bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes and sudden cardiac death in a nationwide, unselected population
Authors: Skjelbred T , Lynge T H , Winkel B G , Tfelt-Hansen J 
Published: October 2024

Abstract

Background and purpose
Sudden cardiac death (SCD) remains a prominent cause of mortality, with individuals afflicted by diabetes mellitus (DM) bearing a heightened risk of ventricular arrhythmias and SCD. However, comprehensive investigations in a nationwide, unselected context are lacking. Therefore, this study aimed to compare the incidence rates (IR) of SCD among individuals with Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM) to the general population.

Methods
The study included the entire Danish population (approximately 5.5 million individuals) in 2010. SCD cases were identified through the detailed Danish death certificates and discharge summaries, yielding 6851 cases of SCD. The Danish Register of Medicinal Product Statistics, containing comprehensive prescription data from Danish pharmacies, facilitated the identification of individuals with T1DM and T2DM. Loss of life years was estimated for both T1DM and T2DM patients.

Results
Among the identified 6851 SCD cases, 272 (4%) were diagnosed with T1DM, and 833 (12%) with T2DM. Incidence rates of SCD were consistently elevated across all age groups for individuals with diabetes, compared to the general population (Figure 1). Patients with T1DM exhibited higher incidence rates than patients with T2DM (Figure 1). Notably, individuals aged 30-40 years with DM showed the greatest differences in incidence rates of SCD compared to the general population, with incidence rate ratios of 20.0 (95% confidence interval: 11.8-80.0) and 5.6 (95% confidence interval: 2.7-14.0) for T1DM and T2DM, respectively. On average, each 30-year-old patient with either T1DM or T2DM experiences a reduction of 3.7 and 3 life-years, respectively, due to the increased risk of SCD in these groups (Figure 2).

Conclusion
This nationwide study examines the incidence rates of SCD among individuals with and without a history of DM across all age brackets. Notably, patients with DM display consistently elevated incidence rates across age groups, with a particularly pronounced risk observed in those with T1DM. For both T1DM and T2DM, SCD is an important contributing factor to their shorter life expectancy compared to the general population. The heightened risk among individuals with DM underscores the importance of improved risk stratification for these patients.Incidence rates of SCDStacked cumulative incidence curves
3D target definition and initial results from the electroanatomic substrate-guided stereotactic ablative radiotherapy for refractory ventricular tachycardia (ELSTAR-VT)
Authors: Kaya Y S , Stoks J , Hazelaar C , Elmpt W , Gommers S , Cluitmans M J M , Dilling-Boer D , De Ruysscher D K M , Verhoeven K , Volders P G A , Ter Bekke R M A 
Published: October 2024

Abstract

Background/introduction
Noninvasive stereotactic radiotherapy (STAR) is an emerging transmural ablative therapy for refractory ventricular tachycardia (VT). Delineation of the arrhythmogenic gross target volume (GTV) relies on electrical (exit and isthmus) VT characteristics and anatomical scar detailing. 17-AHA segmental approaches or eyeballing techniques are adopted to transfer the GTV to the treatment planning CT. An individualized 3D GTV delineated with ADAS3D based on the areas of interest of each modality could lead to a smaller GTV compared to 17-AHA segmental approaches.

Purpose
We investigated whether our workflow using ADAS3D for the delineating of the GTV renders smaller GTV compared to 17-AHA segmental approaches whilst remaining effective for VT treatment during follow-up.

Methods
We targeted 3D-personalized GTV with STAR in patients with refractory VT in structural heart disease. Electroanatomical detailing was achieved by combining high-resolution invasive and noninvasive (ECG imaging during noninvasive programmed stimulation) mapping, combined with wall thickness analyses by cardiac CT. After coregistration in ADAS3D, a 3D DICOM-radiation therapy file including the delineated target volume was generated and transferred into the free-breathing and respiration-corrected 4D CT scan. Standard STAR using a single-fraction of 20-25 Gy was applied. We compared conventional (17-AHA segmental approaches) versus 3D-based GTV demarcation, and assessed VT burden and procedural safety.

Results
From January 2023 to February 2024 STAR was successfully performed in three patients (all male, mean age 73±1 years, two ischemic cardiomyopathy, one laminopathy) with persistent VT despite ≥2 catheter-based (endocardial/epicardial) ablation procedures. The 3D-derived GTVs showed a statistical trend towards smaller volumes compared to conventional segmental delineation (11±4 versus 21±3 cm3, p=0.07). VT burden and ICD therapy was reduced by 100% over 9 patients-months (8-week blanking period). No acute or subacute adverse events occurred. One patient died of progressive heart failure.

Conclusion
3D-individualized target volume annotation may hold promise for effective and safe STAR employment.ELSTAR workflow
Neutrophil extracellular traps are an important component of chronic myocardial inflammation in patients with heart failure
Authors: Costin S , Krizanic F , Richter M , Ritter O , Pagonas N 
Published: October 2024

Abstract

Background and aim
We have previously shown that heart failure (HF) is characterized by chronic inflammation. However, the role of neutrophils (N) and extracellular neutrophil traps (NETs) in the myocardium of patients with HF is largely unknown. The present study investigated the number of neutrophils (N) and their proportion that develop NETs in HF.

Methods
We used quantitative confocal microscopy and NETs markers in the left ventricular biopsies obtained from 5 controls and from patients with HF due to dilated (DCM, n=7), ischemic (ICM, n=7) and inflammatory (infCMP, n=7) cardiomyopathy. We used immunolabeling for CD45 (N) and for NETs (citrullinated histone 3 (CitH3), peptidylarginine deiminase-4 (PAD-4), neutrophil elastase (NE) and myeoloperoxidase (MPO).

Results
Compared to the control, the number of N was 4.3-5.7 times higher in HF. Using single labeling for NETs marker revealed that 41.1±4.6% of N in DCM, 42.9±4.1% in ICM and 47.6±2.9% in infCMP developed NETs. The use of dual labeling (MPO with CitH3, MPO with PAD-4 and CitH3 with NE) resulted in 54.5±4.7% of N-developing NETs in DCM, 59.5±4.1% in ICM and 77.6%±4.2 in infCMP. The difference between N-undergoing NETs was statistically different in infCMP than in DCM.and ICM. The proportion of N-forming NETs in control tissue was less than 5% and was significantly different from that in HF patients regardless of etiology.

Conclusions
This is the first study to show the presence of NETs in human hearts in situ and demonstrates that NETs are an important component of chronic inflammation in HF due to cardiomyopathies.
Age-predicted maximal heart rate reserve as an alternative prognostic parameter in patients with heart failure with preserved ejection fraction -insights from PURSUIT-HFpEF registry-
Authors: Okada M , Tanaka N , Iwakura K , Seo M , Hayashi R , Yano M , Nakagawa A , Nakagawa Y , Yamada T , Yasumura Y , Hikoso S , Okada K , Nakatani D , Sotomi Y , Sakata Y 
Published: October 2024

Abstract

Background
Heart rate reserve (HRR), a measure of chronotropic response, is a prognostic parameter in patients with heart failure with preserved ejection fraction (HFpEF). However, exercise testing and measuring maximum heart rate (HR) are sometimes difficult in patients with heart failure with preserved ejection fraction (HFpEF). Assessing age-predicted maximal HRR (APHRR), defined as the difference between the resting HR and the age-predicted maximum HR (220 - age), would be a simple alternative to HRR.

Purpose
To assess the impact of APHRR at discharge on prognosis in patients with HFpEF.

Methods
An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1231 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide level ≥100 pg/ml. Excluding patients with permanent pacemakers, we enrolled 918 patients (age, 81 ± 9 years; men, 45%; atrial fibrillation, 38%) whose follow-up data after survival discharge were available.

Results
There was a moderate correlation between HR (median 69, interquartile range [IQR] 61-79 beats per minute [bpm]) and APHRR at discharge (71, 59-81 bpm) (r² = 0.68, p &lt;0.001). During the median follow-up period of 23.8 months [IQR, 12.5-36.3] after discharge, 267 patients (15.4%) died, and the mortality rates incrementally decreased according to the APHRR quartiles (Q1, 44.6%; Q2, 26.6%; Q3, 26.2%; Q4, 18.4%; p &lt;0.001). Cox regression analysis revealed that both the resting HR (hazard ratio per quartile increase, 1.16; 95% confidence interval, 1.04-1.30, p = 0.008) and APHRR (0.67; 0.60-0.75, p &lt;0.001) were associated with mortality. However, the diagnostic accuracy was significantly superior in the APHRR than in resting HR (area under the curve; 0.628 vs. 0.552, p &lt;0.001).

Conclusions
Assessment of the APHRR at discharge was a simple and useful method for risk stratification of patients with HFpEF. An incremental favorable prognosis indicated the prognostic importance of having a functional reserve during physiologic stress.
Gene-echocardiography: refining genotype-phenotype correlations in cardiomyopathy patients with restrictive phenotype
Authors: Zhou N 
Published: October 2024

Abstract

Background
The restrictive phenotype, the least frequent and genetically complex form of cardiomyopathy, is the focus of this investigation. The aim is to clarify the association between restrictive phenotype and genetic variants in cardiomyopathy patient.

Methods
We utilized whole-exome sequencing in a cohort of 568 cardiomyopathy patients and performed echocardiographic evaluations to identify restrictive phenotypes. Comprehensive analysis of cardiac characteristics and functionality was also undertaken.

Results
Among the cohort, 33 patients exhibited a restrictive phenotype. These patients were distributed as follows: 7 within the restrictive cardiomyopathy group (RCM), 20 in the hypertrophic cardiomyopathy group (HRCM), and 6 in the dilated cardiomyopathy group (HDRCM). A notable prevalence of gene mutations, mainly in the MYBPC3 gene, was found in these individuals. We observed that mutation carriers, characterized by smaller aortic sinus dimension, demonstrated an association with the mutation and diminished myocardial work. Furthermore, MYBPC3 mutation carriers showed a thicker ventricular wall and a higher predisposition for septal hypertrophy. Both HRCM and HDRCM groups displayed consistent hypertrophic manifestations, with the latter demonstrating a higher frequency of interventricular septal hypertrophy. The 5-year survival rate was calculated at 54.5%, with gene mutations not significantly affecting longevity.

Conclusion
Genetic factors profoundly influence the restrictive phenotype of cardiomyopathy. There is a strong link between restrictive phenotype and genetic variants in cardiomyopathy, providing a foundation for more accurate genetic testing and personalized management of patients. The emerging "gene-echocardiography" concept may refine the accuracy and productivity of genetic counseling and testing in cardiomyopathy.
A flexible, calibrated transformer-based risk model for prediction of clinical outcomes in patients with heart failure; an open cohort study using linked UK EHR
Authors: Rao S , Salimi-Khorshidi G , Rahimi K 
Published: October 2024

Abstract

Background
Numerous risk scores, both uni- and multi-variable, have been developed to conduct prognostication for a range of clinical outcomes in heart failure (HF) patients [1,2]. However, these models provide only modest discrimination and often depend on complex test data (e.g., ejection fraction) collected outside of routine clinical care [2]. Furthermore, transparency in reporting of key individual-level metrics (e.g., precision, recall) is notably lacking.

Purpose
We developed and validated a novel deep learning model, the second version of the Transformer-based Risk assessment survival model (TRisk2), for 36-month prediction of all-cause mortality, cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes in patients with HF using routine, linked UK electronic health records (EHR) data.

Methods
An open cohort of 405 thousand patients with HF between 40 and 90 years of age was identified using linked EHR from 1,063 and 355 English general practices, which were used for TRisk2 model development and external validation, respectively. Comparison was conducted against MAGGIC [2], modified for use on routine linked EHR. Additional analyses compared discriminatory performance in other age groups, by sex, and by baseline disease. All analyses were repeated for prediction of cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes.

Results
TRisk2 demonstrated superior discrimination with Concordance index (C-index) of 0.828; 95% confidence interval (CI): 0.824 to 0.832 for all-cause mortality prediction outperforming MAGGIC. The proposed model’s performance was found to be stable across stratified analyses by sex, age, and baseline disease status. Both models were overall well-calibrated, and TRisk2 demonstrated greater net benefit than MAGGIC across reasonable decision boundaries in decision curve analyses. At exemplar risk threshold of 50% for 36-month prediction, TRisk2 outperformed MAGGIC by 0.08 for both, precision and recall and identified 10% more events. At the same threshold for 12-month prediction, TRisk2 outperformed MAGGIC by 0.14 and 0.26 precision and recall respectively and captured 70% more events. The well-calibrated TRisk2 similarly outperformed MAGGIC in prediction of cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes.

Conclusion
Utilising solely routine EHR from primary and secondary care, TRisk2 enabled more accurate prediction than MAGGIC with 10-20% gain in C-index across the four outcome investigations. Integration of TRisk2 into routine clinical care could simultaneously eliminate the reliance of complex tests and improve prognostication of key clinical outcomes, thereby refining management of HF.Models' discrimination on four outcomes
Risk factors of all-cause mortality in heart failure with mildly reduced ejection fraction patients with different post-discharge left ventricular ejection fraction variation patterns
Authors: Zhu Y L , Peng X , Liu Z C , Huang H B , Wu M X , Zhang L L , Liao M , Zhao W J , He W F , Tan D , Zeng J P 
Published: October 2024

Abstract

Background
The identification of risk factors for all-cause mortality in patients diagnosed with heart failure with mildly reduced ejection fraction (HFmrEF) and exhibiting varying post-discharge left ventricular ejection fraction (LVEF) patterns remains incomplete. This study aimed to determine the independent risk factors of all-cause mortality among HFmrEF patients with different LVEF variation patterns post-discharge.

Methods
This retrospective study analyzed data from 807 HFmrEF patients admitted to our hospital between January 2015 and August 2020. Patients were categorized into three groups based on LVEF variation patterns within 6 months to one year post-discharge: Group A (transitioning to heart failure with reduced ejection fraction [HFrEF], n=225), Group B (remaining as HFmrEF, n=335), and Group C (reverting to heart failure with preserved ejection fraction [HFpEF], n=227). Patients were followed up for a mean of 33 months, with all-cause mortality as the primary endpoint. Multivariate Cox regression analysis was conducted to identify independent risk factors for all-cause mortality in each group.

Results
The mortality rates for Groups A, B, and C were 43.11%, 23.94%, and 24.67%, respectively (P&lt;0.001). Independent risk factors for all-cause mortality in Group A included age (HR=1.04, P=0.007), obesity (HR=1.76, P=0.040), higher creatinine (&gt;100 µmol/L, HR=1.83, P=0.029), higher E/e’ (HR=1.06, P=0.001), absence of PCI (HR=0.51, P=0.019), and non-use of ACEI/ARB (HR=0.039, P=0.006). In Group B, independent risk factors for all-cause mortality were age (HR=1.06, P&lt;0.001), higher NT-proBNP (&gt;2505 pg/ml, HR=2.50, P=0.002), and absence of PCI (HR=0.040, P=0.005). Group C exhibited age (HR=1.04, P=0.002), pleural effusion (HR=2.38, P=0.007), higher creatinine (&gt;100 µmol/L, HR=2.84, P&lt;0.001), and non-use of ACEI/ARB (HR=0.42, P=0.021) as significant independent risk factors associated with increased all-cause mortality risk.

Conclusion
This study highlights distinct risk factors associated with all-cause mortality in HFmrEF patients exhibiting different post-discharge LVEF variation patterns. Age emerged as a consistent risk factor across all groups, underscoring the importance of age-related considerations in managing HFmrEF patients. Additionally, factors such as obesity, renal function, echocardiographic parameters, and medication adherence played varying roles in influencing mortality risk depending on the evolution of LVEF following discharge. These findings emphasize the need for personalized risk stratification and tailored management strategies for HFmrEF patients to improve outcomes and reduce mortality rates.
Prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening heart failure
Authors: Yamada Y , Konishi M , Kagiyama N , Kasai T , Kamiya K , Saito H , Saito K , Maekawa E , Kitai T , Iwata K , Jujo K , Wada H , Momomura S , Hibi K , Matsue Y 
Published: October 2024

Abstract

Background
Subjective symptoms, represented by the New York Heart Association (NYHA) class, are well-established prognostic indicators and treatment goals of heart failure (HF). However, older patients may be less likely to develop subjective symptoms due to an impaired physical performance.

Purpose
To evaluate the prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening HF.

Methods
We carried out a sub-analysis of FRAGILE-HF, a prospective multicenter study, including 1272 consecutive older (&gt;=65 years) hospitalized patients with HF (median age 80; 57.2% male; left ventricular ejection fraction 46±17%). NYHA class and gait speed were documented before discharge. The patients were prospectively followed-up for two years after discharge.

Results
At the time of discharge, 715 patients (56%) remained symptomatic (NYHA2-4) whereas 557 patients (44%) were asymptomatic (NYHA1). Patients were classified into 4 groups according to symptom relief and physical performance represented by slow (&lt;0.8 m/s) or normal (&gt;=0.8 m/s) gait speed: 279 slow-asymptomatic, 278 normal-asymptomatic, 402 slow-symptomatic, and 313 normal-symptomatic patients, respectively. During the follow-up period, 266 patients (20.9%) died. Slow-asymptomatic (hazard ratio (HR) 1.72[1.09-2.72], p=0.019 in comparison with normal-asymptomatic patients as a reference) and slow-symptomatic (HR 1.85[1.21-2.82], p=0.004) status was associated with high mortality in a Cox regression analysis adjusted for the Meta-analysis Global Group in Chronic Heart Failure score and B-type natriuretic peptide level (Figure). Furthermore, the combined endpoint of HF rehospitalization and all-cause death within 90 days were more frequently observed in slow-asymptomatic (HR 1.94[1.05-3.60], p=0.034), normal-symptomatic (HR 1.89[1.06-3.36], p=0.031), and slow-symptomatic (HR 1.97[1.10-3.52], p=0.022) patients than normal-asymptomatic patients (Figure).

Conclusions
Symptom relief achieved at the time of discharge was not associated with a lower mortality in patients with low physical performance, for whom careful follow-up may be needed especially in the early period after discharge because the symptoms may be masked due to low physical performance.
Temporal trends in treatment patterns, morbidity, and mortality in patients with new-onset heart failure compared to heart failure survivors: a nationwide 23-year perspective
Authors: Boysen E , Koeber L , Kjoebek Lamberts M , Godsk Joergensen P , Ditlev Tuxen C , Wolsk E , Ersboell M , Barasa A , Rauhe Mouridsen M , Kiilerich Lauridsen T , Dridi N , Petersen M , Thune J J , Schou M , Elmegaard Malik M 
Published: October 2024

Abstract

Background
New therapy options have improved the prognosis of heart failure (HF) over recent decades. However, temporal trends in the prognosis and treatment disparities between patients with new-onset HF and HF survivors remain unexplored.

Purpose
To investigate temporal trends in HF treatment patterns, worsening HF and all-cause mortality, in new-onset HF patients compared to HF survivors.

Methods
We defined two separate cohorts of patients with HF, using the Danish nationwide registers. One cohort comprised all patients with new-onset HF each year from 1996 to 2018, included at the date of HF diagnosis (new-onset HF patients). The second cohort comprised patients with HF who have survived at least three years since being diagnosed with HF, included on January 1st of each year from 1996 to 2018 (HF survivors). Patients were allowed to contribute in both cohorts. The proportion of patients in guideline recommended therapy and the absolute five-year risk of worsening HF and all-cause mortality were assessed in the two cohorts separately, accounting for competing risks where relevant.

Results
From 1996 to 2018, the proportion of HF survivors tripled, while the number of yearly new-onset HF patients remained constant (figure 1). The proportion of new-onset HF patients who redeemed a prescription of BB increased from 17.1% in 1996 to 78.2% in 2018, while it increased from 15.9% to 69.4% in HF survivors during the same period. The proportion of patients in ACEi/ARB therapy increased from 49.1% to 81.5% in the new-onset HF patients, while it increased from 37.8% to 69.0% in HF survivors. The proportion of patients in MRA therapy increased from 14.4 to 33.0% in those with new-onset HF, and from 19.1% to 24.8% in HF survivors. The absolute risk (AR)[±95CI] for all-cause mortality decreased from 68.4% [67.9-68.9] in the first year group (1996-2000) to 45.7% [45.0-46.3] in the latest year group (2013-2018) for new-onset HF patients, while it decreased from 58.4% [58.2-58.9] to 39.7% [39.4-40.0] for the HF survivors. Additionally, the AR for worsening HF went from 27.4% [26.9-27.8] in the first year group to 27.8% [27.3-28.2] in the latest year group for the new-onset HF patients, whereas it for the HF survivors decreased from 19.6% [19.3-20.0] to 16.7% [16.4-19.9].

Conclusions
Over a 23-year period, the annual number of patients with incident HF has remained constant while the number of HF survivors has increased by 304%. Although HF survivors show a lower prescription redemption prevalence for essential HF medications compared to incident HF patients, they exhibit significantly lower risk of all-cause mortality and worsening HF.Figure 1:OverviewFigure 2:Prescription redememption rates