Ibopamine in heart failure. Efficacy and safety in clinical and experimental studies.

The aim of this thesis was to assess t e role of ibopamine, in the treatment of patients with heart failure. Ibopamine is an orally active dopamine agonist which has beneficial hemodynamic and neurohumoral effects. In the 10 Appendices both clinical and experimental studies are reported that were designed to examine the efficacy and safety of ibopamine. The clinical studies, which constitute Appendices 1-7, were conducted in patients with mild, moderate and severe heart failure. In these studies, we evaluated the influence of ibopamine on hemodynamics (Appendices 3,4,6), renal function (Appendices 5,6), neurohumoral parameters (Appendices 1,2,3), arrhythmias and electrophysiology (Appendices 1,3), exercise tolerance (Appendices 1,2), signs and symptoms of heart failure and side-effects (Appendices 1,5,7). ... Zie: Summary and conclusion

The objective burden in partners of heart failure patients; development and initial validation of the Dutch objective burden inventory

BACKGROUND: Measures on objective caregiver burden in partners of Heart Failure patients are hardly available and never include HF specific aspects. AIM: The main objective of our study was to develop an inventory that assesses the objective caregiver burden of partners of HF patients, including the full range of potential care giving demands. METHODS: To develop the inventory, six domains of caregiving demands were identified. Items for the domains were generated from the literature, expert opinion and existing scales. The original 50-items self-report inventory was administered to 321 partners of HF patients. Demographic data of HF partners were collected by questionnaire. Clinical data of the HF patients were collected by chart review. RESULTS: Component analysis led to exclusion of 12 original items and to a meaningful four-factor solution with a total explained variance of 43%. The components reflected four different kinds of care giving tasks; personal care, emotional, motivational and practical (treatment related) support. They demonstrated good internal consistency and initial validity was supported by a pattern of meaningful associations with external variables. CONCLUSION: The Objective Burden Inventory is a promising inventory to assess objective care giving tasks performed by HF partners, including emotional and motivational support. It provides information on the caregiver situation that may help to develop effective intervention

Factor Xa Inhibition with Apixaban Does Not Influence Cardiac Remodelling in Rats with Heart Failure After Myocardial Infarction

Background: Heart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). We tested the hypothesis that anticoagulation with the factor Xa (FXa) inhibitor apixaban would ameliorate cardiac remodelling in rats with HF after myocardial infarction (MI). Methods and Results: Male Sprague-Dawley rats were either subjected to permanent ligation of the left ascending coronary artery (MI) or sham surgery. The MI and sham animals were randomly allocated to treatment with placebo or apixaban in the chow (150 mg/kg/day), starting 2 weeks after surgery. Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac hypertrophy were assessed in the left ventricle (LV). Apixaban resulted in a fivefold increase in anti-FXa activity compared with vehicle, but no overt bleeding was observed and haematocrit levels remained similar in apixaban- and vehicle-treated groups. After 10 weeks of treatment, LV ejection fraction was 42 ± 3% in the MI group treated with apixaban and 37 ± 2 in the vehicle-treated MI group (p > 0.05). Both vehicle- and apixaban-treated MI groups also displayed similar degrees of LV dilatation, LV hypertrophy and interstitial fibrosis. Histological and molecular markers for pathological remodelling were also comparable between groups, as was the activity of signalling pathways downstream of the PAR1 receptor. Conclusion: FXa inhibition with apixaban does not influence pathological cardiac remodelling after MI. These data do not support the use of FXa inhibitor in HF patients with the aim to amend the severity of HF. [Figure not available: see fulltext.]

Natriuresis guided therapy in acute heart failure:rationale and design of the Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial

AIMS: Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis guided therapy in patients with acute HF improves natriuresis and clinical outcomes. METHODS: The Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-hour urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-hour sodium excretion, length of hospital stay, and percentage change in N-terminal pro Brain Natriuretic Peptide at 48 and 72 hours. CONCLUSION: The PUSH-AHF study will investigate whether natriuresis guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF. This article is protected by copyright. All rights reserved

Natriuresis-guided diuretic therapy in acute heart failure:a pragmatic randomized trial

Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were &lt;70 mmol l -1. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 . </p