Abstract
Aims
Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early ...discharge, preventing hospitalizations, and in palliative care. A high-concentration, pH-neutral furosemide formulation has been developed for SC administration via a small patch infusor pump. We aimed to compare the bioavailability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of a new SC furosemide formulation with conventional IV furosemide and describe the first use of a bespoke mini-pump to administer this formulation.
Methods and results
A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 mL (infused over 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with IV furosemide. The second study investigated the same SC furosemide preparation delivered by a patch infusor in patients hospitalized with HF. Primary outcome measures were treatment-emergent adverse events, infusion site pain, device performance, and PK measurements.
The absolute bioavailability of SC furosemide in comparison to IV furosemide was 112%, resulting in equivalent diuresis and natriuresis. When SC furosemide was administered via the patch pump, there were no treatment-emergent adverse events and 95% of participants reported no/minor discomfort at the infusion site.
Conclusion
The novel preparation of SC furosemide had similar bioavailability to IV furosemide. Administration via a patch pump was feasible and well tolerated.
Graphical Abstract
Graphical Abstract
After reading this article the reader should be familiar with: Current guidelines for implantable cardioverter defibrillator (ICD) use post myocardial infarction (MI) and ischaemic cardiomyopathy. ...Primary prevention ICD guidelines. Secondary prevention ICD guidelines. Non-sustained ventricular tachycardia in patients post MI and the use of ICDs. Programming ICDs.
Purpose of Review
Treatment with a defibrillator can reduce the risk of sudden death by terminating ventricular arrhythmias. The identification of patient groups in whom this function reduces overall ...mortality is challenging. In this review, we summarise the evidence for who benefits from a defibrillator.
Recent Findings
Recent evidence suggests that contemporary pharmacologic and non-defibrillator device therapies are altering the potential risks and benefits of a defibrillator.
Summary
Who benefits from a defibrillator is determined by both the risk of sudden death and the competing risk of other, non-sudden causes of death. The balance of these risks is changing, which calls into question whether historic evidence for the use of defibrillators remains robust in the modern era.
Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated ...further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).
Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization.
Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.
Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical ...studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems.
Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues.
Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T).
Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement.
ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.
Abstract Heart failure (HF) is a clinical syndrome characterized by dyspnoea, fatigue and fluid retention accompanied by objective evidence of cardiac dysfunction. The syndrome affects around 2% of ...the general population, affecting men more commonly than women (under the age of 80), with incidence and prevalence rising steeply with age. HF causes substantial morbidity and reduced life expectancy, and coronary artery disease accounts for two-thirds of cases in developed countries. Investigation is important to ascertain the diagnosis, identify the aetiology (which might be reversible) and give some indication of prognosis. Currently, more than 40% of people die within 18 months of a new diagnosis of HF. Treatment has been revolutionized by large randomized-controlled clinical trials studying the effects of antagonism of the renin–angiotensin–aldosterone and sympathetic nervous systems, and, more recently, the effects of device therapy. Cardiac transplantation remains an option for patients who are severely symptomatic (and at high risk) despite optimal medical and appropriate device therapy.
Abstract
Background:
Glomerular filtration rate (GFR) has major prognostic implications in heart failure. Our objective was to validate the MDRD prediction equations for GFR in patients with advanced ...heart failure, and to compare their predictive performance to that of the Cockcroft-Gault (CG) equation.
Methods:
We analysed GFR in 45 patients referred for heart transplantation evaluation. 51Cr-EDTA-measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations, CG equation using actual body weight, and ideal body weight. Regression analyses and Pearson correlations were performed, and Bland and Altman plots were drawn. ROC curves were obtained to illustrate each equation's ability to predict a GFR less than 60 ml/min/1.73 m2 (moderate renal impairment).
Results:
Patients had a mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR was 46.9±17.2 ml/min/1.73 m2. The MDRD1 equation provided the best predictive model (narrowest limits of agreement; r=0.766, p<0.001), and the highest performance in predicting a GFR less than 60 ml/min/1.73 m2 (area under curve: 0.901).
Conclusions:
MDRD equations, especially MDRD1, adequately predict GFR in advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has higher performance in predicting a GFR less than 60 ml/min/1.73 m2.
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