Intravenous diuretic administration in the home environment

Chronic heart failure is a condition associated with ageing, affecting 1–2% of the adult population, raising to 70% of the adult population over 70 years of age. Diuretics are often the first-line treatment for patients with symptomatic heart failure, not just oedema. Traditionally, intravenous (IV) diuretic therapy has been administered only in hospitals. In 2012, the British Heart Foundation ran a pilot study investigating the effectiveness of IV diuretic administration within the home. Since then, there has been an increase in these services. This article examines the advantages and disadvantages of this service, whether community nurses are best placed to deliver this, and what the benefits to the patient might be.

Understanding donor preferences to optimise charity marketing and communications

This case study explores how a leading charity, the British Heart Foundation (BHF), used research to ensure that the focus of its marketing and communications contributed to a story that people found engaging and were compelled to support. Amongst some staff, there was a view that the methodology of some of the BHF’s previous market research was not robust enough and that studies often lacked the quantitative data needed to develop marketing and communication strategies with confidence. Behavioural economics shows that there is usually a disconnect between what people say they will do and what they do in real life, the BHF wanted to develop a methodology that would interrogate this paradox. In doing so, it hoped to identify the areas of its work the public found most engaging and which would encourage people to support them. This insight would then be used to inform their new marketing communications plans. This note explains what the BHF learnt from involving explicit and implicit testing via a mix of qualitative and quantitative techniques.

Reflections of research: united colours of myocytes

The annual image competition, Reflections of Research, provides a glimpse into the cutting-edge heart and circulatory research funded by the British Heart Foundation

Plasma extracellular vesicles modulate immune cell gene expression following myocardial infarction

Background Myocardial infarction (MI) induces activation of immune cells and alters their gene expression en route to the injured myocardium but the underlying mechanisms coordinating immune cell programming following MI remain unknown. Plasma extracellular vesicle (EV) numbers are elevated in MI, correlate with the extent of myocardial injury and mobilises immune cells from the splenic reserve to peripheral blood. Here, we describe the role of plasma EV-microRNAs (miRs) in the modulation of peripheral blood mononuclear cell (PBMC) transcriptomes post-MI. Methods PBMCs were exposed to plasma EVs followed by whole transcriptome RNA-sequencing. Plasma EVs were isolated by size-exclusion chromatography and ultra-centrifugation (2 hours at 120,000 x g) from patients presenting with ST-segment elevation MI (STEMI) (N=9) and non-STEMI (NSTEMI) (N=11) control patients. Plasma EVs were characterised by western blot and Nanoview for EV markers CD9 and CD63, transmission electron microscopy (TEM) for morphology and Nanoparticle Tracking Analysis for size and concentration. High sensitive C-reactive protein (hs-CRP) and PCSK9 were determined in plasma by ELISA and compared to plasma EV number using Pearson's correlation. Plasma EV-miRs were measured by Agilent microarray and miR-mRNA putative targets assessed by TargetScanHuman. Results Plasma EVs were positive for EV markers CD9 and CD63, displayed typical EV morphology by TEM and had a heterogeneous size and concentration distribution profile as determined by Nanoparticle Tracking Analysis. Plasma EV number correlated significantly with hs-CRP at presentation (R2= 0.20 and P<0.05). miRNA array analysis revealed STEMI plasma-EVs contained significantly more miR-4487 (P<0.001), miR-6511b-5p (P<0.001), miR-4508 (P<0.001) vs NSTEMI control plasma-EVs at the time of injury. STEMI-plasma-EVs induced differential gene expression in PBMCs vs. NSTEMI-control-plasma-EVs. Gene set enrichment analysis (GSEA) showed STEMI-plasma-EVs upregulated pro-inflammatory pathways including: interferon-α (IFN-α) (P<0.01), IFN-γ (P<0.01), tumour necrosis factor-α (TNF-α) (P<0.01) and interleukin-6 (IL-6)-STAT3 signalling of the acute phase response (P<0.05). miR-4487 (P<0.001) and miR-6511-5p (P<0.05) predicted mRNA targets were significantly enriched in PBMC transcriptomes following treatment with STEMI plasma-EVs. Conclusions Plasma EVs mediating immune cell transcriptional programming following MI by promoting inflammatory pathways in PBMCs is a novel finding. Targeting PBMCs with EVs may allow modulation of the immune response following myocardial injury, to perturb inflammatory immune mediated damage following ischaemic injury. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation Centre of Research Excellence Awards, British Heart Foundation Project Grant, Novo Nordisk Fonden the Tripartite Immunometabolism Consortium and Wellcome Institutional Strategic Support Fund (ISSF)

Genetic background, sex, age and pacing cycle length affect left atrial electrophysiology in Langendorff-perfused isolated murine hearts

Background Studying cardiac electrophysiology in isolated perfused beating murine hearts is a well-established method. The ranges of normal values for left atrial (LA) action potential durations (LA-APD), activation times (LA-AT) and effective refractory periods (atrial ERP) in murine wildtype (WT) are not well known. Purpose This study aimed to establish reference values for LA-APD, LA-AT and atrial ERP and to identify the influence of genetic background, sex and age on these electrophysiological parameters in WT mice. Method We combined results from isolated beating heart Langendorff experiments carried out in WT mice between 2005 and 2019 using an octopolar catheter inserted into the right atrium and a monophasic action potential electrode recording from the LA epicardium. Electrophysiological parameters (LA-APD at 50%, 70%, 90% repolarization (APD50, APD70, APD90), LA-AT and atrial ERP) at different pacing cycle lengths (PCL) were summarized. We analysed effects of PCL, genetic background, age, gender, heart weight to body weight ratio (HW/BW), LA weight to body weight ratio (LAW/BW) as well as coronary flow and temperature as experimental conditions. Results Electrophysiological parameters from 222 isolated hearts (114 female, mean age 6.6±0.25 months, range 2.47–17.7 months) of different backgrounds (77 C57BL/6, 23 FVB/N, 33 MF1, 69 129/Sv and 20 Swiss agouti) were combined. Coronary flow rate, flow temperature and start of isolation to cannulation time were constant experimental conditions over the timespan of experiments. LA-APD was longer while LA-AT decreased with longer PCL throughout all genetic backgrounds (Figure 1A). Genetic background showed strong effects on all electrophysiological parameters. LA-APD70 and atrial ERP were significantly shorter in Swiss agouti background compared to others. LA-APD70 was also significantly prolonged in 129/Sv background compared to MF1 (Figure 1B). LA activation was delayed in 129/Sv compared to other backgrounds (Figure 1C). Atrial ERP was longer in FVB/N compared to other backgrounds. Atrial ERP was also significantly prolonged (+ 3.4 ms, + 13.5%) in female mice compared to males (Figure 1D). Age effects were compared in groups. Atrial ERP was significantly longer in mice younger than 3 months compared to older mice (Figure 1E). Conclusion This dataset summarises left atrial electrophysiological parameters in the beating mouse heart and can serve as a reference for design and interpretation of electrophysiological experiments in murine models of commonly used genetic backgrounds. We demonstrate that PCL, genetic background, age and gender affect atrial electrophysiological parameters. Awareness of these will support successful experimental design. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This work was partially supported by the European Commission (grant agreements no. 633196 [CATCH ME]) to LF and PK, Deutsche Forschungsgemeinschaft DFG FA413, British Heart Foundation (FS/13/43/30324 to LF and PK; AA/18/2/34218 to LF and PK).The Institute of Cardiovascular Sciences has received the British Heart Foundation (BHF) Accelerator Award (AA/18/2/34218). JO has received financial support for abroad studies within his scholarship of the Studienstiftung des deutschen Volkes (German Academic Scholarship Foundation).

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

BackgroundThe medium-term effects of Coronavirus disease (COVID-19) on multiple organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.MethodsFifty-eight COVID-19 patients post-hospital discharge and 30 comorbidity-matched controls were prospectively enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments.FindingsAt 2-3 months from disease-onset, 64% of patients experienced persistent breathlessness and 55% complained of significant fatigue. On MRI, tissue signal abnormalities were seen in the lungs (60%), heart (26%), liver (10%) and kidneys (29%) of patients. COVID-19 patients also exhibited tissue changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domain relative to controls. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance (405±118m vs 517±106m in controls, p<0.0001) were significantly reduced in patients. The extent of extra-pulmonary MRI abnormalities and exercise tolerance correlated with serum markers of ongoing inflammation and severity of acute illness. Patients were more likely to report symptoms of moderate to severe anxiety (35% versus 10%, p=0.012) and depression (39% versus 17%, p=0.036) and a significant impairment in all domains of quality of life compared to controls.InterpretationA significant proportion of COVID-19 patients discharged from hospital experience ongoing symptoms of breathlessness, fatigue, anxiety, depression and exercise limitation at 2-3 months from disease-onset. Persistent lung and extra-pulmonary organ MRI findings are common. In COVID-19 survivors, chronic inflammation may underlie multiorgan abnormalities and contribute to impaired quality of life.FundingNIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

Reflections of research: life-altering algae

The annual image competition, Reflections of Research, provides a glimpse into the cutting-edge heart and circulatory research funded by the British Heart Foundation.