+/-22 to 380+/-42 pmol/l (p = 0.019) and BNP from 3.3+/-0.4 to 8.5+/-2.0 pmol/l (p = 0.020). There was a significant correlation between the increase in plasma ANP and the decrease in LVEF (r = -0.447, p = 0.029), and a trend towards significance between the increase in NT-proANP and the decrease in LVEF (r=-0.390, p=0.059). The decrease in LVEF started very early and could already be seen after the cumulative doxorubicin dose of 200 mg/m2, whereas the increase in plasma natriuretic peptides was not evident until the cumulative doxorubicin dose of 400 mg/m2. Our results show that neuroendocrine activation - increased concentrations of plasma natriuretic peptides - occurs when left ventricular function has reduced substantially and its compensatory capacity has been exceeded resulting in atrial and ventricular overload. Thus, serial natriuretic peptide measurements cannot be used in predicting the impairment of left ventricular function. On the other hand, our study suggests that natriuretic peptides are useful in the detection of subclinical left ventricular dysfunction in patients receiving doxorubicin therapy.

Topics: Adult; Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Doxorubicin; Female; Heart Diseases; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Function, Left

A patient is described with the syndrome of inappropriate antidiuresis (SIAD) and renal sodium retention secondary to a lymphoma. The basal atrial natriuretic peptide (ANP) level and the ANP response to volume expansion were normal (age adjusted) but the natriuretic effect of ANP was attenuated by an unidentified factor. The case emphasizes the dominance of circulating volume over plasma tonicity in the regulation of ANP secretion.

Topics: Aged; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Volume; Female; Humans; Inappropriate ADH Syndrome; Kidney; Lymphoma, Non-Hodgkin; Osmolar Concentration; Renin; Sodium