John GF Cleland

BackgroundWomen might benefit more from cardiac resynchronization therapy(CRT) than men, and do so at shorter QRS durations(QRSd).ObjectiveTo determine if sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension(LVEDD).MethodsWe analyzed patient-level data from CRT trials (MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using Bayesian Hierarchical Weibull regression models. Relationships between QRSd and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRSd by height, BSA, or LVEDD. Endpoints were heart failure hospitalization (HFH) or death and all-cause mortality.ResultsCompared with men (n=5,628), women (n=1,439) were shorter (1.62[IQR 1.57-1.65]m versus 1.75[IQR 1.70-1.80]m; p<0.001) with smaller BSAs (1 …

Introduction With expansion of family screening, genetic testing and advanced cardiovascular imaging, more patients are being diagnosed with early-stage non-ischaemic cardiomyopathy (early-NICM), often before symptom-onset. Observational studies of such patients are lacking. We sought to characterise early-NICM phenotype, evaluate risk of adverse outcomes and assess the rate of disease progression.Materials and Methods We conducted a prospective observational cohort study of patients with early-NICM assessed by LGE-CMR. Cases were classified based on presence/absence of LV dilatation and reduced LVEF into subgroups: isolated LV dilation (early-NICM H-/D+) in cases with LV dilatation without hypokinesia; non-dilated LV cardiomyopathy (early-NICM H+/D-) in cases with hypokinesia without dilatation; early dilated cardiomyopathy (early-NICM H+/D+) in cases with LV dilatation and mild …

BackgroundPatients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban.Methods and ResultsStroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was …

Aim To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide. Methods and results In this randomized, double‐blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT‐proBNP at baseline was 1487 (interquartile range: 847–2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure …

Purpose of Review Fluid retention or congestion is a major cause of symptoms, poor quality of life, and adverse outcome in patients with heart failure (HF). Despite advances in disease-modifying therapy, the mainstay of treatment for congestion—loop diuretics—has remained largely unchanged for 50 years. In these two articles (part I: loop diuretics and part II: combination therapy), we will review the history of diuretic treatment and current trial evidence for different diuretic strategies and explore potential future directions of research.Recent Findings We will assess recent trials, including DOSE, TRANSFORM, ADVOR, CLOROTIC, OSPREY-AHF, and PUSH-AHF, and assess how these may influence current practice and future research. Summary There are few data on which to base diuretic therapy in clinical practice. The most robust evidence is for highdose loop diuretic treatment over low-dose treatment for …

Aims Approximately half of patients with heart failure and a reduced ejection fraction (HeFREF) are discharged from hospital on triple therapy [angiotensin‐converting enzyme inhibitors (ACE‐Is) or angiotensin receptor blockers (ARBs), beta‐blockers (BBs), and mineralocorticoid receptor antagonists (MRAs)]. We investigated what proportion of patients are on optimal doses prior to discharge and how many might be eligible for initiation of sacubitril–valsartan or sodium‐glucose co‐transporter‐2 inhibitors (SGLT2Is). Methods and results Between 2012 and 2017, 1277 patients admitted with suspected heart failure were enrolled at a single hospital serving a local community around Kingston upon Hull, UK. Eligibility for sacubitril–valsartan or SGLT2I was based on entry criteria for the PIONEER‐HF, DAPA‐HF, and EMPEROR‐Reduced trials. Four hundred fifty‐five patients had HeFREF with complete data on renal …

The ARIC (Atherosclerosis Risk In Communities) study is an ongoing longitudinal cohort that enrolled 15,792 communitydwelling adults aged 45-64 years from 4 centers in the United States between 1987 and 1989. 1 A previous analysis using baseline measurements on a subset of 1,063 participants (mean age: 53 years; 62% women) found, as have others, a U-shaped relationship between serum ferritin and the risk of a new diagnosis of heart failure defined as any mention (primary, secondary, or incidental) on hospital discharge or death records, 1 with a nadir of risk at a serum ferritin of 121 μg/L. A new analysis from ARIC, including 3,472 participants (mean age: 74 years; 56% women) with samples taken at the fifth follow-up visit (2011-2013) now reports a linear inverse relationship between serum ferritin and the risk of heart failure, predominantly with heart failure and preserved left ventricular ejection fraction …

Introduction Myocardial infarction with no obstructive coronary arteries (MINOCA) occurs in approximately 1 in 9 presentations with acute coronary syndrome. Cardiac MRI is guideline indicated in the investigation of aetiology for MINOCA which includes a spectrum of pathophysiology, for which there is no evidence-based therapy. The presence of ischaemic late gadolinium enhancement is prognostic in myocardial infarction and represents irreversible myocardial damage. However, factors predicting the likelihood of ischaemic late gadolinium enhancement in patients with MINOCA are unclear.Materials and Methods The overall aim is to undertake a prospective, registry-based clinical trial in MINOCA [NCT05198791]. Specific aims (1) assess the feasibility of enrolling patients during acute NHS care into a therapeutic trial, (2) in all-comers (registry), undertake multisystem phenotyping using objective, quantitative …

Aims High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables. Methods and results In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population‐based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater …

For patients with heart failure and reduced left ventricular ejection fraction, intravenous iron is likely to deliver clinical and prognostic benefits for those with anaemia and transferrin saturation <20%, especially if serum ferritin exceeds 100 μg/l. A serum ferritin of <100 μg/l does not appear to be useful as a marker of iron deficiency.

Prehabilitation for people undergoing cardiac surgery - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Cochrane Database Syst Rev PMC10823574 Other Formats PDF (192K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Cochrane Database Syst Rev PMC10823574 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Logo of cochrev Cochrane Database Syst Rev. 2024; 2024(1): CD015336. Published online 2024 Jan 29. doi: 10.1002/14651858.…

Heart failure (HF) is a clinical syndrome characterized by renal retention of salt and water due to cardiac dysfunction. 1 About 70% of the blood volume is contained in the systemic venous circulation. Due to their thin walls and high compliance, veins may dilate and accommodate large increases in blood volume with little or no increase in intravascular pressure. However, eventually, once the buffering capacity of the systemic venous system is exhausted, venous pressure will rise, leading to an increase in atrial and left ventricular filling pressures and wall stress and enhanced secretion of natriuretic peptides that should promote salt and water excretion, thereby limiting or reversing congestion. When the natriuretic peptide system is overwhelmed, congestion worsens, and the syndrome of HF develops. The rise in systemic venous pressure leads to increased transudation of water into the tissues, and when that …

Non-anaemic iron deficiency (NAID) is a strategic target in cardiovascular medicine because of its association with a range of adverse effects in various conditions. Endeavours to tackle NAID in heart failure have yielded mixed results, exposing knowledge gaps in how best to define ‘iron deficiency’ and the handling of iron therapies by the body. To address these gaps, we harness the latest understanding of the mechanisms of iron homeostasis outside the erythron and integrate clinical and preclinical lines of evidence. The emerging picture is that current definitions of iron deficiency do not assimilate the multiple influences at play in patients with heart failure and, consequently, fail to identify those with a truly unmet need for iron. Additionally, current iron supplementation therapies benefit only certain patients with heart failure, reflecting differences in the nature of the unmet need for iron and the modifying effects of …

Introduction A subset of patients with dilated cardiomyopathy (DCM) undergo substantial left ventricular reverse remodelling with guideline-directed therapies to the point of normalisation of cardiac size and LVEF. However, it is unclear whether such patients have residual subclinical phenotypic abnormalities compared to healthy volunteers.Materials and Methods The REMIT-DCM study (Reverse remodelling and remission markers in the serial evaluation of DCM) was a prospective single-centre observational cohort study including patients with recent-onset DCM and age-/sex-matched healthy volunteers (HVOLs). Patients with DCM underwent CMR at baseline, 3-months and 12-months. Clinical remission from DCM was defined at 12-months if indexed LV end-diastolic volume (LVEDVi) had normalised, LVEF had risen by ≥10% to LVEF ≥50%, NT-proBNP had fallen below 250ng/L and symptom had resolved …

BackgroundMitral regurgitation (MR) frequently coexists with heart failure (HF).ObjectivesTo better understand potential pathophysiological differences between patients with HF with or without moderate-severe MR, we compared differentially expressed circulating biomarkers between these two groups.MethodsThe Olink Proteomics® Multiplex Cardiovascular (CVD) -II, CVD-III, Immune Response and Oncology-II panels of 363 unique proteins from different pathophysiological domains were used to investigate the biomarker profiles of HF patients from index and validation cohorts of the BIOSTAT-CHF study stratified according to the presence of moderate-to-severe MR or no-mild MR.ResultsThe index cohort included 888 patients (46%) with moderate-to-severe MR and 1029 (54%) with no-mild MR at baseline. The validation cohort included 522 patients (33%) with moderate-to-severe MR and 1076 (66%) with no …

In the STOP-ACEi trial, the outcome was similar whether or not renin–angiotensin system inhibitors (RASi) were discontinued. We now investigate whether the effect of withdrawing angiotensin converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) differed. In this open label trial patients with estimated glomerular filtration rates (eGFR) under 30ml/min per 1.73 m2 and progressive chronic kidney disease (CKD) were randomized to stop or continue RASi. The primary outcome was eGFR at three years. The composite of kidney failure, over 50% fall in eGFR, or kidney replacement therapy (KRT) was also assessed. Of patients randomized, 99 stopped and 123 patients continued ACEi while 104 stopped and 77 continued ARB at baseline. At three years, the eGFR was similar whether or not patients were withdrawn from ACEi or from ARB. Kidney failure or initiation of KRT occurred in 65% of those …

BackgroundIntracellular copper depletion may cause cardiovascular dysfunction among those with heart failure with reduced ejection fraction (HFrEF). Copper depletion may be corrected by administration of the copper chaperone trientine-HCL. In a placebo-controlled multicenter Phase 2 trial of patients with HFrEF (TRACER-HF; NCT03875183), 150 and 300 mg doses of trientine-HCL treatment resulted in ∼20% reduction in N-terminal pro-B type natriuretic peptide (NT-proBNP) by 4 and 8 weeks, accompanied by favorable trends in change in LV remodeling, 6-minute walk distance (6MWD) and health status (assessed with the Kansas City Cardiomyopathy Questionnaire Overall Summary Score, KCCQ-OSS). Greater effects of trientine-HCL on NT-proBNP concentrations were observed in study participants with an LV ejection fraction (EF) ≤30% (Pinteraction=0.05). The present analysis details effect of trientine …

Atrial myopathy and HFpEF - when a label does more harm than good - Enlighten Publications Skip to main content Accessibility information Site navigation Study Research About us Student life Alumni Support us Contact Site tools AZ Lists Subjects AZ Staff AZ Academic units AZ University of Glasgow logo Home Enlighten Publications Enlighten Publications About Latest Additions Search Browse Browse by Author Browse by Year Browse by Journal Browse by Research Funder Name Browse by Colleges/Schools Open Access ORCID My Publications Login Atrial myopathy and HFpEF - when a label does more harm than good Pellicori, P. and Cleland, JGF (2024) Atrial myopathy and HFpEF - when a label does more harm than good. European Journal of Heart Failure, (Accepted for Publication) [img] Text 316182.pdf - Accepted Version Restricted to Repository staff only 131kB Item Type: Articles Status: Accepted …

Aims We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI). Methods and results HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow‐up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between‐group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase‐7 (MMP‐7), galectin‐4 (GAL4 …

Aim To explore the frequency, causes, and pattern of hospitalisation for patients with chronic heart failure (HF) in the 12 months preceding death. We also investigated cause of death. Methods Patients referred to a secondary care HF clinic were routinely consented for follow-up between 2001 and 2020 and classified into three phenotypes: (i) HF with reduced ejection fraction (HFrEF), (ii) HF with preserved ejection fraction (HFpEF) with plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) 125–399 ng L−1, and (iii) HFpEF with NT-proBNP ≥400 ng L−1. Hospital admissions in the last year of life were classified as: HF, other cardiovascular (CV), or non-cardiovascular (non-CV). The cause of death was systematically adjudicated. Results A total of 4925 patients (38% women; median age at death 81 [75–87] years) had 9127 hospitalisations in the last …