Abstract 364: Pathological Effects of Trimethylamine N-oxide (TMAO) on Pressure Overload-induced Heart Failure

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Chelsea L Organ ◽  
Hiroyuki Otsuka ◽  
Jessica Bradley ◽  
Shashi Bhushan ◽  
Rishi Trivedi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Control Diet ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Increased Risk ◽  
Failure Severity ◽  
Heart Failure Severity

Rationale: Trimethylamine N-oxide (TMAO), a metabolite formed in the metabolism of dietary phosphatidylcholine, is elevated in the circulation of patients at increased risk for heart attack and adverse prognosis during heart failure. Objective: We investigated the effects of dietary choline and TMAO on the severity of heart failure following transverse aortic constriction (TAC). Methods and Results: Male C57Blk/6J mice were fed either control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) at 3 weeks prior to surgical TAC and were studied for 12 weeks. Left ventricular (LV) structure and function were monitored at 3 week intervals and myocardial tissue was collected at 12 weeks. Plasma TMAO levels were significantly (p < 0.01) increased in the choline (28.64 ± 2.30 μM) and TMAO (28.18 ± 4.27 μM) compared to the control group (1.87 ± 0.26 μM). Left ventricular ejection fraction (LVEF) was significantly (p < 0.05) worse in mice fed TMAO compared to control diet. LV end-diastolic and end-systolic diameters were significantly (p < 0.05) increased in the TMAO group compared to control diet. Myocardial fibrosis as measured with Picrosirius Red staining was also significantly greater (p < 0.01) in the TMAO and choline groups. Circulating BNP levels were significantly (p < 0.05) increased in the TMAO and choline groups. Conclusions: These data demonstrate that heart failure severity is significantly enhanced in mice fed diets containing either TMAO or choline. Our results suggest that consumption of food high in dietary nutrients that increase TMAO levels such as phosphatidylcholine may increase heart failure severity.

scholarly journals Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003–2015

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helen Sjöland ◽  
Jonas Silverdal ◽  
Entela Bollano ◽  
Aldina Pivodic ◽  
Ulf Dahlström ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Temporal Trends ◽  
Physical Symptoms ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Continuous Change ◽  
Ventricular Ejection Fraction ◽  
Increased Risk ◽  
Over Time

Abstract Background Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003–2015. Methods DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003–2007 (Period 1, n = 2029), 2008–2011 (Period 2, n = 3363), 2012–2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. Results Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). Conclusions From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

scholarly journals A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

2014 ◽  
Vol 9 ◽  
pp. IMI.S13939 ◽  
Author(s):  
Bandi Hari Krishna ◽  
Pravati Pal ◽  
G. K. Pal ◽  
J. Balachander ◽  
E. Jayasettiaseelon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Medical Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Tei Index ◽  
Ventricular Ejection Fraction ◽  
Yoga Therapy ◽  
Standard Medical Therapy

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Endothelial Function ◽  
Training Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Lv Function ◽  
Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

scholarly journals Prognostic algorithms for the progression of chronic heart failure depending on the clinical phenotype

2019 ◽  
Vol 18 (3) ◽  
pp. 41-47
Author(s):  
E. A. Polunina ◽  
L. P. Voronina ◽  
E. A. Popov ◽  
I. S. Belyakova ◽  
O. S. Polunina ◽  
...  
Keyword(s):  
Heart Failure ◽  
Logistic Regression ◽  
Chronic Heart Failure ◽  
Clinical Phenotype ◽  
Left Ventricular ◽  
Regression Method ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Logistic Regression Method

Aim. To develop a mathematical equation (algorithm) to predict the development of chronic heart failure (CHF) for three years, depending on the clinical phenotype.Material and methods. Three hundred forty five patients with CHF with a different left ventricular ejection fraction (preserved, mean, low) were examined. The control group included somatically healthy individuals (n=60). In all patients, 48 parameters that most widely characterize the pathogenesis of CHF (gender-anamnestic, clinical, instrumental, biochemical) were analyzed. To isolate phenotypes, dispersive and cluster analysis was used: the hierarchical classification method and the k-means method. In the development of algorithms we used binary logistic regression method. We used ROC curve to assess the quality of the obtained algorithms.Results. We identified four phenotypes in patients with CHF: fibro-rigid, fibro-inflammatory, inflammatory-destructive, dilated-maladaptive. For the first three phenotypes, a mathematical logistic regression method was used to develop mathematical models for predicting the progression of CHF for three years, with the release of predictors for each phenotype. Belonging to the dilatedmaladaptive phenotype according to the results of the analysis is already an indicator of an unfavorable prognosis in patients with CHF.Conclusion. The developed algorithms based on the selected phenotypes have high diagnostic sensitivity and specificity and can be recommended for use in clinical practice.

scholarly journals Prognostic value of atrial fibrillation in patients with heart failure and different left ventricular ejection fraction: results of the multicenter RIF-CHF register

2021 ◽  
Vol 26 (1) ◽  
pp. 4200
Author(s):  
I. V. Zhirov ◽  
N. V. Safronova ◽  
Yu. F. Osmolovskaya ◽  
S. N. Тereschenko
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Cardiovascular Mortality ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Number Of Patients ◽  
Increased Risk

Heart failure (HF) and atrial fibrillation (AF) are the most common cardiovascular conditions in clinical practice and frequently coexist. The number of patients with HF and AF is increasing every year.Aim. To analyze the effect of clinical course and management of HF and AF on the outcomes.Material and methods. The data of 1,003 patients from the first Russian register of patients with HF and AF (RIF-CHF) were analyzed. The endpoints included hospitalization due to decompensated HF, cardiovascular mortality, thromboembolic events, and major bleeding. Predictors of unfavorable outcomes were analyzed separately for patients with HF with preserved ejection fraction (AF+HFpEF), mid-range ejection fraction (AF+HFmrEF), and reduced ejection fraction (AF+HFrEF).Results. Among all patients with HF, 39% had HFpEF, 15% — HFmrEF, and 46% — HFrEF. A total of 57,2% of patients were rehospitalized due to decompensated HF within one year. Hospitalization risk was the highest for HFmrEF patients (66%, p=0,017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15,5% vs 5,4% in other groups, p<0,001) but not ischemic stroke (2,4% vs 3%, p=0,776). Patients with HFpEF had lower risk to achieve the composite endpoint (stroke+MI+cardiovascular death) as compared to patients with HFmrEF and HFrEF (12,7% vs 22% and 25,5%, p<0,001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and selected therapy had different effects on the risk of unfavorable outcomes depending on ejection fraction group.Conclusion. Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with unfavorable outcomes. The demographic and clinical characteristics of patients with mid-range ejection fraction demonstrate that these patients need to be studied as a separate cohort.

scholarly journals CORRELATION BETWEEN VAS OPRESSIN CONCENTRATION AND CHRONIC HEART FAILURE SEVE RITY: CHARAC TERISTICS OF PA TIENTS WITH TERMINAL AND DECOMPE NSA TED HEART FAILURE

The Clinician ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 36-42
Author(s):  
E. S. Trofimov ◽  
A. S. Poskrebysheva ◽  
N. А. Shostak
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Symptoms ◽  
Left Ventricular ◽  
Stage Iii ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Significant Difference ◽  
Functional Classes

Objective: to evaluate vasopressin (VP) concentration in patients with varying severity of chronic heart failure (CHF), intensity of clinical symptoms, and decreased level of left ventricular ejection fraction (LVEF). Materials and methods. In total, 120 patients (44 males, 76 females) with CHF of varying genesis (mean age 72.12 ± 10.18 years) and 30 clinically healthy individuals (18 males, 12 females) as a control group (mean age 33.4 ± 6.23 years) were examined. All patients underwent comprehensive clinical and instrumental examination in accordance with the standards for patients with CHF. The VP level was determined using ELISA. Statistical analysis was performed using the IBM SPSS Statistics v. 23 software.Results. The patients with CHF had significantly higher blood VP levels compared to the control group (72.91 ± 53.9 pg/ml versus 6.6 ± 3.2 pg/ml respectively; p <0.01). At the same time, patients with stage III CHF had significantly lower VP levels than patients with stages IIВ and IIА (35.61 ± 21.53 pg/ml versus 71.67 ± 48.31 pg/ml and 86.73 ± 59.78 pg/ml respectively; p<0.01). A similar picture was observed for the functional classes (FC). For instance, for CHF FC II and III, the VP level was 91.93 ± 67.13 pg/ml and 77.95 ± 54.01 pg/ml respectively, while for FC IV it decreased to 50.49 ± 28.18 pg/ml (p <0.01). The VP concentration in patients who subsequently perished was significantly lower than in patients who survived (48.79 ± 26.30 pg/ml versus 79.72 ± 57.73 pg/ml; p = 0.012). Moreover, in patients with LVEF <50 %, the VP level was significantly lower than in patients with LVEF >50 % (59.43 ± 42.51 pg/ml versus 86.43 ± 62.46 pg/ml respectively; p <0.05).Conclusion. The observed significant differences in VP in patients with stage III and IV CFH can indicate depletion of neurohumoral mediators in this patient category. However, a correlation between the VP level and the level of LVEF decrease can indicate a significant difference in the role of VP in CHF pathogenesis in patients with preserved and decreased LVEF. This observation requires further research.

scholarly journals P971 The echocardiographic phenotype in patients with cardiac amyloidosis and heart failure with preserved ejection fraction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M D M Perez Gil ◽  
V Mora Llabata ◽  
A Saad ◽  
A Sorribes Alonso ◽  
V Faga ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Amyloidosis ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Apical Rotation ◽  
Dynamic Torsion

Abstract BACKGROUND New echocardiographic phenotypes of heart failure (HF) are focused on myocardial systolic involvement of the left ventricle (LV), either endocardial and/or transmural. PURPOSE. To study the pattern of myocardial involvement in patients (p) with HF with preserved left ventricular ejection fraction (pLVEF) and cardiac amyloidosis (CA). METHODS. Comparative study of 16 p with CA and HF with pLVEF, considering as cut point LVEF &gt; 50%, in NYHA class ≥ II / IV, and a control group of 16 healthy people. Longitudinal Strain (LS) and Circumferential Strain (CS) were calculated using 2D speckle-tracking echocardiography, along with Mitral Annulus Plane Systolic Excursion (MAPSE) and Base-Apex distance (B-A). Also, the following indexes were calculated: Twist (apical rotation + basal rotation, º); Classic Torsion (TorC): (twist/B-A, º/cm); Torsion Index (Tor.I): (twist/MAPSE, º/cm) and Deformation Index (Def.I): (twist/LS, º). We suggest the introduction of these dynamic torsion indexes as Tor.I and Def.I that include twist per unit of longitudinal systolic shortening of the LV instead of using TorC which is the normalisation of twist to the end-diastolic longitudinal diameter of the LV. RESULTS There were no differences of age between the groups (68.2 ± 11.5 vs 63.7 ± 2.8 years, p = 0.14). Global values of LS and CS were lower in p with CA indicating endocardial and transmural deterioration during systole, while TorC and Twist of the LV remained conserved in p with CA. However, there is an increase of dynamic torsion parameters such as Tor.I and Def.I that show an increased Twist per unit of longitudinal shortening of the LV in the CA group (Table). CONCLUSIONS In p with CA and HF with pLVEF, the impairment of LS and CS indicates endocardial and transmural systolic dysfunction. In these conditions, LVEF would be preserved at the expense of a greater dynamic torsion of the LV. Table LS (%) CS (%) Twist (º) TorC (º/cm) Tor.I (º/cm) Def.I (º/%) CA pLVEF (n = 16) -11.7 ± 4.2 17.2 ± 4.8 19.8 ± 8.3 2.5 ± 1.1 27.7 ± 13.5 -1.8 ± 0.9 Control Group (n = 15) -20.6 ± 2.5 22.7 ± 4.9 21.7 ± 6.1 2.7 ± 0.8 16.4 ± 4.7 -1.0 ± 0.3 p &lt; 0.001 &lt; 0.01 0.46 0.46 &lt; 0.01 &lt; 0.01 Dynamic Torsion Indexes and Classic Torion Parameters in pLVEF CA patients vs Control group.

Myocardial T2* in Patients with Cardiac Failure Secondary to Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3838-3838 ◽  
Author(s):  
Mark A. Tanner ◽  
John B. Porter ◽  
Mark A. Westwood ◽  
Sunil V. Nair ◽  
Lisa J. Anderson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Thalassaemia Major ◽  
Ventricular Ejection Fraction ◽  
Symptomatic Heart Failure ◽  
Increased Risk

Abstract Introduction: Myocardial iron overload is a well established cause of heart failure in a number of haematological disorders and is the leading cause of death in β-thalassaemia major (TM). Once overt heart failure develops prognosis is very poor and it would therefore be desirable to identify patients at risk, prior to the development of symptomatic heart failure. Myocardial iron can now be rapidly and reproducibly assessed using a validated cardiac magnetic resonance (CMR) T2* technique. Left ventricular ejection fraction has been demonstrated to relate to myocardial T2* (normal >20ms), and accordingly iron overloaded patients with symptomatic heart failure are likely to have a low T2* but there are no reports of the myocardial T2* level in newly presenting patients with heart failure and the threshold for increased risk is also unknown. Purpose: To establish the distribution of myocardial T2* values in patients presenting with symptomatic heart failure secondary to iron overload. Methods: Database records of CMR T2* assessments over a 5 year period were reviewed to identify iron overloaded patients presenting with heart failure. Results: 28 patients (median age 29y, 11–79) with iron overload and documented heart failure were identified. 22 patients had thalassaemia major, 3 hereditary haemochromatosis, and 3 had miscellaneous transfusion dependent anaemias. The mean myocardial T2* in all groups was 6.8+/− 2.2ms reflecting severe iron loading by clinical criteria. See figure 1. Myocardial T2* values were similar between sub-groups as follows: TM patients 6.7+/− 2.4ms, haemochromatosis 7.7ms (6.7–7.4ms), miscellaneous 6.8ms (4.8–9.1ms). Conclusion: In this database review, the patients developing heart failure secondary to iron overload all had abnormal myocardial T2*, and overall 89% of heart failure patients had values less than 10ms, which reflects severe myocardial iron loading. This data suggests a myocardial T2* <10ms should be considered a threshold for risk of heart failure (with its attendant high mortality) and such patients should be treated aggressively with increased iron chelation. It also suggests that clinical heart failure occurs nearly exclusively in patients with severe myocardial iron loading. Distribution of myocardial T2+ values in symptomatic heart failure (n=28) Distribution of myocardial T2+ values in symptomatic heart failure (n=28)

scholarly journals Novel antisense therapy targeting microRNA-132 in patients with heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Taubel ◽  
W Hauke ◽  
S Rump ◽  
J Viereck ◽  
S Batkai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Pharmacodynamic Effects ◽  
Amino Terminal ◽  
Patients With Heart Failure

Abstract Background Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. Purpose The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study. Methods Patients had left ventricular ejection fraction between ≥30% and &lt;50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) &gt;125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. Results CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers. Conclusions This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH

Interest of NT-proBNP To Detect Chemotherapy Regimens Cardiotoxicity in Patients with Hematological Malignancies: Preliminary Results.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1331-1331
Author(s):  
Gerard Dine ◽  
Vincent Genty ◽  
Said Brahimi ◽  
Nadia Ali Ammar ◽  
William Mendes ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Natriuretic Peptide ◽  
Hematological Malignancies ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Plasma Fraction ◽  
Increased Risk ◽  
The Mean

Abstract The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-based regimens are extremely effective for various hematological malignancies. The main disadvantage is cardiotoxicity particularly, in elderly patients who are frequently treated with a consequent dose reduction. The diagnosis and prognosis in patients with suspected heart failure needs a specific monitoring by echocardiography during and after chemotherapy regimens. We tested the interest of NT-proBNP as alternative marker for the detection of left ventricular dysfunction. Brain or B-type natriuretic peptide (BNP) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP) are considered to be valuable biomarkers for the detection of disease state in patients with suspected heart failure. Methods During 1 year, blood samples of 31 patients with hematological malignancies, treated with usual chemotherapy were selected on a routine basis. Patients had the diagnosis of acute leukemia (AL), B-chronic lymphocytic leukemia (B-CLL), multiple myeloma (MM) and non Hodgkin lymphoma (NHL). Venous blood was drawn in the early morning and centrifuged at 2000 g for 15 minutes. The obtained clear plasma fraction was stored at −20°C until the assay. All plasma samples were analyzed for NT-proBNP using an electro chemiluminescence immuno assay (proBNP kit Roche Diagnostics, Mannheim, Germany) on Elecsys 2010 analyser. All assays were performed blind to clinical informations on the patients. Results The mean age of the patients was 72 (range: 36–88). There were 15 men (48 %) and 16 women (52 %). Five patients were smokers (16 %) and 7 (22.6%) had cardiovascular diseases (4 hypertension, 2 heart failure, 1 pace maker). Only 3 patients had a subnormal renal function. There were 6 patients with AL, 6 with B-CLL, 11 with MM and 8 with NHL. The administered medications were divided in 3 cardio-toxicity stages: 10 (32.25 %) patients received stage 3 cardiotoxicity regimens, 10 (32.25 %) stage 2 and 11 (35.5 %) stage 1. Fourteen patients (45 %) died in relation with hematological malignancies and none in relation with heart failure. But treatment regimens have been reduced, discontinued, modified or stopped in 7 patients after heart failure diagnosis with echocardiography. All these patients received stage 2 or 3 cardiotoxicity chemotherapy regimens and 4 had prior cardiovascular diseases. The mean age was 74 (range: 66–82). Only one patient is alive in this subgroup. Considering the age and the heart state of our 31 patients, chemotherapeutic treatments need or not to be adjust. The cardiac risk at diagnosis was assessed by left-ventricular ejection fraction (VEF) measurement. We shows that NT-proBNP brings reliable results to assess that risk, with a positive correlation to the VEF. Figure Figure Conclusion Despite the limitations of this preliminary study the measurement of the NT-proBNP concentration at baseline and during cardiotoxic regimens in patients with hematological malignancies seems to be a promising method to identify patients with an increased risk of cardiovascular adverse effects for it evolves earlier than VEF and is very well correlate to VEF loss and cardiotoxicity.

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