bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cause-specific death in heart failure across the ejection fraction spectrum
Authors: Settergren C , Benson L , Dahlstrom U , Savarese G , Thorvaldsen T , Shahim B , Lund L H 
Published: November 2023

Abstract

Background
Heart failure (HF) is associated with increased cardiovascular (CV) and non-CV mortality, but little data is available on underlying causes of death in HF phenotypes based on ejection fraction (EF). Knowledge about causes of mortality may have implications for healthcare decisions, treatment priorities and clinical trial design.

Purpose
To examine cause-specific mortality in patients with HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF).

Methods
Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. The causes and incidence rates of death across the EF categories were studied. In addition, to examine the association between EF categories and cardiovascular (CV) and non-CV mortality, sub-distributional hazards models were performed accounting for competing risk of death from other causes and adjusted for age and sex.

Results
Among 100,584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (IQR) was 75.0 (66.0-82.0) and 36.5% were females. Of those who died within 5 years, most deaths were ascribed to CV deaths across all EF categories (65% in HFrEF, 59% in HFmrEF and 58% in HFpEF, respectively). Within 5 years, patients with HFpEF had higher risk of non-CV mortality (adjusted HR 1.38, 95% CI 1.33-1.43, p&lt; 0.001) and lower risk of CV mortality (adjusted HR 0.80, 95% CI, 0.78-0.83, p&lt; 0.001) compared to patients with HFrEF. Ischemic heart disease (IHD) was the most common cause of CV-death while cancer was the most common cause of non-CV death across all EF categories. The incidence rate of CV death due to IHD was higher in HFrEF while the incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation were higher in HFpEF compared to HFrEF and HFmrEF (Figure 1). Patients with HFpEF had higher incidence rate of non-CV deaths due to cancer, respiratory disease, accidents and infections including covid -19 compared with HFrEF and HFmrEF patients (figure 2).

Conclusion
In this large and contemporary cohort of patients with HF, CV death was more common than non-CV death across all EF categories although the risk of non-CV mortality within 5-years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category. Patients with HFpEF had a higher burden of non-CV causes of death than patients with HFrEF and HFmrEF.Incidence rate CV deathIncidence rate non-CV death
Usefulness of a scoring evaluation for practical introduction of the guideline-directed medical therapy (GDMT) in heart failure patients
Authors: Matsukawa R , Itonaga J , Kisanuki H , Hara A , Sada M , Okabe K , Okahara A , Tokutome M , Kawai S , Matsuura H , Mukai Y 
Published: November 2023

Abstract

Backgrounds
Guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced EF (HFrEF) based on the accumulating clinical evidence. However, it is difficult to introduce all the trial-proven drugs to every patient in a real-world setting.

Purpose
We developed a simple GDMT score consisting of RAS (renin-angiotensin system) inhibitor, beta-blocker, MRA (mineralocorticoid receptor antagonist), and SGLT2 (sodium-glucose cotransporter 2) inhibitor, which is a modification of the previously proposed GDMT score, and investigated whether this score is related to the prognosis of HF patients and how this score can be used in daily clinical practice.

Methods
We retrospectively analyzed 1782 consecutive patients with ADHF at our hospital from April 2015 to March 2022. One thousand fifty-four patients with HFrEF and HFmrEF (HF with mildly reduced EF) were extracted, excluding 61 patients who died in hospital, 53 patients with dialysis, and 614 patients with HFpEF. First, we calculated the simple GDMT score in these patients. Then, the association with clinical outcomes (composite outcome: HF readmission or all-cause death, HF readmission, all-cause death) was examined.

Results
The cut-off value for the association between the composite outcome and the simple GDMT score was 4 points (AUC = 0.607, 95%CI = 0.57-0.64) using the receiver operating characteristic (ROC) curve. Multivariate analysis showed that high simple GDMT score (more than 5 points) was strongly associated with the composite outcome (HR = 0.606, 95%CI = 0.403-0.912, p = 0.016), HF readmission (HR = 0.207, 95%CI = 0.077-0.558, p = 0.001) and all-cause death (HR = 0.250, 95%CI = 0.093-0.669, p = 0.005). The Kaplan-Meier curve showed that events were less frequent in the group with a high simple GDMT score group. Furthermore, a simple GDMT score of 5 or higher was associated with a good prognosis in both subgroups.

Conclusions
The designed GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if for some reason all four drugs cannot be introduced, a regimen with the simple GDMT score ≧ 5 may improve the prognosis in HF patients.
Comparison of long-term prognostic impact of sarcoidosis as etiology with dilated cardiomyopathy in patients with heart failure in a nationwide heart failure registry
Authors: Bollano E , Bobbio E , Pivodic A , Bjorkestam M , Dahlstrom U , Fu M 
Published: November 2023

Abstract

Background
It remain largely unknown whether the prognostic impact of sarcoidosis (SC) prior to heart failure (HF) differs from dilated cardiomyopathy in patients with HF over time.

Aim
To investigate the prognostic impact of prior sarcoidosis in HF patients and compare to those with HF due to dilated cardiomyopathy (DCM) by access to Swedish Heart Failure Registry which is further validated by cross linkage with Swedish National Patient Register and supplemented by Swedish National Cause of Death Register.

Methods
Patients with sarcoidosis before HF diagnosis (SC-HF group) versus patients with HF due to DCM (DCM-HF group) were identified from the Swedish Heart failure Registry between 2003-2020. The primary outcome is all-cause mortality and secondary outcome is composite CV death or hospitalization due to worsening HF in both overall cohort and propensity score-matched cohort.

Results
A total of 422 patients (69.6±13.5, male 60,7%) in SC-HF group and 6913 patients (61.7±13.5, male 72.5%) in DCM-HF group were identified. Patients with DCM were younger, had less comorbidities (renal failure, hypertension, atrial fibrillation, valvular heart disease, chronic obstructive pulmonary disease, diabetes, stroke, cancer, musculoskeletal disease) and more prescriptions of ACEI/ARB/ARNI, beta blockers and MRA) and less treatment with corticosteroids (10.6% vs 44.1%) but similar in diuretics and device therapy (ICD, CRT). In overall cohort, after adjustment for age, sex, HF duration, NYHA, LVEF, NT-proBNP cat., eGFR, the risk for all-cause mortality in SC-HF was significantly higher in SC-HF than DCM-HF [the hazard ratio (95% CI): 1.54 (1.32 - 1.81) p = &lt;.0001]. Likewise, the risk for composite CV death or HF hospitalization in SC-HF was significantly higher in SC-HF than DCM-HF (the hazard ratio (95% CI): 1.21 (0.95 - 1.54), p = 0.131.40 (1.24 - 1.59), p = &lt;.0001. Furthermore, in a propensity score-matched cohort in which 365 from SC-HF group were compared with 736 patients in DCM-HF group. Over a median follow -up of 3,1 years (1.4-5.79), SC-HF group has a higher risk of all-cause mortality [ HR: 1.35 (1.11 - 1.65), p = 0.0033], and of CV death or HF Hospitalization [1.28 (1.09 - 1.50), p = 0.0021] than DCM-HF group.

Conclusion
Sarcoidosis has greater negative impact on prognosis for heart failure than dilated cardiomyopathy with increased risk for both mortality and morbidity.
Elevated plasma adiponectin in risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: observational and mendelian randomization studies
Authors: Nielsen M B , Colak Y , Benn M , Mason A , Burgess S , Nordestgaard B 
Published: November 2023

Abstract

Background and purpose
Adiponectin, an adipocyte-secreted protein-hormone, may play an important protective role in heart failure and associated cardiovascular diseases through insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties. We hypothesized that plasma adiponectin is associated observationally and causal, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction.

Methods
In the Copenhagen General Population Study (CGPS), we examined 30,045 individuals with plasma adiponectin measurements observationally and 96,903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1,030,836 individuals using 12 genetic variants.

Results
In observational analyses, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37–1.66) for heart failure, 1.63 (1.50–1.78) for atrial fibrillation, 1.21 (1.03–1.41) for aortic valve stenosis, and 1.03 (0.93–1.14) for myocardial infarction; levels above the median was also associated with increased risk of myocardial infarction. Corresponding genetic, causal risk ratios were 0.92 (0.65–1.29), 0.87 (0.68–1.12), 1.55 (0.87–2.76), and 0.93 (0.67–1.30) in one-sample Mendelian randomization analyses, while corresponding causal risk ratios were 0.99 (0.89–1.09), 1.00 (0.92–1.08), 1.01 (0.79–1.28), and 0.99 (0.86–1.13) in two-sample Mendelian randomization analyses, respectively.

Conclusion
Elevated plasma adiponectin was associated with increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for those associations.Observational associationObservational and genetic association
Prevalence of pulmonary hypertension in reduced left ventricular systolic function and its influence on outcomes
Authors: Ratwatte S , Stewart S , Playford D , Strange G , Celermajer D 
Published: November 2023

Abstract

Background/Introduction
Reduced left ventricular (LV) systolic function can lead to pulmonary hypertension (PHT). However, the significance of PHT complicating reduced LV systolic function remains poorly characterised.

Purpose
We aimed to describe the prevalence and prognostic importance of PHT in a large cohort of adults with at reduced left ventricular ejection fraction (LVEF).

Methods
We analysed the National Echocardiography Database of Australia (data from 2000-2019). Adults with a recorded tricuspid regurgitation (TR) peak velocity and LVEF &lt;50% were included. Patients with moderate or greater left sided valvular pathology were excluded, as were patients with prior aortic or mitral valve replacements. These subjects (n= 23675) were then categorised according to their TR peak velocity. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 2.9 years, interquartile range 1.0-5.4years).

Results
Subjects were aged 70±15years and 31.7% were female. Overall, 8801 (37.2%), 7061 (29.8%), 5676 (24.0%), and 2137 (9.0%) patients had normal (TR peak velocity &lt;2.5m/sec), borderline (2.5-2.8m/sec), intermediate (2.9-3.4m/sec), or high risk PHT (&gt;3.4m/sec), respectively. An echocardiographic phenotype for ‘left heart disease’ was evident with worsening PHT, showing rising E:e’ ratio and a greater proportion of right ventricular (RV) dilation and dysfunction (p&lt;0.0001 for all). Left and right atrial sizes increased from low-intermediate risk, before plateauing at high risk PHT (p&lt;0.0001). With increasing risk of PHT, 1- and 5-year actuarial mortality increased from 13.3% and 43.8%, to 41.5% and 81.4% respectively (p&lt;0.0001). After adjustment for age, sex, LVEF, LV end diastolic diameter and LA volume index, the risk of mortality increased as TR peak velocity increased (adjusted hazard ratio (aHR) 1.31, 95% confidence interval 1.23-1.38 in borderline risk, to aHR2.38, 95%CI 2.21-2.56 in high risk PHT) (Figure 1). The cohort was also assessed in two groups based on LVEF severity according to guidelines. The sub-group of patients with mildly reduced LVEF (40-49%, n = 12495) showed that mortality risk increased as risk of PHT increased; (aHR 1.38, 95%CI 1.27-1.50 in borderline risk, to aHR2.82, 95%CI 2.52-3.15 in high risk PHT). Similarly, those with reduced LVEF (&lt;40%, n = 11180) mirrored these trends (aHR 1.23, 95%CI 1.14-1.33 in borderline risk, to aHR2.07, 95%CI 1.88-2.28 in high risk PHT). There was a mortality threshold seen from TR peak velocity 2.41m/sec onwards (aHR1.18, 95%CI 1.04-1.33) (Figure 2).

Conclusion(s)
In this large cohort study, we demonstrate that PHT risk is common in patients with reduced LV systolic function and mortality increases as PHT becomes more severe. A threshold for higher mortality lies within the range of "borderline-intermediate" risk PHT.Adjusted Risk for All-Cause MortalityThreshold for Mortality
Prognostic impact of thyroid dysfunction in patients with incident heart failure: a nationwide study
Authors: Petersen J , Yafasova A , Bager L G V , Ali S A , Kristensen S L , Rorth R , Selmer C , Kober L , Fosbol E , Ostergaard L 
Published: November 2023

Abstract

Background
Thyroid hormones directly affect the cardiovascular system. Thyroid dysfunction can cause a variety of haemodynamic alterations and has been associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and all-cause mortality. However, a paucity remains regarding knowledge on the prognostic impact of thyroid dysfunction in patients with HF.

Purpose
To examine the impact of the whole spectrum of thyroid dysfunction in patients with HF on the associated risk of AF, HF admissions, and all-cause mortality.

Methods
This Danish cohort study included patients with a first-time HF diagnosis from 2000–2021. According to blood samples within 6 months prior to the HF diagnosis, the study population was categorized based on thyroid function in 1) overt hypothyroidism, 2) subclinical hypothyroidism, 3) euthyroidism, 4) subclinical hyperthyroidism, and 5) overt hyperthyroidism. With up to one year of follow-up from the date of HF diagnosis, we used Aalen-Johansen estimator to examine the cumulative incidence frequency (CIF) of AF and HF admissions and Kaplan-Meier estimates to assess all-cause mortality. Multivariable Cox proportional hazard analysis was performed to investigate differences in outcomes among groups.

Results
Of the 7,380 individuals included in this study (56.6% female, median age 76.5 years [p25-p75: 67.9-84.1]), 102 (1.4%) had overt hypothyroidism, 1,706 (23.1%) had subclinical hypothyroidism, 4,374 (59.3%) were euthyroid, 691 (9.4%) had subclinical hyperthyroidism, and 507 (6.9%) had overt hyperthyroidism. Compared with euthyroid patients, the adjusted one-year hazard ratio (HR) for AF was 0.77 (95% CI, 0.49-1.20) for overt hypothyroidism, 1.01 (95% CI, 0.90-1.13) for subclinical hypothyroidism, 1.18 (95% CI, 1.01-1.38) for subclinical hyperthyroidism, and 1.19 (95% CI, 1.01-1.39) for overt hyperthyroidism (Figure). The adjusted one-year HR for HF hospitalizations was 1.51 (95% CI, 1.06-2.14) in patients with overt hypothyroidism, 1.07 (95% CI, 0.96-1.20) in patients with subclinical hypothyroidism, 0.99 (95% CI, 0.84-1.16) in patients with subclinical hyperthyroidism, and 1.26 (95% CI, 1.06-1.50) in patients with overt hyperthyroidism. The adjusted one-year HR for mortality was 1.81 (95% CI, 1.25-2.63) in patients with overt hypothyroidism, 1.25 (95% CI, 1.10-1.42) in patients with subclinical hypothyroidism, 1.15 (95% CI, 0.96-1.37) in patients with subclinical hyperthyroidism, and 1.46 (95% CI, 1.20-1.78) in patients with overt hyperthyroidism.

Conclusion
In patients with HF, overt and subclinical hyperthyroidism was associated with an increased rate of AF. Both hypo and hyperthyroid states were associated with increased risk of HF admission and mortality. Increased awareness regarding thyroid status in patients with HF is warranted.
Non-invasive measurement of global myocardial work to predict all-cause death and heart failure hospitalization in non-ischemic cardiomyopathy
Authors: Rodenas-Alesina E , Lozano Torres J , Badia C , Tobias P , Vila R , Calvo M , Casas-Masnou G , Cesareo M , Giustiniani A , Fernandez-Galera R , Soriano-Colome T , Olivella A , Mendez-Fernandez A B , Ferreira-Gonzalez I , Rodriguez-Palomares J F 
Published: November 2023

Abstract

Background
Global myocardial work (GMW) can be non-invasively calculated using a dedicated software using global longitudinal strain (GLS) and blood pressure. The prognostic value of GMW in patients with non-ischemic cardiomyopathy (NICM) has not yet been demonstrated.

Purpose
To stablish the prognostic significance of GMW in NICM.

Methods
Patients with NICM with an available echocardiogram between 2015 and 2019 and left ventricular ejection fraction (LVEF) &lt;50% were retrospectively included. A dedicated software was used to analyze GMW, global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). All quantitative variables were modelled as a spline with three knots to account for non-linear associations. Patients were followed up until the occurrence of death, heart failure hospitalization or lost to follow-up. The primary endpoint was a composite of all-cause death of heart failure hospitalization (HFH).

Results
A total of 524 patients with NICM in whom GMW analysis was feasible were included in the study. Median LVEF was 35 (IQR 27 – 42), and median GMW was 968 (IQR 670 – 1282). There were no significant differences in clinical characteristics between patients with GMW above or below median, except for higher rates of HFH during the previous year in patients with lower GMW. Patients with lower GMW displayed lower LVEF, greater LV dilatation, worse GLS, lower TAPSE and a higher E/e’ ratio (Table 1). GMW and GCW were significantly collinear with GLS (Pearson’s r = -0.85 and -0.83 respectively, p&lt;0.001), GWE was moderately collinear (Pearson’s r = -0.64, p&lt;0.001) whereas GWW was not (Pearson’s r = 0.05, p = 0.23). During a median follow-up of 4.8 years, 164 (31.3%) patients presented the primary endpoint. After adjusting for age, LVEF, end-diastolic volume and TAPSE, GMW showed a significant, non-linear association with the primary endpoint (Figure 1), at the expense of both death and HFH when separately analyzed. Risk progressively increased with a GMW below 2500 mmHg% and plateaued at 1000 mmHg%. Only GCW retained an association with the primary outcome like the one observed with GMW, whereas GWW and GWE did not. Adding GMW to the model led to an improved risk discrimination (AUC increased from 0.66 to 0.69, p = 0.043).

Conclusions
Global myocardial work and GCW are new independent echocardiographic predictors of all-cause death and HFH in NICM, with higher rates of the outcome at lower GMW and GCW values, whereas GWW and GWE were not associated with event rates in NICM.
Level of education and mortality in the vulnerable period following an acute heart failure hospitalization
Authors: Pereira Da Cunha G , Melo L H S , Neto J D , Duarte M B , Moretti R , Vercka K , Senger C R , Pain J R , Silvestre O , Nadruz W , Matos L G , Adam E L , Cirino R D , Taniguchi F B , Fernandes-Silva M M 
Published: November 2023

Abstract

Introduction
Patients hospitalized for acute heart failure (HF) are at increased risk of death in the early post-discharge period, so-called the "vulnerable period" (1). Post-discharge treatment strategies can help improve outcomes, but the role of the patient's level of education on this regard is unclear.

Purpose
To analyse the association between level of education and 180-day mortality after discharge from acute HF hospitalization.

Methods
We performed a prospective cohort study of patients who were discharged alive following hospitalization for acute HF in 26 hospitals in Brazil from February 2016 and September 2021. Patients were classified according to the International Standard Classification of Education 2011 into four groups: Less than Basic, Basic, Intermediate and Advanced. We analysed all-cause mortality in the 180 days following hospital discharge using Cox regression.

Results
We evaluated 2724 patients (mean age 61±15 years; 42% women) hospitalized for acute HF, who were divided according to education level: less than basic (n = 280, 10%), basic (n = 1503, 55%), intermediate (n = 716, 26%) and advanced (n = 225, 8%). Patients with lower education levels were older (68±12 vs 62±14 vs 56±16 vs 58±15 years, p-for-trend&lt;0.001), more frequently women (47% vs 43% vs 40% vs 37%, p-for-trend = 0.005) and non-whites (77% vs 66% vs 65% vs 53%, p-for-trend&lt;0.001), compared with those with higher education levels. At discharge, a prescription of both angiotensin-converting enzyme inhibitors /angiotensin receptor blockers, beta-blocker and mineralocorticoid receptor antagonists (41% vs 45% vs 49% vs 53%, p-for-trend = 0.001), vaccine counselling (52% vs 50% vs 55% vs 62%, p-for-trend = 0.002) and weigh management counselling (72% vs 69% vs 72% vs 81%, p-for-trend = 0.007) were less frequently provided for patients with lower education. Education level was inversely associated with the risk of death in the follow-up period (Hazard ratio (HR) 0.71, 95%CI 0.61 – 0.84, p = &lt;0.001; Figure). This association remained significant after adjusting for baseline characteristics (age, sex, race, left-ventricle ejection fraction, previous HF, HF aetiology, cardiac resynchronization therapy/implantable cardiac defibrillator use, chronic kidney disease and income) and prescription of disease-modifying drugs, vaccine and weight management counselling at discharge (adjusted HR 0.78, 95% CI 0.64 – 0.95, p = 0.011).

Conclusion
In this large cohort of patients discharged after hospitalization for acute HF, lower education levels were independently associated with higher mortality rates in the vulnerable period.