scholarly journals The Effects of Neuropeptide Y Overexpression on the Mouse Model of Doxorubicin-Induced Cardiotoxicity

2019 ◽  
Vol 20 (3) ◽  
pp. 328-338
Author(s):  
Minttu Mattila ◽  
Mirva Söderström ◽  
Liisa Ailanen ◽  
Eriika Savontaus ◽  
Mikko Savontaus
Keyword(s):  
Ejection Fraction ◽  
Neuropeptide Y ◽  
Mass Gain ◽  
Whole Body ◽  
Wild Type ◽  
Cardiac Pathology ◽  
Reduced Ejection Fraction ◽  
Therapeutic Implications ◽  
The Impact ◽  
Lower Ejection Fraction

AbstractDoxorubicin is a potent anticancer drug with cardiotoxicity hampering its use. Neuropeptide Y (NPY) is the most abundant neuropeptide in the heart and a co-transmitter of the sympathetic nervous system that plays a role in cardiac diseases. The aim of this work was to study the impact of NPY on doxorubicin-induced cardiotoxicity. Transgenic mice overexpressing NPY in noradrenergic neurons (NPY-OEDβH) and wild-type mice were treated with a single dose of doxorubicin. Doxorubicin caused cardiotoxicity in both genotypes as demonstrated by decreased weight gain, tendency to reduced ejection fraction, and changes in the expression of several genes relevant to cardiac pathology. Doxorubicin resulted in a tendency to lower ejection fraction in NPY-OEDβH mice more than in wild-type mice. In addition, gain in the whole body lean mass gain was decreased only in NPY-OEDβH mice, suggesting a more severe impact of doxorubicin in this genotype. The effects of doxorubicin on genes expressed in the heart were similar between NPY-OEDβH and wild-type mice. The results demonstrate that doxorubicin at a relatively low dose caused significant cardiotoxicity. There were differences between NPY-OEDβH and wild-type mice in their responses to doxorubicin that suggest NPY to increase susceptibility to cardiotoxicity. This may point to the therapeutic implications as suggested for NPY system in other cardiovascular diseases.

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Total Mortality ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

Comparison of the prognosis and outcome of heart failure with reduced ejection fraction patients treated with sacubitril/valsartan according to age

2021 ◽  
Author(s):  
Mohammad Abumayyaleh ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Christina Pilsinger ◽  
Katherine Sattler ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Older Patients ◽  
Left Ventricular ◽  
Adult Patients ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
The Impact

The treatment with sacubitril/valsartan in patients suffering from chronic heart failure with reduced ejection fraction increases left ventricular ejection fraction and decreases the risk of sudden cardiac death. We conducted a retrospective analysis regarding the impact of age differences on the treatment outcome of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction. Patients were defined as adults if ≤65 years (n = 51) and older if >65 years of age (n = 76). The incidence of ventricular arrhythmias at 1-year follow-up was comparable in both groups (30.8 vs 26.5%; p = 0.71). The mortality rate in adult patients is significantly lower as compared with older patients (2 vs 14.5%; log-rank = 0.04). Older patients may suffer remarkably more side effects than adult patients (21.1 vs 11.8%; p = 0.03).

P1634Comparison of inflammation based prognostic scores in patients with stable heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
A Cho ◽  
S Prausmueller ◽  
G Spinka ◽  
J Novak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Nyha Class ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Reduced Ejection Fraction ◽  
Lymphocyte Ratio ◽  
Nutritional Risk Index ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Elevated inflammatory markers and malnutrition are characteristic for heart failure with reduced ejection fraction (HFrEF) correlating with disease severity and prognosis. Nutritional decline is closely linked to inflammation. Evidence emerges that heart failure can be triggered by inflammation directly, meaning that progression of HF is a function of individual inflammatory host response. We aimed to investigate and compare the impact of well-established inflammation based scores and inflammation-related nutritional scores on survival in HFrEF. Methods Stable HFrEF-patients undergoing routine ambulatory care between 2011 and 2017 have been identified from a prospective registry. Comorbidities and laboratory data at baseline were assessed. All-cause mortality was defined the primary endpoint. The modified Glasgow Prognostic Score (mGPS: 0/1/2 based on CRP and albumin), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) as well as the Nutritional Risk Index (NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight (kg)) and the Prognostic Nutritional Index (PNI = albumin (g l–1) × total lymphocyte count × 109 l–1) were calculated. The association of the scores with HF severity and impact on overall survival were determined. Results Data of 443 patients receiving well titrated guideline directed HF therapy have been analyzed. Median age was 64 years (IQR 53–72), 73% were male. Median body mass index (BMI) was 26.6kg/m2 (IQR 23.8–30.2), median NT-proBNP was 2053pg/ml (IQR 842–4345) with most patients presenting in NYHA class II (178, 40%) and III (173, 39%). The mGPS was 0 for 352 (80%), 1 for 76 (17%) and 2 for 14 (3%) patients, respectively. All scores correlated with HF severity reflected by NT-proBNP [p<0.001 for mGPS, r=−0.48; p<0.001 for PNI] and NYHA class [p<0.001 for mGPS and PNI]. All scores were associated with all-cause mortality in univariate analysis. After adjustment for age, gender and kidney function only mGPS, PLR, NRI and PNI remained significantly associated with outcome. Out of these the ROC were highest for PNI and mGPS [0.674 and 0.652 respectively] and solely these scores remained significantly associated with mortality after including NT-proBNP in the multivariate model [adj.HR 1.87 (95% CI: 1.20–2.91), p=0.006 for mGPS; 0.62 (95% CI: 0.40–0.96), p=0.032 for PNI]. Kaplan Meier analysis confirmed the discriminatory power of mGPS and PNI (Figure 1). Conclusions Enhanced inflammation and malnutrition are more common in advanced heart failure. Among established inflammation and nutritional scores merely mGPS and PNI are associated with survival in HFrEF patients independently of NT-proBNP. This relationship emphasizes the significance of the individual proinflammatory response on prognosis.This easily available score may help clinicians to identify HFrEF patients with worse prognosis with urgent need for intensified therapy and/or alternate treatment options.

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