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AimsPatients visiting the emergency department (ED) or hospitalized for heart failure (HF) are at increased risk for subsequent adverse outcomes, however effective risk stratification remains challenging. We utilized a machine-learning (ML)-based approach to identify HF patients at risk of adverse outcomes after an ED visit or hospitalization using a large regional administrative healthcare data system.Methods and resultsPatients visiting the ED or hospitalized with HF between 2002-2016 in Alberta, Canada were included. Outcomes of interest were 30-day and 1-year HF-related ED visits, HF hospital readmission or all-cause mortality. We applied a feature extraction method using deep feature synthesis from multiple sources of health data and compared performance of a gradient boosting algorithm (CatBoost) with logistic regression modelling. The area under receiver operating characteristic curve (AUC-ROC) was used to assess model performance. We included 50,630 patients with 93,552 HF ED visits/hospitalizations. At 30-day follow-up in the holdout validation cohort, the AUC-ROC for the combined endpoint of HF ED visit, HF hospital readmission or death for the Catboost and logistic regression models was 74.16 (73.18-75.11) versus 62.25 (61.25-63.18), respectively. At 1-year follow-up corresponding values were 76.80 (76.1-77.47) versus 69.52 (68.77-70.26), respectively. AUC-ROC values for the endpoint of all-cause death alone at 30-days and 1-year follow-up were 83.21 (81.83-84.41) versus 69.53 (67.98-71.18), and 85.73 (85.14-86.29) versus 69.40 (68.57-70.26), for the CatBoost and logistic regression models, respectively.ConclusionsML-based modelling with deep feature synthesis provided superior risk stratification for HF patients at 30-days and 1-year follow-up after an ED visit or hospitalization using data from a large administrative regional healthcare system.

IntroductionShort-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15–20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear.MethodsA multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3–6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized.DiscussionLong-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease.Study registrationclinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).

Abstract Background Left ventricular (LV) circumferential and longitudinal strain provide important insight into LV mechanics and function, each contributing to volumetric changes throughout the cardiac cycle. We sought to explore this strain-volume relationship in more detail, by mathematically integrating circumferential and longitudinal strain and strain rate to predict LV volume and volumetric rates of change. Methods Cardiac magnetic resonance (CMR) imaging from 229 participants from the Alberta HEART Study (46 healthy controls, 77 individuals at risk for developing heart failure [HF], 70 patients with diagnosed HF with preserved ejection fraction [HFpEF], and 36 patients with diagnosed HF with reduced ejection fraction [HFrEF]) were evaluated. LV volume was assessed by the method of disks and strain/strain rate were assessed by CMR feature tracking. Results Integrating endocardial circumferential and longitudinal strain provided a close approximation of LV ejection fraction (EFStrain), when compared to gold-standard volumetric assessment (EFVolume: r = 0.94, P

Abstract The feasibility and value of linking electrocardiogram (ECG) data to longitudinal population-level administrative health data to facilitate the development of a learning healthcare system has not been fully explored. We developed ECG-based machine learning models to predict risk of mortality among patients presenting to an emergency department or hospital for any reason. Using the 12-lead ECG traces and measurements from 1,605,268 ECGs from 748,773 healthcare episodes of 244,077 patients (2007–2020) in Alberta, Canada, we developed and validated ResNet-based Deep Learning (DL) and gradient boosting-based XGBoost (XGB) models to predict 30-day, 1-year, and 5-year mortality. The models for 30-day, 1-year, and 5-year mortality were trained on 146,173, 141,072, and 111,020 patients and evaluated on 97,144, 89,379, and 55,650 patients, respectively. In the evaluation cohort, 7.6%, 17.3%, and 32.9% patients died by 30-days, 1-year, and 5-years, respectively. ResNet models based on ECG traces alone had good-to-excellent performance with area under receiver operating characteristic curve (AUROC) of 0.843 (95% CI: 0.838–0.848), 0.812 (0.808–0.816), and 0.798 (0.792–0.803) for 30-day, 1-year and 5-year prediction, respectively; and were superior to XGB models based on ECG measurements with AUROC of 0.782 (0.776–0.789), 0.784 (0.780–0.788), and 0.746 (0.740–0.751). This study demonstrates the validity of ECG-based DL mortality prediction models at the population-level that can be leveraged for prognostication at point of care.

Deep learning can automate the interpretation of medical imaging tests. Here, the authors formally assess the interchangeability of deep learning algorithms with expert human measurements for interpreting echocardiographic studies.

Background: An unanswered question is whether the combination of advances in medical and device therapy over the past decade has translated into improved outcomes for patients with heart failure (HF) in Canada. Methods: The Canadian Institute for Health Information (CIHI) Hospital Morbidity Database was used to identify hospitalizations for HF among patients aged 18 years and older in Canadian hospitals during fiscal years 2009/2010 and 2018/2019. We assessed interprovincial differences in age, sex, length of stay (LOS), discharge disposition, type of admitting hospital, and most responsible service, for all HF admissions. National and provincial rates of HF admissions and all-cause 30-day readmissions were calculated. Results: After adjusting for age, the rate of HF admissions in Canada was 216 per 100,000 population in 2009/2010 and 2018/2019. The majority of patients with HF were admitted to general internal medicine and community hospitals in both 2009/2010 and 2018/2019. The national, crude, all-cause 30-day readmission rate stayed constant at 20.6%, and the majority of patients were readmitted with the diagnosis of HF in both 2009/2010 (62.5%) and 2018/2019 (59.0%). Median and interquartile range of HF LOS also remained unchanged at 7 days (3-14). Conclusions: The national rate of HF admissions, 30-day readmissions, and HF LOS have remained unchanged from 2009/2010 to 2018/2019, despite advances in medical and device therapy during this timeframe. Résumé: Introduction: La question demeure de savoir si, au cours de la dernière décennie au Canada, la combinaison des avancées dans les traitements médicaux et à l’aide d’un dispositif s’est traduite par de meilleurs résultats cliniques chez les patients atteints d’insuffisance cardiaque (IC). Méthodes: Nous avons utilisé la base de données sur la morbidité hospitalière de l’Institut canadien d’information sur la santé (ICIS) pour recenser les hospitalisations de patients atteints d’IC âgés de 18 ans et plus dans les hôpitaux du Canada au cours des années financières 2009/2010 et 2018/2019. Nous avons évalué les différences interprovinciales selon l’âge, le sexe, la durée du séjour (DDS), l’état à la sortie, le type d’hôpital à l’admission et le service le plus tenu à la prise en charge du patient, de toutes les admissions liées à l’IC. Nous avons calculé les taux provinciaux et national des admissions liées à l’IC et les réadmissions toutes causes confondues dans les 30 jours. Résultats: Après ajustement en fonction de l’âge, le taux d’admissions liées à l’IC au Canada était de 216 pour 100 000 habitants en 2009/2010 et en 2018/2019. La majorité des patients atteints d’IC avaient été admis en médecine interne générale et dans les hôpitaux communautaires en 2009/2010 et en 2018/2019. Le taux national, brut, toutes causes confondues de réadmissions dans les 30 jours était resté constant à 20,6 %, et la majorité des patients avaient eu des réadmissions liées au diagnostic d’IC en 2009/2010 (62,5 %) et en 2018/2019 (59,0 %). L’écart interquartile et la médiane de la DDS liée à l’IC étaient aussi demeurés inchangés après 7 jours (3-14). Conclusions: Le taux national des admissions liées à l’IC, les réadmissions dans les 30 jours et la DDS liée à l’IC étaient demeurés inchangés de 2009/2010 à 2018/2019, malgré les avancées des traitements médicaux et à l’aide d’un dispositif durant cette période de temps.

Abstract We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction

Summary: Background: Echocardiography (echo) based machine learning (ML) models may be useful in identifying patients at high-risk of all-cause mortality. Methods: We developed ML models (ResNet deep learning using echo videos and CatBoost gradient boosting using echo measurements) to predict 1-year, 3-year, and 5-year mortality. Models were trained on the Mackay dataset, Taiwan (6083 echos, 3626 patients) and validated in the Alberta HEART dataset, Canada (997 echos, 595 patients). We examined the performance of the models overall, and in subgroups (healthy controls, at risk of heart failure (HF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)). We compared the models' performance to the MAGGIC risk score, and examined the correlation between the models’ predicted probability of death and baseline quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Findings: Mortality rates at 1-, 3- and 5-years were 14.9%, 28.6%, and 42.5% in the Mackay cohort, and 3.0%, 10.3%, and 18.7%, in the Alberta HEART cohort. The ResNet and CatBoost models achieved area under the receiver-operating curve (AUROC) between 85% and 92% in internal validation. In external validation, the AUROCs for the ResNet (82%, 82%, and 78%) were significantly better than CatBoost (78%, 73%, and 75%), for 1-, 3- and 5-year mortality prediction respectively, with better or comparable performance to the MAGGIC score. ResNet models predicted higher probability of death in the HFpEF and HFrEF (30%–50%) subgroups than in controls and at risk patients (5%–20%). The predicted probabilities of death correlated with KCCQ scores (all p

Abstract Aims N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) values may be influenced by patient factors beyond the severity of illness, including atrial fibrillation (AF), renal dysfunction, or increased body mass index (BMI). We hypothesized that these factors may influence the achievement of NT‐proBNP targets and clinical outcomes. Methods A total of 894 patients with heart failure with reduced ejection fraction were enrolled in The Guiding Evidence‐Based Therapy Using Biomarker Intensified Treatment trial. NT‐proBNP was analysed every 3 months. Results Forty per cent of patients had AF, the median estimated glomerular filtration rate (eGFR) was 59 mL/min/1.73 m2 [interquartile range (IQR) 43–76], and median BMI was 29 kg/m2 (IQR 25–34). Patients with AF, eGFR 60 mL/min/1.73 m2, P

Background: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. Methods: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. Results: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. Conclusions: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients. Résumé: Introduction: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. Méthodes: L’étude portait sur des patients adultes de l’Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l’Institut canadien d’information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. Résultats: Parmi les 88 536 GU, 23,4 % n’avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. Conclusions: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D’autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d’aplatir la courbe des coûts chez ces patients aux besoins complexes.

Abstract Aims Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. Methods and results A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow‐up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan–Meier analyses compared to those with no remodelling, log‐rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. Conclusions Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long‐term outcomes whereas change in left ventricular ejection fraction did not.

Abstract Background Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. Methods Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. Results GLS_EPI distinguished all groups with preserved LVEF (controls − 16.5 ± 2.4% vs. at-risk − 15.5 ± 2.7% vs. HFpEF − 14.1 ± 3.0%, p 55%), in whom lower strains were associated with increased concentricity.

Abstract Aims The aim of this study is to determine factors associated with long‐term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group. Methods and results Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1‐year follow up. Using pre‐enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization‐free survival to 5 years was performed. The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15–7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin‐T with further increase at follow up 0.55(0.33–0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed. Conclusions Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling.

This joint Canadian Heart Failure Society and the CCS Heart Failure guidelines report has been developed to provide a pan-Canadian snapshot of the current state of clinic-based ambulatory heart failure (HF) care in Canada with specific reference to elements and processes of care associated with quality and high performing health systems. It includes the viewpoints of persons with lived experience, patient care providers, and administrators. It is imperative to build on the themes identified in this survey, through engaging all health care professionals, to develop integrated and shared care models that will allow better patient outcomes. Several patient and organizational barriers to care were identified in this survey, which must inform the development of regional care models and pragmatic solutions to improve transitions for this patient population. Unfortunately, we were unsuccessful in incorporating the perspectives of primary care providers and internal medicine specialists who provide the majority of HF care in Canada, which in turn limits our ability to comment on strategies for capacity building outside the HF clinic setting. These considerations must be taken into account when interpreting our findings. Engaging all HF care providers, to build on the themes identified in this survey, will be an important next step in developing integrated and shared care models known to improve patient outcomes. Résumé: Ce rapport conjoint des lignes directrices de la Société canadienne d'insuffisance cardiaque et de la Société canadienne de cardiologie (SCC) sur l'insuffisance cardiaque a été élaboré pour fournir un aperçu pancanadien de l'état actuel des soins ambulatoires de l'insuffisance cardiaque (IC) en clinique au Canada, en se référant spécifiquement aux éléments et aux processus de soins associés à des systèmes de santé très performants et de qualité. Il comprend les points de vue de personnes ayant une expérience vécue de l'IC, de prestataires de soins aux patients et d'administrateurs. Il est impératif de s'appuyer sur les thématiques identifiées dans cette enquête, en y engageant tous les professionnels de la santé, pour développer des modèles de soins intégrés et partagés qui permettront de meilleurs pronostics pour les patients. Plusieurs obstacles relatifs aux patients et organisationnels dont il faudra se soucier ont été identifiés dans cette enquête, qui doit servir de base à l'élaboration de modèles de soins régionaux et de solutions pragmatiques pour améliorer les transitions pour cette population de patients. Malheureusement, nous n'avons pas réussi à intégrer les points de vue des prestataires de soins primaires et des spécialistes en médecine interne qui fournissent la majorité des soins en IC au Canada, ce qui limite notre capacité à commenter les stratégies de renforcement des capacités en dehors du cadre des cliniques d’IC. Ces considérations doivent être prises en compte lors de l'interprétation de nos conclusions. L'engagement de tous les prestataires de soins de santé en IC à s'appuyer sur les thématiques identifiées dans cette enquête constituera une prochaine étape importante dans le développement de modèles de soins intégrés et partagés connus pour améliorer le pronostic des patients.

Abstract Aims Sodium–glucose co‐transporter (SGLT)‐2 inhibitors have been shown to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in patients with type 2 diabetes mellitus (DM) and high cardiovascular risk in two large clinical outcome trials: empagliflozin in EMPA‐REG OUTCOME and canagliflozin in CANVAS. The scope of eligibility for SGLT‐2 inhibitors (empagliflozin and canagliflozin) among patients with type 2 DM and HF, based on clinical trial criteria and current US Food and Drug Administration (FDA) labelling criteria, remains unknown. Methods and results Using data from the US Get With The Guidelines (GWTG)—Heart Failure registry, we evaluated the proportion of patients with DM and HF eligible for SGLT‐2 inhibitor therapy based on the clinical trial criteria and the US FDA labelling criteria. The GWTG‐HF registry is a quality improvement registry of patients admitted in hospital with HF in the USA. We included GWTG‐HF registry participants meeting eligibility criteria hospitalized between August 2014 and 30 June 2017 from sites fully participating in the registry. The initial inclusion time point reflects when both drugs had FDA approval. Among the 139 317 patients (out of 407 317) with DM hospitalized with HF (in 460 hospitals; 2014 to 2017), the median age was 71 years, 47% (n = 65 685) were female, and 43% (n = 59 973) had HF with reduced ejection fraction. Overall, 43% (n = 59 943) were eligible for the EMPA‐REG OUTCOME trial, 45% (n = 62 818) were eligible for the CANVAS trial, and 34% (n = 47 747) of patients were eligible for either SGLT‐2 inhibitors based on the FDA labelling criteria. Among the FDA‐eligible patients, 91.5% (n = 43 708) were eligible for either the EMPA‐REG OUTCOME trial or the CANVAS trial. Patients who were FDA eligible, compared with those who were not, were younger (70.0 vs. 72.0 years of age), more likely to be male (57.7 vs. 50.3%), and had less burden of co‐morbidities. Conclusions The majority of patients with DM who are hospitalized with HF are not eligible for SGLT‐2 inhibitor therapies. Ongoing studies evaluating the safety and efficacy of SGLT‐2 inhibitors among patients with HF may potentially broaden the population that may benefit from these therapies.

Background: Restricting dietary sodium consumption has been considered a major component of self-care management in heart failure (HF); however, the evidence supporting this recommendation has not been conclusive. The Study of Dietary Intervention Under 100 MMOL in Heart Failure (SODIUM-HF) trial aims to assess the effects of dietary sodium reduction on clinical outcomes in a HF population using a pragmatic design to provide empirical evidence to guide dietary sodium intake recommendations in patients with chronic HF. Methods: SODIUM-HF is a multicentre, open-label, blinded adjudicated endpoint, randomized controlled trial in ambulatory patients with chronic HF. This trial involves participants recruited from sites in Canada, Australia, New Zealand, Mexico, Colombia, and Chile, who are followed up to 24 months. Rationale and methods of the SODIUM-HF trial were published elsewhere. As an international pragmatic dietary trial, SODIUM-HF was designed to address several challenges, such as defining the most suitable intervention to account for country-specific variations in food intake and availability. In SODIUM-HF, we implemented the Nutrition-Care Model to provide a comprehensive intervention delivered directly to patients, focusing on modifying the nutrient composition of the diet (sodium restriction), using a personalized counselling and close follow-up. Results: Available upon completion of the trial. Conclusions: This long-term dietary trial is one of the first in its type in the HF field. This article describes in detail the rationale and methods for the dietary intervention employed and the region-specific adaptation of the SODIUM-HF intervention, so that the learning and processes taken in this trial can be applied to future multicountry dietary clinical trials. Résumé: Contexte: La restriction de l’apport en sodium alimentaire est considérée comme étant un élément important de l’auto-prise en charge de l’insuffisance cardiaque (IC); or, les données à l’appui de cette recommandation ne sont pas concluantes. L’étude SODIUM-HF (Study of Dietary Intervention Under 100 MMOL in Heart Failure) vise à évaluer en contexte réel les effets de la réduction de l’apport en sodium alimentaire sur les résultats cliniques au sein d’une population de patients atteints d’IC, afin d’obtenir des données empiriques qui serviront à orienter les recommandations en matière d’apport en sodium alimentaire chez les patients atteints d’IC chronique. Méthodologie: L’étude SODIUM-HF est un essai multicentrique contrôlé avec répartition aléatoire et mené en mode ouvert auprès de patients ambulatoires atteints d’IC chronique, dont les paramètres sont évalués à l’insu. Les participants sont recrutés dans des centres situés au Canada, en Australie, en Nouvelle-Zélande, au Mexique, en Colombie et au Chili, et font l’objet d’un suivi pendant 24 mois. La raison d’être et la méthodologie de l’étude SODIUM-HF sont présentées ailleurs. Comme il s’agit d’une étude internationale sur l’alimentation menée en contexte réel, l’étude SODIUM-HF a été conçue de manière à résoudre plusieurs difficultés, dont la façon la plus appropriée de tenir compte des variations entre pays en matière d’apport alimentaire et de disponibilité des aliments. L’étude met en œuvre le processus de soins en nutrition, afin d’assurer directement auprès des patients une intervention exhaustive axée sur la modification de la composition en nutriments de l’alimentation (restriction de l’apport en sodium) et faisant appel à des conseils personnalisés et à un suivi étroit. Résultats: Les résultats seront publiés à la fin de l’étude. Conclusions: Cette étude de longue durée sur l’alimentation est l’une des premières en son genre dans le domaine de l’IC. Les auteurs décrivent en détail la raison d’être et la méthodologie des mesures d’intervention alimentaire employées ainsi que les adaptations propres à chaque région mises en œuvre dans le cadre de l’étude SODIUM-HF, afin que les apprentissages et les processus issus de l’étude puissent être utilisés dans d’autres études cliniques multinationales sur l’alimentation.

Abstract Objectives The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact on short term clinical and biomarker outcomes. We hypothesize that continuation of RAAS inhibition will be superior to temporary discontinuation with regards to the primary endpoint of a global rank sum score. The global rank sum score has been successfully used in previous cardiovascular clinical trials. Trial design This is an open label parallel two arm (1,1 ratio) randomized control superiority trial of approximately 40 COVID-19 patients who are on chronic RAAS inhibitor therapy. Participants Adults who are admitted to hospital within the McGill University Health Centre systems (MUHC) including Royal Victoria Hospital (RVH), Montreal General Hospital (MGH) and Jewish General Hospital (JGH) and who are within 96 hours of COVID-19 diagnosis (confirmed via PCR on any biological sample) will be considered for the trial. Of note, the initial protocol to screen and enrol within 48 hours of COVID-19 diagnosis was extended through an amendment, to 96 hours to increase feasibility. Participants have to be 18 years or older and would have to be on RAAS inhibitors for at least a month to be considered eligible for the study. Additionally, RAAS inhibitors should not have been held for more than 48 hours before randomization. A list of inclusion and exclusion criteria can be found in the full protocol document. In order to prevent heart failure exacerbation, patients with reduced ejection fraction were excluded from the trial. Once a patient is admitted on the ward with a diagnosis of COVID-19, we will confirm with the treating physician if the participant is suitable for the RAAS-COVID trial and meets all the inclusion and exclusion criteria. If the patient is eligible and informed consent has been obtained we will collect data on sex, age, ethnicity, past medical history and list of medications (e.g. other anti-hypertensives or anticoagulants), for further analysis. Intervention and comparator All the study participants will be randomized to a strategy of temporarily holding the RAAS inhibitor [intervention] versus continuing the RAAS inhibitor [continued standard of care]. Among participants who are randomized to the intervention arm, alternative guide-line directed anti-hypertensive medication will be provided to the treating physician team (detail in study protocol). In the intervention arm RAAS inhibitor will be withheld for a total of 7 days with the possibility of the withdrawn medication being initiated at any point after day 7 or on the day of discharge. The recommendation for re-initiating the withdrawn medication will be made to the treating physician. The re-initiation of these therapies are according to standard convention and follow-up as per Canadian guidelines. Additionally, the date of restarting the withdrawn medication or whether the medication was re-prescribed on discharge or not, will be collected. This will be used to conduct a sensitivity analysis. Furthermore, biomarkers such as troponin, c-reactive protein (CRP) and lymphocyte count will be assessed during the same time period. Samples will be collected on randomization, day 4 and day 7. Main outcomes Primary endpoint In this study the primary end point is a global rank score calculated for all participants, regardless of treatment assignment ( score from 0 to 7). Please refer to table 4 in the full protocol. In the context of the current trial, it is estimated that death is the most meaningful endpoint, and therefore has the highest score ( score of 7). This is followed by admission to ICU, the need for mechanical ventilation etc. The lowest scores ( score of 1) are assigned to biomarker changes (e.g. change in troponin, change in CRP). This strategy has been used successfully in cardiovascular disease trials and therefore is applicable to the current trial. The primary endpoint for the present trial is assessed from baseline to day 7 (or discharge). Participants are ranked across the clinical and biomarker domains. Lower values indicate better health (or stability). Participants who died during the 7th day of the study will be ranked based on all events occurring before their death and also including the fatal event in the score. Next, participants who did not die but were transferred to ICU for invasive ventilation will be ranked based on all the events occurring before the ICU entry and also including the ICU admission in the score. Those participants who did not die were not transferred to ICU for invasive ventilation, will be ranked based on the subsequent outcomes. The mean rank score will then be compared between groups. In this scheme, a lower mean rank score indicates greater overall stability for participants. Secondary endpoints : The key secondary endpoints are the individual components of the primary components and include the following: death, transfer to ICU primarily for invasive ventilation, transfer to ICU for other indication, non-fatal MACE ( any of following, MI, stroke, acute HF, new onset Afib), length of stay > 4 days, development of acute kidney injury ( > 40% decline in eGFR or doubling of serum creatinine), urgent intravenous treatment for high blood pressure, 30% increase in baseline high sensitivity troponin, 30% increase in baseline BNP, increase in CRP to > 30% in 48 hours and lymphocyte count drop> 30%. We will also look at the World Health Organization (WHO) ordinal scale for clinical improvement (in COVID-19) in our data. In this scale death will be assigned the highest score of 8. Patients with no limitation of activity will be assigned a score of 1 which indicates overall more stability (3). Additionally, we will evaluate the potential effects of discontinuing RAAS inhibition on alternative schedules (longer/shorter than 7 days, intermittent discontinuation) using a mechanistic mathematical model of COVID-19 immunopathology calibrated to data collected from our patient cohort. In particular, we will assess the impact of alternative schedules on primary and secondary endpoints including increases to baseline CRP and lymphocyte counts. Randomization Participants will be randomized in a 1:1 ratio. Randomization will be performed within an electronic database system at the time of enrolment using a random number generator, an approach that has been successfully used in other clinical trials. Neither participant, study team, or treating team will be blinded to the intervention arm. Blinding This is an open label study with no blinding. Numbers to be randomised (sample size) The approximate number of participants required for this trial is 40 patients (randomized 1:1 to continuation versus discontinuation of RAAS inhibitors). This number was calculated based on previous rates of outcomes for COVID-19 in the literature (e.g. death, ICU transfer) and statistical power calculations. Trial Status Protocol number: MP-37-2021-6641, Version 4: 01-10-2020. Trial start date September 1st 2020 and currently enrolling participants. Estimated end date for recruitment of participants : July 2021. Estimated end date for study completion: September 1st 2021. Trial registration Trial registration: ClincalTrials.gov : NCT04508985 , date of registration: August 11th , 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Abstract Background Pulmonary edema is a cardinal feature of heart failure but no quantitative tests are available in clinical practice. The goals of this study were to develop a simple cardiovascular magnetic resonance (CMR) approach for lung water quantification, to correlate CMR derived lung water with intra-cardiac pressures and to determine its prognostic significance. Methods Lung water density (LWD, %) was measured using a widely available single-shot fast spin-echo acquisition in two study cohorts. Validation Cohort: LWD was compared to left ventricular end-diastolic pressure or pulmonary capillary wedge pressure in 19 patients with heart failure undergoing cardiac catheterization. Prospective Cohort: LWD was measured in 256 subjects, including 121 with heart failure, 82 at-risk for heart failure and 53 healthy controls. Clinical outcomes were evaluated up to 1 year. Results Within the validation cohort, CMR LWD correlated to invasively measured left-sided filling pressures (R = 0.8, p 20.8% (mean + 2 standard deviations of healthy controls) was an independent predictor of death, hospitalization or emergency department visit within 1 year, hazard ratio 2.4 (1.1–5.1, p = 0.03). Conclusions In patients with heart failure, increased CMR-derived lung water is associated with increased intra-cardiac filling pressures, and predicts 1 year outcomes. LWD could be incorporated in standard CMR scans.

Abstract Aims Most patients with acute heart failure (AHF) are treated with supplemental oxygen during hospitalization. In this study, we investigated the effect of oxygen titrated to high vs. low pulse oximetry targets in patients hospitalized with AHF. Methods and results In a pilot, open‐label randomized controlled trial (RCT), 50 patients who were admitted with AHF were randomized to either high (≥96%) or low (90–92%) SpO2 targets. Oxygen was manually titrated to the assigned target ranges for 72 h. The primary endpoint was the change in N‐terminal pro‐brain‐type natriuretic peptide (NT‐proBNP) from randomization to 72 h, and secondary endpoints included patient‐reported dyspnoea by visual analogue scale (VAS), patient global assessment (PGA), peak expiratory flow (PEF) within 72 h, and clinical outcomes up to 30 days following hospital discharge. The median age was 73.5 years, and 42% were women. The change in NT‐proBNP was −6963 (−13 345, −1253) pg/mL in the high SpO2 group and −2093 (−5692, −353) pg/mL in the low SpO2 group (P = 0.46), and the 72 h to baseline NT‐proBNP ratio was similar between groups (0.7 vs. 0.6, P = 0.51). There were no differences between arms in change in dyspnoea VAS (P = 0.86), PGA (P = 0.91), PEF (P = 0.52), in‐hospital mortality (4.0% vs. 8.0%, P = 0.50), or 30 day heart failure readmission rates (20.8% vs. 8.7%, P = 0.22). Conclusions In this study, no differences were observed in the primary or secondary outcomes for patients randomized to high vs. low SpO2 targets. Further RCTs with larger sample sizes are warranted to determine the efficacy and safety of oxygen therapy in patients with AHF.

Background: Emergency Heart Failure Mortality Risk Grade (EHMRG) assesses the risk of death within 7 days of emergency department (ED) presentation for patients with acute heart failure (AHF). We aimed to externally validate and refine the EHMRG model in patients who presented to the ED with AHF. Methods: We performed a cohort study using administrative data for all ambulance-transported patients from Alberta (2012-2016) presenting to the ED with a primary diagnosis of AHF. Results: Among 6708 patients with AHF, the 7-day mortality was 0.0%, 0.8%, 1.6%, 4.0%, 4.2%, and 12.0% across EHMRG risk categories (1-4, 5A and 5B). The EHMRG score had a c-index of 0.73 (95% confidence interval [CI], 0.71-0.76) for 7-day mortality and 0.71 (95% CI, 0.70-0.73) for 30-day mortality, but lower c-statistics for other outcomes (0.61-0.67). The inclusion of natriuretic peptides to the EHMRG model improved prediction (Net Reclassification Improvement, 0.268; 95% CI, 0.173-0.363; P < 0.01) for 7-day mortality, as did the addition of the Canadian Triage and Acuity Scale (Net Reclassification Improvement, 0.111; 95% CI, 0.005-0.218; P = 0.04). Conclusion: The EHMRG model exhibited moderate discriminative ability in a large population-based cohort of patients with AHF in the ED. Revision of the EHMRG score through factor inclusion and exclusion could improve the model’s performance. Résumé: Introduction: Le Emergency Heart Failure Mortality Risk Grade (EHMRG) permet d’évaluer le risque de mortalité dans les 7 jours qui suivent la consultation au service des urgences (SU) des patients souffrant d’insuffisance cardiaque aiguë (ICA). Nous avions pour objectif de valider et d’affiner à l’externe le modèle EHMRG chez les patients qui se présentaient au SU en raison d’une ICA. Méthodes: Nous avons réalisé une étude de cohorte à partir des données administratives de tous les patients de l’Alberta transportés par ambulance (2012-2016) au SU en raison d’un diagnostic principal d’ICA. Résultats: Parmi les 6708 patients souffrant d’ICA, la mortalité dans les 7 jours était de 0,0 %, de 0,8 %, de 1,6 %, de 4,0 %, de 4,2 % et de 12,0 % dans toutes les catégories de risque EHMRG (1-4, 5A et 5B). Le score EHMRG montrait un C-index (indice de concordance) de 0,73 (intervalle de confiance [IC] à 95 %, 0,71-0,76) pour la mortalité dans les 7 jours et de 0,71 (IC à 95 %, 0,70-0,73) pour la mortalité dans les 30 jours, mais des statistiques C plus faibles pour les autres résultats cliniques (0,61-0,67). L’inclusion de peptides natriurétiques au modèle EHMRG améliorait la prédiction (indice Net Reclassification Improvement [NRI], 0,268; IC à 95 %, 0,173-0,363; P < 0,01) pour la mortalité dans les 7 jours, de la même manière que l’ajout de l’Échelle canadienne de triage et de gravité (indice NRI, 0,111; IC à 95 %, 0,005-0,218; P = 0,04). Conclusion: Le modèle EHMRG a montré une capacité discriminative modérée dans une vaste cohorte en population générale auprès de patients souffrant d’ICA au SU. La révision du score EHMRG par l’inclusion et l’exclusion de facteurs pourraient permettre d’améliorer la performance du modèle.

Background Improving health‐related quality of life is an important goal in the management of patients with heart failure (HF). Defining health‐related quality of life changes over time in patients with HF with preserved (HFpEF) or reduced ejection fraction and showing their association with other important clinical events could support the use of health‐related quality of life as a measure of quantifying HF care. Methods and Results In the Alberta HEART (Heart Failure Aetiology and Analysis Team) cohort (n=621), patients were categorized into 4 subgroups: healthy controls (n=98), at risk (n=163), HFpEF (n=191), and HF with reduced ejection fraction (n=169). The change of the Kansas City Cardiomyopathy Questionnaire (KCCQ), EuroQOL 5 dimensions, and Functional Assessment of Cancer Therapy—Anemia over 12 months, and its association with a composite of death or rehospitalization within 3 years were assessed. At baseline, the KCCQ overall summary score was 73 (interquartile range, 53–86) in HFpEF and 78 (interquartile range, 56–90) in HF with reduced ejection fraction (P=0.22). Overall, 30.5% of patients with HF experienced ≥5‐point improvements and 32.4% had ≥5‐point worsening in KCCQ overall summary score at 12 months, which did not differ between HFpEF and HF with reduced ejection fraction (P=0.23). Clinical events were higher in patients with HF who had a decline in KCCQ over 12 months as compared with those with stable KCCQ scores (70.2% versus 52.0%, P=0.012). The results were similar for the Functional Assessment of Cancer Therapy—Anemia and EuroQOL 5 dimensions. Conclusions In patients with HF, the KCCQ quantified clinically meaningful changes over time, which were associated with important clinical outcomes in patients with HFpEF. Given the observed variability and prognostication in different patient trajectories, health‐related quality of life measures could be valuable for quantifying the quality of care in healthcare systems.

Background There are conflicting data regarding the benefit of primary prevention implantable cardioverter‐defibrillators (ICDs) in patients with diabetes mellitus and heart failure (HF) with reduced ejection fraction. We aimed to assess the comparative effectiveness of ICD placement in patients with diabetes mellitus and HF with reduced ejection fraction. Methods and Results Data were obtained from the Get With the Guidelines–Health Failure registry, linked with claims from the Centers for Medicare & Medicaid Services. We used a Cox proportional hazards model censored at 5 years with propensity score matching. Of the 17 186 patients with HF with reduced ejection fraction from the Centers for Medicare & Medicaid Services claims database (6540 with diabetes mellitus; 38%), 1677 (646 with diabetes mellitus; 39%) received an ICD during their index HF hospitalization or were prescribed an ICD at discharge. Patients with diabetes mellitus and an ICD (n=646), as compared with those without an ICD (n=1031), were more likely to be younger (74 versus 78 years of age) and have coronary artery disease (68% versus 60%). After propensity matching, ICD use among patients with diabetes mellitus, as compared with those without an ICD, was associated with a reduced risk of all‐cause mortality at 5 years after HF discharge (54% versus 59%; multivariable hazard ratio, 0.73; 95% CI, 0.64–0.82; P

PurposeChronic heart failure (CHF) is characterized by heightened sympathetic nervous activity, carotid chemoreceptor (CC) sensitivity, marked exercise intolerance and an exaggerated ventilatory response to exercise. The purpose of this study was to determine the effect of CC inhibition on exercise cardiovascular and ventilatory function, and exercise tolerance in health and CHF.MethodsTwelve clinically stable, optimally treated patients with CHF (mean ejection fraction: 43 ± 2.5%) and 12 age- and sex-matched healthy controls were recruited. Participants completed two time-to-symptom-limitation (TLIM) constant load cycling exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg⋅kg–1⋅min–1; order randomized). Ventilation was measured using expired gas data and operating lung volume data were determined during exercise by inspiratory capacity maneuvers. Cardiac output was estimated using impedance cardiography, and vascular conductance was calculated as cardiac output/mean arterial pressure.ResultsThere was no change in TLIM in either group with dopamine (CHF: saline 13.1 ± 2.4 vs. dopamine 13.5 ± 1.6 min, p = 0.78; Control: saline 10.3 ± 1.2 vs. dopamine 11.5 ± 1.3 min, p = 0.16). In CHF patients, dopamine increased cardiac output (p = 0.03), vascular conductance (p = 0.01) and oxygen delivery (p = 0.04) at TLIM, while ventilatory parameters were unaffected (p = 0.76). In controls, dopamine improved vascular conductance at TLIM (p = 0.03), but no other effects were observed.ConclusionOur findings suggest that the CC contributes to cardiovascular regulation during full-body exercise in patients with CHF, however, CC inhibition does not improve exercise tolerance.

Background Postoperative clinical outcomes associated with the preoperative continuation or discontinuation of angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) before cardiac surgery remain unclear. Methods and Results In a single‐center, open‐label, randomized, registry‐based clinical trial, patients undergoing nonemergent cardiac surgery were assigned to ACEI/ARB continuation or discontinuation 2 days before surgery. Among the 584 patients screened, 261 met study criteria and 126 (48.3%) patients were enrolled. In total,121 patients (96% adherence; 60 to continuation and 61 to ACEI/ARB discontinuation) underwent surgery and completed the study protocol, and follow‐up was 100% complete. Postoperative intravenous vasopressor use (78.3% versus 75.4%, P=0.703), vasodilator use (71.7% versus 80.3%, P=0.265), vasoplegic shock (31.7% versus 27.9%, P=0.648), median duration of vasopressor (10 versus 5 hours, P=0.494), and vasodilator requirements (10 versus 9 hours, P=0.469) were not significantly different between the continuation and discontinuation arms. No differences were observed in the incidence of acute kidney injury (1.7% versus 1.6%, P=0.991), stroke (no events, mortality (1.7% versus 1.6%, P=0.991), median duration of mechanical ventilation (6 versus 6 hours, P=0.680), and median intensive care unit length of stay (43 versus 27 hours, P=0.420) between the treatment arms. Conclusions A randomized study evaluating the routine continuation or discontinuation of ACEIs or ARBs before cardiac surgery was feasible, and treatment assignment was not associated with differences in postoperative physiological or clinical outcomes. These preliminary findings suggest that preoperative ACEI/ARB management strategies did not affect the postoperative course of patients undergoing cardiac surgery. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02096406.

BackgroundAs questions have been raised about the appropriateness of direct oral anticoagulant (DOAC) dosing among outpatients with atrial fibrillation, we examined this issue in patients being managed by primary care providers. Methods and ResultsThis was a retrospective cohort new‐user study using electronic medical records from 744 Canadian primary care clinicians. Potentially inappropriate DOAC prescribing was defined as prescribing lower or higher doses than those recommended by guidelines for patients with nonvalvular atrial fibrillation. Of the 6658 patients with nonvalvular atrial fibrillation who were prescribed a DOAC (mean age: 74.8; 55% male), 626 (9.4%) had a CHADS2 score of 0, and 168 (2.5%) had a CHADS‐VASc score of 0. Of the DOAC prescriptions, 527 (7.7%) were deemed potentially inappropriate: 496 (7.2%) were potentially underdosed, and 31 (0.5%) were prescribed a dose that was higher than recommended. Patients were more likely to be prescribed lower‐than‐recommended doses if they were female (adjusted odds ratio [aOR]: 1.3 [95% confidence interval (CI), 1.0–1.5]), had multiple comorbidities (aOR: 1.4 [95% CI, 1.1–1.8])—particularly heart failure (aOR: 1.6 [95% CI, 1.2–2.0]) or dementia (aOR: 1.4 [95% CI, 1.1–1.8])—or if they were also taking aspirin (aOR: 1.7 [95% CI, 1.3–2.1]) or nonsteroidal anti‐inflammatory drugs (aOR: 1.2 [95% CI, 1.02–1.5]). Potentially inappropriate DOAC dosing was more common in rural practices (aOR: 2.1 [95% CI, 1.7–2.6]) or smaller practices (aOR: 1.9 [95% CI, 1.6–2.4] for practices smaller than median). ConclusionsThe vast majority of DOAC prescriptions in our cohort of primary care–managed patients appeared to be for appropriate doses, particularly since prescribing a reduced dose of DOAC may be appropriate in frail patients or those taking other medications that predispose to bleeding.

BackgroundHigher body mass index (BMI) is associated with lower circulating levels of N‐terminal‐pro‐b‐type natriuretic peptide (NT‐proBNP). The Interaction between BMI and NT‐proBNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. Methods and ResultsA total of 686 patients from the biomarker substudy of the ASCEND‐HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT‐proBNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI