bluuebunny/crossref_metadata_2025 huggingface dataset:
A web-based tool for the early identification and real time assessment of drug-induced proarrhythmic and torsade de pointes safety risk
Authors: Baretta A , Bisotti M.A , Palazzin A , Cano J , Gomis-Tena J , Romero L , Saiz J , Bursi R
Published: November 2020

Introduction

It is well recognized that early identification of drug-induced proarrhythmic safety risks is crucial to drug development for ethical, animal sparing and costs reduction considerations. The availability, however, of easily accessible, user-friendly tools for real time assessments of the proarrhythmic potential of chemical compounds has been lacking. The novel Tx index, implemented in the presented web-based tool, was applied to a dataset of 84 compounds.

Materials and methods

The tool is based on 206,766 cellular simulations of compound-induced effects on Action Potential Duration (APD) in isolated endocardial, midmyocardial, and epicardial cells and on 7,072 tissue simulations on QT prolongation in a virtual tissue. Simulations were performed by blocking the slow and the fast components of the delayed rectifier current (IKs and IKr, respectively) and the L-type calcium current (ICaL) at different levels. Based on these simulations, four Tx indices were defined as the ratio of drug concentration leading to a 10% prolongation of the APDendo, APDmid, APDepi or QT over the maximum Effective Free Therapeutic Plasma Concentration (EFTPC), respectively. A dataset of 44 non-torsadogenic and 40 torsadogenic drug compounds was used to validate the performance of the tool. The workflow of the web-based tool was built on the cloud environment, in compliance with the highest standards of security and privacy.

hERG test (positive response: hERG pIC50 >6) was applied to the 84 compounds to compare performances.

Results

Receiver operating characteristic (ROC) curves were constructed on the four estimated Tx indices for each compound in the dataset to enable the identification of torsadogenic potential cut-off values2. These were identified as 8, 8, and 6.4 for Tx-APDendo, Tx-APDmid, Tx-APDepi and as 9.2 for Tx-QT, respectively.

The classification of the 84 compounds resulted in an accuracy ranging between 87% and 88% for the four Tx indices Tx-APDendo, Tx-APDmid, Tx-APDepi and Tx-QT.

Discussion and conclusion

hERG block exhibits poor performance. When applying the hERG test to the 84 compounds, it exhibited a TPR of 55%, a TNR of 89%, and an A of 73%, in close agreement with previous studies. In comparison, the in silico Tx tests described in this study yield TPRs of 85%, TNRs of 86–89% and As of 86–87%.

This method does not include drug effects on Na+ channels, which is related to the misclassification of 3 compounds (quetiapine, ranolazine, and lamotrigine – significant Na+ channels blockers at EFTPC). Future work will include this channel.

The presented web-based tool is a highly innovative method for an accurate torsadogenic risk assessment. Each assessment required only a few seconds of computational time.

Illustration workflow of the web tool

Funding Acknowledgement

Type of funding source: None
Xanthine oxidase inhibition attenuates doxorubicin-induced cardiotoxicity in mice
Authors: Tanaka Y , Nagoshi T , Yoshii A , Oi Y , Takahashi H , Kimura H , Kashiwagi Y , Tanaka T.D , Yoshimura M
Published: November 2020

Background

Accumulating evidence suggests that high serum uric acid (UA) is associated with left ventricular (LV) dysfunction. Although xanthine oxidase (XO) activation is a critical regulatory mechanism of the terminal step in ATP and purine degradation, the pathophysiological role of cardiac tissue XO in LV dysfunction remains unclear.

Objectives

We hypothesized that cardiac XO is activated in doxorubicin-induced LV dysfunction, and XO inhibitors ameliorate LV function by inhibiting cell death signals as well as by modifying cardiac purine metabolism.

Methods

Either doxorubicin (10 mg/kg) or vehicle was intraperitonially administered in a single injection to ICR mice. Mice were treated with or without oral XO inhibitors (febuxostat 3 mg/kg/day or topiroxostat 5 mg/kg/day) for 8 days starting 24 hours before doxorubicin-injection. The LV function was assessed by echocardiography at day 6 and by ex vivo heart perfusion at day 7.

Results

Cardiac tissue XO activity measured by a highly sensitive assay with liquid chromatography/mass spectrometry (n=8 each) and cardiac UA content (n=3–6) were significantly increased in doxorubicin-treated mice at day 7 and dramatically reduced by XO inhibitors. Accordingly, XO inhibitors substantially improved LV ejection fraction (n=8 each) and LV developed pressure (n=9 each) that had been impaired by doxorubicin administration. Intriguingly, the expression of GPX4, a negative regulator of ferroptosis, was decreased in doxorubicin-treated hearts but improved by XO inhibitors (n=6 each). Furthermore, metabolome analyses revealed an enhanced purine metabolism in doxorubicin-treated hearts, and XO inhibitors suppressed the serial metabolic reaction of hypoxanthine–xanthine–UA.

Conclusions

Doxorubicin administration induces cardiac tissue XO activation associated with an impaired LV function. XO inhibition attenuates the doxorubicin-induced cardiotoxicity partly through an anti-ferroptotic effect and the conservation of tissue ATP levels by modulating purine metabolism. The present study suggests that pharmacological XO inhibition represents a potential therapeutic strategy for the treatment of doxorubicin-induced cardiotoxicity.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported in part by grants-in-aid for Ministry of Education Culture, Sports, Science and Technology.
Electrocardiographic evaluation of depolarization and repolarization abnormalities in breast cancer patients with HER2-inhibitor related cardiac dysfunction
Authors: Kinoshita T , Yuzawa H , Wada R , Yano K , Yao S , Akitsu K , Koike H , Shinohara M , Abe A , Fujino T , Ogata H , Ikeda T
Published: November 2020

Background

The arrhythmic substrates of the myocardium such as depolarization and repolarization abnormalities are thought to reflect cardiac dysfunction prior to the morphologic left ventricular dysfunction. Activation time (AT), recovery time (RT) and T wave peek-end interval dispersion (Tpe-dispersion) are useful indicators of the arrhythmic substrate. We examined the appearance of depolarization and repolarization abnormalities in patients with cancer therapeutics-related cardiac dysfunction (CTRCD) using AT, RT and Tpe-dispersion.

Methods

We conducted a standardized case-control study of CTRCD with 40 patients who developed breast cancer and treated with trastuzumab (13 cases and 27 controls). We assessed the relation between electrocardiographic indexes, including AT, RT and corrected Tpe-dispersion, and CTRCD. QT intervals were measured by Fridericia method, and QT observer 3 software were used for the measurement of all electrocardiographic indexes.

Results

LVEF in case and control group were 45.7±8% and 69.2±6%, respectively. AT in aVR lead was significantly higher in case group compared with control (28.8±7ms vs 22.8±5ms, P=0.02). corrected Tpe-dispersion tended to be higher in case group than that of control group (43.2±19ms vs 31.9±10ms, P=0.06). QT dispersion and RT dispersion were not different between case and control group.

Conclusions

Our study demonstrated that AT in aVR may predict cardiac dysfunction in breast cancer patients with HER2-inhibitor related cardiac dysfunction. More detailed studies using other modalities which can detect depolarization and repolarization abnormalities, including ventricular late potentials and T wave alternans, are needed.

Funding Acknowledgement

Type of funding source: None
Prevalence of drug to drug interactions in critical cardiac patients
Authors: Mohamed Ariff A.M , Abd Hadi H , Win N.T , Thoulath M.I , Aktifanus A.T.J , Mutaya S.M , Nalliah S , Mohamed Yusof A.K
Published: November 2020

Background

Pharmacotherapy in the management of cardiovascular disease patients with multiple co-morbidities has been challenging due to polypharmacy (five or more drugs). They have been attributed with potential drug – drug interactions (DDI). Detecting the clinically significant drug interactions allows the opportunity for prevention through clinical drug decision support system (CDDSS) and clinical management.

Purpose

To identify significant potential DDI in critical cardiac patients

Method

We prospectively observed patients admitted at CCCU received multiple medications leading to potential DDI from Feb 2018 to July 2018 using two commercially available CDDSS along clinical management and pharmacovigilance algorithm.

Results

Patients admitted at CCCU co-administered with two or more drugs were analyzed. The mean age was 61.1 years. Total 649 patients were screened, resulting 87.7% (569/649) patients took more than five drugs. Of the 4249 potential DDI 543 were unique interacting drug pairs. On average, CCU patients were prescribed with 12.1 drugs, potentiating 14.1 potential DDI. Older patients (>60 years) received more medications than younger ones (mean 18.7 vs 15.1 drugs). 82.1% patients had one or more potential DDI with major and moderate severity detected by one or both CDDSS. Common potential clinical adverse was bleeding, QTc prolongation and CYP3A4 inhibition. Both CDDSS agreed on the severity ratings in 36.9%. There were significant association of potential DDI with specific risk factors (geriatric, female, Indian and heart failure patients)

Conclusions

Rate of potential DDI adversely influenced by polypharmacy, antiarrhythmic drugs, comorbidities and LOS. Significant potential DDI occur in the CCU, highlighting the need for CDDSS potentially prevent patient harm. Identified risk factors (geriatrics population, female sex, Indian ethnicity and heart failure patients) can be used in mitigating adverse DDI.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): NATIONAL HEART INSTITUTE
Daily intra-individual variability of positive but not negative affect impacts moderate to vigorous physical activity
Authors: Wierenga K , Moore S.E , Fresco D.M
Published: November 2020

Introduction

The World Health Organization recommends moderate to vigorous physical activity (MVPA) for 150 minutes per week to reduce the risk of primary or secondary cardiovascular diseases (CVD). Adherence to these recommendations is only around 30% in the US. Identifying reliable barriers or facilitators of time spent in MVPA is a critical component to primary and secondary CVD prevention. Negative affect, including feelings such as being sad, nervous, and restless, is known to diminish time spent in MVPA, whereas positive affect, which includes feelings such as being calm, happy, or full of life is associated with MVPA increases. Relatedly, variability in positive but not negative affect is associated with poorer physical health. What is unclear is how intra-individual variability of positive and negative affect may influence MVPA.

Research question

What is the influence of variations (i.e. intra-individual day-to-day) in positive and negative affect on variations in MVPA? Method. Guided by the individual and self-management theory, a secondary analysis was conducted of data from a nationwide US sample of participants. Using data from the Midlife in the United States (MIDUS) Refresh Wave Study Daily Diary Project, we analyzed eight consecutive days of affect and MVPA assessments in a sample of 553 healthy participants (54% women, 86% white, mean age = 48.7 years). Latent trajectory models were computed to determine the influence of daily positive and negative affect on daily MVPA.

Results

Affect variability, calculated as the standard deviation of daily positive and negative affect, was positively correlated with MVPA variability. An autoregressive cross-lagged latent trajectory model provided the best fit to examine relationships between positive affect, negative affect, and MVPA (χ2=946.54, df=379, p<0.001; CFI=0.95; RMSEA=0.05, SRMR = 0.06). Positive, but not negative affect, intercepts were significantly correlated with MVPA trajectories (r=0.19, p<0.05). Individuals who initially begin the eight day time span with a higher reported positive affect show a modest increase in MVPA over the same time period (r=0.19, p<0.001). By contrast, individuals evidencing increases in positive affect over the time span showed a decreased rate of change in MVPA over that same time (r=−0.32, p<0.001).

Conclusion

The association of positive affect to MVPA necessitates a complex analysis to more fully understand intra-individual-level interactions. Relatively higher positive affect with fewer fluctuations was associated with greater MVPA. These intriguing preliminary findings must be considered in light of important limitations (e.g., only eight days of data; affect and MVPA do not necessarily follow diurnal patterns). Still, findings support the view that beginning with positive affect may lead to stability in time spent in MVPA.

Funding Acknowledgement

Type of funding source: None
Exercise motivation in patients with heart failure
Authors: Klompstra L , Jaarsma T , Stromberg A , Van Der Wal M.H.L
Published: November 2020

Background

Being physically active is important for patients with heart failure (HF) to improve clinical outcome, however, adherence to exercise is low (<50%). To tailor intervention that increase physical activity, it is important to know what motivates HF patients to exercise. Therefore, the aim of the study is to describe motivations of HF patients to exercise and describe variables that are related to their exercise motivation.

Methods

This is a cross-sectional analysis of baseline data of 605 patients with HF (mean age 67±12, 71% male, 60%NYHA I/II) who were included in the HF-Wii study. Stepwise regression modelling was used with exercise motivation as dependent variable. Exercise motivation was measured with the Exercise Motivation Index, including 15 statements with answers ranging from 0 (not important) to 4 (extremely important), with 3 subscales (physical, psychological and social motivation).

Based on previous research the following predictors were included in the model: quality of life (MLwHFQ), self-efficacy (Exercise self-efficacy scale), cognition (MoCA), depression (HADs), sleeping difficulties (MISS), HF symptoms (fatigue, shortness of breath), age, gender, NYHA-class, comorbidity and educational level.

Results

Mean total motivation to exercise was 2.3±0.9 and physical and psychological motivation were rated as the more important (2.7±0.9 and 2.5±0.9) than social motivation (1.8±1.1). Motivation statements that were considered extremely important were being healthier (55% rated 4), slow down the ageing process (38% rated 4) and increasing well-being (31% rated 4). From the multiple linear regression model lower quality of life (β=−0.31, P<0.0001), lower self-efficacy (β=0.16, P<0.0001), experiencing shortness of breath (β=−0.28, P<0.0001), having COPD (β=−0.14, P=0.001) and low educational level (β=−0.09, P<0.028) were predictors related to lower motivation. This model explained 17% of the exercise motivation variability (p<0.0001). Cognition, sleeping difficulties, age, gender, NYHA-class and experiencing fatigue were not significantly related to motivation.

Conclusion

Lower quality of life, lower self-efficacy, experiencing shortness of breath, having COPD and lower educational level, decreases the motivation to exercise and may therefore be considered as barriers for exercise. These barriers should be assessed and considered when motivating patients to become more physically active.

Funding Acknowledgement

Type of funding source: None
Frailty is associated with vascular thrombosis events in chronic hemodialysis patients
Authors: Wu C.C , Cheng J.H , Yang H.J , Ps L.I.N , Liu S.J , Huang S.C , Lo C.M
Published: November 2020

Background

Frailty is common in chronic hemodialysis patients and is associated with increased risk of mortality. In hemodialysis patients, cardiovascular disease is the most cause of mortality but the impact of frailty on cardiovascular disease remained unknown.

Purpose

To access if there was an association between frailty and vascular thrombotic events among chronic hemodialysis patients.

Methods

This is a multi-center cohort study of chronic hemodialysis patients conducted since Jan, 2018 (last follow-up in December, 2020). Baseline data were collected from medical records and hemodialysis records. Frailty was defined by the Fried's criteria, a composite construct that incorporated poor physical functioning, exhaustion/fatigue, low physical activity, and undernutrition using a self-reported questionnaire. The primary outcome was vascular thrombosis events, defined as myocardial infarction, ischemic stroke, acute or critical limb ischemia, and dialysis vascular access thrombosis. The outcomes were assessed from a prospectively-collected nationwide registration system which was updated every 3 months and verified after review of medical records or discussion with caring physicians.

Results

During the study period, 571 chronic hemodialysis patients were enrolled. The mean age of study participants was 66 years old (SD, 13) and 55% of them were male. A total of 247 patients (43%) were categorized as frail. At baseline, logistic regression analysis revealed that older age, female sex, diabetes, low albumin and history of stroke were independently associated with frailty. During the follow-up period (median, 18 months), 57 patients (10%) died and 182 patients (31.9%) had vascular thrombosis events, including 101 arterial thrombosis (17.7%) and 105 dialysis access thrombosis (18.4%). In the primary outcome analysis, Cox proportional hazards modeling indicated that frailty was independently associated with vascular thrombosis events (Hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.132–2.597). In the secondary analysis, frailty was associated death (HR 2.25, CI 1.16–4.37), arterial thrombosis events (HR 1.92, CI 1.16–3.18), and dialysis vascular access thrombosis events (HR 1.90, CI 1.24–2.91).

Conclusion

Frailty phenotype is extremely common in hemodialysis patients. It is associated with mortality and vascular thrombosis events among chronic hemodialysis patients. Given its prevalence and consequence, research focus on interventions aimed to prevent or attenuate frailty in hemodialysis patients should be warranted.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Grants from National Taiwan University Hospital, Hsinchu Branch.
Multichannel electrocardiograms obtained by a smartwatch for the diagnosis of acute coronary syndromes: the SMARTAMI TRIAL
Authors: Spaccarotella C.S , Polimeni A.P , Principe E.P , Curcio A.C , Migliarino S.M , Mongiardo A.M , De Rosa S.D , Indolfi C
Published: November 2020

Background

Smartwatches are increasingly popular and used for digital health information. A new smart watch introduced an integrated ECG tool, which allows recording a single-lead ECG that has been used for atrial fibrillation detection. The aim of the present study was to prospectively investigate the feasibility and the accuracy of the Apple Watch in patients admitted in the CCU with the diagnosis of Acute Coronary Syndrome compared with a standard 12-lead ECG.

Methods

A commercially available smart watch series 4 was used and the posterior sensor of the watch was positioned in different standardized body positions to obtain nine bipolar ECGs (corresponding to Einthoven leads I, II and III and Precordial leads V1-V6) that were compared with a simultaneous standard 12-lead ECG.

One hundred subjects were included in the study. Fifty-five patients had a STEMI, twenty-seven patients had an NSTEMI all treated with percutaneous coronary revascularization. Eighteen age-matched subjects were included as controls.

Results

A very good agreement was found between Smartwatch ECG and Standard ECG for the identification of normal ECG, ST segment elevation and NSTE alterations (Cohen's kappa 0.90 [95% CI 0.78 to 1], 0.88 [95% CI 0.78 to 0,97], 0.85 [95% CI 0.74 to 0.96]), respectively.

The sensitivity and specificity of Smartwatch ECG for the diagnosis of normal ECG were 84% (95% CI 60 to 97) and 100% (95% CI 95 to 100), STE deviation were 93% (95% CI 82 to 99) and 95% (95% CI 85 to 99), NSTE ECG alterations were 94% (95% CI 81 to 99) and 92% (95% CI 83 to 97), respectively.

No significant differences between Smartwatch ECG and Standard ECG for the amplitude of ST changes were reported for each lead (see Figure).

Conclusions

The Smart Ami Trial demonstrated a very good agreement between the Smartwatch ECG and Standard ECG for the identification of ST-segment elevation and ST depression in patients with acute coronary syndromes opening the possibility of using this tool when a standard ECG is not available.

Figure 1

Funding Acknowledgement

Type of funding source: None
P wave dispersion – fading light of a popular parameter
Authors: Zawadzki J , Mercik J , Marecka A , Zawadzki G , Adamowicz J , Zysko D , Slawuta A , Gajek J
Published: November 2020

Background

The P wave dispersion concept was created to describe the non-uniform atrial conduction as a separate AF factor. However the major assumptions of the theory are inconsistent with the main principle of electrocardiography, which assumes that 12 leads of ECG, recorded simultaneously, register the same events at the same time. The presence of dispersion suggests the presence of a P wave in one lead, while in the other one it has ended and no longer exists. This observation per se could be considered as a methodological artifact.

Objective

The major objective is to present that the P wave dispersion descends from imprecise measurements in various ECG leads. We intend to demonstrate that more accurate measurements make this parameter disappear.

Methods

Our study included 150 patients (89F, 61M) assessed using the electrophysiological system, which allowed to assess the sinus P waves. The P wave duration was measured by 3 independent researchers in all leads twice: 1. paper speed=50 mm/s, enhancement 16x (basic measurement) 2. paper speed=200 mm/s, enhancement 128–256x, simultaneously measuring the P wave dispersion. All measurements were repeated 3 times.

Results

The results are presented in Table 1

Conclusion

1. The P wave dispersion is the artifact of measurement. It is clear that after using much more accurate tools, the parameter disappears. 2. The P-wave dispersion is connected with Pmax, therefore may be apparently clinically useful but as a matter of fact, doesn't carry any meaning itself. 3.The significant P wave duration parameter should be a total atrial activation time, from the beginning of the earliest recorded P wave, till the end of the last Pwave recorded in any lead.

Funding Acknowledgement

Type of funding source: None
Micro-simulation model to predict effects of low-dose aspirin on colorectal cancer, cardiovascular disease and safety outcomes among low-dose aspirin users
Authors: Bollaerts K , Biccler J , Pareen V , Sole E , Garcia Rodriguez L.A , Lanas A , Langley R , Holl K , Verstraeten T , Soriano-Gabarro M
Published: November 2020

Background

Regular use of low-dose aspirin (LDA) has been shown to reduce the risk of cardiovascular disease (CVD). Recent evidence indicates that regular LDA use also reduces the risk of colorectal cancer (CRC). Use of LDA has also been associated with an increased risk of gastrointestinal (GI) bleeding, peptic ulcers and intracranial hemorrhage (ICH).

Purpose

We aim to evaluate the population-level benefits and risks of daily and/or regular LDA among individuals taking LDA for primary or secondary CVD prevention in the United Kingdom (UK) accounting for the evidence on the reduced CRC risk.

Methods

Individual-level state transition modelling was used to predict the impact of LDA on CRC, CVD, safety events (GI bleeding, ICH and symptomatic peptic ulcers) and related deaths in a UK population. Individual event histories were simulated for hypothetical cohorts of 1 million adults aged 50–59 years and aged 60–69 years indicated to take LDA for primary or secondary CVD prevention. The QRISK CVD prediction score was used to simulate adults indicated to use LDA for CVD prevention. Model parameters were informed based on published scientific literature on CVD, CRC and safety outcomes mimicking the UK epidemiology and prevention guidelines. Monte Carlo simulation was used to account for parameter uncertainty.

Results

In the cohort of subjects for which low-dose aspirin use was initiated between 50–59 years, the decrease in incidence rates (IRs) (per 100,000person years) of non-fatal CVD was smaller when low-dose aspirin use was initiated for primary prevention compared to initiation for secondary prevention (−203 [95% UI, −277 to −115] versus −794 [95% UI, −997 to −536]). Similar results were obtained for fatal CVD (−97 [95% UI, −136 to −60] versus −381 [95% UI, −502 to −257]). Whether low-dose aspirin treatment was initiated for primary or secondary CVD prevention did not greatly influence the changes in the IR of the non-CVD outcomes. The changes in IR for fatal CRC were −46 [−69, −31] and −44 [−67, −26] for primary and secondary CVD prevention while the changes in IR for fatal bleeding were 5 [1, 9] and 5 [1, 10]. Similar results were obtained when low-dose aspirin use was initiated between 60–69 years.

Conclusions

In all simulation settings considered, low-dose aspirin related reductions in non-fatal and fatal CVD outcomes were larger in case of secondary CVD prevention compared to primary CVD prevention. These reductions were larger than the increases in fatal safety events. This favorable benefit-risk profile is more pronounced in the case of secondary CVD prevention. The results from the simulation model can be used to inform discussions with patients about the potential benefits and risk of LDA initiation.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Bayer AG
M-health and telemedicine: are people ready for the future? A real-world survey
Authors: Dossi F , Marini A , Sanna G.D , Saba P.S , Parodi G
Published: November 2020

Background

Many scientific societies highlight the importance of using e-Health and Telemedicine in everyday life. Are patients truly ready for this changing scenario in the cardiovascular field? Considering the current limited evidence on this topic we conducted a real-world data analysis in a rural area.

Purpose

The aim of the present study was to assess the attitude of a rural area population towards the use of m-Health and Telemedicine for the improvement of cardiovascular healthcare-organization and prevention.

Methods

An observational cross-sectional study, surveying 200 adult-subjects, with a multiple-choice questionnaire, was carried out by the authors during local health-fair events. We gathered self-reported demographics, digital skills, attitude towards telemedicine, and data regarding primordial, primary and secondary cardiac prevention, along with the strengths and the weaknesses of m-Health use.

Results

Of the 200 surveyed subjects, only 179 [90%] completed the poll. Overall, 40% [n=71] appeared to be aware of telemedicine and 86% [n=154] stated to be interested in its use for everyday health-organization and cardiovascular prevention. No significative difference emerged regarding basic and advanced technological skills after subject stratification based on the education level, residence or age, except for the oldest subjects (i.e. over 80 years of age) which resulted less technologically skilled [p<0.05]. According to the respondents, Personal Computer, smartphone and wearable devices were considered useful tools to improve treatment adherence [median value: 4 out of 5 - IQR 4–5], save time [median value: 4 out of 5 - IQR 4–5] and develop a tailored treatment approach [median value: 4 out of 5 - IQR 1–5]. Nonetheless, m-Health was unknown to half of the respondents; in fact, only 48% [n=86] of the interviewed subjects were aware of its existence and 35% [n=63] affirmed to use apps for a preventive purpose on a daily basis. Otherwise, the large majority of subjects reported to be interested in its use [75%, n=135]. Privacy issues emerged as a major concern for app users in the setting of primary and secondary prevention; while, only 19.4% of those using apps for primordial prevention showed the same degree of concern [p<0.05]. No other significative difference appeared among tested queries.

Conclusions

Our unselected population showed good technological skills and looked with favour at the advantages of telemedicine in everyday health-management because it provides reliable and feasible tools to improve cardiovascular healthcare in rural areas. However, awareness of its existence remains limited, underlining the need for more effective advertising policies. Although privacy and reliability issues currently make m-Health less feasible for primary and secondary prevention, m-Health has proved to be an excellent tool for primordial prevention.

Funding Acknowledgement

Type of funding source: None
Detection of new-onset atrial fibrillation in heart failure patients using daily non-invasive ECG monitoring in the TIM-HF2 telemedicine trial
Authors: Stegmann T , Koehler K , Schulze M , Laufs U , Wachter R , Koehler F
Published: November 2020

Background

Heart failure (HF) and atrial fibrillation (AF) impair the prognosis when they occur concomitantly. Recent telemedical studies suggest that HF patients with AF may derive a greater benefit from telemedicine care but the results are inconsistent. The rate of newly detected AF in HF patients by daily non-invasive electrocardiogram (ECG) monitoring is unknown and a possible influence on the outcome of remote patient management (RPM) remains unclear.

Purpose

We aimed to investigate the detection of new atrial fibrillation in patients assigned to RPM in comparison to patients assigned to usual care (UC) in the

TIM-HF2 trial.

Methods

The prospective, multicentre and controlled TIM-HF2 trial randomised 1538 patients (765 RPM, 773 UC). All patients had a 12-channel ECG at baseline and after one year at the final study visit. Patients who were assigned to RPM additionally transmitted a daily ECG to the telemedical centre (TMC). We excluded all patients with pacemaker including implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy (CRT) in the baseline ECG, leaving 879 patients for analysis (RPM: 442 and UC: 437). The patients were stratified into patients with SR and patients with AF according to the rhythm documented at baseline. The primary endpoint of this analysis was newly documented AF within one year after randomisation. We analysed the daily to the telemedical centre transmitted ECGs of patients assigned to RPM with the documented rhythm status of the ECGs performed at the final study visit of patients assigned to UC.

Results

569 patients had SR and 310 patients had AF at baseline. The proportion of patients with AF was nearly the same in the RPM (159, 36.0%) and the UC (151, 34.6%) group. 68 patients (24.0%) were detected with new atrial fibrillation in the RPM group compared to 22 patients (7.8%) in the UC trial arm during the one-year follow-up (p<0.001, number needed to screen 6).

Conclusion

In patients with heart failure and daily ECG transmission, atrial fibrillation was detected three times more frequently in comparison to usual care within one year.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The TIM-HF2 study was supported by a research grant of the German Federal Ministry of Education and Research (grant numbers 13KQ0904A, 13KQ0904B, 13KQ1104A). The TIM-HF2 study was a part of the research and development project “Gesundheitsregion der Zukunft Nordbrandenburg – Fontane” (Fontane). The Fontane system was developed in private–public partnership (PPP) supported by research and development grants from the German Federal Ministry of Education and Research, the European Regional Development, and the Federal State Brandenburg.
Reliable detection of atrial fibrillation with a medical wearable under inpatient conditions (CoMMoD-A-fib)
Authors: Jacobsen M , Dembek T.A , Ziakos A.P , Kobbe G , Kollmann M , Heinemann L , Sause A , Deubner N , Isenmann S , Seyfarth M
Published: November 2020

Background

Atrial fibrillation (A-fib) is the most common arrhythmia; however, detection of A-fib is a challenge due to irregular occurrence.

Purpose

Evaluating feasibility and performance of a non-invasive medical wearable for detection of A-fib.

Methods

In the CoMMoD-A-fib trial admitted patients with a high risk for A-fib carried the wearable and an ECG Holter (control) in parallel over a period of 24 hours under not physically restricted conditions. The wearable with a tight-fit upper arm band employs a photoplethysmography (PPG) technology enabling a high sampling rate. Different algorithms (including a deep neural network) were applied to 5 min PPG datasets for detection of A-fib. Proportion of monitoring time automatically interpretable by algorithms (= interpretable time) was analyzed for influencing factors.

Results

In 102 inpatients (age 71.0±11.9 years; 52% male) 2306 hours of parallel recording time could be obtained; 1781 hours (77.2%) of these were automatically interpretable by an algorithm analyzing PPG derived intervals. Detection of A-Fib was possible with a sensitivity of 92.7% and specificity of 92.4% (AUC 0.96). Also during physical activity, detection of A-fib was sufficiently possible (sensitivity 90.1% and specificity 91.2%). Usage of the deep neural network improved detection of A-fib further (sensitivity 95.4% and specificity 96.2%). A higher prevalence of heart failure with reduced ejection fraction was observed in patients with a low interpretable time (p=0.080).

Conclusion

Detection of A-fib by means of an upper arm non-invasive medical wearable with a high resolution is reliably possible under inpatient conditions.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Internal grant program (PhD and Dr. rer. nat. Program Biomedicine) of the Faculty of Health at Witten/Herdecke University, Germany. HELIOS Kliniken GmbH (Grant-ID 047476), Germany
Process mining tools: where should we build another PCI centre to reduce STEMI mortality?
Authors: Borges-Rosa J , Oliveira-Santos M , Simoes M , Teixeira C , Ibanez-Sanchez G , Fernandez-Llatas C , Monteiro S , Carvalho P , Goncalves L
Published: November 2020

Introduction

The expected delay of transport between patient location and percutaneous coronary intervention (PCI) centre is paramount for choosing the adequate reperfusion therapy in ST-segment elevation myocardial infarction (STEMI). The central region of Portugal has heterogeneity in PCI assess due to geographical reasons. However, this data is usually presented numerically without providing a visual distribution of patients.

Purpose

We aimed to analyse the impact of distance to PCI centres on mortality in patients with STEMI through visual maps of patients' flow by using an experimental process mining tool, integrated in EIT Health's project PATHWAYS.

Methods

Using the Portuguese Registry of Acute Coronary Syndromes (ProACS), we retrospectively assessed patients with an established diagnosis of STEMI, geographical presentation specified, reperfusion option identified (PCI, fibrinolysis or no reperfusion), short-term outcomes defined as discharge or in-hospital death. With the 2 317 patients that fulfilled the criteria, we used a process mining tool to build national and regional models that represent the flow of patients in a healthcare system, enhancing differences between groups.

Results

Colour gradient in nodes and arrows changes from green to red, with green representing a lower number of patients as opposed to red. In the national model, most patients from all regions had PCI. Mortality was similar between PCI and fibrinolysis groups (4%) but higher in those without reperfusion (9%). In the central region model, one third of the patients were more than 120 minutes away from a PCI centre. Despite that, almost one third of these patients had PCI instead of fibrinolysis. In this model, fibrinolytic therapy had higher in-hospital survival rate than PCI (98% vs. 94%). Overall mortality was higher in the central model compared with the national model (6.92% vs. 5%). Central region had less PCI (53% vs. 73%), more fibrinolysis (15% vs. 7%) and more patients with no reperfusion (32% vs. 20%).

Conclusion

In the ProACS registry, mortality was higher in the central region compared with national data. Even though global interpretation of these findings is limited by underrepresentation from certain central areas, process mining offers an easily understandable view of patients flow. With its statistical upgrade and continuous development, this tool will facilitate the analysis of big data and comparison between groups.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): EIT Health
Evaluation of new-onset atrial fibrillation using continuous patch monitor in patients undergoing transcatheter aortic valve replacement
Authors: Miki T , Senoo K , Okura T , Sato Y , Shiraishi H , Shirayama T , Matoba S
Published: November 2020

Background

Transcatheter aortic valve replacement (TAVR) has emerged as an important therapeutic option among intermediate- and high-risk patients with symptomatic severe aortic stenosis. Heart rhythm disorders frequently complicate TAVR, particularly atrial fibrillation (AF), which can affect >40% patients undergoing the procedure. There is wide variation in rates of new-onset AF (NOAF) following TAVR across the initial pivotal randomized trials and observational studies, but burden of AF in each patient is not well known. The aim of this study is to evaluate AF burden detected by continuous patch ECG monitor (WR-100; Fukuda-Denshi, Tokyo,Japan) in patients after TAVR.

Method

Among KPUM-TAVR cohort, 58 consecutive patients (mean age:85.5±5.5, 44 females) kept recording continuous patch ECG monitor for 14 days after the procedure of TAVR. We excluded 11 patients with ECG indicating AF before procedure (paroxysmal AF 5, persistent AF 6). Finally, 47 eligible patients were selected according to the study criteria. AF was defined as a presence of AF more than 30sec on ECG monitor. The incidence and burden of NOAF was assessed.

Results

We identified 9 of 47 patients (19.1%) who developed NOAF (94% of transfemoral access patients, 6% of non- transfemoral access patients). Patients developing NOAF and had higher Society of Thoracic Surgeons risk scores (5.9±3.8 vs 9.9±6.3 p=0.0187). AF was first observed from day1 to day13. Despite having a median CHA2DS2-VASc score of 5 (25th and 75th percentile: 5 to 6), only 33% of patients with NOAF were given oral anticoagulation during the follow-up.

Conclusion

By using continuous patch ECG monitor, NOAF can be identified in 19.1% of patients after TAVR, with wide variety of first onset of AF. Given the clinical significance of post-TAVR AF, additional studies are necessary to describe the optimal management strategy in this high-risk population.

Figure 1

Funding Acknowledgement

Type of funding source: None
Relationship between previous HbA1c value and subsequent severe hypoglycaemia in patients with coronary artery disease and type 2 diabetes. Data from the DMP in North Rhine, Germany
Authors: Hagen B , Groos S , Kretschmann J , Macare C , Weber A
Published: November 2020

Background and purpose

Based on the documentation data of DMP type 2 diabetes in North Rhine from 2018, it was examined to what extent the HbA1c value from 2012 influenced the emergence of severe hypoglycaemia from 2013 in patients with coronary artery disease (CAD).

Methods

The predictors were determined in separate logistic regression models. The database was the last follow-up documentation of 2018. For all patients it was determined which HbA1c value was available in 2012 and whether severe hypoglycaemia has been documented for the first time since 2013.

Results

Within a group of a total of 98,950 patients, 2,520 new cases of severe hypoglycaemia have been documented since 2013. Treatment with insulin (odds ratio OR 7.00; 95-%-CI 5.80–8.44), HbA1c over 8.5% in 2012 (OR 1.66; 1.43–1.93), and the presence of diabetic complications (OR 1.37; 1.23–1.52) were the greatest risk factors, adjusted for age, gender, duration of DMP care and blood pressure. When the up to 70-year-old patients were analyzed separately, the two main predictors turned out to be somewhat weaker (insulin OR 5.40; 3.76–7.76; HbA1c >8.5% OR 1.61; 1.23–2, 11), on the other hand, they were somewhat more pronounced for patients over 70 years of age (insulin OR 7.58; 6.09–9.44; HbA1c >8.5% OR 1.72; 1.42–2.07). The influence of comorbidity was comparably high in both subgroups (≤70 years, OR 1.45; 1.16–1.79; >70 years OR 1.34; 1.19–1.51).

Conclusion

In patients with CAD and type 2 diabetes, the insulin prescription, a previously high HbA1c value and comorbidity are significant predictors for the later recurrence of severe hypoglycaemia; these influences are somewhat weaker in younger patients and somewhat more pronounced in older patients. A association between low HbA1c values and an increased risk of new onset of severe hypoglycaemia could not be demonstrated even in older patients with CAD and T2D.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Joint Establishment Disease Management Programs North Rhine
Conflicts of interest among authors of the ESC guidelines for the management of atrial fibrillation
Authors: Schneider B , Stoellberger C
Published: November 2020

Background

In 2011, the Institute of Medicine (IOM) published standards for developing trustworthy clinical practice guidelines. It is recommended that “Whenever possible guideline development group members should not have conflicts of interest (COIs). In some circumstances, a guideline development group may not be able to perform its work without members who have COIs, such as relevant clinical specialists. Members with COIs should represent not more than a minority of the guideline development group members. The chair or cochairs should not be a person with COIs.”

Aim

Aim of the present study was to assess if the ESC guidelines for the management of atrial fibrillation are in accordance with the standards proposed by the IOM.

Methods

The declaration of COIs from task force members (TFM) and reviewers of the 2010 and 2016 ESC atrial fibrillation guidelines were retrieved from the ESC homepage. The number and the type of COIs were assessed for each guideline and compared.

Results

Regarding the 2010 guidelines, 8 of the 25 TFM (32%) reported no COI. In the remaining 17 TFM, 148 COIs were reported (8.7±10.2 per member, range 1–44). The chairperson declared 11 COIs. Consulting and advising was reported by 15 and research contacts by 13 TFM. Among the guideline reviewers, 12/26 (46%) reported no COI, and 14 reviewers declared 72 COIs (5.1±3.3 per reviewer, range 2–14).

Regarding the 2016 guidelines, 3 of the 17 TFM (18%) reported no COI. The remaining 14 TFM declared 182 COIs (13.0±10.4 per member, range 1–32). The chairperson of the task force had the second most COIs (n=30). Direct personal payment was reported by 14 and research funding of the department by 10 TFM. Among the guideline reviewers, 16/79 (20%) reported no COI, and 63 reviewers declared 473 COIs (7.5±6.8 per reviewer, range 1–34).

Comparing the 2010 and the 2016 guidelines, there was an increase of TFM with COIs (from 68% to 82%), of the number of COIs per TFM (from 8.7±10.2 to 13.0±10.4) and the COIs of the chairperson (from 11 to 30). Moreover, the proportion of TFM receiving personal payment (60% vs 82%) and the number of COIs due to personal payment (5.9±7.3 vs 7.7±7.4) were higher in the 2016 guidelines. In addition, more guideline reviewers had COIs in 2016 (54% vs 80%).

Conclusion

The high and increasing rate of TFM and reviewers with COIs is not in accordance with the recommendations of the IOM. Since COIs can influence healthcare decision makers and may consciously or unconsciously influence choices made throughout the guideline development process, the ESC should follow the standards of the IOM.

Funding Acknowledgement

Type of funding source: None
Cardio-vascular risk factors according to different profiles of night work and shift work
Authors: Esquirol Y , Bourgkard E , Dziurlac M , Ferrieres J , Ribet C , Boini S
Published: November 2020

Background

The shift-night work concerns around 17% workers in our modern society with evident need of this type of organisation for productivity and economic reasons for the companies. if the impact of this global organisation pattern on cardiovascular disease or risk factors is more and more documented, it remains unclear which types of rotating or night work are really involved and which are the impact on cardiovascular risk of being exposed currently or in the past to these different types of shift-night work.

Purpose

To study possible relationships between arterial blood pressure, anthropometric markers, fasting biomarkers, and sleep disturbances, and different exposure profiles of night work and/or shift work.

Methods

A cross-sectional study was conducted among 65.126 workers aged 18–70 at baseline in the French random population-based Constances cohort. Four exposure groups were defined: (1) workers with current permanent night work, (2) current night shift workers 3x8, (3) day workers with past night and/or shift work, (4) day workers without night and/or shift work during their work history (reference group). Logistic regression models adjusted for age, sex, socio-economic position, and personal history of ischemic cardiovascular disease (CVD) were performed to assess associations between clinical risk markers for CVD at baseline and these exposure groups.

Results

Compared with the reference group, current and past night workers had a significant higher risk of obesity (Body Mass Index≥30). Permanent night workers had a significant higher risk of metabolic syndrome, mostly due to abdominal obesity, hypertriglyceridemia (>1.7 mmol/l) and low level of high density lipoprotein. Even if day workers with past night/shift work had no statistically significant over-risk of metabolic syndrome, they presented significantly higher risks for the same three criteria as observed for the permanent night workers. However, only hypertriglyceridemia was significantly more frequent among 3x8 workers. Among current night workers, 3x8 had a higher risk of sleep disturbances while permanent had not. Sleep disturbances over-risk was also observed among day workers with past night/shift work. No over-risk of hypertension, hypercholesterolemia, hyperglycemia, and elevated levels of gamma-glutamyl-transferase was observed among the three groups.

Conclusion

The results support the need for enhanced cardiovascular follow-up of workers exposed to night and/or shift work. However, it is also necessary to follow regularly and specifically current day workers with a past night and/or shift work history.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): INRS: institut National de Recherche et de Sécurité