Long-term follow-up of the TRED-HF trial: Implications for therapy in patients with dilated cardiomyopathy and heart failure remission.

Aims: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal.

Methods And Results: TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months.

Precision prediction of heart failure events in patients with dilated cardiomyopathy and mildly reduced ejection fraction using multi-parametric cardiovascular magnetic resonance.

Aims: To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF).

Methods And Results: We conducted a prospective observational cohort study of patients with DCM and LV ejection fraction (LVEF) ≥40% assessed by CMR, including feature-tracking to assess LV GLS and late gadolinium enhancement (LGE). Long-term adjudicated follow-up included (i) HF hospitalization, LV assist device implantation or HF death, and (ii) SCD or aborted SCD (aSCD).

Comparative prognostic importance of measures of left atrial structure and function in non-ischaemic dilated cardiomyopathy.

Aims: This study aimed to compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular death or non-fatal heart failure events in patients with non-ischaemic dilated cardiomyopathy (DCM).

Methods And Results: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm [median age 54 (interquartile range 44-64) years, 61% men, median left ventricular ejection fraction 42% (30-51%)] were analysed for measures of LA structure [LA maximum volume index (LAVImax) and LA minimum volume index (LAVImin)] and function (LA emptying fraction, LA reservoir strain, LA conduit strain (LACS), and LA booster strain]. Over a median follow-up of 7.

Quantifying the benefit-risk trade-off for individual patients in a clinical trial: principles and antithrombotic case study.

Background: A treatment's overall favorable benefit-risk profile does not imply that every individual patient will benefit from the treatment.

Objectives: To describe a statistical methodology for quantifying the benefit-risk trade-off in individual patients.

Methods: The method requires a large randomized controlled trial containing a primary efficacy outcome and a primary safety outcome, for instance, the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 placebo-controlled trial of vorapaxar in 17 779 patients following myocardial infarction.

A retrospective analysis of 20,178 adult neurological infection admissions to United Kingdom critical care units from 2001 to 2020.

Background: Neurological infection is an important cause of critical illness, yet little is known on the epidemiology of neurological infections requiring critical care.

Methods: We analysed data on all adults with proven or probable neurological infection admitted to UK (NHS) critical care units between 2001 and 2020 reported to the Intensive Care National Audit and Research Centre. Diagnoses, physiological variables, organ support and clinical outcomes were analysed over the whole period, and for consecutive 5-year intervals within it.

Sex Differences in the Clinical Presentation and Natural History of Dilated Cardiomyopathy.

Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.

Objectives: This study aims to investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.

Aims: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).

Methods And Results: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+).

Efficacy of pulmonary artery pressure monitoring in patients with chronic heart failure: a meta-analysis of three randomized controlled trials.

Aims: Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question.

Methods And Results: A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients with HF.

The win ratio method in heart failure trials: lessons learnt from EMPULSE.

Aims: The EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo using the stratified win ratio approach in 530 patients with acute heart failure (HF) after initial stabilization. We aim to elucidate how this method works and what it means, thereby giving guidance for use of the win ratio in future trials.

Methods And Results: The primary trial outcome is a hierarchical composite of death, number of HF events, time to first HF event, or a ≥5-point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change at 90 days.

Comprehensive Phenotypic Characterization of Late Gadolinium Enhancement Predicts Sudden Cardiac Death in Coronary Artery Disease.

Background: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) offers the potential to noninvasively characterize the phenotypic substrate for sudden cardiac death (SCD).

Objectives: The authors assessed the utility of infarct characterization by CMR, including scar microstructure analysis, to predict SCD in patients with coronary artery disease (CAD).

Methods: Patients with stable CAD were prospectively recruited into a CMR registry.

Multimorbidity, functional impairment, and mortality in older patients stable after prior acute myocardial infarction: Insights from the TIGRIS registry.

Background: Data on the association of multimorbidity and functional impairment with cardiovascular (CV) and non-CV outcomes among older myocardial infarction (MI) patients are limited.

Hypothesis: Multimorbidity and functional impairment among older MI patients are associated with CV and non-CV mortality.

Methods: Patients aged ≥65 years, 1-3 years post-MI, and enrolled between June 2013 and Novemeber 2014 from 349 sites in 25 countries in the global TIGRIS registry were categorized by age, number of comorbidities, and presence and degree of functional impairment.

Genetic Architecture of Acute Myocarditis and the Overlap With Inherited Cardiomyopathy.

Background: Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis.

Methods: This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht.

Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study.

Background: Uncertainty remains concerning the association of blood cholesterol with the risk of subsequent dementia. Using data from people with lipid measurements in the UK Clinical Practice Research Datalink (CPRD), we examined the association between blood lipid levels and dementia (both vascular and non-vascular, including Alzheimer's disease) by age at first measurement of blood lipids and duration of follow-up.

Methods: We studied a cohort from the UK CPRD of people aged 40 years or older with a first total cholesterol recording between Jan 1, 1992, and Dec 31, 2009.

The 2nd European Carotid Surgery Trial (ECST-2): rationale and protocol for a randomised clinical trial comparing immediate revascularisation versus optimised medical therapy alone in patients with symptomatic and asymptomatic carotid stenosis at low to intermediate risk of stroke.

Background: Carotid endarterectomy is currently recommended for patients with recently symptomatic carotid stenosis ≥50%, based on randomised trials conducted 30 years ago. Several factors such as carotid plaque ulceration, age and associated comorbidities might influence the risk-benefit ratio of carotid revascularisation. A model developed in previous trials that calculates the future risk of stroke based on these features can be used to stratify patients into low, intermediate or high risk.

Long-term outcomes in patients who received veno-venous extracorporeal membrane oxygenation and renal replacement therapy: a retrospective cohort study.

Background: Acute kidney injury (AKI) is a frequent complication in patients with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO). However, little is known of long-term kidney function in ECMO survivors. We aimed to assess the long-term mortality and kidney outcomes in adult patients treated with veno-venous ECMO (VV-ECMO).

Survival Outcomes and Prognostic Factors in Glioblastoma.

Background: IDH-wildtype glioblastoma is the most common malignant primary brain tumour in adults. As there is limited information on prognostic factors outside of clinical trials; thus, we conducted a retrospective study to characterise the glioblastoma population at our centre. Methods: Demographic, tumour molecular profiles, treatment, and survival data were collated for patients diagnosed with glioblastoma at our centre between July 2011 and December 2015.

Socioeconomic Deprivation: An Important, Largely Unrecognized Risk Factor in Primary Prevention of Cardiovascular Disease.

Background: Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores.

Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Reduced.

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may induce an early post-initiation decrease of estimated glomerular filtration rate (eGFR), which does not impact the SGLT2i benefits. The occurrence, characteristics, determinants, and clinical significance of an initial eGFR change among patients with heart failure with reduced ejection fraction require further study. In this study we aimed to describe eGFR change from randomization to week 4 (as percent of change relative to randomization) and assess its impact in EMPEROR-Reduced.

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.

Background: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.

Objectives: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification.

Covariate Adjustment in Cardiovascular Randomized Controlled Trials: Its Value, Current Practice, and Need for Improvement.

In randomized controlled trials, patient characteristics are expected to be well balanced between treatment groups; however, adjustment for characteristics that are prognostic can still be beneficial with a modest gain in statistical power. Nevertheless, previous reviews show that many trials use unadjusted analyses. In this article, we review current practice regarding covariate adjustment in cardiovascular trials among all 84 randomized controlled trials relating to cardiovascular disease published in the New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association during 2019.