bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter operator variability of machine learning researchers predicting all-cause mortality in patients admitted to intensive care unit
Authors: Jones Y , Cleland J , Li C , Pellicori P , Friday J
Published: October 2021

Background

The number of publications using machine learning (ML) to predict cardiovascular outcomes and identify clusters of patients at greater risk has risen dramatically in recent years. However, research papers which use ML often fail to provide sufficient information about their algorithms to enable results to be replicated by others in the same or different datasets.

Aim

To test the reproducibility of results from ML algorithms given three different levels of information commonly found in publications: model type alone, a description of the model, and complete algorithm.

Methods

MIMIC-III is a healthcare dataset comprising detailed information from over 60,000 intensive care unit (ICU) admissions from the Beth Israel Deaconess Medical Centre between 2001 and 2012. Access is available to everyone pending approval and completion of a short training course.

Using this dataset, three models for predicting all-cause in-hospital mortality were created, two from a PhD student working in ML, and one from an existing research paper which used the same dataset and provided complete model information. A second researcher (a PhD student in ML and cardiology) was given the same dataset and was tasked with reproducing their results. Initially, this second researcher was told what type of model was created in each case, followed by a brief description of the algorithms. Finally, the complete algorithms from each participant were provided. In all three scenarios, recreated models were compared to original models using Area Under the Receiver Operating Characteristic Curve (AUC).

Results

After excluding those younger than 18 years and events with missing or invalid entries, 21,139 ICU admissions remained from 18,094 patients between 2001 and 2012, including 2,797 in-hospital deaths. Three models were produced: two Recurrent Neural Networks (RNNs) which differed significantly in internal weights and variables, and a Boosted Tree Classifier (BTC). The AUC of the first reproduced RNN matched that of the original RNN (Figure 1), however the second RNN and the BTC could not be reproduced given model type alone. As more information was provided about these algorithms, the results from the reproduced models matched the original results more closely.

Conclusions

In order to create clinically useful ML tools with results that are reproducible and consistent, it is vital that researchers share enough detail about their models. Model type alone is not enough to guarantee reproducibility. Although some models can be recreated with limited information, this is not always the case, and the best results are found when the complete algorithm is shared. These findings have huge relevance when trying to apply ML in clinical practice.

Funding Acknowledgement

Type of funding sources: None.
Detecting cardiomyopathies in pregnancy and the postpartum period using ECG
Authors: Adedinsewo D , Johnson P W , Douglass E J , Attia Z I , Phillips S D , Goswami R M , Yamani M H , Connolly H M , Rose C H , Sharpe E E , Lopez-Jimenez F , Friedman P A , Carter R E , Noseworthy P A
Published: October 2021

Background

Cardiovascular disease (CVD) has been identified as a major threat to maternal health in the US and UK with cardiomyopathy being one of the most common acquired CVD in the pregnant and postpartum period. Diagnosing cardiomyopathy in pregnancy is challenging due to an overlap of cardiovascular symptoms with normal pregnancy symptoms.

Purpose

The purpose of this study was to evaluate the effectiveness of an ECG based deep learning model in identifying cardiomyopathy among pregnant and postpartum women.

Methods

We utilized an ECG based deep learning model to detect cardiomyopathy in a cohort of pregnant or postpartum women seen at multiple hospital sites. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters.

Results

1,807 women were included. 7%, 10% and 13% had LVEF ≤35%, <45% and <50% respectively. The ECG based deep learning model identified cardiomyopathy with an AUC of 0.92 for left ventricular ejection fraction (LVEF) ≤35%, 0.89 for LVEF <45% and 0.87 for LVEF <50%. For LVEF ≤35%, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to white (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 and 0.72 respectively.

Conclusions

A deep learning model effectively identifies cardiomyopathy in pregnant or postpartum women, outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): This study was made possible using resources supported by the Mayo Clinic Women's Health Research Center and the Mayo Clinic Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program funded by the National Institutes of Health (NIH), grant number K12 HD065987. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The relationships among the pulse rate, use of beta-blockers, and prognosis in patients with ischemic heart disease in a real-world database using a storage system
Authors: Oba Y , Kohro T , Sato H , Nochioka K , Nakayama M , Fujita H , Mizuno Y , Kiyosue A , Iwanaga Y , Miyamoto Y , Matoba T , Tsutsui H , Nakamura T , Usuku K , Nagai R
Published: October 2021

Background

The use of β-blockers has the effect of improving the prognosis of patients with ischemic heart disease (IHD). One of the underlying mechanisms is a decrease in the cardiac load due to a reduction in the heart rate.

Purpose

To clarify the relationships among the pulse rate, the use of β-blockers, and the prognosis in patients with IHD in a multicenter study using a storage system.

Methods

The Clinical Deep Data Accumulation System (CLIDAS) collects (1) basic patient information, prescriptions, and laboratory data from electronic medical records from the Standardized Structured Medical Information eXchange (SS-MIX2) standard storage, and (2) the results of physiological tests, cardiac catheterization, and cardiac catheter intervention reports from the SS-MIX2 extended storage. 8540 cases who underwent cardiac catheterization from 6 university hospitals and the national cardiovascular center in Japan were registered (male: 77%, average age: 70.2 years). We evaluated these patients' pulse rate at admission and at the discharge of cardiac catheterization in 6,598 patients. We divided the pulse rates at discharge into quartiles (Q1: <60, Q2: 60–66, Q3: 67–75, Q4: ≥76 bpm), and we analyzed the relationship between the pulse rate and the prognosis by dividing the patients into the stable angina group (n=2,631) and the acute coronary syndrome (ACS) group (n=2,394). Regarding the use of β-blockers, we compared the pulse rates of the patients taking carvedilol (n=1,728) and those taking bisoprolol (n=2,761) at admission and discharge. Major adverse cardiovascular events (MACE) were defined as cardiovascular death, non-fatal myocardial infarction, unstable angina, heart failure, stroke, and other hospitalized cardiovascular events.

Results

A total of 600 MACEs occurred during an average observation period of 890 days. The incidence of cardiovascular events was significantly higher in the Q4 patients in the stable angina group (hazard ratio 1.79, 95% confidence interval 1.32–2.41, but there was no significant difference among the four pulse rate subgroups in the ACS group. The bisoprolol-treated patients had lower pulse rates at discharge (67.4±12.2 vs. 68.8±11.8 bpm, p<0.001) and a lower percentage of patients in the Q4 group (21.2 vs. 24.9%, p=0.005) compared to the carvedilol-treated patients. The pulse rate at admission was similar in the bisoprolol- and carvedilol-treated patients (74.3±19.3 vs. 73.2±29.5 bpm, p=0.328).

Conclusion

In a real-world database using a storage system, a pulse rate of ≤75 bpm was associated with a good prognosis in patients with ACS. Compared to carvedilol, bisoprolol was associated with a decreased pulse rate at discharge.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Kowa Company, Ltd.
Improving adherence to cholesterol lowering guidelines through an interactive digital tool
Authors: Rashid S , Suero-Abreu G A , Tysarowki M , Um H , Zhang Y , Shah K , Douglas A , Matassa D
Published: October 2021

Background

Statins are the cornerstone of primary and secondary prevention of atheroscleoric cardiovascular disease (ASCVD). Our previous retrospective analysis of 1042 consecutive patient encounters at a large urban academic institution found that one in five patients were not prescribed an appropriate statin therapy. These patients tended to be younger, of Black race, and met statin-eligibility solely via a 10-year ASCVD risk score ≥7.5%. Only one-third of patients had follow-up cholesterol levels ordered to monitor treatment efficacy.

Purpose

To improve adherence to cholesterol guidelines at our academic institution.

Methods

We implemented multiple interventions over a four-month period to support clinical decision making of guideline directed statin therapy: a) development of an online interactive tool, b) physician education on updated cholesterol guidelines and utilization of the tool, c) display of guideline summary in the workspace, and d) a documentation reminder in the electronic health record. We randomly selected encounter dates, from which 622 consecutive patient visits were analyzed. The primary outcome measures were: prescription rates of statins, documentation of a 10-year ASCVD risk score, and follow-up cholesterol levels ordered to monitor treatment efficacy.

Results

Out of the 622 patients, 232 met statin indication. In this post-intervention group, statin prescriptions rates improved when compared to the pre-intervention group (90.5% vs 82.3%, p=0.006). Among the patients who met statin indication solely via a 10-year ASCVD risk score ≥7.5%, there was an increase in documentation of the calculated 10-year ASCVD risk score (72.3% vs 57.8%; p=0.039) and in statin prescription rate (90.8% vs 67.6%; p<0.001). In addition, there was an increase in follow-up cholesterol levels ordered in all patients included in our study who met statin indication (64.1% vs 33.3%; p<0.001).

Conclusion

Our study showed higher rates of statin prescription, 10-year ASCVD risk score documentation, and treatment monitoring after multiple interventions, including an easily accessible online interactive tool, at a large urban academic institution.

Funding Acknowledgement

Type of funding sources: None. Statin Prescription Rates
Racial disparities of internet access in the united states: a multiyear analysis of the national behavioral risk factors surveillance system
Authors: Ahmed A I , Soliman A , Han Y , Qureshi W T , Al-Mallah M H
Published: October 2021

Introduction

The COVID 19 pandemic has led to a dramatic rise in the use of Telehealth. Studies have shown racial/ethnic disparities in internet access, a basic prerequisite for telehealth. However, little is known on the extent of this “digital divide” amongst racial minorities with cardiovascular comorbidities.

Purpose

To investigate racial disparities in internet access amongst those with cardiovascular diseases and risk factors, and explore the degree to which this exists amongst those with different levels of comorbidities.

Methods

Behavioral Risk Factors Surveillance System data from the years 2013–2017, during which survey respondents were asked the main outcome of interest (“Have you used the internet in the past 30 days”) were pooled. Respondents were included if they responded yes to questions on selected cardiovascular diseases and risk factors of interest. Multivariable logistic regression was used to analyze the odds of internet use by racial groups adjusting for several socioeconomic factors.

Results

There were a total of 1,478,214 individuals representing 150,235,244 million adults (non-Hispanic Blacks 11.31% and Hispanics 13.75%). Hispanics and Non-Hispanic Blacks reported the lowest prevalence of internet use (66.1% and 64.4% respectively) compared to Non-Hispanic Whites (81.9%). On regression analysis, racial minorities consistently reported lower rates of internet use, averaging 50% lower odds compared to non-Hispanic Whites. Results remained statistically significant even after controlling for several sociodemographic variables.

Conclusion

Using a large nationally representative cohort, we demonstrated differences in internet access amongst racial minorities and those with multiple comorbidities, placing them at distinct disadvantage with access to telecare. Our study adds to a growing body of literature that shows the disproportionate impact of the pandemic on minorities and calls for a concerted effort to reduce disparities in healthcare delivery.

Funding Acknowledgement

Type of funding sources: None.
Assessment of ECG during hybrid comprehensive telerehabilitation in heart failure patients – subanalysis of the TELEREHabilitation in heart failure patients – TELEREH-HF randomized clinical trial
Authors: Piotrowicz E , Orzechowski P , Zareba W , Glowczynska R , Szalewska D , Pluta S , Irzmanski R , Kalarus Z , Banach M , Opolski G , Pencina M , Kowalik I , Piotrowicz R
Published: October 2021

Background

Exercise training in heart failure (HF) patients (pts) should be monitored to ensure patients safety. That is why we use ECG telemonitoring during hybrid comprehensive telerehabilitation (HCTR).

Purpose

Assessment of frequency of cardiac arrhythmias during telerehabilitation in HF patients.

Methods

The present analysis formed part of TELEREH-HF multicenter, randomized (1:1), controlled trial that enrolled 850 HF pts with New York Heart Association class I, II, or III and left ventricular ejection fraction (LVEF) of 40% or less. Patients were randomized 1:1 to 9 week HCTR plus usual care or usual care only. This subanalysis focuses on 386 pts (aged 62±11 years, LVEF 31±7%) randomized to HCTR based on Nordic walking training 5 times/week. HCTR was tele-monitored with an EHO mini device adjusted to record 16-second fragments of ECG (from three precordial leads) and to transmit the data via mobile phone network to the monitoring center. The timing of automatic ECG recording were pre-set and coordinated with exercise training.

Results

In all, 16622 HCTR sessions were registered and 66488 ECGs transmitted fragments were evaluated (four 16-second recording per patient per one session were recorded). A sinus rhythm was present in 320 (83%) pts, permanent atrial fibrillation in 66 (17%) pts. Assessment of ECG during HCTR procedure is presented in Table 1.

Conclusions

Telerehabilitation in heart failure patients is safe without evidence for symptomatic cardiac arrhythmias requiring discontinuation of training.

Non-sustained ventricular tachycardia and paroxysmal atrial fibrillation episodes were rare but have required adjustment of the telerehabilitation regimen.

The most common arrhythmias were ventricular and supraventricular premature beats.

These arrhythmias did not result in any changes in rehabilitation and therapy regimens.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The National Centre for Research and Development, Warsaw, Poland.
Gene and protein expression profiles of selected molecular targets mediating electrophysiological function in pgc-1-alpha deficient murine ventricles
Authors: Saadeh K , Chadda K R , Ahmad S , Valli H , Nanthakumar N , Fazmin I T , Edling C E , Huang C L H , Jeevaratnam K
Published: October 2021

Background

The risk of cardiac arrhythmias increases significantly in patients with metabolic disorders such as obesity and diabetes mellitus. The mechanisms linking metabolic conditions and electrophysiological changes underlying cardiac arrhythmias remain poorly understood. Central to the energetic abnormalities characterising these conditions is mitochondrial dysfunction. Peroxisome proliferator activated receptor-γ (PPARγ) coactivator-1 (Pgc-1) regulate mitochondrial biogenesis and function. Their expression is impaired in metabolic disorders. Murine Pgc-1α−/− hearts replicate disrupted mitochondrial function and model the associated pro-arrhythmic electrophysiological abnormalities.

Purpose

To explore the molecular mechanisms underlying the pro-arrhythmic electrophysiological changes in the Pgc-1α−/− murine model of mitochondrial dysfunction.

Methods

Ventricular tissue samples were obtained from aged (>12 months) wild-type (WT) and homozygous Pgc-1α−/− mice. Quantitative PCR was used to examine transcription of 60 genes underlying cardiac tissue excitability, western blotting was used to examine expression of proteins relating to cardiac conduction velocity, and histological analysis was used to examine cardiac tissue fibrotic change.

Results

qPCR analysis implicated downregulation of genes related to Na+-K+ ATPase activity (Atp1b1), surface Ca2+ entry (Cacna1c), action potential repolarisation (Kcnn1), autonomic function (Adra1d, Adcy4, Pde4d, Prkar2a), and morphological properties (Myh6, Tbx3) in murine Pgc-1α−/− ventricles. Western blotting revealed reduced NaV1.5 but normal Cx43 expression. Histological analysis revealed increased tissue fibrosis in the Pgc-1α−/− ventricles.

Conclusions

These results identified molecular mechanisms underlying previously reported electrophysiological abnormalities such as impaired ventricular activation and reduced conduction velocity in arrhythmic substrate associated with Pgc-1 deficiencies. Results also correlated with earlier findings including functional effects of elevated Ca2+ concentrations. The present findings clarify possible mechanisms by which mitochondrial dysfunction affects electrophysiological function and identify potential pharmacological targets for anti-arrhythmic therapy.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Medical Research Council; the Wellcome Trust; British Heart Foundation
Investigations regarding the role of NOS1AP in the heart using a conditional overexpression mouse model
Authors: Jaensch M , Trum M , Williams T , Schmitt J , Schuh K , Qadri F , Maier L , Bader M , Ritter O
Published: October 2021

Background

35.3% of deaths in 2019 in Germany are caused by cardiovascular diseases (Destatis). 95% of these people were 60 years and older. To increase survival rate in elderly patients we investigate the relevance of altered expression of neuronal nitric oxide synthase 1 (NOS1) adaptor protein (NOS1AP) acting as an L-type calcium channel (CaV1.2) modulator via directing NOS1 to CaV1.2 on cardiac electrophysiology. Genome-wide association studies have linked genetic polymorphisms in NOS1AP to variations in QT interval duration (QTc). The QT interval reflects ventricular de- and repolarization. It may predispose individuals to ventricular tachycardia and sudden cardiac death (SCD) if prolonged, shortened or otherwise unregularly. In addition, about 20% of families with a clinically proven diagnosis of long QT syndrome (LQTS) host no mutation in any of the 16 associated genes.

Methods and results

Transgenic mice with conditional overexpression of NOS1AP in cardiac myocytes were used as model organism. We confirmed the interaction of NOS1AP with NOS1 and CaV1.2. Electrocardiography in NOS1AP overexpressing mice showed atrial and ventricular tachycardia both spontaneously and upon programmed stimulation associated with a significant decrease in QTc. Heart rates in NOS1AP overexpressing mice were similar to non-induced animals. Survival was significantly reduced (only 60% after 12 weeks vs. 100% in non-induced mice). Induced QTc alterations and accompanied deaths subsided upon re-administration of doxycycline.

Whole-cell patch-clamp measurements in isolated adult ventricular myocytes were performed and action potential duration at 90% of repolarization (APD90) was significantly reduced in induced transgenic NOS1AP overexpressing mice compared to control littermates.

In addition, we investigated the functional effect of the human SNP rs16847548 (T/C) located within the NOS1AP promoter. The SNP was found to decrease the transcriptional activity of NOS1AP in vitro and therefore, potentially leading to a decrease in NOS1AP expression in humans.

Conclusion

Myocardial overexpression of NOS1AP leads to short QT syndrome with increased susceptibility to atrial and ventricular arrhythmias and cardiac death. In accordance, APD90 is significantly shortened in overexpressing animals. The human SNP rs16847548, which is located in the promoter region of NOS1AP, results in a reduced NOS1AP promoter activity in vitro, hereby providing an explanation for the frequently published elongation of QT intervals. In summary, not only mutations in ion channels themselves but also genetic alterations in the expression of ion channel modulators such as NOS1AP, have an impact on QTc and arrhythmogenesis and represent a promising therapeutic target for LQTS patients.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Gesundheitscampus Brandenburg (MWFK)
Protective effects of different types of bariatric surgeries on myocardial ischemia-reperfusion injury in non-obese non-diabetic rats
Authors: Polozov A S , Kornyushin O V , Sonin D L , Chervyak M V , Bulavinova M V , Masley V V , Istomina M S , Mukhametdinova D V , Neimark A E , Cheburkin Y V , Toropova Y G , Derkach K V , Shpakov A O , Galagudza M M
Published: October 2021

Introduction

Prior bariatric surgery (BS) significantly improves survival after myocardial infarction (MI). We assume that reduction in fatal MI after BSs could be attributed to the infarct size-limiting effect of the interventions and that this effect is not associated with an improvements in the diabetes mellitus and obesity.

Purpose

The aim of the study was to evaluate the infarct-limiting effect of various types of bariatric surgery in non-obese non-diabetic rats.

Methods

Rats were randomized into the following groups: no surgery (CON), sham surgery (SHAM), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and ileal transposition (IT). 10 weeks after BS, the animals were subjected to ischemia-reperfusion, followed by histochemical determination of infarct area (IA) and no-reflow zone. At the 90th minute of reperfusion, all animals were injected intravenously with indocyanine green at a dose of 1 mg/kg to measure size of no-reflow zone.

Results

None of bariatric surgery procedures led to body weight reduction. A temporal high postprandial glucose was observed during oral glucose tolerance test (OGTT) in SG and RYGB rats at 30th minute followed by decrease at 120 minutes in comparison with SHAM. Blood insulin concentration increased at 60th minutes in response to OGTT glucose in the SG group compared to CON and SHAM. On the contrary, there was a decrease in insulin level in the IT group after 60 and 120 minutes. In RYGB, basal leptin was low at 120 minutes after glucose administration, while in SG it decreased at 60 and 120 minutes compared with CON and SHAM. Compared to the SHAM, the rats with RYGB and SG had lower IA by 22% and 10% and no-reflow size by 38% and 32%.

Conclusions

We demonstrated that both bariatric surgeries procedures, RYGB and SG, increase myocardial tolerance to ischemia-reperfusion injury in rats without diabetes and obesity. The infarct-limiting effect was accompanied by a significant decrease in basal plasma leptin level.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health Care of Russian Federation. Governmental funding research
Quantitative evaluation of coronary artery occlusion by 3D coronary volume reconstruction in a large animal model of acute myocardial infarction
Authors: Bruno V D , Sammut E , Gall A , Baz-Lopez D , Ascione R , Johnson T W
Published: October 2021

Background

Large animal models of acute myocardial infarction (MI) offer an important platform to test novel therapies. Consistency of infarct size between animals is critical to ensure an accurate assessment of therapies against control. However, anatomical variation challenges the ability to achieve a consistent infarct size and care must be taken to respect the principles of the 3Rs through minimisation of interventional fatalities.

Purpose

To standardise the approach of a closed chest model of balloon occlusion-facilitated MI. Novel 3-dimensional quantitative coronary angiography (3DQCA) software has been used retrospectively to identify a correlation between coronary volume occlusion and the extension of the myocardial scar.

Methods

Twenty-four Yorkshire pigs (mean weight 63.1±3 kg) underwent a closed chest MI model via percutaneous occlusion of the mid portion of the left anterior descending artery (LAD) for 60 minutes. The evaluation of the myocardial damage was obtained via cardiac magnetic resonance imaging (CMR) between 24 and 48 hours after the MI model (Acute) and at 4–5 weeks after MI (Chronic). Troponin I was also measured at multiple timepoints. 3DQCA reconstruction (QAngio XA 3D, Medis medical imaging systems NL) was generated from 2 angiographic projections with segmental analysis of all 3 major epicardial vessels including lumen volume, reference diameters, and segment length. The occlusive volume and vessel length was identified through co-registration of balloon position.

Results

At the short term timepoint, a significant correlation was found between the LAD volume occluded and the scar size as percentage of the LV mass (Spearman correlation 0.72, p value <0.01, Fig. 1). Using Youden index analysis we identified a cut-off point of 32.8% of the LAD volume to determine a scar volume >20% (Fig. 2). At chronic phase the correlation between these two variables was not significant, although there was a trend towards significance (p value = 0.06, Cor = 0.54). No significant correlation was found with serum Troponin I.

Conclusions

There is a significant correlation between the LAD volume occluded and the overall scar size in the acute phase and at least 32.8% of the LAD volume should be occluded to determine a scar volume >20% of the entire LV. This indicates that a prospective measure of occluded LAD volume might minimise the intra-experimental variability in studies aiming to reduce infarct size and acute myocardial injury.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): This research work was supported by grants awarded to Professor Ascione: the British Heart Foundation (BHF) (BHF IG/14/2/30991, BHF RM/13/2/30158), and the Medical Research Council (MRC) (MRC MR/L012723/1).
Medical model of the diagnosis of multifocal atherosclerosis in patients with stable ischemic heart disease
Authors: Skorodumova E G , Kostenko V A , Skorodumova E A , Siverina A V , Rysev A V
Published: October 2021

Purpose

To build a model according to which it would be possible to predict the presence of multifocal atherosclerosis (MFA) in patients with stable forms of coronary heart disease.

Materials and results

The study included 102 patients with exertional angina, (62 men (60.8%) and 40 women (39.2%), mean age 64.2±12.7 years. A search was carried out among the parameters of the local register of patients with coronary artery disease (385 items), which had the strongest relationship and influenced the presence of MFA. These turned out to be: chronic obstructive pulmonary disease (r=0.270 at p=0.006, F-criterion 5.169 at p=0.07), chronic kidney disease (r=0.330 at p=0.001, F-criterion 12.203 at p=0.001), level of the coefficient of variation of erythrocytes (RDW-CV) (r=0.228 at p=0.004, F-criterion 2.022 at p=0.015), leukocyte count (r=0.243 at p=0.016, F-criterion 6.329 at p<0.001), segmented neutrophils (r=0.231 at p=0.022, F-criterion 5.900 at p<0.001), eosinophils (r=0.336 at p=0.02, F-criterion 1.900 at p=0.002), C-reactive protein (r=0.431 at p=0.01, F-criterion 3.40 at p=0.002) increase in liver density in the form of steatosis or fibrosis according to ultrasound scanning data (r=0.427 at p=0.042, F-criterion 5.579 at p=0.022), level blood sodium (r=0.476 at p=0.011, F-criterion 4.723 at p=0.011). The following parameters were combined into one integral model using the linear modeling method: RDW-CV, leukocyte count, segmented neutrophils, eosinophils, total blood cholesterol, increased liver density according to ultrasound scan data in the form of steatosis or fibrosis and chronic obstructive pulmonary disease. The F-criterion of the full model was 4.8, the coefficient of determination R2=0.407; R2>0.3, significance level p=0.02. Thus, the resulting medical and mathematical model was generally acceptable. The threshold values of indicators were determined using the method of classification trees. This model visualized that the diagnostic levels of the scale values were: cholesterol level – 6.27 mmol/L, RDW-CV – 16.0%, neutrophils – 50%, eosinophils – 6%, leukocytes – 8.9%. In addition, the decision tree. shows that in individuals with cholesterol levels less than 6.27 mmol/l, without an increase in liver density according to ultrasound data, no obstructive pulmonary disease/RDW-CV level is less than 16%, only 1 patient had MFA, versus 24 patients who had cholesterol levels less than 6, 27 mmol/l, had an increase in liver density according to ultrasound, and the level of inflammatory granulocytes: neutrophils above 70%, eosinophils above 6% against the background of the total number of leukocytes 8.9x109 (l). In individuals with a GC above 6.27 mmol/L, MFA was observed in 14 people (100%)

Funding Acknowledgement

Type of funding sources: None. Diagnostic model
No dynamic changes in plasma ACE2 activity in patients with acute coronary syndrome
Authors: Hamilton G , Patel S K , Azraai M , Burrell L M
Published: October 2021

Background

Angiotensin converting enzyme 2 (ACE2) is expressed in the human myocardium and blood vessels and degrades the vasoconstrictor peptide angiotensin (Ang) II. Plasma ACE2 activity is elevated in patients with cardiovascular disease (CVD) and is a predictor of major adverse cardiovascular events (MACE) in obstructive coronary artery disease. However, it is unknown whether acute coronary syndrome (ACS) causes dynamic changes in plasma ACE2 activity.

Purpose

We investigated dynamic changes in serial troponin-T and plasma ACE2 activity in patients presenting with ACS who underwent invasive coronary angiography (ICA).

Methods

Consecutive patients admitted with ACS from October-November 2019 were screened. Those meeting the Fourth Universal Definition of Myocardial Infarction who had both ICA and serial troponin-T testing were included. The study was approved by the hospitals Human Research Ethics Committee. All patients had routine plasma samples taken over 3 time-points for measurement of troponin-T; the same sample was used to measure plasma ACE2 activity. Catalytic ACE2 activity was measured using a validated, sensitive quenched fluorescent substrate-based assay. Serial median troponin and ACE2 activity levels were analysed using the Friedman test for repeated measures.

Results

Forty-nine patients were included. The mean age of participants was 63.9±11.0 years, and 36 (74%) patients were male. Overall, 16 (36%) patients presented with ST-elevation myocardial infarction (STEMI) and 29 (74%) with non-ST-elevation myocardial infarction (NSTEMI). Twenty-nine (59%) patients had a history of hypertension and 14 (29%) a history of ischaemic heart disease; 13 (27%) with priorMI, 11 (22%) had previous PCI and 2 (4%) had prior coronary artery bypass grafting. Over the 3 time points, there was a clear rise in median troponin-T levels representing myocardial injury (p<0.001), with no change in median plasma ACE2 activity (p=0.23, table 1). There was no difference in median ACE2 activity in those presenting with STEMI vs. NSTEMI (6.9 [2.1–9.5] vs. 6.0 [1.8–12.1], p=0.87), nor in those who underwent PCI to a culprit lesion compared to those who did not have a culprit lesion stented (5.8 [0.9–10.5] vs. 7.3 [2.8–14.9], p=0.37).

Conclusions

Patients with ACS had higher plasma ACE2 levels compared to levels previously reported in healthy controls. There were no dynamic changes in ACE2 activity in the setting of ACS, despite a significant rise in troponin-T. These results suggest that plasma ACE2 levels reflect underlying endothelial dysfunction rather than acute myocardial injury or infarction. Studies are now underway to assess if plasma ACE2 activity in ACS predicts MACE.

Funding Acknowledgement

Type of funding sources: None. Table 1
Chondroitin sulfate n-acetylgalactosaminyltransferase-2 (ChGn-2) plays a significant role in cardiac remodeling and heart failure following pressure overload
Authors: Haryono A , Ikeda K , Nugroho D B , Kitagawa H , Igarashi M , Hirata K , Emoto N
Published: October 2021

Background

Cardiac extracellular matrix (ECM) is critically involved in cardiac homeostasis by providing mechanical support as well as modulating growth factor signaling. Cardiac ECM dysregulation has been shown in heart failure pathogenesis, and accumulation of chondroitin sulfate glycosaminoglycans (CS-GAGs) was previously shown to exacerbate heart failure by augmenting inflammation and fibrosis at the chronic phase. However, it remains unclear whether and the mechanism by which CS-GAGs cause cardiac dysfunction, especially at the acute phase.

Purpose

The purpose of this study is to elucidate the role of CS-GAGs in heart failure.

Methods

In this study, we analyzed the role of CS-GAGs in heart failure using mice with target deletion of chondroitin sulfate N-acetylgalactosaminyltransferase (ChGn)-2 that elongates CS chains of GAGs. Heart failure was induced by transverse aortic constriction (TAC) in mice. Since cardiac fibroblasts (CFs) are the primary cells for ECM production in the heart, we explored the role of CF-derived ECM in cardiomyocyte apoptosis. CFs were given stretch stimuli that mimic pressure overload conditions.

Results

Significant CS-GAGs accumulation was detected in the heart of WT mice after TAC, which was substantially reduced in the heart of ChGn2−/− mice. Unexpectedly, loss of ChGn-2 deteriorated left ventricular systolic dysfunction accompanied by augmented cardiac hypertrophy and increased cardiomyocyte apoptosis. Stretch stimuli increased ChGn-2 expression and enhanced GAG production in CFs. Interestingly, only conditioned medium (CM) derived from stretched CFs showed protective effects on cardiomyocyte death induced by doxorubicin. Degradation of CS-GAGs in CFs-derived CM by using Chondroitinase ABC abolished its cardioprotective effect. Further experiments revealed that this cardioprotective effect is at least partially through CS-GAGs-derived PI3K/AKT pathway activation via CD44.

Conclusion

Our data revealed that CF-derived GAGs protect cardiomyocytes from death in the acute phase of heart failure due to pressure overload; thus, insufficient GAGs production caused by loss of ChGn-2 exacerbated heart failure.

Funding Acknowledgement

Type of funding sources: None.
The long non-coding RNA Heat4 is upregulated in heart failure and decreases the immune response of non-classical monocytes
Authors: Kneuer J , Meinecke T , Weiss R , Gaul S , Haas J , Meder B , Garfias-Veitel T , Von Haehling S , Kogel A , Keller T , Speer T , Thiele H , Lurz P , Laufs U , Boeckel J.-N
Published: October 2021

Background and purpose

Activation of the immune system correlates with the severity and the prognosis of patients with heart failure (HF). This study aims to identify and characterize long non-coding RNAs (lncRNAs) as a potential mechanistic link between the pathophysiology of HF and the activation of the immune system.

Methods and results

Next-generation sequencing (NGS) studies identified a 2.05-fold increase of the lncRNA Heat4 in the blood of patients with HF compared to controls, which was validated in a larger cohort (HF: N=63; Controls: N=38; p<0.05). Interestingly, the lncRNA Heat4 is encoded in the well-known immune receptor locus CD300, together with 8 CD300-receptors which are associated with activation of the immune system. To determine the cellular origin of Heat4 in blood, we performed MACS and identified Heat4 to be enriched in non-classical monocytes compared to classical monocytes (3.37-fold, p<0.05). The expression of Heat4 in non-classical monocytes was further validated by single-cell RNA sequencing. Overexpression of Heat4 in monocytes decreased levels of pro-inflammatory cytokines such as TNFα (38.6% reduction, p<0.05). Conversely, the knockdown of Heat4 resulted in elevated levels of pro-inflammatory cytokines, including IL6 (10.83-fold, p<0.05) and TNFα (4.14-fold, p<0.05). In a larger cohort including patients with HF, Heat4 was able to determine the prevalence of heart failure by AUC=0.734 (p<0.05). Moreover, in a 4-year follow-up of the same cohort, Heat4 predicted mortality by AUC=0.789 (HF: N=63, Dead=32; Controls: N=38, Dead=0; p<0.05).

Conclusion

The long non-coding RNA Heat4 is elevated in the blood of HF patients. Mechanistically, Heat4 limits the extent of the inflammatory response of non-classical monocytes. Therefore, Heat4 may provide a regulatory link between inflammation and HF.

Funding Acknowledgement

Type of funding sources: None.
Genetic variants as determinants of outcome in lamin A/C-related cardiac disease
Authors: Garcia Hernandez S , Ortiz-Genga M , Ochoa J P , Lamounier A , Fernandez X , Cardenas I , Garcia-Giustiniani D , Brogger M N , Fernandez G , Valverde M , Monserrat L , McKenna W J
Published: October 2021

Background

Current guidelines for the diagnosis and management of familial dilated cardiomyopathy highlight the variables “male sex” and “non-missense type variants” as risk factors for malignant ventricular arrhythmias.

Objective

Quantitative evaluation of prognostic differences between different LMNA variants associated with cardio-laminopathy.

Method

Analysis of cardiac event-free survival (sudden death, major arrhythmic events, death from heart failure and transplantation) with Kaplan-Meier approach in relation to gender & variant LMNA type. The data come from a specific database containing information on more than 1200 carriers of disease-causing LMNA variants. In the first analysis, the groups of comparison were truncating-type variants (LMNAtv) VS the global of pathogenic missense variants in the gene associated with cardiolaminopathy (LMNAm), segregated by gender. In the second analysis, it was considered missense LMNA affecting different residues (p.Arg190, p.Arg377 and p.Arg541), located in different functional domains, with enough data for comparison and with statistically different clinical behavior from that of global pathogenic variants in the gene. They were compared with the group of LMNAtv variants, as reference. The variants included were p.Arg377Cys/His, p.Arg541Cys/Ser/Gly/Pro/His and p.Arg190Trp/Gln/Pro, all of them pathogenic and associated with cardio-laminopathy.

Results

No significant differences were observed in survival between LMNAtv versus LMNAm variants (log rank=0.56) with slightly worse outcomes in males (log rank 0.03). Median survival time was 56 years for men compared to 60 years for women with LMNAtv, and 55 years compared to 66 years, respectively, among carriers of LMNAm (analysis A). In analysis B, statistically significant differences were observed between the groups considered (Log Rank p<0.001). These differences were also clinically relevant (median survival time in groups p.Arg377, LMNAtv, p.Arg190 and p.Arg541 was 60, 58, 50 and 35 years, respectively). Importantly, more than 70% of the cardiac events observed were related to major ventricular arrhythmic episodes.

Conclusions

This quantitative analysis demonstrates that certain missense variants in LMNA may have a similar and even more adverse clinical course than the set of truncation-type variants. These findings highlight the relevance of the specific variant rather than the variant type in guiding actionable therapies to prevent adverse outcomes. Regarding the differences observed between genders, even though they are statistically significant, their magnitude could be clinically not relevant.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Health in Code
Current litigation - what can we learn?
Authors: Harvey Richard
Published: October 2021

This presentation explores the issues raised in the first presentation by examining current cases before European courts: (i) Union of Swiss Senior Women for Climate Protection v. Swiss Federal Council and Others. The application was rejected by the Swiss Federal Supreme Court on legal standing grounds - the heat stress-related aspects were not specific enough. The case has been appealed to the European Court of Human Rights. (ii) Youth for Climate Justice v. Austria, et al The European Court of Human Rights has dismissed a coordinated effort by 33 governments to overturn its October 2020 decision to fast-track the case. Governments had until May 27 2021 to submit their defences. The current status of both cases will be reviewed and the lessons for strategic litigation discussed.
Nutritional psychiatry: implications for public health
Authors: Jacka F
Published: October 2021

With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. The 20th century has seen major shifts in dietary intakes globally, with a marked increase in the consumption of sugars, snack foods, take-away foods and high-energy foods. At the same time, the consumption of nutrient-dense foods, such as high-nutrient vegetables and raw fruits, is diminishing. Poor diet is now recognized as the leading risk factor for illness and early mortality globally. However, there is now overwhelming body of evidence to tell us that unhealthy diet is also a key risk factor for psychiatric illnesses, including depression, anxiety and dementia. Current evidence highlights major developments in understanding the mechanistic pathways linking diet to neurodevelopmental and neurodegenerative outcomes. New research activities are underway in this field, however there is already a strong evidence for diet as a key strategy for improving mental and brain health. There is a need to address all the recent advances in the public health and policy imperatives and for translating the evidence into improvements to individual and population health.
Magic bullet for public mental health: is cheap also cheerful?
Authors: Ali S
Published: October 2021

The Global Burden of Disease studies have consistently shown that mental health challenges are among the leading causes of lost disability-adjusted life years (DALYs), and represent one of the biggest public health problems of our time. The World Health Organization (WHO) estimates that around 450 million people struggle with mental health issues at any one time - this is only exacerbated by the current pandemic. Now, more than ever, there is strong argument for WHO proposition of ‘no health without mental health'. The current weapon for tackling the mental health crisis is largely based on a medical model. After decades of medication-based treatments, this model has seen a significant shift towards ‘talking therapies'. More so, the last few years, particularly during the pandemic, virtual care has become the significant mechanism of providing mental health support. Our research has identified a number of challenges in the current approach that remain unaddressed: 1) recovery rates from talking therapies are low and inequitably distributed; 2) improvements in mental health depend more on individual-level factors and circumstances than the person providing therapy; and 3) most people who recover from mental health problems relapse within a year. In this session, we will discuss these findings and ask: are we approaching mental health with the right approach, or is this time to rewrite the vows between public health and primary care to tackle the mental health crisis?
Place of death in Europe: trends and associations in a 30-country panel (2005-2017)
Authors: Jiang J , May P
Published: October 2021

Background

End-of-life care attracts major policy interest. Place of death is an important metric of individual experience and health system performance. Most people prefer to die at home, but hospital is the most common place of death in high-income countries. Little is known about international trends in place of death over time.

Methods

We aimed to collate population-level data on place of death in Europe for the years 2005-2017, and to evaluate association with national characteristics and policy choices. We sought outcome data from the 32 European Economic Area countries. We identified national economic, societal, demographic and health system predictors from Eurostat, OECD and the WHO. We analysed these cross-national panel data using linear regression with panel-corrected standard errors.

Results

Our analytic dataset included 30 countries accounting for over 95% of Europe's population and economic activity. Average national proportion of deaths occurring in hospital in the study period ranged from 26% to 68%, with a median of 52%. Trends vary markedly by region and wealth, with low and decreasing hospital deaths in the North-West, and high and increasing prevalence in the South and East. Controlling for demographic and economic factors, strong palliative care provision and generous government finance of long-term care were associated with fewer hospital deaths.

Conclusions

We found modifiable policy choices associated with hospital mortality, as well as wider structural economic and societal factors. Policymakers can act to curb worrisome trends in-hospital mortality. Data on places of death outside hospital can improve future research, policy and practice.

Key messages

Cross-national longitudinal analysis. Trends of hospital deaths in Europe, association between hospital mortality rate, palliative care and other healthcare factors.