atrial-natriuretic-factor and Heart-Failure--Systolic

Systolic heart failure (HF) is a progressive disorder that often begins with asymptomatic left ventricular (LV) systolic dysfunction and culminates in symptoms from fluid overload and poor end-organ perfusion. The progression to symptomatic HF is accompanied by marked activation of neurohormonal and cytokine systems, as well as a series of adaptive LV anatomical and functional changes, collectively referred to as LV remodelling. However, the mechanisms underlying symptom appearance have not been delineated and the weight of experimental and clinical evidence suggests that the development of symptomatic HF occurs independently of the haemodynamic status of the patient. The left atrium is a muscular chamber strategically located between the left ventricle and the pulmonary circulation with important mechanical function (modulation of LV filling), which is closely coupled with its endocrine (atrial natriuretic peptide synthesis and secretion) and regulatory (contribution to the control of sympathetic activity and vasopressin release) functions. In this narrative review we provide evidence supporting the concept that left atrial dilation and systolic dysfunction (left atrial remodelling) contributes to the progression of asymptomatic LV dysfunction to chronic symptomatic systolic HF as it is a prerequisite for the development of the pulmonary congestion and marked neuronhormoral activity that characterize the symptomatic state.

Topics: Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Disease Progression; Heart Failure, Systolic; Humans; Pressoreceptors; Ventricular Dysfunction, Left; Ventricular Remodeling

We have previously reported that asymptomatic systolic heart failure (HF) is characterized by an impaired renal response to volume expansion due to lack of activation of urinary cGMP which is corrected by subcutaneous (SQ) BNP. In the current study, we sought to define the cardiorenal response to intravascular volume expansion after 12 weeks of SQ BNP therapy.. We utilized a double-blinded, placebo-controlled study to compare 12 weeks of twice-daily SQ BNP 10 µg/kg (n = 22) or placebo (n = 12) in asymptomatic systolic HF. Subjects underwent two study visits: baseline and after 12 weeks of therapy. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular volume expansion. The primary endpoint was change in urinary sodium excretion in response to volume expansion at 12 weeks, and we observed a greater increase in urinary sodium excretion [166 (77, 290) vs. 15 (-39, 72) mEq/min; P = 0.02] with SQ BNP treatment vs. placebo. Secondary endpoints included change in urine flow and glomerular filtration rate (GFR) in response to volume expansion at 12 weeks. We observed a significant increase in urine flow (P < 0.01) and trend for differential response in GFR (P = 0.08) with SQ BNP treatment vs. placebo.. Among patients with asymptomatic systolic HF, twice-daily SQ BNP therapy improved the cardiorenal response to volume expansion at 12-week follow-up. Further studies are warranted to determine if these beneficial physiological observations with chronic natriuretic peptide administration translate into a delay in the progression to symptomatic HF.

Topics: Aged; Asymptomatic Diseases; Atrial Natriuretic Factor; Cyclic GMP; Double-Blind Method; Echocardiography; Female; Fluid Therapy; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Infusions, Subcutaneous; Kidney; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Sodium

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers.. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers.. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders.. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency; Troponin I

Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.. A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up.. Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54).. Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Disease Progression; Echocardiography; Endothelin-1; Female; Glycopeptides; Heart Failure, Systolic; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prognosis; Protein Precursors; Risk Assessment; Stroke Volume

To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).. It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF.. Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed.. Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions).. Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Neostigmine; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Troponin T

A 64-year-old man was admitted to our hospital with new-onset acute decompensated heart failure (ADHF). He had left ventricular systolic dysfunction and chronic atrial fibrillation with a rapid ventricular response. Initial treatment with low-dose recombinant human atrial natriuretic peptide (hANP) alone and no loop diuretics had an immediate effect on ADHF and left ventricular systolic dysfunction. This case demonstrates that low-dose hANP (0.01 microg/kg/min) monotherapy can be safe and effective for ADHF, with no loop diuretics being required during hospitalization. However, clinical trials will be needed to further evaluate the acute efficacy and safety of hANP monotherapy in patients with ADHF.

Topics: Acute Disease; Atrial Natriuretic Factor; Heart Failure, Systolic; Humans; Male; Middle Aged; Radiography; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Ventricular Dysfunction, Left

Serum oxidative stress (OS) level has an important role in the inflammatory process of heart failure.. The study was designed to analyze serum OS levels in chronic heart failure (HF) patients and to examine the relation between OS levels and other clinical and prognostic parameters of HF.. We studied 82 consecutive chronic symptomatic HF patients with systolic LV dysfunction (ejection fraction <45%). The serum OS level was determined using thermochemiluminescence assay. We compared the serum OS levels with patients' clinical and prognostic parameters.. Higher serum OS levels were associated with higher New York Heart Association class (P = .01), worse renal function (serum urea, creatinine, and creatinine clearance) (P<.001) and higher serum levels of hs-C-reactive protein and N-terminal pro brain natriuretic peptide (P = .001, P<.001, respectively).. In chronic systolic HF patients, high serum OS levels correlate with advanced disease and known markers of poor prognosis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure, Systolic; Humans; Male; Oxidative Stress; Predictive Value of Tests; Prognosis; Protein Precursors; Severity of Illness Index

Midregional pro-atrial natriuretic peptide (MR-proANP) was assessed for the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power compared with B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (HF).. MR-proANP is a biologically stable natriuretic peptide measured by a recently developed assay, with potential advantages over conventional natriuretic peptides such as BNP and NT-proBNP.. We measured MR-proANP, BNP, and NT-proBNP in 797 patients with chronic HF.. All 3 natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [95% confidence interval (CI): 0.753 to 0.844]), BNP (0.803 [95% CI: 0.757 to 0.849]), and NT-proBNP (0.730 [95% CI: 0.681 to 0.778]). During a median observation time of 68 months, 492 (62%) patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables. Proportion of explained variation showed that NT-proANP (4.36%) was a significantly stronger predictor of death than both NT-proBNP (2.47%, p < 0.0001) and BNP (2.42%, p < 0.0001).. Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

Topics: Atrial Natriuretic Factor; Confidence Intervals; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Risk Factors; ROC Curve; Sensitivity and Specificity; Ventricular Dysfunction, Left

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF.. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis.. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017).. There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; E-Selectin; Electrocardiography; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Humans; Male; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index; Stroke Volume; Ventricular Function, Left; von Willebrand Factor