A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency.

Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l).

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

Background: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics.

Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo P magnetic resonance spectroscopy study.

Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID.

Methods And Results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers.

Tissue Doppler-Derived Left Ventricular Systolic Velocity Is Associated with Lethal Arrhythmias in Cardiac Device Recipients Irrespective of Left Ventricular Ejection Fraction.

Background: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF).

Effect of ferric carboxymaltose on calculated plasma volume status and clinical congestion: a FAIR-HF substudy.

Aims: Iron deficiency worsens symptoms, quality of life, and exercise capacity in chronic heart failure (CHF) and might do so by promoting fluid retention. We assessed whether iron repletion improved congestion in CHF and appraised the prognostic utility of calculated plasma volume status (PVS), a novel index of congestion, in the FAIR-HF data set.

Methods And Results: In FAIR-HF, 459 iron deficient CHF patients were randomized to intravenous ferric carboxymaltose (FCM) or saline and assessed at 4, 12, and 24 weeks.

Cardioprotective Effect of the Mitochondrial Unfolded Protein Response During Chronic Pressure Overload.

Background: The mitochondrial unfolded protein response (UPR) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPR in the heart is unclear.

Calculated plasma volume status and outcomes in patients undergoing coronary bypass graft surgery.

Objectives: Congestion is associated with worse outcomes in critically ill surgical patients but can be difficult to quantify noninvasively. We hypothesised that plasma volume status (PVS), estimated preoperatively using a validated formula that enumerates percentage change from ideal plasma volume (PV), would provide incremental prognostic utility after coronary artery bypass graft (CABG) surgery.

Methods: In this retrospective cohort study, patients who underwent CABG surgery (1999-2010) were identified from a prospectively collected database.

The impact of catheter ablation for atrial fibrillation in heart failure.

Atrial fibrillation (AF) commonly co-exists with systolic heart failure (SHF) and its presence is associated with a worse prognosis. Despite this, a rhythm control approach using antiarrhythmic drugs (AADs) to reduce AF burden has demonstrated no prognostic benefit. Catheter ablation (AFA) is more effective than AADs at reducing AF burden.

Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency.

Background: Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Background: Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.

Methods: We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality.

Registry report of structural and functional cardiac abnormalities diagnosed by echocardiography in an asymptomatic population.

Background: The epidemiology of heart disease is changing, with rheumatic heart disease becoming less common but degenerative valve disorders, heart failure and atrial fibrillation (AF) increasing.

Objective: We sought to determine the prevalence of structural cardiac abnormalities in the apparently symptom-free adult population within our prospective echocardiography (echo) registry.

Methods: Our echo registry comprised echo studies and associated demographic and clinical data obtained prospectively from 362 consecutive asymptomatic subjects aged 50-74 years and without known heart disease referred between 2011 and 2012 from general practices in the South East of England.

Metabolic abnormalities of the heart in type II diabetes.

Type 2 diabetes mellitus escalates the risk of heart failure partly via its ability to induce a cardiomyopathic state that is independent of coronary artery disease and hypertension. Although the pathogenesis of diabetic cardiomyopathy has yet to be fully elucidated, aberrations in cardiac substrate metabolism and energetics are thought to be key drivers. These aberrations include excessive fatty acid utilisation and storage, suppressed glucose oxidation and impaired mitochondrial oxidative phosphorylation.

Calculated plasma volume status and prognosis in chronic heart failure.

Aims: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients.

Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure.

Background: We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling.

Methods And Results: The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality.

Basal septal hypertrophy.

A significant clinical problem is patients presenting with exercise-limiting dyspnoea, sometimes with associated chest pain, in the absence of detectable left ventricular (LV) systolic dysfunction, coronary artery disease, or lung disease. Often the patients are older, female, and have isolated basal septal hypertrophy (BSH), frequently on a background of mild hypertension. The topic of breathlessness in patients with clinical heart failure, but who have a normal ejection fraction (HFNEF) has attracted significant controversy over the past few years.

Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information.

Background: Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug.

Progressive rise in red cell distribution width is associated with poor outcome after transcatheter aortic valve implantation.

Objective: To investigate the prognostic value of baseline and temporal changes in red cell distribution width (RDW) in patients undergoing transcatheter aortic valve implantation (TAVI).

Design: Single-centre retrospective observational study.

Setting: Tertiary cardiac centre.

Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure.

Background: An elevated red cell distribution width (RDW) and iron deficiency (ID) at baseline predict enhanced mortality in chronic heart failure (CHF), but little is known about the prognostic implications of their temporal trends. We sought to determine the survival implications of temporal changes in RDW and evolving ID in patients with CHF.

Methods: The relation between red cell indices on first consultation and over time with mortality in 274 stable patients with systolic CHF was analysed.