Ify Mordi

Targeting Metabolic Modulation and Mitochondrial Dysfunction in the Treatment of Heart Failure

Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability. Therefore, the development of potential metabolic therapeutics has commenced including trimetazidine, ranolazine and perhexiline, as well as specific mitochondrial-targeting pharmaceuticals, such as elamipretide. Large randomised controlled trials are required to confirm the role of metabolic-modulating drugs in the treatment of heart failure, but early studies have been promising in their possible efficacy for the management of heart failure in the future.

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer-reviewed journal. Trial registration number NCT03226457; Pre-results.

Iron Therapy in Heart Failure: Ready for Primetime?

There is an increasing awareness of the prevalence of iron deficiency (ID) in patients with heart failure (HF) and its contributory role in the morbidity and mortality of HF. It is important to note that many HF patients have ID without being anaemic, hence it is vital to screen for ID even in patients with haemoglobin within the normal laboratory range. This review summarises the pathophysiology and epidemiology of ID in HF before discussing the evidence for iron replacement therapy in HF patients. Finally, it discusses the ongoing large outcome trials evaluating iron replacement in HF.

Heart failure in the outpatient versus inpatient setting: findings from the BIOSTAT-CHF study: HF outpatients versus inpatients

Patients with symptomatic heart failure (HF) require additive therapies and have a poor prognosis. However, patient characteristics and clinical outcome between HF patients treated in the outpatient setting vs. those who are hospitalized remain scarce.

Efficacy of noninvasive cardiac imaging tests in diagnosis and management of stable coronary artery disease

The aim of this review was to discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20 years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In this review, we examine the current state-of-the-art in noninvasive imaging to provide an up-to-date analysis of current investigation and management options.

007 Comprehensive echocardiographic and cardiovascular magnetic resonance evaluation differentiates between patients with heart failure with preserved ejection fraction, hypertensive patients and healthy controls and identifies those with reduced exercise capacity on cardiopulmonary exercise testing

Objectives The aim of this study was to investigate the utility of a comprehensive imaging protocol including echocardiography and cardiovascular magnetic resonance (CMR) in the diagnosis and differentiation of hypertensive heart disease and heart failure with preserved ejection fraction (HFpEF). Background Hypertension is present in up to 90% of patients with HFpEF and is a major aetiological component. Despite current recommendations and diagnostic criteria for HFpEF, no non-invasive imaging technique has as yet shown the ability to identify any structural differences between patients with hypertensive heart disease and HFpEF. Methods We conducted a prospective cross-sectional study of 112 well-characterised patients (62 with HFpEF, 22 with hypertension and 28 healthy controls). All patients underwent cardiopulmonary exercise and biomarker testing and an imaging protocol including echocardiography with speckle tracking analysis and CMR including T1 mapping pre- and post-contrast. Results Echocardiographic global longitudinal strain (GLS) and extracellular volume (ECV) measured by CMR were the only variables able to independently stratify between the three groups of patients. ECV was the best technique for differentiation between hypertensive heart disease and HFPEF (AUC 0.88; GLS AUC 0.78, p<0.001 for both). Using ECV, an optimal cut-off of 31.2% gave 100% sensitivity and 75% specificity. ECV was significantly higher and GLS was significantly reduced in subjects with reduced exercise capacity (lower peak VO2 and higher VE/VCO2). Conclusions Both GLS and ECV are able to independently discriminate between hypertensive heart disease and HFpEF and identify patients with prognostically significant functional limitation. ECV is the best diagnostic discriminatory marker of HFpEF and could be used as a surrogate end-point for therapeutic studies.

P20 A comparison of the cardiovascular effects of empagliflozin and liraglutide: a systematic review and meta-analysis

Background With the recent publication of the EMPA-REG Outcome and LEADER trials, we now have two diabetes drugs which improve cardiovascular outcome. The aim of this study was to conduct a meta-analysis of the CV effects of empagliflozin and liraglutide to provide a better understanding of the mechanisms that may have led to these positive results. Methods A systematic search was carried out. RCT of empagliflozin and liraglutide against both placebo and active comparator were included. In total 52 studies were included, involving 33,500 patients in total (empagliflozin: 14,415 patients; liraglutide: 19,085 patients). Various CV parameters were compared. Meta-analysis was conducted using REVMAN 5.3. Results Both empagliflozin and liraglutide caused a significant reduction in weight and systolic blood pressure. Empagliflozin also caused a significant drop in BP. There was a significant increase in heart rate with liraglutide. Liraglutide caused a significant decrease in lipid parameters whereas empagliflozin caused a significant increase in lipids. Conclusions The results of this meta-analysis might provide some explanation for the cardiovascular effects seen in LEADER and EMPA-REG. Empagliflozin’s reduction in weight and BP may partially explain its beneficial effects on heart failure, while the increase in cholesterol may also explain why there was no significant difference in MI and a trend to increased stroke risk. The reduction in cholesterol and blood pressure caused by liraglutide may explain the reduction in MI, however this is offset by an increase in heart rate which may explain the lack of benefit in heart failure outcomes.