bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient characteristics and mortality trends among octogenarians with heart failure over two decades - a Danish nationwide study
Authors: Garred C A H , Elmegaard M , Christensen D M , Zahir D , Malmborg M , Fosboel E , Pardeep J , Mcmurray J , Petrie M , Andersson C , Koeber L , Schou M 
Published: October 2024

Abstract

Background
Mortality rates among octogenarians with heart failure (HF) have changed little despite significant advancements in care over recent decades. Investigating the factors contributing to this trend may offer valuable insights for devising targeted management strategies for the oldest HF patients.

Purpose
We aimed to examine different patient characteristics associated with mortality among octogenarians with HF over the past 20 years.

Methods
From nationwide Danish healthcare registries, we included all patients with new-onset HF between 2001-2020 who were ≥ 80 years old at the time of diagnosis. The patients were categorized into 5-year calendar periods depending on the time of their diagnosis, the first period being between 2001-2005 and the last 2016-2020. The Kaplan-Meier estimator was used to assess the mortality risk. Mortality rates were examined with multivariable Cox regression models, comparing the first (reference) and the last calendar period and adjusting for predefined covariables.

Results
We included 47,754 octogenarian patients with new-onset HF, of whom 13,293 (51%) were diagnosed between 2001-2005 and 12,813 (49%) between 2016-2020. The distribution of males and females changed between the two calendar periods, with 5696 (43%) males in the first period and 6631 (52%) in the last period. The 3-year absolute mortality risk decreased by 8% [95% CI, 7.9-8.0] from 2001-2005 (64% [95% CI, 63.9-64.7]) to 2016-2020 (56% [95% CI, 55.3-56.7]) (p-value &lt;0.001) (Figure 1). After adjustment for covariables, patients diagnosed in the last period exhibited a mortality hazard ratio (HR) of 0.94 [CI 95% 0.90-0.99] (p-value 0.02) compared to those diagnosed in the first period. An interaction was observed between the first and the last calendar periods among patients with a history of myocardial infarction and those aged &lt;85 years. The survival rates improved over time for patients with a history of myocardial infarction (HR 0.80 [95% CI, 0.72-0.90], p-value for interaction&lt;0.001), as well as for those aged between 80 and 85 years (HR 0.86 [95% CI, 0.80-0.91], p-value for interaction&lt;0.001) (Figure 2).

Conclusion
Over two decades the mortality risk among octogenarians with HF has improved slightly, however it remains high. Patients with a history of myocardial infarction and those aged 80 to 85 years emerge as subgroups experiencing the most improved survival rates over time.3-year mortality riskMortality rates in selected subgroups
Disparities in clinical characteristics, treatment, and prognosis among immigrants and native patients in Denmark with new-onset heart failure and reduced ejection fraction
Authors: Sam Aiyad S A A , Vinding N E V , Butt J H B , Kroll J K , Larsson J E L , Schou M S , Fosbol E L F , Logstrup B B L , Schjodt I S , Jhund P S J , Kober L K , Gustafsson F G , Sattar N S , Mcmurray J M , Kristensen S L K 
Published: October 2024

Abstract

Background
Major variations exist in the causes, age at diagnosis, and outcomes of heart failure (HF) in patients from different parts of the world.

Purpose
To elucidate this issue further, we compared the characteristics and outcomes of immigrants living in Denmark and native Danish patients presenting with new-onset HF with reduced ejection fraction (HFrEF).

Methods
By linkage of the Danish Heart Failure Registry, and nationwide administrative registries, we identified patients with new onset HFrEF, from 2005-2021, grouped according to immigration status and, if not native Danish, region of origin, according to the World Bank classification. Outcomes were a 1) composite of HF hospitalization or all-cause death at 3 years follow-up, and 2) initiation and up-titration of guidelines-directed medical therapy (GDMT) at 12 months follow-up. Cox regression analyses adjusted for age, sex, calendar year, HF severity, socioeconomic status, and major comorbidities were used to compare the primary composite outcome.

Results
Of 33,297 patients included, 31,602 (97.9%) were native Danish patients (DK), 1031 (3.1%) were originally from Europe/Central Asia (EUR/CA), 439 (1.3%) from Middle East/North Africa (ME/NAF), 225 (0.7%) from South Asia (SA). The median time since immigration ranged from 20 to 30 years. Compared to DK, patients originating from ME/NAF, and SA were around 10 years younger (median age 62-64 vs. 71 years), had similar median left ventricular ejection fraction (30% vs. 30%), had lower New York Heart Association (NYHA) ≥ class III (14-16% vs. 23%), had more diabetes (39-51% vs. 20%) and ischemic heart disease (IHD) (69-75 vs. 48%), and had less atrial fibrillation (AF) (9-14% vs. 32%) (all p &lt; 0.0001), patients from EUR/CA were generally similar to DK. The crude 3-year cumulative risk of the primary composite outcome was 34% (DK), 31% (EUR/CA), 27% (SA), and 23% (ME/NAF) (Figure 1) In adjusted analyses with DK as the reference, only ME/NAF was associated with a lower risk; hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.62-0.94) (Figure 2). No major differences in the initiation and up-titration of GDMT were observed across groups.

Conclusions
Non-Western immigrants living in Denmark who presented with new-onset HFrEF had a distinct clinical profile, being generally younger, had lower NYHA class but similar LVEF, a greater prevalence of diabetes and IHD and less AF compared to native Danish patients. In addition, they had lower adjusted rates of the primary outcome of HF hospitalization or all-cause death and a similar likelihood of GDMT initiation and up-titration. The reasons for these differences deserve more research.Figure 1 Crude cumulative riskFigure 2 Adjusted rates
Influence of prior heart valve intervention on treatment and disease trajectory after diagnosis of heart failure with reduced ejection fraction
Authors: Sam Aiyad S A A , Ostergaard L M O , Ersboll M K E , Butt J G B , Petersen J K P , Begun X B , Schou M S , Gustafsson F G , Fosbol E L F , Kober L K , Kristensen L K 
Published: October 2024

Abstract

Background and aim
Among patients with heart failure with reduced ejection fraction (HFrEF), knowledge is scarce on whether patients with prior valvular heart disease (VHD) intervention are distinct regarding clinical characteristics, treatment, and prognosis.

Methods
Using the Danish Heart Failure Registry and nationwide administrative registries, we identified patients with new-onset HFrEF from 2008 to 2021. Within this cohort, patients with a prior VHD intervention were identified and matched 1:5 on age-, sex-, in/outpatient presentation, and year of HFrEF diagnosis with remaining patients (controls). Outcomes were 1) baseline use and up-titration of guidelines-directed medical therapy (GDMT) and implementation of implantable cardioverter-defibrillator or cardiac resynchronization therapy with pacemaker/defibrillator (ICD/CRT-P/D) at 6 months follow-up, and 2) a composite of HF hospitalization or all-cause death at 3 years follow-up. The Kaplan-Meier estimator and Cox regression models, adjusted for HF severity, socioeconomic status, and major comorbidities, were used to compare the composite outcome, with patients without prior heart valve intervention as reference.

Results
The study cohort comprised 32,713 patients, of whom 1196 (3.6%) underwent a prior VHD intervention (median time since intervention 10 months). After matching, the study population were 1151 cases (median age 74 years, 82% men), and 3769 matched controls. Among cases and controls, median left ventricular ejection fraction was similar (30% vs. 30%) and the proportion in New York Heart Association (NYHA) class II was alike (82% vs 83%). At the time of HFrEF diagnosis, numerically more cases were on a beta-blocker (62% vs. 53%), ACEi/ARB/ARNI (48% vs. 44%), MRA (19% vs. 14%), and more had an implementation of (ICD/CRT-P/D) (17 % vs. 7%) (Figure 1). At 6 months, ≥ 50% of the daily target dose was achieved in (46% vs. 46%) for beta-blockers, (47% vs. 47%) for ACEi/ARBs/ARNI, (31% vs. 33%) for MRA, and implementation of ICD/CRT-P/D was attained in (28% vs. 18%), among cases and controls, respectively (Figure 1). The 3-year risk of HF hospitalization or all-cause death was 25% in cases and 24% in controls (Figure 2) with no significant differences (hazard ratio (HR) 0.95 , 95% confidence interval (CI) 0.84-1.08) compared to controls.

Conclusions
Patients with new-onset HFrEF and prior VHD interventions received more GDMT and had a higher implementation of ICD/CRT-P/D at the time of HFrEF diagnosis. However, following diagnosis, no major differences in GDMT initiation and up-titration, implementation of ICD/CRT-P/D, and the adjusted rates of HF hospitalization or all-cause death were observed among patients with and without prior heart valve intervention.Figure 1 Guideline-directed medicationFigure 2 Crude cumulative risk
Assessing one-year risk of heart failure following first time myocardial infarction and subsequent five-year mortality risk: a nationwide study of 34,401 patients
Authors: Zahir D , Christensen D M , Elmegaard M E , Nouhravesh N N , Garred C G , Fosboel E F , Butler J B , Hernandez A H , Petrie M A R K , Kober L K , Schou M S 
Published: October 2024

Abstract

Introduction
A comprehensive understanding of the post-myocardial infarction (MI) trajectory leading to heart failure (HF) and its profound impact on long-term mortality is imperative for effective secondary prevention and risk assessment.

Methods
We conducted a registry-based nationwide cohort study of all Danish patients with a first MI during 2014 to 2020. Excluding patients with prior HF, individuals were followed for one year post-MI, assessing HF incidence through hospital admissions and visits to elective HF ambulatory clinics. Among those who survived one year, long-term mortality 1-6 years post-index MI was assessed using landmark analysis and Cox proportional hazards models adjusting for age, gender and comorbidities and hazard. Patients were categorized into three groups: not HF, referred for elective HF outpatient follow-up, and acute admission for HF.

Results
Among 34,301 individuals with a first MI and surviving the first year (median age 67.5, and 66.9 % male), 3.3 % were admitted acute for HF while 11.2 % had an elective HF outpatient follow-up within one year of the MI event (see Figure 1a). We observed a significant association between acute HF admissions post-MI and increased five-year mortality risk (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.40-1.90, p-value &lt;0.001, see Figure 1b) (absolute 5-year risk: 18.4 %). In contrast, the five-year mortality risk for patients with elective outpatient HF follow-up was comparable to that of individuals without HF (HR 1.06 [0.94-1.19], p-value 0.34) (absolute 5-year risk: 9.6 vs 8.5 %).

Conclusion
Our findings suggest that acute admission for HF after a first time MI occur in 3.3 % of the patients with a subsequent significantly increased mortality risk compared to patients that do not develop clinical HF. Admission for HF in patients with a first time MI should be considered as a relatively rare but fatal complication.
Anxiety or depression in heart failure across the ejection fraction spectrum
Authors: Settergren C , Benson L , Dahlstrom U , Thorvaldsen T , Savarese G , Lund L H , Shahim B 
Published: October 2024

Abstract

Background
Anxiety or depression are commonly described in patients with heart failure (HF) but few data exist on characteristics and clinical outcomes associated with anxiety or depression across the different HF phenotypes.

Purpose
To assess the prevalence of patient characteristics and clinical outcomes associated with anxiety or depression in patients with HF with preserved, mildly reduced and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF).

Methods
Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. Self-reported anxiety or depression was collected using EuroQoL 5-dimensional questionnaire (EQ-5D) at baseline and follow-up visits. Anxiety or depression was categorized as "not anxious or depressed", "moderately anxious or depressed" or "severe anxious or depressed". The independent associations between baseline characteristics and presence of anxiety or depression were assessed by a multivariable multinominal regression analysis. Cox proportional hazards regressions were performed to model the time to first event according to levels of anxiety or depression. Outcomes included all-cause death and all-cause hospitalizations.

Results
A total of 45,247 patients were included among whom 58% reported none, 38% moderate and 5% severe anxious or depressed with similar distribution across the HF phenotypes (Figure). Several characteristics were associated with anxiety or depression with the strongest ones for severe versus none being higher NYHA class (OR 3.10 (2.77-3.47)), liver disease (OR 1.99 (1.56-2.55)), in-patient setting (OR 1.62 (1.43-1.84)), smoking (OR 1.75 (1.52-2.00)) while others were inversely related including male sex (OR 0.51 (0.46-0.56)), higher age (OR 0.60 (0.53-0.67)), referral to HF nurse clinic (OR 0.82 (0.72-0.94)) and higher income level (OR 0.68 (0.62-0.76)). The risk of all-cause death and all-cause hospitalizations increased with increasing levels of anxiety or depression across all HF phenotypes during 12 months of follow up. Severe anxiety or depression had a stronger association with all-cause death in hospitalized patients and all-cause hospitalizations in out-patients.

Conclusion
In this large contemporary cohort of patients with HF in a real-world setting, anxiety or depression was frequently and similarly distributed across all HF phenotypes. Higher NYHA class, liver disease and in-patient setting were strongly associated with the anxiety or depression while male sex, higher age, and higher income were inversely related with anxiety or depression. Anxiety or depression was significantly associated with worse outcomes at 12 months follow up.Proportion anxiety or depression
Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death
Authors: Kany S , Melloni G E M , Jurgens S J , Berg D , Bonaca M , Giugliano R P , Wiviott S D , Bhatt D L , Steg P G , Raz I , Pirruccello J P , Sabatine M S , Ruff C T , Ellinor P T , Marston N A 
Published: October 2024

Abstract

Background
Rare genetic variants predisposing to cardiomyopathy (CMP) confer increased risk for adverse events. The prevalence of CMP variants in contemporary cardiovascular (CV) trials and their association with prevalent heart failure (HF) and incident HF hospitalizations (HHF) is not established.

Purpose
We aimed to identify carriers of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in well-phenotyped clinical trial cohorts and to evaluate their prognostic significance.

Methods
Rare variants were identified from high-quality exome sequencing data from 5 large clinical trials (ENGAGE AF-TIMI 48, SAVOR-TIMI 53, PEGASUS-TIMI 54, DECLARE-TIMI 58, FOURIER (TIMI 59)). Putatively pathogenic variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from ClinVar. We conducted logistic regression for prevalent disease and Cox proportional hazard models for incident HHF, both adjusted by age, sex, trial, and first 10 principal components and using those without CMP variants as the reference. Sensitivity analysis by history of HF at baseline was performed for prospective outcomes.

Results
In 63,700 participants, we identified 866 CMP variant carriers of which 518 identified as DCM carriers (age 65±9 yrs, male 66%), 194 HCM carriers (65.5±9 yrs, male 69%), and 125 ARVC carriers (66±9 yrs, male 77%). Out of the 518 DCM variant carriers, 402 had a PLP variant in TTN.
DCM variant carriers had higher odds of history of HF (Odds ratio [OR] 1.94, 1.57-2.39, p&lt;0.0001) whereas this was not observed for HCM variant carriers (OR 1.18, 0.85-1.65, p=0.33) or ARVC variant carriers (OR 1.23, 0.80-1.90, p=0.35).
Over a mean follow-up of 2.5 years, the rate of HHF was significantly higher for DCM variant carriers (Hazard ratio [HR] 1.58, 1.14-2.20, p=0.006), HCM variant carriers (HR 2.78, 1.87-4.13, p&lt;0.001), and ARVC variant carriers (HR 1.89, 1.02-3.53, p=0.04). These associations were, if anything, stronger in patients without HF at baseline (HR 2.06, 1.30-3.25) than in patients with HF at baseline (HR 1.48, 1.12-1.95). DCM variant carriers also had a higher rate of CV death (HR 1.50, 1.05-2.12, p=0.02), which was not observed for HCM (HR 1.10, 0.57-2.11, p=0.78) or ARVC (HR 0.35, 0.09-1.41, p=0.14) variant carriers.

Conclusion
In 5 contemporary CV trials, CMP variant carriers have an increased rate of HHF, while DCM variant carriers also have a higher rate of CV death. These findings motivate better identification of these high-risk individuals and the incorporation of genetic testing in CV trials.
Multimorbidity patterns in adults admitted to hospital with heart failure: an analysis of 175 million hospitalisation episodes
Authors: Carson O , Batty J A , Del Toro T , Hall M 
Published: October 2024

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 &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 &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&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.
Sex-specific clinical outcomes and healthcare resource utilization in the 5 years following hospitalization for heart failure
Authors: Averbuch T , Lee S F , Zagorski B , Pandey A , Petrie M C , Biering-Sorensen T , Xie F , Van Spall H G C 
Published: October 2024

Abstract

Background
Heart failure (HF) a leading cause of hospitalization, and sex differences in care have been described.

Purpose
We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF.

Methods
This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals enrolled in the Patient-Centred Care Transitions in HF pragmatic cluster-randomized trial. Primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets.

Results
The 4441 patients (50.7% female) had high event rates. At 5 years of follow-up, 63.6% male and 65.5% of male and female patients, respectively, had died (p=0.19); 85.4% and 84.4% of male and female patients, respectively, were readmitted with no sex differences in mean [SD] all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p=0.54) or HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p=0.80) per person. The mean (SD) annual total healthcare costs per patient was $80334 (116762) for males and $81010 (112625) for females, with no sex difference (p=0.90); however, there were sex differences in cost breakdown: males incurred greater costs from specialist, hemodialysis, and day surgical care, and females incurred greater costs from home visits and long-term care.

Conclusions
Males and females were at similarly high risk of mortality and readmissions, and had similar total healthcare costs following hospitalized for HF. Notwithstanding similar risks, males received relatively more specialist and invasive care, and females received relatively more supportive care.