bluuebunny/crossref_metadata_2025_split huggingface dataset:
A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study
Authors: Chang H C , Sung S H 
Published: October 2024

Abstract

Background
Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear.

Purpose
We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort.

Methods
Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from &lt;20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF.

Results
94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF&gt; 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes.

Conclusions
A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure
Kidney status and events preceding death in heart failure: A real world data study on 18,456 patients with heart failure
Authors: Zahir D , Elmegaard M E , Garred C G , Jhund P , Petrie M , Mcmurray J , Kober L K , Schou M S 
Published: October 2024

Abstract

Background
Despite advancements in heart failure (HF) management, kidney dysfunction remains a significant clinical challenge, and is associated with higher mortality rates and other adverse outcomes. However, there are few studies of kidney events preceding death in patients with HF in the real world.

Methods
Using registry-based data, the prevalence of kidney events preceding death in patients with HF over the period 2014-2018 in Denmark. All deaths in patients with a diagnosis of HF within the previous 10 years were included. Kidney events occurring during within 1 year of death compromised of: acute kidney injury, chronic renal replacement therapy, sustained eGFR&lt;15 mL/min/1.73 m2, or renal transplantation. The prevalence of kidney events preceding death was calculated and different subgroups were compared.

Results
Among the 18,586 HF patients who died, a total of 3107 (16.7%) experienced kidney events during within 1 year of death. The prevalence of HF patients with kidney events before death was 15.5% for acute kidney injury, 5.8% for chronic renal replacement therapy, 7.4% for an eGFR&lt;15 mL/min/1.73 m2, and 0.18% for renal transplantation (see Figure 1). Acute kidney injury episodes were frequently observed in the last month before death (7.5%) (Figure 2). Age-specific analysis revealed a higher proportion of deaths associated with kidney dysfunction in patients under the age of 65 years compared to those aged 80 years and above (24.3% vs 13.4%). Furthermore, male sex, death in-hospital, reduced pre-existing kidney function, a higher degree of frailty, and lower educational status were associated with higher frequency of death associated with kidney dysfunction.

Conclusion
In this real-world study, a significant proportion of deaths among HF patients were associated with kidney dysfunction, particularly with acute kidney injury. Further research and awareness of renal complications are necessary to improve outcomes in this population.
Prognostic value of myocardial redox signalling: a machine learning multi-omics approach
Authors: Kotanidis C P , Akawi N , Chauhan J , Polkinghorne M , Akoumianakis I , Antonopoulos A S , Foran D , Badi I , Farid S , Srivastava V , Krasopoulos G , Sayeed R , Channon K M , Antoniades C 
Published: October 2024

Abstract

Background
Oxidative stress has been proposed to be implicated in cardiovascular pathology. Studies have linked myocardial oxidative stress with the development of atrial fibrillation, but its role in the prediction of long-term outcomes and mortality is yet to be elucidated.

Purpose
To apply discovery network transcriptomics and genomics to atrial tissue (AT) obtained from patients undergoing cardiac surgery, to phenotype myocardial redox-state and identify potential therapeutic targets.

Methods
We included 1,032 patients undergoing cardiac surgery. Arm 1 included 258 patients in whom atrial tissue (right atrial appendage) was used for ex-vivo quantification of NOX-derived superoxide by lucigenin-enhanced chemiluminescence. Arm 2 included 414 patients in whom exploratory, unsupervised gene network analysis in human atrial tissue RNA sequencing data was performed to identify atrial tissue redox-sensitive signatures (blue signature). Arm 3 included 881 patients genotyped with the genome-wide SNP array UK Biobank Axiom Array and used for machine learning construction of GenRedOx, a SNP model built to predict the blue transcriptomic signature. Associations with future incidence of major adverse myocardial events (MAME: cardiovascular death and/or heart failure) was assessed across all arms using cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, and plasma TNFa).

Results
Over a median follow-up of 5.27 years [IQR: 4.29-6.83] high atrial tissue (AT) NOX-derived superoxide was independently associated with MAME risk (Adj. HR[95%CI]: 11.7 [2.18 , 62.82], p=0.004, a). Unsupervised transcriptomic analysis in Arm 2 revealed 15 coexpressed gene ‘modules’ or 'signatures' (b). The blue signature was significantly associated with AT superoxide production with "immune response-regulating and activating signalling" being amongst the top enriched pathways. Patients with high eigengene values for the blue signature showed a 5.5-fold higher adjusted risk of MAME (c). In Arm 3, extreme gradient boosting of SNP data, trained using the blue transcriptomic signature as ground truth, revealed GenRedOx (d), a genomic artificial intelligence score, which was found to be prognostic of MAME in the validation stage (e). Homozygosity for the minor allele of SNP rs723897 in the Chemokine-Like Factor Super Family 7 (CMTM7) gene had the highest gain in the model.

Conclusion
We present for the first time two novel human myocardial transcriptomic and genomic signatures that reflect changes in redox state and identify long-term cardiovascular risk. Targeting pathways in the myocardium related with immune response signalling may lead to the development of novel therapeutics in cardiovascular disease.
In-hospital economic impact and mortality of bariatric surgery on congestive heart failure in the USA: a nationwide analysis
Authors: Perry J , Sinclair S , Akinti O A , Allen Mcnamara A M , Adarsh Balaji A B , Khan A 
Published: October 2024

Abstract

Background
Congestive Heart Failure (CHF) remains a significant economic burden in the inpatient setting. There is a complex correlation between obesity and Congestive Heart Failure (CHF). Bariatric surgery has emerged as a critical intervention for patients with morbid obesity. However, there is limited data on how this intervention impacts hospital economic metrics and patient outcomes in the context of CHF post-bariatric surgery.

Purpose
The purpose of this study is to assess the in-hospital economic impact and mortality among patients with congestive heart failure who have undergone bariatric surgery.

Methods
We queried the National Inpatient Sample from 2016 to 2020; this retrospective observational cohort study identified CHF patients who had undergone bariatric surgery through ICD-10 codes. Univariate and multivariate logistic regression analyses were performed to determine Total Charges (TOTCH) and Length of Stay (LOS), adjusting for confounders including the Elixhauser comorbidity index, hospital region, quarterly income, and hospital location to identify the economic impact on CHF (Table 1).

Results
Out of 25,900,000 patients with congestive heart failure, 5,983,684 (23%) were obese, and 208,220 (0.8%) had undergone bariatric surgery. The demographic profile showed a mean age of 63 predominance of females (65%) and the White population (69.5%) (Table 1). The mean TOTCH for patients undergoing bariatric surgery was $66,235, compared to $76,046 for those who did not undergo the surgery, with a significant mean decrease in TOTCH of -$11,454 (p&lt;0.001, 95% CI: -$12,472 to -$10,435). The mean LOS was 5 days for patients with bariatric surgery versus 6 days for those without, showing a mean decrease in LOS of 0.93 days (95% CI: -0.99 to -0.87). Additionally, there was a significant decrease in overall mortality risk among patients who had bariatric surgery (2.1%) compared to those who did not (5%), with an (OR 0.4 p&lt;0.001, 95% CI: 0.38 to 0.43).

Conclusion
Our research demonstrates that bariatric surgery in obese individuals with congestive heart failure (CHF) markedly decreases in-hospital mortality, reduces hospital charges, and shortens the length of hospital stays. These findings underscore the potential of bariatric surgery as a cost-effective intervention for improving outcomes in patients with CHF and obesity, highlighting the importance of considering surgical weight loss options in the management of CHF.Table 1
Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients
Authors: Phoksiri A , Srisuwan T , Tajarernmuang P , Osataphan N , Kanjanavanit R , Wongcharoen W , Phrommintikul A 
Published: October 2024

Abstract

Background
A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease.

Methods
This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT.

Results
A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT.

Conclusion
Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.
Left atrial reservoir strain differentiates cardiac amyloidosis and hypertrophic cardiomyopathy
Authors: Winkelbauer L , Santner V , Schwegel N , Hoeller V , Gollmer J , Kolesnik E , Wallner M , Von Lewinski D , Zirlik A , Ablasser K , Verheyen N , Zach D 
Published: October 2024

Abstract

Aims
Availability of mortality-reducing therapies for cardiac amyloidosis (CA) has led to an increase in referral rates to tertiary care centers. Investigations to improve diagnosis rates are urgently needed, as diagnosis of CA requires a multimodal approach and its early diagnosis is crucial due to high mortality in untreated patients. The aim of this study is to evaluate the accuracy of the left atrial reservoir strain (LASr) in differentiating CA patients from patients with hypertrophic cardiomyopathy (HCM).

Methods
This is a cross-sectional analysis from the Graz HCM Registry, a prospective single-center cohort study enrolling consecutive patients with a HCM phenotype. This analysis included HCM and CA patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses in 100 HCM and 95 CA patients.

Results
Compared to HCM patients, CA patients were more frequently male [79 (83%) vs. 54 (54%); p&lt;0.001] and older [78 (73-81) vs. 58 (47-70) years; p&lt;0.001]. Moreover, CA patients had a lower BMI [25.0 (22.8-26.9) vs. 26.5 (24.3-29.7) kg/m²; p=0.002] as well as lower systolic [134±20 vs. 142±25 mmHg; p=0.018] and diastolic blood pressure [78±12 vs. 84±12 mmHg; p&lt;0.001]. Additionally, CA patients had higher NT-proBNP [2533.0 (1146.0-5016.0) vs. 543.0 (195.0-1381.0) pg/ml; p&lt;0.001] and lower eGFR [58.4±19.1 vs. 80.1±22.2 ml/min/1.73m²; p&lt;0.001]. LASr was significantly worse in CA patients compared to HCM patients [9.2 (5.6-13.0) vs. 21.7 (14.8-27.6) %; p&lt;0.001]. Multivariable logistic regression analysis revealed LASr as an independent predictor of CA [OR=0.936 (95% CI 0.877-0.998)], adjusting for covariates. ROC analysis showed an AUC of 0.80 (95% CI 0.73-0.86) for LASr to discriminate CA from HCM. LASr ≤14.3% demonstrated a 80% sensitivity and 79% specificity for the identification of CA patients. Sensitivity analyses involving 74 sex- and age-matched patients yielded materially unchanged results.

Conclusion
Compared to HCM patients, LASr was diminished in CA patients and an independent predictor of CA. Moreover, LASr showed high diagnostic accuracy in differentiating CA and HCM patients. Prospective studies are needed to evaluate the added value of left atrial strain in the diagnostic work-up of CA patients.ROC curve of LASr
Interleukin-6 and suPAR are associated with diastolic function in type 1 diabetes: The Thousand & 1 Study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rasmussen L J H , Eugen-Olsen J , Rossing P , Jensen M T 
Published: October 2024

Abstract

Background
Heart failure (HF) is a common complication in individuals with type 1 diabetes (T1D). Inflammation is an important contributor to the pathogenesis and progression of both T1D and HF – especially HF with preserved ejection fraction (HFpEF). Diastolic dysfunction is a hallmark of HFpEF. Despite this, the association between diastolic function and inflammatory biomarkers is not well-known in individuals with T1D.

Methods
The Thousand & 1 study of individuals with T1D without known heart disease was studied. Diastolic parameters, including E/e’, was obtained by echocardiography and associated with Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP). These inflammatory biomarkers were analysed as continuous variables and dichotomized in above/below 3 pg/mL (IL-6), 4 ng/mL (suPAR), and 4 mg/L (hsCRP). In multivariable regression analysis, adjustments were made for age, gender, body mass index, duration of diabetes, HbA1c, systolic blood pressure, left ventricular ejection fraction, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity levels. In an additional analyse, we also adjusted for N-terminal pro–B-type natriuretic peptide (NT-proBNP).

Results
We included 1,014 individuals (52% male, mean age 50±15). IL-6 was elevated in 207 individuals, suPAR in 182 individuals, and hsCRP in 863 individuals. Mean E/e’ was 7.6 and mean left ventricular ejection fraction was 58±5%. In fully adjusted models, inflammatory biomarkers were significantly associated with diastolic function. Thus, individuals with IL-6 &gt; 3 pg/mL had 0.6 (95% confidence intervals: 0.2 to 1.0), P=0.001) higher E/e’ compared to individuals with IL-6 &lt; 3 pg/mL. For every doubling of suPAR levels, E/e’ increased by 0.5 (0.2 to 0.9, P=0.003). For every doubling of hsCRP levels, E/e’ increased by 0.1 (0.02 to 0.2, P=0.022). Individuals with elevated levels of all three biomarkers had 1.9 (0.5 to 3.2, P=0.006) higher E/e’ compared to low levels of all three biomarkers. Including NTproBNP to the model did essentially not change the estimates.

Conclusions
Firstly, in T1D, elevated levels of IL-6, suPAR and hsCRP are associated with diastolic function assessed by E/e’, independent of traditional risk factors including NT-proBNP. Secondly, IL-6, suPAR and hsCRP may contain information about diastolic function in T1D which is not detected by NT-proBNP.Figure 1Figure 2
Point-of-care screening for heart failure with reduced ejection fraction using simple pulse oximetry
Authors: Bohm A , Jajcay N , Segev A , Lucka J , Kollarova M , Jankova J , Holly O , Schwarz S , Sebenova Jerigova V , Toth S , Johanesova L , Bezak B 
Published: October 2024

Abstract

Background
More than 64 million patients with heart failure (HF) are burdened with poor quality of life, frequent hospitalizations, and high readmission rates. While HF with reduced ejection fraction (HFrEF) accounts for approximately half of these patients, there is currently no effective tool for performing cost-effective and reliable early-stage screening. For this purpose, we derived and cross-validated a machine learning (ML) based system capable of identifying HFrEF based on analysis of the photoplethysmographic (PPG) signal recorded by a simple pulse-oximeter.

Methods
Patients attending a routine ambulatory check-up at an outpatient clinic were included in the study. Left ventricular ejection fraction was determined by standard transthoracic echocardiography. Diagnosis of HF was based on the latest ESC recommendations for HF. PPG was measured using a standard oximeter modified to record raw PPG signal. Before processing, the quality of the measured PPG signal was assessed by signal quality indices to determine whether the quality of signal was sufficient for further analysis. In brief, the signal processing involved noise removal, filtering for specific frequencies, automatic artifact detection and identification of individual heartbeats, on which specific parts of the signal and signal characteristics, necessary for further analysis, were identified. Four different ML processing pipelines with different approaches to feature selection and class balancing were deployed, validated using the K-fold cross-validation and compared.

Results
A total of 371 patients were included in the study: 54 patients with HFrEF (mean age 66.87 ± 14.35, 74.07% male) and 317 patients with HFmrEF (4), HFpEF (42) or no history of HF (271) (mean age 54.12 ± 17.79, 51.73% male). From the 4 ML pipelines, LightGBM with SMOTE + Edited Nearest Neighbors balancing had the highest cross-validated predictive performance for detection of HFrEF (c-statistics 0.8, CI 0.69 – 0.89).

Conclusions
Our results suggest that HFrEF can be effectively screened using a simple pulse oximeter, thanks to ML signal analysis. This solution could be adapted to a simple, non-invasive, readily available, time-saving, and inexpensive point-of-care diagnostic tool for primary care. Early disease detection and referral to a cardiologist (or HF specialist) would have a positive impact on patient morbidity and mortality.Receiver Operating Characteristics CurveModel Performance Metrics
High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome
Authors: Byrne C , Kragholm K H , Torp-Pedersen C , Pareek M 
Published: October 2024

Abstract

Background
In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized.

Purpose
We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS.

Methods
Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: &lt;20%, &gt;20 to 50%, or &gt;50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (&lt;=9 ng/l, 10-15 ng/l, 16-66 ng/l, &gt;=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling.

Results
The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample.

Conclusions
In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure