bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amiodarone-related thyroid dysfunction and associated outcomes in patients with heart failure - a matched case-control study
Authors: Sam Aiyad S A A , Selmer C S , Ersboll M K E , Butt J G B , Rorth R R , Westergaard L M W , Ostergaard L M O , Jons C J , Gustafsson F G , Fosbol E L F , Kober L K , Kristensen S L K 
Published: October 2024

Abstract

Aim
The association between amiodarone-related thyroid dysfunction and the risk of worsening heart failure (HF) or death has been reported with conflicting results.

Methods
The study cohort was patients with HF and without a history of thyroid dysfunction (defined by medical treatment or diagnosis) who initiated treatment with amiodarone in the period 1996-2021. Within this cohort, those who developed thyroid dysfunction (cases) were identified and matched 1:3 on age, sex, calendar year, duration of HF, and time since initiation of amiodarone with patients (controls) from the same cohort and followed for the primary outcome of HF hospitalization or all-cause death at 1-year, assessed by Kaplan Meier curves and Cox regression models adjusted for ischemic heart disease, chronic kidney disease, malignancy, atrial fibrillation and ventricular tachycardia.

Results
The study cohort comprised 21,947 patients, of whom 4,137 (19%) developed thyroid dysfunction following initiation of amiodarone. After matching, the study population consisted of 4,063 cases (mean age 69 years, 68% men, 41.6% developed thyroid dysfunction within the first year after initiation of amiodarone) and 10,940 matched controls, (Figure 1). The index date was the date of thyroid dysfunction for cases, and for matched controls a date at a similar distance since amiodarone initiation. At 1-year follow-up, the primary outcome occurred in 1,543 (38.0%) cases and 3,681 (33.6%) matched controls (reference), adjusted hazard ratio (HR) 1.13 (95%, confidence interval CI 1.07-1.20), although this was solely driven by HF hospitalization (28.9% vs 21.8%; HR 1.32 (95% CI 1.23-1.41), whereas all-cause death was lower among cases (18.2% vs. 20.4%, HR 0.85 (95% CI 0.78-0.93), (Figure 2).

Conclusions
Among HF patients treated with amiodarone, the development of thyroid dysfunction was associated with an increased risk of HF hospitalization or all-cause death, but this was solely driven by the excess risk of HF hospitalization, whereas it was associated with a lower risk of all-cause death. The absence of excess mortality indicates that thyroid complications are manageable in this vulnerable population of patients with HF.Figure 1 Flowchart of the populationFigure 2 Cumulative risk
Effects of short-term exposures to lower air temperature and cold spells on myocardial infarction hospital admissions: a nationwide study in Sweden
Authors: Ni W , Stafoggia M , Zhang S , Ljungman P , Breitner S , Bont J D , Jernberg T , Atar D , Agewall S , Schneider A 
Published: October 2024

Abstract

Background
Exposures to lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood.

Purpose
We aimed to evaluate the short-term effects of lower air temperature and cold spells on MI hospital admissions within the nationwide SWEDEHEART registry.

Methods
This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature was estimated at 1 km2 spatial resolution across Sweden using a three-stage machine learning approach and percentiles of daily temperatures experienced by individuals in the same municipality were employed as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least two consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model using lag 0-1 and lag 2-6 days was employed to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI).

Results
We found significant increases in risk for total MI, NSTEMI, and STEMI in association with a decrease of one percentile in temperature at a lag of 2-6 days, indicated by ORs (95% CI) of 1.099 (1.057-1.142), 1.110 (1.06-1.164), and 1.076 (1.004-1.153), respectively. Additionally, we found that cold spells were significantly associated with increased risks for total MI, NSTEMI, and STEMI at a lag of 2-6 days, with ORs (95% CI) of 1.077 (1.037-1.12), 1.069 (1.02-1.119), and 1.095 (1.023-1.172), respectively. Moreover, independent effects of lower air temperature and cold spells on MI occurrence were found after adjusting for each other. Conversely, we observed that lower air temperature and cold spells were associated with decreased risks for MI at a lag of 0-1 days.

Conclusions
This nationwide case-crossover study demonstrated a novel biphasic pattern in MI risk following exposure to lower air temperatures and cold spells, characterized by an initial transient reduction in risk at lags 0-1 day, followed by a significant increase in risk at lags 2-6 days. As climate change continues to induce complex shifts in regional weather patterns, enhancing protections to reduce future cold-related cardiac hospitalizations is crucial.
The health and wellbeing of cardiology trainees in the united kingdom
Authors: Jenner W , Brown O I , Camm C F 
Published: October 2024

Abstract

Background
Cardiology is a rewarding medical speciality. However, the intense workload can burden cardiologists with physical and psychological demands, and risks contributing to ill health. Cardiologists suffering poor health may increase absenteeism, stretching a workforce, and potentially reduce quality of patient care.

Purpose
We sought to describe the prevalence of physical and mental health conditions of cardiology trainees within the United Kingdom. We also aimed to identify factors associated with risk of burnout and negative drivers of psychological wellbeing.

Methods
The British Junior Cardiologists Association (BJCA) is a professional body which represents cardiology trainees in the UK. The BJCA conducts an annual survey of trainees, covering various aspects of working lives and all UK cardiology trainees are eligible to participate. For the 2023 survey, in addition to demographics and training questions, we asked questions on ill health, burnout, support for wellbeing, and invited responders to complete validated screening questionnaires for anxiety (GAD-7) and depression (PHQ-9). Responders were eligible for inclusion if they consented to take part in the health and wellbeing questions, and if they had completed four demographic questions. Anxiety and depression were deemed significant if scoring in the moderate or severe range (PHQ-9≥10; GAD7≥10). Significant burnout was defined as responders indicating being "somewhat" or "very" close to burnout. Logistic regression was used to determine odds ratios (OR) between univariate predictors of burnout, anxiety, and depression.

Results
Of the 398 responders, 212 fulfilled inclusion criteria (66% male, age 34±4 years, 42% had dependents). A physical health condition was reported by 11% of trainees, and 9% a reported a mental health condition. Significant burnout was reported by 76% of trainees. Those with dependents reported lower rates of burnout compared to those without (OR 0.35, 95% CI 0.18-0.67, p&lt;0.01). Significant depression scores were reported by 25%, significant anxiety scores in 18%, and significant scores of either depression or anxiety in 29% (Fig 1). Scores from 17% of trainees were consistent with significant depression or anxiety and yet not known to have a mental health condition. Less Than Full Time trainees reported higher rates of anxiety (OR 4.38, 95% CI 1.37-14.10, p=0.01) and depression (OR 10.31, 95% CI 2.98-35.71, p&lt;0.01). Training was reported to have a negative impact on physical health by 43% of trainees, and 47% reported a negative impact on mental health. Principal drivers of negative wellbeing included the amount of service provision; curriculum requirements, and lack of training opportunities (Fig 2).

Conclusions
The prevalence of anxiety, depression and burnout is high amongst cardiology trainees. Urgent action is needed by training bodies and employers to ensure training programmes consider the physical and mental wellbeing of trainees.Depression and Anxiety ScreeningNegative Drivers of Wellbeing
A meta-analysis of the safety and efficacy of pulsed-field versus conventional thermal ablation for atrial fibrillation
Authors: Amin A M , Abuelazm M , Nazir A , Ibrahim A A , Elbenawi H , Aboutaleb A , Ellabban M , Arnaout M , Abouzid M , Abdelazeem B 
Published: October 2024

Abstract

Background
Since pulsed-field ablation (PFA) specifically targets myocardial tissue, it has become a cutting-edge substitute for radiofrequency (RF) and cryoablation.

Purpose
We aim to compare the safety and efficacy of PFA vs thermal ablation for AF ablation.

Methods
We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) and observational comparative studies, which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through September 2023. RevMan version 5.4 software was used to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI).

Results
Seventeen studies with a total of 2,255 patients were included. PFA was significantly associated with a decreased AF recurrence (RR: 0.65, 95% CI [0.51, 0.84], P= 0.0010) but not any arrhythmia recurrence (RR: 0.87, 95% CI [0.69, 1.09], P= 0.22). Also, PFA was significantly associated with decreased total procedure time (MD: -15.15, 95% CI [-20.23, -10.07], P&lt; 0.00001) and heart rate (MD: -7.56, 95% CI [-12.78, -2.34], P= 0.005); however, there was no significant difference between PFA and thermal ablation in fluoroscopy time (MD: 2.83, 95% CI [-0.38, 6.04], P= 0.08). PFA decreased phrenic nerve palsy (RR: 0.38, 95% CI [0.15, 0.98], P= 0.05) and esophageal lesions (RR: 0.09, 95% CI [0.01, 0.69], P= 0.02); however, PFA was significantly associated with increased pericardial tamponade (RR: 6.14 with 95% CI [1.43, 26.33], P= 0.01).

Conclusion
PFA was significantly associated with decreased AF recurrence, heart rate, total procedure time, phrenic nerve palsy, esophageal lesion, and increased incidence of pericardial tamponade compared with thermal ablation. However, current evidence is mainly weighted by observational studies, requiring further large-scale randomized trials.Figure
The protective role of Baz2b ablation in aging-related heart failure
Authors: Zang T , Xu F , Cai S , Shen L 
Published: October 2024

Abstract

Background
The elderly population is increasing year by year. Aging has become an important risk factor for cardiac dysfunction and heart failure. Previous studies have found that bromodomain adjacent to zinc finger 2B (Baz2b) is closely associated with neurodegeneration, but its role in aging-related heart failure remains unclear.

Purpose
We aim to explore the mechanism of Baz2b in aging-induced heart failure and doxorubicin-induced heart failure. We also investigate whether Baz2b and its downstream mechanism can serve as targets for clinical intervention.

Methods
We injected doxorubicin intraperitoneally in Baz2b knockout and cardiac-specific Baz2b knockdown mice to produce in vivo models. The effects of Baz2b and its downstream regulators were further explored via RNA-sequence, chromatin immunoprecipitation-sequence (ChIP-seq) and assay for transposase-accessible chromatin-sequence (ATAC-seq). Besides, we elucidated the function of Baz2b in alpha-myosin heavy chain-induced myocarditis.

Results
we found that Baz2b expression was upregulated in both aged and doxorubicin-induced mice heart. Baz2b knockout resulted in cardiac function recovery accompanied by a decline in apoptosis in aged mice and doxorubicin-induced mice. In contrast to control mice, cardiac-specific Baz2b knockdown alleviated doxorubicin-induced cardiac dysfunction and apoptosis. Mechanistically, Baz2b was closely associated with inflammatory responses in heart. It regulates Stat1, an important inflammatory downstream regulator via H3k4me3. Furthermore, the overexpression of Stat1 was able to abolish the protective role of Baz2b in doxorubicin-induced cardiotoxicity. Besides, cardiac-specific Baz2b knockdown could alleviated myocarditis, in line with the fact that Baz2b was linked to inflammation.

Conclusion
Taken together, this study provides new insights that Baz2b plays an important role in aging-related heart dysfunction. Since epigenetic readers were previously unrecognized, these findings may shed on novel clinical therapeutic choice for patients with chemotherapy-induced cardiotoxicity.The schematic diagram of Baz2b in heart
Transoesophageal echocardiography-guided cardioversion and thromboembolism
Authors: Lunden M , Engvall J , Jansson K , Lindstrom L , Digerfeldt C , Almroth H , Hubbert L 
Published: October 2024

Abstract

Background
To perform electrical cardioversion of atrial fibrillation or atrial flutter with a duration of more than 48 hours, it is recommended to initiate anticoagulation therapy for at least three weeks beforehand. In cases where cardioversion is necessary earlier, it is suggested to precede the procedure with a transoesophageal echocardiography to rule out the presence of a thrombus in the left atrium (referred to as TOE-guided cardioversion). This strategy is outlined in current ESC guidelines for atrial fibrillation. However due to limited evidence, no specific level of recommendation for its use is provided.

Purpose
This study aimed to characterize patients treated by TOE-guided cardioversion in two hospitals and to conduct a safety analysis of the procedure. The 30-day incidence of thromboembolic events was chosen as the main safety objective, the 30-day mortality as the secondary.

Method
This was a retrospective, two center, cohort register study where information was obtained from patients medical records. All patients who underwent TOE-guided cardioversion between 2012-2020 in the first institute, and between 2015-2020 in the second were included. From the medical records all the patient characteristics and the clinical outcomes were identified.

Result
A total of 259 patients, with TOE-guided cardioversions, arrhythmia duration over 48 hours and without adequate anticoagulation therapy were included. Patient characteristics are shown in table 1. It was equal incidence of a 30-day thromboembolic event (n=6) and the 30-day mortality (n=6), 2,3% respectively. Three of the six patients died of non-cardiovascular cause. One of the 30-day thromboembolic event resulted in mortality at day 31. Table 2 summarize the data related to the thromboembolic events. There was no statistically significant predictor of any of the two endpoints when comparing the patients with event and patients without.

Conclusion
This study shows that the risk of thromboembolic events after TOE-guided cardioversion is not negligible, 2,3% within a 30-day follow up. The 30-day mortality was 2,3%, half of which were non-cardiovascular. To analyse potential clinical predictors for any events, larger studies specifically powered for such a question is needed.
ND15, subunit of the electron transport chain protein-complex I, age-dependently worsens cardiac performance in Drosophila melanogaster
Authors: Gaub F 
Published: October 2024

Abstract

Introduction
In the natural aging process of the heart, aside others, mitochondrial dysfunction is an essential driver for the development of reduced cardiac performance. Previous analysis of protein expression levels in cardiomyocytes of aged mice and have found aberrancies in subunits of the mitochondrial Complexes I – IV of the electron transport chain. Especially, the complex I subunit ND15 was highly downregulated. To elucidate the functional effects of this gene on the cardiac performance, we generated cardiomyocyte specific ND15 knock-downs in Drosophila melanogaster.

Methods
We generated Drosophila with heart-specific (+/+; Hand4.2-GAL4/UAS-ND15; tdtK/+) (ND15-KD)knockdown of ND15 using the UAS/GAL4 system. The flies' cardiomyocytes endogenously express tdTomato, facilitating fluorescence-based live imaging of the heart by high-resolution video fluorescence microscopy. The recorded data was processed using a R-Script, resulting in

Results
We compared wild type (WT) flies to ND15-KD flies at age 3 weeks(young) and 7 weeks(old).
Knockdown of ND15 resulted in impaired cardiac function. Most parameters deteriorated in aged flies in comparison to young flies. The heart frequency was significantly reduced (WT:6 beats/s – KD:4 beats/s – p&lt;0.0001) in the 7 weeks old group, end-diastolic diameter of the heart tube increased significantly in 3 weeks old ND15KD flies compared to controls(WT:65µm – KD:74µm p&lt;0,0001), resulting in a dilated heart tube Interestingly enough, this dilation in ND15-KD disappeared in 7 weeks old flies.
The fractional shortening was significantly decreased in young(WT:33,5% - KD:30% p&lt;0,01) and deteriorated in old flies (WT:35% - KD:22% p&lt;0,0001), indicating a reduced contraction capability. For both 3 weeks and 7 weeks old groups, the heart-rate adjusted interbeat interval variance (WT:22% -KD: 40% p&lt;0,0001) as well as the time of no cardiac action (WT: 22% - KD: 35% p&lt;0,0001) increased and showed significant irregularities. The duration of systole and diastole combined also exhibited arrhythmic patterns (WT:15% - KD:20.5% p&lt;0,0001). A general arrhythmia index (AI) increased significantly (WT: 0.25 – KD:0.5 p&lt;0,0001) These arrhythmia parameters emphasize the arrhythmogenic potential of the ND15-knockdown.
The relative relaxation capabilities drastically worsened with age, displaying a diastolic dysfunction in the 7 weeks old group.
At half-time relaxation, the WT was at 60% relaxation, ND15KD at 46%).

Conclusion
This study demonstrates that heart-specific deletion of ND15 results in a marked impairment of systolic and diastolic cardiac function in Drosophila accompanied by pro-arrhythmogenic actions. We could identify ND15 as a new mitochondrial molecular target for the maintenance of regular cardiac function and rhythmicity, especially with increasing age. Further mechanistic studies and translation to mammalian organisms are ongoing.
ATM: a protein involved in glucose and lipid metabolism in the heart
Authors: Carotenuto M , Paolillo R , Caterino M , D'apice S , Pezone A , Boccella N , Polese P , Ioele D , Pirozzi M , Coppola L , Lombardi A , Esposito G , Ruoppolo M , Avvedimento V E , Perrino C 
Published: October 2024

Abstract

Backround
Post-mitotic cells, such as neurons and cardiomyocytes, cannot repair DNA lesions with DNA replication and rely for their survival on efficient sensors and effectors that orchestrate the DNA damage response (DDR). The Ataxia Telangiectasia Mutated (ATM) protein kinase is the most important sensor of oxidative stress and the DNA damage response (DDR) and is implicated in cellular metabolism. It is believed that while transient DNA damage and DDR can temporarily improve cardiovascular function, persistent activation of DDR (and ATM) might promote the onset and development of heart failure (HF).

Purpose
We hypothesised that ATM might control and regulate energy metabolism in the heart under stress to promote DNA repair.

Methods
We analyzed the effects of ATM inactivation on cardiomyocyte hypertrophy, cardiac function, DDR and metabolism in hearts from wild-type (Atm+/+) or Atm-mutated (Atm-/-) mice under sham conditions or after pressure overload by transverse aortic constriction (TAC).

Results
ATM inactivation in Atm-/- mice induced cardiomyocyte hypertrophy, fetal gene expression re-activation and a specific metabolomic signature in the heart, characterized by significant accumulation of pyruvate, branched chain amino-acids, short-medium acyl-carnitines and metabolites of tricarboxylic acid cycle. The levels of the glycolytic enzymes, hexokinase-2 (HK2) and phosphofructokinase (PFK), were elevated. pyruvate was trapped in the cytosol because mitochondrial carriers were suppressed and the enzymes that process pyruvate were dysregulated. Because of pyruvate metabolic block, fatty acids oxidation was inefficient and resulted in the accumulation of acyl-carnitines and insulin resistance. These metabolic changes were amplified by TAC, which rapidly induced heart failure in Atm-/- mice.
ATM inactivation also increased basal and TAC-induced genomic stress in cardiomyocytes, as shown by the levels of p-γ-H2AX, 8-oxodG glycosylase (OGG1/2) and apurinic site nuclease (APE1). These results prove that ATM rewires the metabolism of cardiac cells by inducing glycolysis and fatty acids oxidation. ATM stimulates glycolysis to repair DNA lesions and protect the heart against stress-induced dysfunction. The metabolic block due to ATM inactivation accelerates heart failure.

Conclusions
Our data suggest that ATM favors the metabolic flexibility of the heart by stimulating glucose entry and balancing glucose catabolism with fatty acid oxidation, thus preventing mechanical stress-induced cardiac systolic dysfunction.
Sex differences in the expression of metabolic and pro-inflammatory markers in the initial post-COVID-19 phase
Authors: Estepa M , Haritonow N , Marx L , Nnaji M , Ladilov Y , Barcena M 
Published: October 2024

Abstract
Cardiovascular complications are a common manifestation of post-acute COVID-19 infection. Post-COVID-19 syndrome is often associated with the female sex and exacerbated inflammation; however, the underlying molecular mechanisms of this sex difference remain poorly understood. In the present study, we aimed to investigate several metabolic, mitochondrial, autophagy, oxidative stress, and inflammatory markers in peripheral blood mononuclear cells (PBMCs) and plasma isolated from older (&gt;75) male and female patients at the initial phase (1-2 weeks) after COVID-19 pneumonia. Age-matched non-infected women and men were used as a control group.
We found a significantly higher plasma TNF-α in post-COVID-19 women, but not in men, compared to the control group. Similarly, a significant elevation of IL-1β and IL-18 mRNA in PBMCs from post-COVID-19 women, but not men, was observed. These effects were associated with marked activation of AMPK (defined as pAMPK/AMPK ratio), suggesting potential metabolic stress in female post-COVID-19 PBMCs. Further analysis revealed increased expression of mitochondrial genes, which may be due to AMPK activation as a compensatory reaction to metabolic stress. Analysis of autophagy or oxidative stress (serum 8-OHdG) markers did not reveal any differences between the groups investigated.
We conclude that women in the initial phase of post-COVID-19 have elevated expression of inflammatory markers in plasma and in immune cells, which is associated with metabolic stress. This may contribute to the cardiovascular complications in female post-COVID-19 patients.