Acute Chronic Congestive Heart Failure Research Articles

Aqueous fish extract increases survival in the mouse model of cytostatic toxicity

BackgroundTreatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX.MethodsA LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (~25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality.ResultsMortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect in vitro.ConclusionThe aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.

Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: A ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy

Obesity is associated with lower B-type natriuretic peptide (BNP) levels in healthy individuals and patients with chronic congestive heart failure (CHF). Neither the mechanism of natriuretic peptide suppression in the obese patient nor whether obesity affects natriuretic peptide levels among patients with acute CHF is known. The associations of amino-terminal pro-BNP (NT-proBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute CHF. Multivariable regression analyses were performed to identify factors independently related to NT-proBNP and BNP levels. Across clinical strata of normal (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2) patients, median NT-proBNP and BNP levels decreased with increasing BMI (both P values < .001). In multivariable analyses adjusting for covariates known to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and BNP remained ( P < .05 for both). Using a cut point of 900 pg/mL, NT-proBNP was falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m2) and 15% in obese patients (> or =30 kg/m2). Using the standard cut point of 100 pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight and obese patients. The assays for NT-proBNP and BNP exhibited similar overall sensitivity for the diagnosis of CHF. When adjusted for relevant covariates, compared with normal counterparts, overweight and obese patients with acute CHF have lower circulating NT-proBNP and BNP levels, suggesting a BMI-related defect in natriuretic peptide secretion. NT-proBNP fell below the diagnostic cutoff for CHF less often than BNP in overweight and obese individuals; however, when used as a diagnostic tool to identify CHF in such patients, both markers may have reduced sensitivity.

Prognostic value of cardiac troponin T in patients with both acute and chronic stable congestive heart failure: comparison with atrial natriuretic peptide, brain natriuretic peptide and plasma norepinephrine

Background The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population. Methods Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death. Results cTn-T (≥0.03 μg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (≥0.03 μg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01). Conclusions BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the “real world” situation.

Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure

ObjectivesThe goal of this research was to test the hypothesis that plasma angiopoietin (Ang-1), its soluble receptor tie-2, and Ang-2 levels would be abnormal in patients with acute and chronic congestive heart failure (CHF) when compared with healthy controls. BackgroundIncreased plasma vascular endothelial growth factor (VEGF) in CHF is suggestive of excess angiogenesis—possibly driven by tissue hypoxia. However, other growth factors also have a major role in angiogenesis, such as those of the angiopoietin family (e.g., Ang-1, which exerts its activity via its receptor, tie-2, and Ang-2). MethodsWe recruited 39 patients with acute CHF (mean age 67 ± 10 years), 40 patients with chronic CHF (mean age 63 ± 9 years), and 17 healthy controls (mean age 67 ± 7 years), all in sinus rhythm. Citrated plasma was analyzed for Ang-1, Ang-2, tie-2, and VEGF by enzyme-linked immunosorbent assay. ResultsAngiopoietin-2 (p < 0.001), tie-2 (p < 0.05), and VEGF (p < 0.05) levels were all higher in acute CHF compared with controls. The Ang-2 levels were higher in acute CHF compared with chronic CHF (p < 0.001), but there were no significant differences in Ang-1 levels between the groups. The principal significant correlations were between Ang-2 and tie-2 (Spearman, r = 0.407; p < 0.0001) and between Ang-2 and ejection fraction (r = −0.241, p = 0.043). Although only marginally raised, levels of VEGF correlated with both Ang-2 (r = 0.468, p < 0.001) and tie-2 (r = 0.569, p < 0.001). ConclusionsWe have demonstrated abnormal levels of Ang-2 and tie-2, but normal Ang-1, in both CHF patients. These abnormalities may, alongside VEGF, indicate a role for these angiogenic factors in the pathophysiology of CHF.

A multidisciplinary, home based intervention reduced deaths and readmissions in patients with chronic congestive heart failure

(1999) Lancet 354, 1077. Stewart S, Marley JE, Horowitz JD. . Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a...

The addition of a home visit by a cardiac nurse to usual multidisciplinary care reduced deaths and readmissions in patients with chronic congestive heart failure

Stewart S, Marley JE, Horowitz JD . Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study. Lancet1999...

Evidence-based medicine and ACE inhibition.

The use of angiotensin-converting enzyme (ACE) inhibitors has been generally beneficial in the treatment of many clinical conditions characterized by a significant degree of cardiovascular and renal involvement. Most of the available data on the benefits of ACE inhibitors have come from well-conducted large clinical trials that have provided much information supporting the use of ACE inhibitors, in agreement with the basic principles of evidence-based medicine. In particular, ACE inhibitors improve blood pressure control in patients with hypertension and have proved to be beneficial in patients with left ventricular (LV) systolic dysfunction and chronic congestive heart failure (CHF). Improved survival rates after the use of ACE inhibitors have been also demonstrated in patients with acute myocardial infarction (MI), whether or not the condition is complicated by acute CHF. More recently, some studies have demonstrated the ability of ACE inhibitors (particularly fosinopril) to prevent the long-term development of CHF in patients treated acutely during MI and without baseline LV dysfunction. ACE inhibitors appear to improve the long-term prognosis of patients with coronary artery disease (CAD) and to reduce the occurrence of re-infarction, as demonstrated in the Studies of Left Ventricular Dysfunction (SOLVD) trial and the Survival and Ventricular Enlargement study (SAVE). Finally, a protective role for ACE inhibitors has been reported even in diabetic hypertensive patients, in whom such agents can significantly reduce the occurrence of major cardiovascular events (CAD and stroke) with a pattern that is largely independent of blood pressure control and is not observed with the use of calcium antagonists. These data confirm the strong involvement of the renin-angiotensin system in the pathophysiology of vascular diseases and strongly support the role of ACE inhibitors as drugs for present and future therapy.

Possibility of downregulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure.

High levels of endogenous atrial natriuretic peptide (ANP) are thought to compensate the condition of patients with heart failure by reducing preload and afterload. However, recent reports have indicated that a high plasma ANP level is a prognostic predictor in patients with heart failure. Therefore, the role of endogenous ANP has not been clearly established in patients with heart failure. The plasma ANP and cGMP levels were determined in the femoral artery and the femoral vein of 97 patients with chronic congestive heart failure (CHF). The plasma ANP level decreased significantly, whereas the plasma cGMP levels increased significantly from the femoral artery to the femoral vein. Among patients with mild CHF (n = 52), the plasma cGMP level correlated with the ANP level, and the calculated ANP extraction level also correlated with the calculated cGMP production in the peripheral circulation (r = 0.70, p < 0.001). In contrast, these correlations were not found in patients with severe CHF (n = 45). Among these patients, the plasma cGMP levels seemed to reach a plateau despite high levels of plasma ANP, and the molar ratio of cGMP production to ANP extraction in the peripheral circulation was significantly lower than in patients with mild CHF (36.7 +/- 9.5 versus 183 +/- 17, p < 0.001). In patients with acute severe CHF (n = 9) and those with mild CHF, patients who were administered exogenous ANP, plasma cGMP levels increased in proportion to those of plasma ANP without saturation. These results indicate that downregulation of ANP receptors coupled to guanylate cyclase may occur in the peripheral vascular beds of patients with chronic severe CHF.

Hemodynamic effects of high dose naloxone in congestive heart failure

In humans, the salutary properties of the opioid agonist morphine in the treatment of acute pulmonary edema and chronic congestive heart failure (CHF) are well known. These are thought to be the result of vasodilatation and concomitant afterload reduction caused by binding with central 1–3 and peripheral 4 opioid receptors. This clinical pharmacologic observation suggests that the endogenous opioid peptides have the potential to contribute favorably to the regulation of the hemodynamic response to acute and chronic CHF. However, contrary to the expectation based on the therapeutic efficacy of morphine, the endogenous opioids may actually exert a deleterious effect on the hemodynamic response to cardiogenic shock and the syndrome of CHF. 5,6 Case reports describe dramatic hemodynamic improvement after the administration of low doses of the narcotic antagonist naloxone to patients suffering cardiogenic shock in the setting of an acute myocardial infarction. 7 The hemodynamic effects of therapeutic (0.02 mg/kg) or maximal (1 mg/kg) doses of naloxone have not been studied in patients with CHF. In normal volunteers naloxone at doses up to 1 mg/kg causes little alteration in blood pressure, heart rate or respiration. 8 If endogenous opioids do play a role in the regulation of the hemodynamic response to chronic myocardial failure, alterations in resting hemodynamics after the administration of an opioid antagonist to patients with CHF should be identified. We report the first study defining the hemodynamic consequences of a graded naloxone infusion in patients with CHF.