bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-lead 3D-vectorcardiography differentiates between high and low cardiovascular risk profiles in patients with suspected or know coronary heart disease
Authors: Schmidt-Lucke C , Kohl S , Kammeier A , Knobl H , Burchert W , Schmidt-Lucke J A , Lischke B , Lindner O 
Published: November 2023

Abstract
5-lead 3D-vectorcardiography (3D-VCG), including a dorsal electrode with ensemble of artificial neural networks (ANN) offers additional information over standard 12-lead electrocardiography (ECG) in the detection of cardiac ischaemia. Artificial Intelligence (AI) and access to a massive global clinical data repository have the potential to boost the performance of VCG beyond conventional techniques. VCG offers ease-of-use at rest and is therefore a promising candidate for becoming a new screening tool for coronary artery diseases (CAD). We, thus, tested the hypothesis of 3D-VCG being able to differentiate between patients with lower and high risk of cardiovascular disease (CVD) and identify those requiring coronary interventions.
In this exploratory study, we analysed patients in a national multicentre trial. Patients were recruited from general cardiologists’ praxis and radiologist centre with patients referred for further diagnosis of suspected or confirmed CVD. Based on the Perfusion (P)-Factor of the 5-lead 3D- vectorcardiography, including 731 parameters, e.g., QRS-T angle and in-house features calculated in time and frequency domains, such as beat moments a P-Index is calculated. Based on the P-Index, patients were either classified as high, medium, or low risk for CVD (medium + high defined as high CVD-risk). Confirmation of CAD was performed according to the practitioners’ discretion blinded to the P-Index. Number of risk factors (mod. PROCAM score) were compared between the high- and low-risk group using an independent t-test.
The 468 patients in this sample (m:w 61:39, age: 66 [40-87] years) showed 3.6 [0 - 7] CVRF, 16% had arrhythmias or conduction disturbances (AF, PM, BBB), 24% pts. had consecutive PCI or CABG. 62% were classified as low while 38% were classified as high risk for CVD by the P-Index. Number of cardiovascular risk factors was significantly higher in the high-risk CVD-group as defined by P-Index compared to low CVD-risk (4.0 [3.0 – 5.0] vs. 3.5 [2.0 – 4.0], p &lt; 0.05). P-Index differentiated between suspected CVD with or without consequent PCI or CABG (Chi2 = 4.02, p&lt;0.05).
The AI-based 3D-VCG is an innovative diagnostic tool that can help determine a patient's cardiovascular risk profile in resting condition for clinical and research purposes. Furthermore, the P-Index identified those with significant stenoses in need for coronary intervention and may thus be a further scalable screening method to differentiate patients with consequent interventional approach or need for risk modification. These preliminary data will have to be confirmed in a prospective, large-scale performance study to verify the diagnostic accuracy.
The role of heart rate variability in predicting the response to beta blocker in patients with frequent premature ventricular contractions
Authors: Chun K J , Seo J H , Ryu D R , Lee B K , Cho B R 
Published: November 2023

Abstract

Background
Frequent premature ventricular contractions (PVCs) in patients with structurally normal heart are not uncommon. Beta blocker is generally used to reduce symptom and burden of PVCs, but the response to beta blockers vary from patient to patient.

Purpose
This study aimed to investigate whether the heart rate variability (HRV) values could predict the response to beta blockers in patients with frequent PVCs.

Methods
We analyzed the patients who underwent 24-hour Holter monitoring and had PVC burden &gt;3% in baseline 24-hour Holter monitoring. Bisoprolol and nebivolol was used to reduce symptom and burden of PVCs. The response to beta blocker was defined as the reduction of PVCs burden more than 50% in follow-up Holter monitoring. Baseline HRV was measured by time domain and frequency domain methods using 24-hour Holter monitoring.

Results
A total of 125 patients (mean age, 52.1 ± 14.7 years; male, 38.3%) underwent repeated 24-hour Holter monitoring were finally analyzed. Mean follow-up duration between the Holter monitoring was 205 ± 200 days. Among 125 patients with frequent PVCs, 45 patients had response to beta blockers. The ratio of low-frequency (LF) and high-frequency (HF) was higher in response group than those with non-response to beta blocker (P=0.016). LF, HF, and other variables measured by time-domain method were not associated with response to beta blocker.

Conclusion
The HRV value, especially LF/HF ratio, could predict the response to beta blockers in patients with idiopathic frequent PVCs.
Quantity and quality of shared decision making incorporation across major international cardiology guidelines
Authors: Macdonald B J , Turgeon R D 
Published: November 2023

Abstract

Background/Introduction
Shared decision-making (SDM) is a key component of the provision of ethical care, but prior reviews have indicated that clinical practice guidelines poorly promote and facilitate SDM.

Purpose
To identify and characterize all pharmacotherapy recommendations integrating SDM within contemporary cardiovascular guidelines using a novel classification system.

Methods
The American College of Cardiology (ACC), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC) digital guideline libraries (2012–2022) were searched for current guidelines, or subsequent updates, that included at least one pharmacotherapy recommendation. We identified all pharmacotherapy recommendations for each guideline. Recommendations that incorporated SDM were rated according to a novel Supporting Higher Patient Autonomy in Recommendations (SHARE) rating framework – which evaluates the quality of SDM incorporation based on directness (1-3; assessing whether SDM was incorporated directly and impartially into the recommendation’s text) and facilitation (A-D; assessing whether decision aids or quantified benefits/harms were provided).

Results
From 65 guidelines and updates, 2,655 recommendations (35% of total) addressed pharmacotherapy. Of these recommendations, 171 (6%) incorporated SDM. By category, general cardiology guidelines contained the highest proportion of pharmacotherapy recommendations incorporating SDM (10%), whereas heart failure and myocardial disease contained the least (3%). The proportion of pharmacotherapy recommendations incorporating SDM was comparable across societies (ACC: 8%, CCS: 9%, ESC: 5%), with no trend for change over time. Only 5/171 (3%) of SDM recommendations met SHARE grade 1A (impartial recommendations for SDM supported by a decision aid), whereas 63% were SHARE grade 3D (SDM mentioned only in supporting text and without any tools or information to facilitate SDM).

Conclusions
Across guidelines published by three cardiovascular societies over the last decade, few recommendations incorporated SDM in any form, and even fewer adequately facilitated SDM. Guidelines should move away from merely advocating for consideration of patient preferences, and toward facilitating meaningful engagement in SDM.
Arterial hypertension, chronic kidney and severe valvular heart disease predict worse outcome after postponing non-emergency cardiac interventions during the COVID-19-pandemic
Authors: Andress S , Felbel D , Mack A , Rattka M , D`Almeida S , Buckert D , Rottbauer W , Imhof A , Stephan T 
Published: November 2023

Abstract

Background
Deferral of non-emergency cardiac procedures is associated with increased early emergency cardiovascular hospitalizations. Criteria to identify patients at risk for adverse events when postponing their scheduled intervention are needed.

Aim
The aim of this study was to identify predictors associated with worse clinical outcome in cardiac patients whose non-emergency cardiovascular intervention has been deferred during the COVID-19 pandemic.

Methods
This monocentric retrospective study included patients whose non-emergency cardiac intervention has been postponed during COVID-19-related lockdown between March 19th and April 30th 2020. Cox regression was performed to identify predictors of the combined endpoint emergency cardiovascular hospitalization and death. Patients’ outcome after 12 months was compared to a seasonal control group undergoing non-emergency interventions in 2019 as scheduled.

Results
The combined endpoint of death and emergency cardiovascular hospitalization occurred in 70 (36.5%) of 193 patients with a postponed cardiovascular intervention. The planned intervention was deferred by a median of 23 [19 – 36] days. Arterial hypertension (Hazard ratio [HR] 2.27; 95%-Confidence interval [CI] 1.00-5.12; P=0.049), chronic kidney disease (HR 1.89; 95%-CI 1.03 – 3.49, P=0.041) as well as severe valvular heart disease (HR 3.08; 95%-CI 1.68-5.64; P&lt;0.001) were independent predictors of death or emergency hospitalization. Kaplan-Maier estimators of the combined endpoint were 31% in patients with arterial hypertension, 56% in patients with severe valvular heart disease and 77% with both risk factors (HR 12.4, 95%-CI 3.8-40.7; P&lt;0.001) and only 9% in patients without these risk factors (log rank P&lt;0.001). Separate analyses of patients with arterial hypertension, chronic kidney disease and severe valvular heart disease revealed that deferred patients showed significantly poorer clinical outcomes when compared to the control group 2019 (log rank P&lt;0.001, P=0.006 and P&lt;0.001, respectively). NT-proBNP cut-off ≥ 1,109 pg/ml best predicts the occurrence of primary endpoint event in deferred patients (AUC 0.71; P&lt;0.001; sensitivity 64%, specificity 69%).

Conclusion
Our results suggest that patients with either arterial hypertension, chronic kidney or severe valvular heart disease are at very high risk for emergency hospitalization and increased mortality in case of postponed cardiac interventions even in supposed stable clinical status. Risk is even higher in patients suffering from a combination of these conditions. In addition, measuring NT-proBNP levels might help to identify those at high or very high risk.
Sex-based analysis of NSTEMI processes of care and outcomes by hospital: a nationwide cohort study
Authors: Moledina S , Nicholas Weight N W , Mohammed Dafaalla M D , Dennis Chen D C , Muhammad Rashid M R , Mohamed Mohamed M M , Harriette Vanspall H V S , Mario Iannaccone M I , Alaide Chieffo A C , Mamas Mamas M M 
Published: November 2023

Abstract

Background
Contemporary studies have demonstrated that in non-ST-segment elevation myocardial infarction (NSTEMI), processes of care vary significantly according to biological sex. Little is known regarding variation in practice between geographical areas and individual centers.

Methods & Results
We identified 305,014 admissions with NSTEMI in the United Kingdom (UK) Myocardial Infarction National Audit Project (MINAP), 2010-2017, including female sex (n = 110,209). Females presented significantly older (77y vs. 69y, P&lt;0.001), were more likely to be Caucasian (93% vs. 91%, P&lt;0.001) and less likely to be current smokers (18% vs. 24%, P&lt;0.001). Females were less frequently treated with GDMT after NSTEMI, less frequently managed with an invasive coronary angiogram (ICA) (58% vs. 75%, P&lt;0.001) during index admission and less frequently underwent PCI (35% vs. 49%, P&lt;0.001) or CABG surgery (5% vs. 9%, P&lt;0.001) compared to males. Structural process of care differed between the sexes, with a lower proportion of females being treated on a dedicated cardiology ward (48% vs. 56%, P&lt;0.001) or admitted under a attending cardiologist (44% vs. 52%, P&lt;0.001). In our hospital-clustered analysis, we show a positive correlation between the risk-standardized mortality rates (RSMR) and increasing proportion of women treated for NSTEMI (R2=0.17, P&lt;0.001). There was a clear negative correlation between the proportion of females who had an optimum opportunity-based quality indicator score (surrogate for optimum process of care) during their admission and RSMR (R2 =0.22, P&lt;0.001), with a far weaker correlation in males (R2 =0.08, P&lt;0.001).

Conclusion
There was a significant in variation of the management of patients with NSTEMI according to sex, with widespread geographical variation. Structural changes are likely required to enable successful change for female patients.
Societal and economic burden of dilated cardiomyopathy
Authors: Wiethoff I , Sikking M A , Evers S M A A , Henkens M T H M , Heymans S R B , Michels M , Verdonschot J A J , Hiligsmann M 
Published: November 2023

Abstract

Background/Introduction
Dilated cardiomyopathy (DCM) is a major cause of heart failure and can be associated with events like arrhythmias, syncope or sudden cardiac death. Next to the physical disease burden and the mental strain for patients, DCM also poses a substantial economic burden on society; however, respective data is missing.

Purpose
This study aims to measure the quality of life (QoL) and societal costs of DCM patients.

Methods
A cross-sectional evaluation of QoL and societal costs of DCM patients was performed through the 5-level EuroQol (EQ-5D-5L) and the Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ), respectively. QoL was translated into numerical values (i.e. utilities) for statistical analysis. Costs were measured from a Dutch societal perspective including medical costs, patient and family costs, productivity losses and costs in other sectors. Final costs were extrapolated to one year, reported in 2022 Euros, and compared between DCM severity according to NYHA classes.

Results
A total of 550 DCM patients were included. Mean age was 61 years, and 34% were women. Among EQ-5D dimensions, DCM patients scored lowest in usual activities, pain/discomfort and mobility (Figure 1). Overall utility was lower than the Dutch population mean (0.840 vs. 0.869, p = .225). Total societal DCM costs were €14,843 per patient per year (Figure 2). Cost drivers were productivity losses (€7,037) and medical costs (€4,621) due to inpatient care (€2,231), outpatient care (€863) and medication (€805). Patients with more symptomatic DCM (i.e. NYHA class III or IV) had significantly higher average DCM costs per year compared to less symptomatic DCM (€31,099 vs. €11,446, p &lt; .001) and significantly lower utilities (0.631 vs. 0.883, p &lt; .001).

Conclusion
DCM is associated with reduced QoL and high societal costs, especially in more advanced disease stages. To our knowledge, this is the first study describing the economic burden of DCM in the Netherlands. More studies in DCM are needed to confirm these results.Quality of life of DCM patientsTotal DCM costs per patient per year
Incidence of cardiovascular diseases over the past 20 years - a population-based study in 22 million individuals
Authors: Conrad N , Jhund P S , Sattar N , Rahimi K , Mcmurray J J V 
Published: November 2023

Abstract

Background
The incidence of atherosclerotic diseases has declined considerably since the early 2000s but the extent to which these reductions have occurred in different subgroups of patients is unknown. Whether there have been similar changes in the incidence of other cardiovascular diseases is also uncertain.

Methods
We used linked primary and secondary electronic health records of 22 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. We calculated the incidence of 10 cardiovascular diseases from 2000 to 2019 and used Poisson regression models to investigate temporal trends and variation by age, sex, and socioeconomic status.
Findings: Among the 22 009 375 individuals included in the study, we identified a total of 2 015 280 patients with a new diagnosis of at least one cardiovascular disease between 2000 and 2019 (mean (SD) age: 68.7 (16.8) years, 49% women). Collectively, the incidence of all 10 cardiovascular disorders (standardised by age and sex) decreased by 8% over the study period (incidence rate ratio (IRR) comparing 2017-2019 vs 2000-2002: 0.92 [0.92, 0.93]). The incidence of ischaemic heart disease and stroke decreased by about 30% over the study period (IRR comparing 2017-2019 vs 2000-2002: 0.72 [0.72, 0.73] and 0.73 [0.72, 0.74] for ischaemic heart disease and stroke, respectively), yet these improvements were largely restricted to older age groups and no improvements were observed in the incidence of atherosclerotic disease before the age of 60 years. The reductions in atherosclerotic diseases were also paralleled by a rising number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases, which increased considerably over the 20 years studied (Figure 1). Most cardiovascular disorders were more common in men than in women of the same age. However, the overall crude incidence of cardiovascular diseases was similar in men and women, due to the higher number of women in older age groups. A socioeconomic gradient was evident across all cardiovascular diseases, did not decrease over time, and was most important for peripheral arterial disease (IRR most deprived compared to least deprived: 1.56 [1.55, 1.58]), heart failure (1.50 [1.49, 1.51]) and ischaemic heart disease (1.48 [1.48, 1.49]) (Figure 2).
Interpretation: Despite important improvements in the prevention of atherosclerotic diseases, the overall burden of cardiovascular diseases remains very high. Further improvements in cardiovascular disease prevention may need to consider the broader spectrum of cardiovascular diseases, such as arrhythmia, valve diseases, and thromboembolic diseases, and examine the specific needs of younger age groups and socioeconomically deprived populations.Figure 1Figure 2
Full cardiac regeneration by MicroRNA and G-actin monomer binding protein
Authors: Liu Y H , Hsieh H T , Lin J L 
Published: November 2023

Abstract
Myocardial infarction causes massive loss of cardiomyocytes, leading to high mortality rate and heart failure. Cardiac regeneration is thought to have therapeutic potential for myocardial infarction and heart failure.
We recently found that Nkx2.5+ cardiac myoblasts exist in declining number in the hearts of postnatal mice. The Nkx2.5+ cardiac myoblasts reactivate after myocardial infarction. They reside mostly in the subepicardium. Using inducible Nkx2.5 enhancer-Cre/ROSA26 reporter double transgenic mice to lineage trace the fate of activated Nkx2.5+ cardiac myoblasts, we documented that the activated Nkx2.5+ cardiac myoblasts proliferate and differentiate into mature cardiomyocyte in vivo. We also documented that Nkx2.5+ cardiac myoblasts originate from the embryonic epicardial cells.
Thymosin ß4 is a G-actin monomer binding protein, involved in cell proliferation, migration, and differentiation. We hypothesized that Thymosin ß4 would promote Nkx2.5+ cardiac myoblasts, an embryonic epicardial-derived cells, mobilization and cardiomyogenesis, after myocardial injury.
Various microRNAs (miR) have been reported to control cardiac development and promote cardiac regeneration. We have transfected neonatal Nkx2.5 cardiac myoblasts with various microRNAs and found miR-590 markedly promotes cardiomyogenesis capacity of cardiac progenitor cells.
We have proved that miR-590 plus Thymosin ß4 (intraperitoneal injection) markedly improved murine cardiac function after myocardial infarction. In the treatment group with miR-590 plus Thymosin ß4 (n=9), LVEF improved from 45% (Day 0) to 77% (Day 7), to 83% (Day 28), to 85% (Day 56) with no LV regional wall motion abnormality and minimal aneurysm formation. In comparison, the control group with miR-mimic plus PBS (n=7), LVEF was 50% (Day 0) to 51% (Day 7), to 56% (Day 28), to 51% (Day 56) with persistent hypokinesia at apex and anterior wall with impaired LV contractility and larger aneurysm was revealed (p&lt;0.001). Heart section of the post-MI mouse receiving miR-590 plus Thymosin ß4 showed minimal fibrosis in the outer layer of myocardium. In contrast, large fibrotic area was noted in the no treatment group. The mice receiving miR-590 plus Thymosin ß4 had a 2-fold increase in survival rate than the control group. Enhanced cardiomyocytes proliferation was documented by phosphorylated histone H3 stain at treated 1-week post-MI heart section.
The study applies the results of our recent studies and successfully demonstrated systemic administration of miR-590 plus Thymosin ß4 markedly enhance cardiac repair/ regeneration. We anticipate the result would promote cardiac regeneration in clinical use.
Large-scale genetic and multi-omics analyses identify molecular pathways underlying dilated cardiomyopathy
Authors: Jurgens S J , Gaziano L , Garnier S , Krijger Juarez C , Kany S , Zheng S , Biddinger K , Tadros R , Ware J S , Schmidt A F , Amin A S , Ellinor P T , Charron P , Aragam K G , Bezzina C R 
Published: November 2023

Abstract

Background
Dilated cardiomyopathy (DCM) is a heart muscle disease that represents a major public health burden. While both common and rare genetic variants are known to affect DCM risk, previous genome-wide association studies (GWAS) have yielded only few loci and the molecular pathways underlying DCM remain largely unknown.

Purpose
We aimed to discover novel genetic loci for DCM by combining data from biobank and case-control studies, and by combining GWAS with multi-trait analyses. We also pursued multi-omics Mendelian randomization to nominate novel molecular pathways underlying DCM.

Methods and results
We first performed a GWAS of ICD-code defined DCM (N=1472 cases) from two large biobank datasets (UK Biobank and Mass General Brigham Biobank), and found good genetic correlation (rg=0.82, SE=0.22) and similar heritability estimates (h2=0.12, SE=0.03 vs. h2=0.14, SE=0.03) when compared with a previously published GWAS of recruited DCM cases. In a large meta-analysis across case-control and biobank datasets (N=4191 cases), we identified 10 loci significantly associated with DCM. We then integrated this novel meta-analysis into a multi-trait GWAS (MTAG) with MRI-derived left ventricular traits from the UK Biobank (LVEF and LVESV; N=36083), which yielded 44 lead variants at 36 significant loci. Novel loci overlap reported Mendelian cardiomyopathy genes (ACTN2, OBSCN, MYH7B), support previous mechanistic findings (HSPB8; heat shock protein family), and include genomic regions also arising from a recent GWAS of hypertrophic cardiomyopathy (notably, SVIL). We then performed Mendelian randomization analyses on the MTAG GWAS, using genetic instruments from published multi-omics datasets. Mendelian randomisation of the blood metabolome suggests potential causal roles for metabolites, notably those involved in the pentose phosphate pathway (ribitol; β=0.25, SE=0.04) and glycemic excursion (1,5-anhydroglucitol; β=0.08, SE=0.02). Analyses of the blood proteome suggest potential causal roles for several serum proteins, including proteins involved in redox balance (glutathione synthetase; β=-0.34, SE=0.05), mTORC1 signalling (LAMTOR3; β=0.08, SE=0.01), and the pentose phosphate pathway (G6PE; β=0.09, SE=0.02).

Conclusion
Our analyses link several new genomic regions with DCM, and implicate redox disbalance and alternative usage of (gluco)metabolic pathways as putative causal mechanisms of disease. Future functional studies could determine whether these represent actionable findings.