Heart Failure Cohort Research Articles

Prognostic impact of gait speed, muscle strength and muscle mass in chronic heart failure-A prospective cohort study.

Heart failure (HF) impairs skeletal muscle mass and function, which contributes to reduced physical performance. We investigated the prognostic impact of gait speed (GS), handgrip strength (HG) and appendicular skeletal muscle index (ASMI) on cardiovascular outcomes in a prospective HF cohort. This single-centre prospective cohort study included adults with stable chronic HF with a previous diagnosis of overtly reduced left ventricular ejection fraction (LVEF) <40% and LVEF<50% at enrolment. GS was measured by the 4m GS test, maximal HG was measured with a hydraulic dynamometer, and ASMI was measured by dual-energy X-ray absorptiometry. The primary combined outcome was cardiovascular death or worsening HF. Fine and Gray regression models were calculated, treating non-cardiovascular death as the competing event. Two hundred five patients (78% male) were analysed. The median age was 66 (quartiles: 58-74) years, 31% had diabetes mellitus, and the median LVEF was 37 (30-43) %. Median GS was 1.0 (0.8-1.0) m/s, median HG was 32 (24-40) kg, and median ASMI was 8.0 (7.2-8.9) kg/m2. During a median follow-up of 4.7 (4.0-5.3) years, the primary outcome was observed in 52 patients. In models adjusted for key clinical covariates, lower GS predicted a higher risk of cardiovascular death or worsening HF [subdistribution hazard ratio (SHR) per 0.1m/s increase=0.81, 95% confidence interval (CI) 0.68-0.95], whereas HG (SHR per 5kg increase=0.97, 95% CI 0.84-1.10) and ASMI (SHR per 1kg/m2 increase=1.17, 95% CI 0.94-1.44) did not. In the analysis of effect modification, these associations were consistent across key clinical subgroups. Higher GS was independently associated with a lower risk of cardiovascular death or worsening HF, whereas HG and ASMI were not. We prospectively confirm GS as a physical performance measure with clear prognostic significance for patients with HF.

Prevalence and clinical correlates of chronic obstructive pulmonary disease in heart failure patients: a cross-sectional study in China

BackgroundDespite chronic obstructive pulmonary disease’s (COPD)'s prevalence in the general populace, its incidence in heart failure (HF) patients is understudied. This study aimed to assess COPD prevalence and clinical associations in Chinese HF patients.MethodsFrom the Chinese Heart Failure Study, demographic and clinical details of 2008 HF patients were analyzed. Divided into 233 COPD cases and 1775 non-COPD controls, a multivariable logistic regression identified factors linked to COPD onset in HF, with thorough examination of intergroup clinical differences.ResultsThe incidence of COPD in HF individuals was 11.60% (233/2008). The COPD subgroup featured a higher ratio of individuals over 60 and males, alongside lower systolic blood pressure (SBP), body mass index (BMI), higher Charlson Comorbidity Index (CCI) scores, and increased PaCO₂ levels (p &amp;lt; 0.05). Type II respiratory failure and right ventricular dysfunction (RVD) were more prevalent in the COPD subgroup (p &amp;lt; 0.001). Binary logistic regression, after adjustments, indicated positive associations between COPD and age over 60 (OR = 3.831, 95%CI: 1.085–13.526, p = 0.037), male sex (OR = 1.587, 95%CI: 1.032–2.441, p = 0.036), higher CCI (OR = 2.214, 95%CI: 1.796–2.729, p &amp;lt; 0.001), elevated PaCO2 (OR = 1.035, 95%CI: 1.015–1.055, p &amp;lt; 0.001), and RVD (OR = 0.605, 95%CI: 0.119–3.063, p = 0.544). Inversely, higher SBP (OR = 0.990, 95%CI: 0.982–0.998, p = 0.020) and log (triglycerides) (OR = 0.183, 95%CI: 0.064–0.552, p = 0.002) were negatively correlated with COPD in HF patients.ConclusionIn a large cohort of Chinese Heart Failure (HF) patients, our study revealed a notable COPD prevalence. Key risk factors included age, sex, elevated PaCO2, CCI score, and right heart failure, while higher SBP and triglyceride levels offered protection. These insights lay groundwork for probing disease mechanisms and therapeutic approaches.

Patients with chronic heart failure and predominant left atrial versus left ventricular myopathy

BackgroundLeft atrial (LA) and ventricular (LV) functional impairment often co-exist in patients with heart failure (HF). However, some patients with HF have a disproportionate LA or LV dysfunction. We aimed to characterize patients with predominant LA and LV myopathy in a cohort of patients with chronic HF across the spectrum of LV ejection fraction (LVEF).MethodsFrom a nationwide, prospective, multi-center, observational HF cohort, transthoracic echocardiographic examination was performed on each patient. LA reservoir strain and LV global longitudinal strain (LVGLS) were measured using dedicated software of the two-dimensional speckle tracking analysis to evaluate LA and LV function and to define the myopathy.ResultsA total of 374 patients with chronic HF (mean age 58.9±11.5 years, 20% female, mean LVEF 39±17%) were included. By calculating the residuals from the linear regression between LA reservoir and LVGLS, we identified 47 patients with predominant LA myopathy, 271 patients with balanced LA/LV and 56 patients with predominant LV myopathy. Patients with predominant LA myopathy were older, had a higher prevalence of atrial fibrillation (AF), diabetes, higher plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), Growth differential factor 15(GDF15), high sensitivity Troponin T (hs-TNT) as well as more dilated left and right atria, and worse right atrial function compared to other groups (all p-values < 0.05). Using multivariable logistic regression adjusted for LVEF and LA size, independent predictors of predominant LA myopathy were the presence of AF, diabetes, and higher GDF15, whereas absence of diabetes independently predicted predominant LV myopathy. Patients with predominant LA myopathy group had a lower probability of survival than the other groups (Log rank p-value = 0.01).ConclusionWhile most patients with HF have balanced LA/LV myopathy, those with predominant LA myopathy are characterized by older age, more AF, more diabetes, higher circulating biomarkers of cardiac stress and injury, and worse outcomes.

How to demonstrate the causal relationship between sodium-glucose cotransporter 2 receptor and prevention of ventricular arrhythmia in heart failure cohorts

How to demonstrate the causal relationship between sodium-glucose cotransporter 2 receptor and prevention of ventricular arrhythmia in heart failure cohorts

Validation Against Polysomnography of a Transthoracic Impedance Sensor for Screening of Sleep Apnea in Heart Failure Patients: A Pooled Analysis of AIRLESS and UPGRADE.

Background/Introduction: Cardiac implantable electronic devices and their integrated thoracic impedance sensors have been used to detect sleep apnea for over a decade now. Despite their usage in daily clinical practice, there are only limited data on their diagnostic accuracy. Methods: AIRLESS and UPGRADE were prospective investigator-driven trials meant to validate the AP scan® (Boston Scientific, Marlborough, MA, USA) in heart failure cohorts. Patients, who either fulfilled the criteria for implantation of an implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), or upgrading to CRT according to most recent guidelines at the time of study conduction, were eligible for enrolment. Sleep apnea and its severity, measured by apnea-hypopnea index (AHI), were assessed by polysomnography. For direct comparison, the apnea sensor-derived AP scan® was used from the identical night. Results: Overall, 80 patients were analyzed. Median AHI was 21.6 events/h (7.1-34.7), while median AP scan® was 33.0 events/h (26.0-43.0). In the overall cohort, the sensor-derived AP scan® correlated significantly with the AHI (r = 0.61, p < 0.001) with a mean difference (MD) of -12.6 (95% confidence interval (CI) -38.2 to 13.0). Furthermore, the AP scan® was found to correlate well with the AHI in patients with obstructive sleep apnea r = 0.73, p = 0.011, MD -5.2, 95% CI -22.7 to 12.3), but not central sleep apnea (r = 0.28, p = 0.348, MD -10.4, 95% CI -35.4 to 14.6). Conclusions: In an exclusive heart failure cohort, the AP scan® correlated well with the PSG-derived AHI. A similar correlation was found in most subgroups except for patients suffering from central sleep apnea.

Presence of Myocardial Fibrosis on Cardiac MRI and its Impact on Short-Term Outcomes in an Asian Cohort of Heart Failure with Preserved Ejection Fraction

Presence of Myocardial Fibrosis on Cardiac MRI and its Impact on Short-Term Outcomes in an Asian Cohort of Heart Failure with Preserved Ejection Fraction

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better

BackgroundSodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.MethodsFrom January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′ < 15; B: SV ≥ 35 ml/m2; E/e′ ≥ 15; C: SV < 35 ml/m2; E/e′ < 15; D: SV < 35 ml/m2; E/e′ ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups.ResultsDapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e′ ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S′ velocity [RVs’], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497).ConclusionsWe demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Evaluating a New Short Self-Management Tool in Heart Failure Against the Traditional Flinders Program.

Background/Objective: Heart failure (HF) is a complex syndrome, with multiple causes. Numerous pathophysiological pathways are activated. Comprehensive and guideline-derived care is complex. A multidisciplinary approach is required. The current guidelines report little evidence for chronic disease self-management (CDSM) programs for reducing readmission and major adverse cardiovascular events (MACE). CDSM programs can be complex and are not user-friendly in clinical settings, particularly for vulnerable patients. The aim of this study was to investigate whether a simplified one-page CDSM tool, the SCReening in Heart Failure (SCRinHF), is comparable to a comprehensive Flinders Program of Chronic Disease Management, specifically in triaging self-management capabilities and in predicting readmission and MACE. Methods:SELFMAN-HF is a prospective, observational study based on community cardiology. Eligible patients, consecutively recruited, had HF with left ventricular ejection fraction <40% and were placed on sodium-glucose co-transporter-2 inhibitors (SGLT2-i) within 3 months of recruitment. SGLT2-i is the newest of the four HF treatment pillars; self-management skills are assessed at this juncture. CDSM was assessed and scored independently via the long-form (LF) and short-form (SF) tools, and concordance between forms was estimated. The primary endpoint is the 80% concordance across the two CDSM scales for predicting hospital readmission and MACE. Results: Of the 117 patients, aged 66.8 years (±SD 13.5), 88 (75%) were male. The direct comparisons for SF versus LF patient scores are as follows: "good self-managers", 13 vs. 30 patients (11.1% vs. 25.6%); "average", 46 vs. 21 patients (39.3% vs. 17.9%), "borderline", 20 vs. 31 patients (17.1% vs. 26.5%), and "poor self-managers" (vulnerable), 38 vs. 35 patients (32.5% vs. 29.9%). These findings underscore the possibility of SF tools in picking up patients whose scores infer poor self-management capabilities. This concordance of the SF with the LF scores for patients who have poor self-management capabilities (38 vs. 35 patients p = 0.01), alongside readmission (31/38 vs. 31/35 p = 0.01) or readmission risk for poor self-managers versus good self-managers (31/38 vs. 5/13 p = 0.01), validates the simplification of the CDSM tools for the vulnerable population with HF. Similarly, when concurrent and predictive validity was tested on 52 patients, the results were 39 (75%) for poor self-managers and 14 (27%) for good self-managers in both groups, who demonstrated significant correlations between SF and LF scores. Conclusions: Simplifying self-management scoring with an SF tool to improve clinical translation is justifiable, particularly for vulnerable populations. Poor self-management capabilities and readmission risk for poor self-managers can be significantly predicted, and trends for good self-managers are observed. However, correlations of SF to LF scores across an HF cohort for self-management abilities and MACE are more complex. Translation to patients of all skill levels requires further research.

Exercise limitations in amyloid cardiomyopathy assessed by cardiopulmonary exercise testing-A multicentre study.

Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy. We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO2). Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO2 of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO2) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO2 slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P<0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161ng/L, P<0.001), peak heart rate (121±28 vs. 115±27 beats/min, P=0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53L/min, P<0.0001) with earlier anaerobic threshold (VO2 at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7mL/min/kg, P<0.0001) compared with HF. Between amyloid patients, AL patients (n=27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81years, P<0.0001), had lower VE/VCO2 slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P=0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1±4.8 vs. 31.4±4.7mmHg, P<0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33mmHg, P=0.039) as compared with ATTR (n=233). A higher VE/VCO2 slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL.

Abstract 4128369: Inpatient Mortality After Catheter Ablation for Atrial Fibrillation Among Heart Failure Patients: A 6-Year Nationwide Analysis

Background: Significant advancements have been made in the safety of catheter ablation for atrial fibrillation (AF) over the past decade. However, large-scale data regarding inpatient mortality among heart failure (HF) patients (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) who undergo AF ablation are lacking. Aim: To compare mortality rates and trends between patients with HF (HF group) and without HF (non-HF group) following AF catheter ablation. Methods: The National Inpatient Sample was utilized from January 2015 to December 2020 to identify the study population using the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification. The primary outcome was in-hospital mortality for patients with and without HF undergoing ablation for AF, and the secondary outcome was mortality in patients with HFrEF compared with those with HFpEF. Results: We evaluated 142,860 patients hospitalized for AF who underwent catheter ablation. Of these, 42.2% (n=60,334) had HF (29% HFrEF; 71% HFpEF). The HF cohort was older (69.7 years) and predominantly male (61.3%) compared with non-HF (66.7 years, P&lt;.001 and 55.7%, P&lt;0.00, respectively). Overall mortality in the HF group was 3-fold higher (1.6% vs 0.5%, P&lt;.001). Within the HF group, mortality in HFrEF was 1.8 times higher than in HFpEF (2.4% vs 1.3%, P&lt;.001). Over the study period, mortality rates declined in the HF cohort (Fig. 1A), both in HFrEF (from 4.1% to 2.2%, P=.012) and HFpEF (from 2.7% to 1.3%, P=.006) (Fig 1B). In non-HF, mortality rates remained relatively unchanged during the study period (from 1.4% to 1.6%, P=.344). Conclusion: Overall mortality following AF ablation is relatively low. Despite the higher mortality observed in patients with HF, the overall rate declined in both HFrEF and HFpEF over the study period. This reduction in mortality may reflect improvements in HF treatment and ablation techniques. Further research is needed to elaborate on the factors contributing to these trends and to develop targeted interventions to reduce mortality in this high-risk population.

Abstract 4140148: Genetic Influence in Patients Transplanted for Myocarditis in the TOPMed-TOPCHeF Cohort of Explanted Hearts

Background: Myocarditis is a leading cause of secondary cardiomyopathy and stems from infection, medications, or immune etiologies. Recent reports identify an overlap between myocarditis and pathogenic / likely pathogenic (P/LP) genetic variants of dilated and arrhythmogenic cardiomyopathies (DCM/ACM). Hypothesis: We hypothesized that myocarditis leading to heart failure and transplantation could be influenced by P/LP mutations for DCM/ACM. Aims: To evaluate the impact of genetics in myocarditis, we investigated a series of patients presenting with symptoms consistent with myocarditis who were found to have P/LP genetic signatures for dilated and arrhythmogenic cardiomyopathies DCM/ACM. Methods: Patients with myocarditis, defined by retrospective clinical diagnosis, were selected from the NHLBI Trans-Omics for Precision Medicine (TOPMed) - Trans-Omics for Precision Medicine for Congestive Heart Failure (TOPCHeF) cohort. After informed consent, patients’ explanted hearts were collected in the University of Colorado Heart Tissue Bank. A total of 837 hearts (697 failing and 140 control hearts) underwent whole genome DNA sequencing (WGS). Results: 11 patients had a diagnosis of myocarditis based on clinical history. None had acute myocarditis at time of transplantation. P/LP variants in DCM/ACM genes were found in 6 patients. The average age at transplantation was 42.8 years for patients with genetic variants and 38.9 without. Demographics are included in table 1. The most common genetic variants were Titin truncations. Full genetic data are included in table 2. Conclusion: 50% of patients undergoing transplantation with a clinical diagnosis of myocarditis in the TOPMed-TOPCHeF population had P/LP variants in DCM/ACM genes. This underscores the importance of genetic testing in patients with a clinical presentation of myocarditis for future management implications.

Abstract 4123872: Unsupervised clustering analysis of large-scale proteomics data identifies molecular phenogroups of heart failure in a population-based cohort

Background: Heart failure (HF) is a heterogeneous syndrome with high mortality. Previous work characterizing HF subgroups primarily relied on clinical data to cluster patients, an approach constrained by the boundaries of documented clinical features. Clustering based on biomarker data, such as proteomics, may provide insights into underlying molecular processes. However, few studies have used this approach, and all used targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. Hypothesis: We used unsupervised clustering analysis to characterize molecular phenogroups in a population-based HF cohort using a large-scale array of circulating plasma proteins. We hypothesized that distinct proteomic-defined phenogroups would exhibit differences in clinical characteristics, mortality, and protein expression. Methods: We measured 7151 SOMAmers (Slow off-rate modified aptamers) targeting human proteins via the SomaLogic 7K SomaScan assay in 1351 HF patients. After feature selection, 831 SOMAmers were used in k-means clustering of patients via R package “ConsensusClusterPlus.” Phenogroups were compared for clinical characteristics, all-cause mortality, and protein expression. Results: Three phenogroups were identified, exhibiting different clinical characteristics ( Table 1 ) and survival probabilities (5-year survival probability in phenogroup 1: 65% [61%, 68%], phenogroup 2: 45% [40%, 51%], and phenogroup 3: 26% [22%, 30%]). In covariate-adjusted Cox models, membership in phenogroups 2 and 3 was significantly associated with increased rate of mortality compared to phenogroup 1. Phenogroups did not differ by ejection fraction or New York Heart Association class. Pathway overrepresentation analysis of differentially expressed SOMAmers identified pathways associated with inflammatory response and immune cell trafficking. Conclusions: Unsupervised clustering analysis using large-scale proteomics data identified three HF phenogroups with different proteomic signatures, clinical characteristics, and outcomes. Future work is necessary to elucidate how molecular differences contribute to heterogeneity in HF to improve risk stratification beyond current recommended clinical guidelines.

Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013–2019

Aims/hypothesisThe aim of this study was to investigate racial and ethnic disparities in the use of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) among older adults with type 2 diabetes and cardiorenal conditions.MethodsUsing Medicare fee-for-service data (2013–2019), this retrospective cohort study identified older adults (≥65 years) with type 2 diabetes initiating second-line therapies (SGLT2is, GLP1-RAs, dipeptidyl peptidase-4 inhibitors [DPP4is] and sulfonylureas [SUs]) with (1) heart failure (HF), (2) atherosclerotic cardiovascular disease (ASCVD), (3) chronic kidney disease (CKD) and (4) no recorded cardiorenal conditions. Participants were classified as non-Hispanic White, non-Hispanic Black and Hispanic. Multinomial regressions, adjusting for sociodemographic, clinical and county-level characteristics, were used to model the odds of initiating SGLT2is or GLP-1RAs within each cohort.ResultsBlack participants with HF, ASCVD, CKD or no recorded cardiorenal conditions had 35% (adjusted OR 0.65 [95% CI 0.61, 0.68]), 33% (0.67 [0.64, 0.69]), 32% (0.68 [0.64, 0.72]) and 24% (0.76 [0.74, 0.79]) lower odds of initiating SGLT2is, respectively, than White participants. Disparities ameliorated from 50–60% lower odds in 2013 to 17–18% in 2019. Similar patterns were observed for GLP-1RA uptake among Black participants. By contrast, Hispanic participants had similar odds of SGLT2i initiation in the HF and CKD cohorts as White participants, but 6% (0.94 [0.91, 0.98]) lower odds in the ASCVD cohort. Notable disparities for Hispanic participants compared with White participants were observed for GLP-1RA uptake in the HF, ASCVD, CKD and no cardiorenal conditions cohorts: 11% (0.89 [0.84, 0.94]), 16% (0.84 [0.81, 0.87]), 16% (0.84 [0.80, 0.89]) and 25% (0.75 [0.72, 0.78]) lower odds, respectively. Participants had greater odds than White participants of initiating DPP4is, which confer no cardiorenal benefits, across all cohorts (HF 1.25 [1.19, 1.31]; ASCVD 1.36 [1.32, 1.40]; CKD 1.32 [1.26, 1.38). Adjustment for social determinants of health did not meaningfully change the study findings.Conclusions/interpretationCompared with White participants, disparities in the uptake of SGLT2is were evident for Black participants, and in the uptake of GLP-1RAs for both Black and Hispanic participants. This study highlights how type 2 diabetes management is evolving, while underscoring historical imbalances that have shown signs of abatement.Graphical

Rural-Urban Disparities in Mortality of Patients with Acute Myocardial Infarction and Heart Failure: A Systematic Review and Meta-Analysis.

Patients with cardiac disease living in rural areas may face significant challenges in accessing care and studies suggest that living in rural areas may be associated with worse outcomes. However, it is unclear whether rural-urban disparities have an impact on mortality in patients presenting with acute myocardial infarction (AMI) and heart failure (HF). This meta-analysis aimed to assess differences in mortality between rural and urban patients presenting with AMI and HF. A systematic search of the literature was performed using PubMed, Embase, MEDLINE and CENTRAL for all studies published until January 16, 2024. A grey literature search was also performed using a manual web search. The following inclusion criteria were applied: (i) studies must compare rural patients to urban patients presenting to hospital with AMI or HF; and (ii) studies must report on mortality. The primary outcome was all-cause mortality. Comprehensive data were extracted including study design, patient characteristics (sex, age and comorbidities), sample size, follow-up period and outcomes. Odds ratios (ORs) were pooled with random-effects model. A subgroup analysis was performed to investigate causes for heterogeneity in which studies were separated based on in-hospital mortality, post-discharge mortality, and region of origin including North America, Europe, Asia and Australia. In total, 37 studies were included (29 retrospective studies, 4 cross-sectional studies and 4 prospective cohort studies) in our meta-analysis; 24 studies for AMI, 11 studies for HF and 2 studies for both AMI and HF. This included a total of 21,107,886 patients with AMI (2,230,264 of which were in rural regions) and 18,434,270 patients with HF (2,655,469 of which were in rural regions). Rural patients with AMI had similar age (mean age 69.8 +/- 5.7; vs 67.5 +/- 5.1) and were more likely to be female (43.2% vs 38.5%) compared to urban patients. Rural patients with HF had similar age (mean age 77.1 +/- 4.4 vs 76.5 +/- 4.2) and were more likely to be female (56.4% vs 49.5%) compared to urban patients. The range of follow-up for the AMI cohort was 0 days to 24 months and the range of follow-up for the HF cohort was 0 days to 24 months. Compared with urban patients, rural patients with AMI had higher mortality rate at follow-up (15.5% vs 13.4%; OR 1.18, 95% CI, 1.13-1.24; I2 = 97%). Compared with urban patients, rural patients with HF had higher mortality rate at follow-up (12.3% vs 11.6%; OR 1.11, 95% CI, 1.11-1.12; I2 = 98%). To our knowledge, this is the first systematic review and meta-analysis assessing mortality differences between rural and urban patients presenting with AMI and HF. We found that patients living in rural areas had an increased risk of mortality when compared to patients in urban areas. Clinical and policy efforts are required to reduce these disparities.

Multimorbidity patterns in adults admitted to hospital with heart failure: an analysis of 175 million hospitalisation episodes

Abstract Background The prevalence of heart failure (HF) is increasing as a result of population ageing, improved survival following myocardial infarction and the widespread uptake of evidence-based HF treatments. Greater understanding of multimorbidity patterns in patients with HF may enable the development of treatment strategies that target multiple, related long-term conditions (LTCs), producing synergistic benefits. Purpose To characterise multimorbidity patterns in patients with HF and compare these to a matched population without HF. Methods A retrospective matched cohort study was conducted using the United States National Readmission Database (NRD), 2010–2020. International Classification of Disease (ICD) codes were used to identify HF and 92 other common LTCs. The most frequent combinations of LTCs were identified for individuals with HF and a control cohort of individuals of the same age and sex, with a non-HF-related hospital admission in the same year (matched in a 1:5 ratio). Multivariable regression analysis (adjusted for age, sex, socioeconomic status, tobacco use, year of hospitalisation, and hospital characteristics) was used to evaluate the association between multimorbidity burden, length of stay (LOS; negative binomial regression) and 30-day readmission (logistic regression). Results From a total of 175,388,410 hospitalisation episodes, 3,913,924 individuals with an HF-related hospitalisation were identified and matched to 19,552,954 controls (Figure 1a). The median (interquartile range, IQR) age of a patient admitted with HF was 74 (63–85) years; 1,856,268 (47.5%) were female. The most common comorbidities in those with HF were hypertension (87.2 vs. 72.8% in matched controls), chronic kidney disease (CKD; 55.3 vs. 34.6%), coronary artery disease (CAD; 53.7 vs. 31.0%), dyslipidaemia (46.9 vs. 39.7%), diabetes (46.6 vs. 33.9%), atrial fibrillation (AF; 43.0 vs. 23.0%) and anaemia (33.2 vs. 30.1%; p all &amp;lt; 0.001). Patients with HF had a greater number of LTCs compared with matched controls (median [IQR] 7 [5–9] vs. 6 [4–8]; p &amp;lt; 0.001). From 2010–2020, the number of LTCs in those with an HF admission increased (from 6 [4–8] in 2020, to 8 [6–10] in 2020; Figure 1b). The most common multimorbidity patterns in those with HF are presented in Figure 2. In the HF cohort, a greater multimorbidity burden was associated with a longer LOS (+6% for each additional LTC; 95% confidence interval [CI] 5–7%; p&amp;lt;0.001) and greater risk of 30-day readmission (adjusted odds ratio [aOR] for 6 vs. 0 LTCs: 1.15, 95% CI 1.08–1.22; aOR for ≥12 vs. 0 LTCs: 1.54, 95% CI 1.45–1.64). Conclusions Patients admitted to hospital with HF have a significant burden of multimorbidity, which has increased over time and is associated with increased length of stay and unplanned hospital re-admission. The high prevalence of multiple LTCs warrants the development of novel treatment strategies that target common multimorbidity patterns observed in HF.

Trends in heart failure mortality in Sweden between 1997 and 2022.

Data from US have shown a reversal in the improvement of heart failure (HF)-related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF-related mortality in the overall national population; and (ii) all-cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022. Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All-cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age-adjusted HF-related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC -2.15%, p < 0.001). In the HF cohort from NPR (n = 423 092), all-cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1-year mortality declined (AAPC -1.10%, p < 0.001) over time regardless of age or sex. In SwedeHF (n = 63 753), the decline in 1-year mortality was less steep with increasing EF (AAPC -2.64%, p < 0.001; -2.30%, p = 0.062; and -2.16%, p = 0.032 in EF <40%, 40-49%, and ≥50%, respectively). Heart failure-related mortality has declined over the last ~25 years in Sweden. All-cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life-saving treatments across the EF spectrum.

Outcomes in patients with light chain cardiac amyloidosis undergoing heart transplantation: a single centre UK study

Abstract Background Light chain cardiac amyloidosis (AL-CA) results in restrictive cardiomyopathy associated with progressive heart failure and poor survival. Traditionally, outcomes following heart transplantation in patients with AL-CA have been worse than in other heart failure cohorts and consequently, many centres do not offer this population transplantation. Purpose and Methods This was a retrospective observational study of 18 patients with AL-CA (age 52.7years +/- 8.3, male 66%) referred to our centre in the UK for assessment for heart transplantation from 2008 to 2023. Seven patients (39%) were listed for transplant, and all received orthotopic heart transplantation (OHT). This study compared pre-transplantation characteristics in those offered cardiac transplantation with those not transplanted. We also examined post-transplantation outcomes in this group (n=7) compared with the overall heart transplantation population (n=95) at our centre. Results Patients with AL-CA who were not offered transplantation (n=11) were older (mean age 54.3 vs 50.3 years), were more likely male (72% vs 57%) but had similar baseline renal function to those transplanted (median eGFR 60.4 vs 54.2ml/min). Reasons against offering OHT included extensive multisystem or renal amyloid deposition (n=4), insufficient haematological response (n=2), heart failure not advanced enough for OHT (n=1) and malignancy (n=1). Pre-transplant right heart catheterisation of patients undergoing OHT demonstrated a mean transpulmonary gradient of 7.8mmHg (+/- 1.9) and cardiac output of 2.94/min (+/- 0.3). Five patients (71%) had a complete and two (29%) a partial haematological response to clonally directed chemotherapy. Three patients were bridged to transplant with biventricular assist devices for 9, 10 and 51 days, respectively. Five patients developed episodes of histologically confirmed rejection of grade 2R that resolved with medical management. One patient experienced first degree atrioventricular block and had a pulseless electrical activity arrest 19 days after transplantation before being fitted with a permanent pacemaker. Two patients went on to receive autologous stem cell transplantation. Patients with AL-CA undergoing OHT had a lower mortality rate compared with non-transplanted patients over a median follow up of 9 months (HR 0.3, 95%CI 0.07-1.3, p = 0.10). Two patients with AL-CA died at 42 days and 7.7 years after OHT. Five patients (71%) are alive under follow up at 4, 7.5, 9, 10 months and 7.7 years post OHT. There was no difference in survival between patients who underwent heart transplantation for AL-CA and patients who underwent heart transplantation for all other indications (HR 1.94, 95%CI 0.3 – 12, p=0.45). Conclusions In selected patients with AL-CA, OHT offers favourable outcomes. After clonally directed therapy to control the underlying plasma cell dyscrasia, heart transplantation should be considered in the absence of widespread systemic disease.

Comparing de novo heart failure and acute decompensated heart failure using a proteomic approach

Abstract Background Acute heart failure (HF) is defined as new or worsening symptoms of HF and stands as the most common cause of unscheduled hospital admission in patients above the age of 65. Acute HF can be classified into de novo HF (DNHF), defined as no previous history of HF, and acutely decompensated HF (ADHF), defined as worsening symptoms of HF in individuals with a prior diagnosis of HF. Clinically, it is relevant to distinguish ADHF from DNHF as they differ regarding aetiology, comorbidities, mortality, and morbidity. The aim of this study was to compare DNHF and ADHF using a proteomic approach. Method Using a proximity extension assay in a Swedish HF cohort, a total of 324 individuals hospitalized for acute HF underwent proteomic analysis of 92 proteins. The population was categorized into DNHF and ADHF, subsequently comparing normally distributed proteins using an independent samples t-test. Non-normally distributed proteins were compared using the Mann-Whitey U-test. To adjust for multiple testing, Benjamini Hochberg method was applied with a false discovery rate of 5%. Fold change was calculated by subtracting the mean or median protein concentration in ADHF from DNHF. As protein concentrations are expressed on a log2-scale, the difference between the groups equals the fold change. Proteins were considered differentially expressed at a fold change threshold of 1.15. The proteins that met a cut-off, were thereafter analysed with a pathway enrichment analysis using Reactome (only a corrected p-value ≤0.05 was considered significant). Results Complete data was available for n=317 (30.3% women; mean age 74.6) individuals (Table 1). After FDR adjustment, differential protein expression analysis yielded 56 differentially expressed proteins. After applying the fold change threshold, 51 proteins were significantly up regulated in ADHF compared to DNHF and one (Paraoxonase 3) was significantly downregulated. The most prominently up-regulated protein was fatty acid binding protein-4 (FABP4) (fold change 1.68, p &amp;lt;0.001). The largest number of proteins were related to neutrophil degranulation (Figure 1). Conclusion In patients hospitalized for acute HF, we identified several common pathways of the proteins differentially expressed in DNHF compared with ADHF. Neutrophil degranulation was related to the largest number of proteins. The most prominently up regulated protein was FABP4. These findings may inspire future investigation into the different underlying molecular mechanisms in ADHF and DNHF and reveal potentially different targets of treatment between the two conditions.Figure 1.Pathway enrichment analysis

Fully automated measurements of echocardiographic mechanical dispersion using deep learning: enhanced prediction of ventricular arrhythmias in a large heart failure cohort

Abstract Background Assessment of left ventricular (LV) myocardial deformation by strain echocardiography has shown improved prognostic value over LV ejection fraction (LVEF). Mechanical dispersion (MD) by strain reflects deformation heterogeneity. Also, MD is a marker of ventricular arrhythmia (VA) that improves risk prediction independently of LVEF in patients with heart failure. However, to analyze MD is time consuming and operator-dependent, and clinical use remains limited. Purpose We aimed to investigate the performance of a novel deep learning (DL) based method for fully automated measurements of MD and evaluate its prognostic utility in patients with heart failure compared to a conventional speckle tracking application. Methods In this prospective multicenter follow up study, the IMPROVE study, we consecutively included patients with recently diagnosed heart failure of all cause with LVEF ≤ 40%. Echocardiograms, ECG, blood samples and clinical data were acquired during index hospitalization. All patients were treated according to contemporary guidelines with optimal medical therapy and revascularization if necessary. Two experienced cardiologists recorded all echocardiograms using Vivid E9 or E95 scanners. We obtained data regarding sudden cardiac death, ventricular arrhythmia and appropriate shock from the ICD from medical records and ICD recordings. The primary endpoint was sudden cardiac death or ventricular arrhythmia (SCD/VA) during follow-up. The prognostic value of DL-based and reference MD measurements was assessed through survival statistics. Results We included 492 patients (mean ± SD 73 ± 13 years old, 32% females). Follow-up time was median (IQR) 5 (3) years. The incidence of SCD/VA was 9% (n=45). Patients with MD ≥70ms had increased risk of SCD/VA both by DL-based and reference measurements (both p &amp;lt;0.001). Furthermore, automated MD measurements using DL had higher prognostic value (HR 4.3) compared to manual reference measurements (HR 3.1) (p &amp;lt;0.001). Conclusion Fully automated measurements of MD using a novel DL method was fast, feasible, and improved prediction of SCD/VA in patients with heart failure and reduced LVEF. The integration of DL measurements may facilitate the clinical implementation of MD assessment and improve risk prediction in echocardiography.

A standards-based software tool to support prognostic modelling: application to exemplar heart failure risk scores

Abstract Introduction Heart failure prognosis is an active research area, with the development of several new risk scores each year. While risk score derivation and evaluation have become common practices, these processes currently lack standardisation. Purpose We aimed to: i) develop a standards-based software tool to support prognostic modelling; and ii) apply the tool to derive, evaluate and compare exemplar heart failure risk models to address a hypothetical question of whether using only non-invasive measurements provides similar prognosis value compared to adding invasive measurements. Methods A software tool was developed based on a prognostic modelling workflow defined using the Common Workflow Language and containing 7 steps: univariate Cox proportional hazard (PH) regression, multivariable Cox PH regression with assessment of proportional hazards and linearity with outcome (Schoenfeld and Martingale residuals), derivation of points per risk factor, risk calculation and stratification, discrimination and calibration assessment. Using data from the PEOPLE heart failure cohort [1], two integer-based risk scores were developed to predict 2-year all-cause mortality. The first model utilised 12 variables available at recruitment informed by prior analysis of the PEOPLE cohort to provide a benchmark for comparison, while the second model is based on 9 non-invasive parameters. The analysis was conducted on cases with complete data (n=781), with no internal or external validation. Results By inputting the dataset and indicating the variables of interest for each model, our software tool automatically generated the patient-specific risk scores, risk strata, c-index, and discrimination and calibration plots. A 12-parameter model based on age, sex, ejection fraction, hypertension, diabetes, atrial fibrillation, ischaemic history, NYHA class, heart rate, systolic blood pressure, creatinine and NT-proBNP yielded reasonable discrimination (c-index=0.77). Graphical assessment of risk strata and calibration (Fig. 1.a and c) revealed good performance overall, apart from the highest risk decile where survival was overestimated. The reduced 9-parameter model excluded creatinine, NT-proBNP, and automatically dropped diabetes status for non-linearity. It showed a substantial drop in discrimination (c-index=0.67), confirmed in graphical assessment of risk strata (Fig. 1.b). Calibration was more variable per decile than seen with the 12-parameter model but was more robust to survival overestimation (Fig. 1.d). Conclusion Our software tool ensures the uniformity and comparability of the two risk models derived by a common statistical process. In this example, we showed how the addition of NT-proBNP, creatinine, and diabetes status improves discrimination for predicting heart failure survival. This tool can be leveraged to test new hypotheses in a standardised and reproducible manner to enhance research in heart failure prognosis.