bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the SGLT2 interaction network and its regulation by SGLT2 inhibitors: a bioinformatic analysis
Authors: Wicik Z , Nowak A , Jarosz-Popek J , Wolska M , Eyileten C , Siller-Matula J , Von Lewinski D , Sourij H , Postula M
Published: October 2022

Background

SGLT2 (Solute Carrier Family 5 Member 2, SLC5A2) is a promising target of a new class of drugs primarily established as kidney-targeting, effective glucose-lowering agents used in diabetes mellitus (DM) patients. Rising evidence indicates that besides renal effects, SGLT2 inhibitors (SGLT2i) have also a systemic impact via indirectly targeting the heart, endothelial cells, liver, adipose tissue. Our hypothesis states that the pleiotropic effects of SGLT2i are associated with its binding force, location of their targets in the SGLT2 networks, target involvement in signaling pathways, and their tissue-specific expression.

Methods

Thus to investigate differences in SGLT2i impact on human organisms, we re-created the SGLT2 interaction network incorporating its inhibitors and analyzed its tissue-specific expression using publicly available datasets. We analyzed it in the context of the so-called key terms (Autophagy, Oxidative stress, Aging, Senescence, Inflammation, AMPK pathways, mTOR pathways) which seems to be crucial to elucidate SGLT2 role in a variety of clinical manifestations.

Results

Our analysis focused on selected organs using the TISSUES database identified in the following order: kidney, liver, adipose tissue, blood, heart, muscle, intestine, brain, and artery showed the highest expression confidence of SGLT2 and its network components. Drug repurposing analysis of known SGLT2i pointed out the influence of SGLT1 regulators on the heart and intestine tissue. Additionally, Dapagliflozin seems to also have a stronger impact on brain tissue through the regulation of SGLT3 and SLC5A11. Shortest paths analysis identified interaction SIRT1-SGLT2 among the top five interactions across six from seven analyzed networks associated with the key terms. Other top first-level SGLT2 interactors associated with key terms were ADIPOQ, INS, GLUT4, ACE, and GLUT1, but also less recognized ILK, ADCY7. Among interactors not associated with key-terms, but which appeared in multiple shortest-paths analyzes were GPT, COG2 and MGAM. Enrichment analysis of SGLT2 network components showed the highest overrepresentation of hypertensive disease, DM related diseases for both levels of SGLT2 interactors. Additionally, for the extended SGLT2 network, we observed enrichment in obesity (including SGLT1) and cancer-related terms.

Conclusion

This study provides comprehensive and ranked information regarding the SGLT2 interaction network in the context of tissue expression and might be helpful to predict the clinical effects of the most commonly used SGLT2i.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agencja badań medycznych - grant number 2019/ABM/01/00037Medical University of Warsaw - grant number 1M9/2/M/MG/N/21
Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study
Authors: Matli K , Chamoun N , Fares A , Zibara V , Al-Osta S , Nasrallah R , Salameh P , Mokhbat J , Ghanem G
Published: October 2022

Background

COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease.

Purpose

Currently, prophylactic dose anticoagulation is considered the standard of care antithrombotic regimen in hospitalised patients with COVID-19. However, high-quality data about the subject is unavailable. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

Methods

A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.

Results

242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.

Conclusion

The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

Funding Acknowledgement

Type of funding sources: None.
Reduced dose, but not reduced risk: rates of inappropriate apixaban dose reduction and stroke and bleeding incidence
Authors: Harrington J , Arps K , Wu A , Carnicelli A P , Chiswell K , Chrischilles E , Shantha G , Vanwormer J , Mundl H , Viethan T , Alexander J H , Lopes R D , Washam J , Patel M R
Published: October 2022

Introduction

Patients with atrial fibrillation (AF) should be prescribed standard-dose (5mg twice daily) apixaban for stroke prevention unless they meet 2 or more criteria: age ≥80, weight ≤60kg, and/or creatinine ≤1.5mg/dL, in which case a reduced-dose (2.5mg twice daily) is indicated. Despite this, some clinicians may also prescribe reduced-dose apixaban to patients who do not meet criteria for dose reduction, in an effort to reduce bleeding risk.

Purpose

To assess apixaban prescribing patterns in patients with AF based on dose reduction criteria and to characterize baseline demographics and incidence of ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) for patients stratified by standard-dose, appropriately reduced-dose, and inappropriately reduced-dose apixaban.

Methods

Using pooled data from 8 large hospitals in PCORnet, a multicenter national healthcare research network, we assessed the standard and reduced-dose apixaban prescribing patterns for patients with AF, with additional stratification of patients prescribed 2.5mg based on presence or absence of 2+ criteria for dose reduction. We then assessed baseline characteristics and 5-year event rate of ischemic stroke, major bleeding, ICH and death.

Results

Of 45,947 patients with AF on apixaban and available dosing information, 38,861 (85%) were prescribed apixaban 5mg and 7086 (15%) were prescribed 2.5mg. Of patients prescribed apixaban 2.5mg, 4321 (61%) did not meet criteria for dose reduction. Patients on reduced dose apixaban were more likely to be female and have comorbidities such as heart failure, hypertension, and prior ischemic stroke. These trends were more pronounced for patients meeting dose adjustment criteria than those not meeting criteria (Table 1).

Unadjusted analyses found patients on 2.5mg of apixaban were significantly more likely to experience ischemic stroke, major bleeding, and all-cause death. Patients with 2+ dose reduction criteria on 2.5mg of apixaban had the highest rates of each event, but patients who were prescribed reduced dose without meeting criteria were also at elevated risk (Table 2).

Conclusion

Many patients prescribed reduced-dose apixaban do not meet criteria for dose reduction. Because patients prescribed reduced dose apixaban are older and have more cardiovascular risk factors, their incidence of stroke, major bleeding, and death exceeds that of full dose treated patients. These risks exist both for patients who do and do not meet criteria for dose reduction, suggesting potential under-treatment for the majority of dose-reduced patients.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Bayer
Comparing dual antiplatelet therapy strategies post-acute coronary syndrome: network meta-analysis
Authors: Turgeon R , Hong C , Wang E H Z , Wong G C , Ellis U
Published: October 2022

Background

Various approaches to dual antiplatelet therapy (DAPT) management exist to balance thrombotic and bleeding risks following acute coronary syndrome (ACS).

Purpose

The aim of this study was to compare and rank different DAPT management strategies in patients with ACS with or without percutaneous coronary interventions.

Methods

We conducted a systematic review with network meta-analysis of randomized controlled trials comparing DAPT strategies in patients with ACS using MEDLINE, Embase, and CENTRAL (2007-July 2021). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death and major bleeding. We performed Bayesian network meta-analyses to compare all interventions simultaneously using the Markov-chain Monte Carlo method, conducted under the assumption of transitivity. We generated odds ratios (ORs) with 95% credible intervals (CrI) from the medians and 2.5th and 97.5th percentiles of the posterior distributions using a hierarchical Bayesian framework, using a random-effects model with informative priors for between-study heterogeneity based on pharmacological interventions with semi-objective outcomes (MACE or bleeding) or death. To rank interventions for each outcome, we calculated the mean surface under the cumulative ranking (SUCRA) curve.

Results

From 5941 articles, we included 24 trials (89,620 patients). Both clopidogrel- and ticagrelor-based DAPT increased MACE compared with pharmacogenomics-guided P2Y12 inhibitor selection (odds ratio [OR] 1.37, 95% credible interval [CrI] 1.08–1.74 and 1.35, 1.05–1.79, respectively) and empiric P2Y12 inhibitor de-escalation (OR 1.53, 95%CrI 1.00–2.30 and 1.51, 1.00–2.27, respectively). Compared with short-duration DAPT, standard DAPT duration with all P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) and pharmacogenomics-guided P2Y12 inhibitor selection increased major bleeding. Ticagrelor-based DAPT increased major bleeding compared with platelet function testing-guided DAPT (OR 1.60, 95%CrI 1.00–2.55). Empiric P2Y12 inhibitor de-escalation ranked best for MACE (SUCRA 0.89), whereas short-duration DAPT ranked best for death (SUCRA 0.89) and major bleeding (SUCRA 0.93).

Conclusions

In patients with ACS, empiric P2Y12 inhibitor de-escalation was most efficacious whereas short-duration DAPT was the safest compared to other DAPT strategies.

Funding Acknowledgement

Type of funding sources: None.
Dual antiplatelet therapy for 1 versus 3 months in high bleeding risk patients with or without oral anticoagulant therapy after coronary stenting
Authors: Cao D , Mehran R , Sartori S , Spirito A , Snyder C , Valgimigli M
Published: October 2022

Background

A short DAPT duration after coronary stenting has been associated with similar ischemic outcomes and fewer bleeding complications in patients at high bleeding risk (HBR). Whether these effects are preserved irrespective of concomitant oral anticoagulant (OAC) therapy remains unclear.

Purpose

To evaluate the safety and efficacy of 1-month versus 3-month DAPT among HBR patients with or without indication to OAC therapy who undergo cobalt-chromium everolimus-eluting stent implantation.

Methods

The XIENCE Short DAPT Program comprises three prospective, international, single-arm studies evaluating 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT in HBR patients who had undergone successful everolimus-eluting XIENCE stent implantation. OAC therapy at discharge was a study inclusion criterion. Subjects were eligible to discontinue DAPT at 1 or 3 months if free from ischemic events and adherent to DAPT. The primary endpoint was the composite of all-cause death or any myocardial infarction (MI). The major secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding. In this exploratory analysis, HBR patients on 1-month DAPT were compared with those on 3-month DAPT according to the presence of background OAC therapy. Ischemic and bleeding outcomes were assessed between 1 and 12 months after index PCI using propensity-score (PS) adjustment.

Results

A total of 3,364 patients, 1,392 on 1-month DAPT and 1,972 on 3-month DAPT, were eligible for the analyses. Patients on OAC therapy (n=1424, 42.3%) were younger, more often male and of white race, and with a lower prevalence of other HBR criteria such as chronic kidney disease and anemia. The incidence of death or MI at 12 months was similar between the two groups (8.0% vs 7.9%) while BARC 2–5 bleeding was higher in OAC patients (12.2% vs 7.2%). After PS adjustment, 1-month DAPT, compared with 3-month DAPT, did not increase the 1-year risk of death or MI in both OAC (adjHR 0.71, 95% CI 0.47–1.08) and non-OAC patients (adjHR 1.24, 95% CI 0.88–1.75; p-interaction = 0.11). The risk of BARC 2–5 bleeding was consistently reduced in both OAC (adjHR 0.71, 95% CI 0.51–1.00) and non-OAC patients (adjHR 0.77, 95% CI 0.53–1.11; p-interaction = 0.69).

Conclusions

Among HBR patients undergoing everolimus-eluting stent implantation, 1-month DAPT compared with 3-month DAPT was associated with similar ischemic outcomes and reduced bleeding, regardless of concomitant OAC therapy.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Abbott
Incidence of drug-drug interactions of QT-prolonging drugs in an onco-hematological outpatient
Authors: Fort E , Otero S , Moliner P , Bleda C , Prats J , Nadal E , Palmero R , Jimenez L , Piulats J M , Rey M , Fontanals S
Published: October 2022

Background

Oral anticancer therapy is increasingly integrated into the care of patients (pts) with cancer. Recognition and management of pharmacodynamic drug-drug interactions is critical to provide efficacious and safe anticancer treatment.

Purpose

We aimed to gain insight into the real-world prevalence of potentially significant drug-drug interactions of QT-prolonging with oral antineoplastic agents used in an Oncohematological Hospital

Methods

We performed a prospective observational study in an oncohematological hospital between October 2020 and June 2021. Consecutive pts diagnosed with an oncohematological neoplasia and who were evaluated before start treatment with an oral anticancer drug or suport treatment (antibiotics, antivirals) were included. Cancer treatment data were obtained from our prescription software System. Demographic data and concomitant medication were obtained from our electronic medical record software. Micromedex was used to find potencial QT-prolonging interactions between anticancer drugs and chronic medication, and were classified as major or moderate.

Results

Oncohematological treatment was started in 1.217 pts during the study period. A total of 266 potential drug-drug interactions were detected in 171 patients (14.5%). A total of 46 drug-drug interactions of QT-prolonging (17.3%) were detected in 37 pts (21.6%), 22 men and 15 women, with a median age of 66.6 (range 40.9–87.3). Twenty-one (45.7%) and 25 (56.3%) drug interactions of QT-prolonging were classified as major and moderate, respectively, with a median interaction per pts 1.24 (1–3). The 3 most common cancers were: Renal carcinoma in 12 pts (32.4%), non-small cell lung carcinoma in 9 pts (24.7%) and prostate carcinoma in 4 pts (10.8%). The most commonly detected interacting drugs were sunitinib 12 pts (26.1%), osimertinib 10 pts (21.7%), and cabozantinib 5 pts (10.9%) among oncohematological drugs, and citalopram 8 (17.4%), quetiapine 6 (13%) and tramadol 5 (10.8%) among concomitant drugs.

Conclusion

Drug-drug interactions can play a significant role in drugs' cardiac safety in oncohematological pts, specially in renal, lung and prostate cancers, with more than one potential interacting drug or at least one major interaction. Cardiac monitorizacion should be considered when potential drug drug interaction is detected.

Funding Acknowledgement

Type of funding sources: None.
Sustained effect on diet quality of a self-care intervention to reduce cardiovascular disease risk among informal rural caregivers of people with chronic illnesses: does health literacy matter?
Authors: Kang J H , Katsumata Y K , Lennie T A L , Chung M L C , Biddle M J B , Miller J M , Moser D K M
Published: October 2022

Background/Introduction

Rural caregivers of those with chronic illnesses have higher cardiovascular disease (CVD) risk than urban caregivers. Diet is a major lifestyle factor that contributes to CVD risk. However, interventions are often not constructed with health literacy in mind. We previously found a moderation effect of health literacy on short-term (4-month) diet quality from a self-care intervention to reduce cardiovascular disease risk (RICHH) among rural caregivers. The RICHH intervention was designed to be equally effective in caregivers with marginal or adequate health literacy.

Purpose

To compare the impact of RICHH intervention on 12-month diet quality in rural caregivers with marginal versus adequate health literacy.

Methods

A total of 296 rural caregivers (54.5±13.7 years old, 76% female) of individuals with chronic illnesses participated. The newest vital sign (NVS) and Healthy Eating Index-2015 (HEI-2015) were used to determine health literacy and diet quality, respectively. The NVS was dichotomized using a cutoff score of 4. The HEI-2015 was computed based on food frequency questionnaires at baseline, 4-month, and 12-month. The RICHH intervention was delivered using video conferencing technology by nurse interventionists once a week for 12 weeks followed by bi-weekly and monthly booster sessions. A piecewise linear mixed-effect model, controlling for age, education, smoking status, and perceived stress, was used to evaluate the impact of the intervention on diet quality between the two health literacy groups.

Results

There was a significant difference in improvement in the HEI-2015 total scores at 4 months between control and intervention in the marginal health literacy group (beta estimate = 1.56, SE=0.74, P=0.039) but not in the adequate health literacy group (beta estimate = 0.27, SE=0.38, P=0.475). The improvement in the marginal health literacy group was sustained at 12-months (beta estimate = 8.12, SE=3.57, P=0.022).

Conclusions

The results of our study indicate that an intervention designed to address health literacy is effective in producing a sustained improvement in diet quality to reduce CVD risk in rural caregivers with marginal health literacy.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health National Institute of Nursing Research
Changes in health-related quality of life following percutaneous coronary intervention – a nationwide prospective cohort study
Authors: Olsen S , Bonaa K H , Hanssen T A
Published: October 2022

Background

In addition to mortality and morbidity, improved health-related quality of life (HRQOL) is a goal of treatment in patients suffering of cardiovascular heart disease. There is a limited knowledge of changes in HRQOL following percutaneous coronary intervention (PCI).

Aims

The aims of this study were to determine total and gender specific changes in HRQOL at baseline and four-years following PCI.

Methods

This study use data from the Norwegian Coronary Stent Trial which included 9013 patients undergoing first time percutaneous coronary intervention in Norway during September 2008–February 2011. HRQOL was assessed using the Short-Form-12 (SF-12) at baseline and at four years of follow up in a representative subgroup (n=775).

Results

The mean age was 64 years (SD 9.2) and 75% were male. Eighty percent were living with a partner and 67% had a higher level of education. The majority of the patients had stable angina as indication for PCI (40%). There was a significant improvement in all domains of SF-12 from baseline to four years of follow up (p<0.001). The highest changes were in Role Physical (43.6 vs. 48.2), Bodily Pain (44.8 vs. 50.1) and Vitality (44.1 vs. 49.3). Analysing gender differences at four years follow-up, men had a higher improvement in the physical component summary score than women (4.8 vs 2.8, p=0.04), but not in the mental component summary score (2.8 vs 4.4, p=0.11).

Conclusion

In patients undergoing first time PCI, HRQOL improved significant from baseline to four years of follow up. Both at baseline and at five years of follow up males report a higher HRQOL compared to females.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Northern Norway Regional Health Authority
Short- and long-term quality of life after electrical cardioversion of atrial fibrillation
Authors: Morken I , Ponitz V , Brugger-Andersen T , Aareskjold O , Aadnanes L , Melberg T , Bru E , Nordrehaug J E
Published: October 2022

Background

Electrical cardioversion (ECV) of atrial fibrillation (AF) is known to be effective in restoring sinus rhythm. However, limited and contradictory data exist on the impact of ECV on short- and long-term quality of life outcomes.

Purpose

To examine the impact of ECV on short- and long-term quality of life in patients with AF.

Methods

This was a prospective cohort study of consecutive patients with AF referred for outpatient electrical cardioversion at a university hospital in Norway. Recruitment started March 2017, and ended December 2019. Baseline demographics, clinical characteristics, and procedure details were obtained from medical records. Quality of life was measured with the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire before electrical cardioversion (baseline), and at three and 12 months after ECV.

Results

Two hundred and ninety-five patients underwent ECV and completed follow-up questionnaires at three months (n-259) and at 12 months (n=258). The median age was 68 years (range 37–86 years) and 79% were men. The mean left ventricular ejection fraction obtained by echocardiography was 51% (±9.2). The mean body mass index score was 28±4.8. Immediate success of electric cardioversion was 91%. Recurrence of AF after successful ECV was 36% within three months. Twenty-two percent of the patient underwent new ECV before three months, and 25% of the patients had persistent AF at three months. The overall mean AFEQT score at baseline was 62.9±21.4, and the domain-specific scores were as follows: symptoms, 72.3±23.1; daily activities, 52±26.6; treatment concerns, 71.1±22.4; and treatment satisfaction, 59.9±25.2. There were significant improvements in the overall mean AFEQT score at three months, 70.8±20.8, (p<0.01) and at 12 months, 72.3±20.8 (p<0.01) compared with baseline values. There were also significant improvement (p<0.01) in all AFQET subscales at three and 12 months. Daily activity scores and treatment satisfactions scores demonstrated highest improvement in mean score with a 10% increase from baseline to three months and 13% increase from baseline to 12 months. Sub-analyses revealed that patients with persistent AF within three months were significantly dissatisfied with treatment (p<0.01) and reported lower activity level (p<0.01) compared with the rest of the sample.

Conclusions

Results indicate both significant improvement in short- and long-term quality of life for patients after electrical cardioversion, in particular when sinus-rythm was maintained.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Stavanger University Hospital
Costs of an exergame intervention for patients with heart failure
Authors: Klompstra L , Mourad G , Jaarsma T , Stromberg A , Alwin J
Published: October 2022

Background

Exergaming is promising for patients with heart failure who are less inclined to start or maintain exercise programmes involving traditional modes of physical activity. It is important to gain insights into aspects related to costs to in order to compare with other costs for rehabilitation and make priorities.

Purpose

To gain insights into aspects related to the costs of an exergame intervention for patients with heart failure and their willingness to pay for such an intervention.

Method

In a randomised controlled trial, the HF-Wii study, the intervention group (n=305) received an introduction to the exergame, the exergame was installed at home and technical and practical support was available when needed for three months. Patients received telephone follow-ups after the installation. The control group (n=300) received activity advice and telephone follow-ups. We collected data on hospital use and costs, costs of the exergame intervention, patient time-related costs and conducted interviews to establish willingness to pay in a subset of patients.

Results

No significant differences were found between the exergame group (n=300) vs. the control group (n=305) in hospital use or costs (one-year number of hospitalisations p=0.60, costs p=0.73). The cost of the intervention was 190 Euros, and the patient time-related costs were 98 Euros (see Table 1). Of the total estimated costs for the intervention, 288 Euros, patients were willing to pay, on average, 58%. Satisfaction level regarding the exergame intervention was significantly correlated with patients' willingness to pay (rs=0.47, p=0.01).

Conclusion

Although the costs of developing a exergame can be high, this study shows that the cost for the implementation of exergaming in an individual for practice was only 288 Euro per patient. Patients were willing to pay more than half of the exergame intervention and patients with higher satisfaction levels were willing to pay more than those with lower satisfaction levels.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish National Science Council
OUES from submaximal cardiopulmonary exercise
Authors: Rudd A , Khan H , Gamble D , Stephen P , Horgan G , Dawson A , Frenneaux M P , Dawson D K
Published: October 2022

Introduction

Cardiopulmonary exercise testing (CPEX) provides valuable diagnostic and prognostic cardiopulmonary function data. However, in clinical setting a maximal test is not always achievable. The Oxygen Efficiency Uptake Slope (OUES) has been proposed as a possible submaximal measure of cardiopulmonary function as it remains relatively stable during the final quartile of the exercise test. This study explored the validity of OUES as a surrogate marker for cardiopulmonary function in the event of a submaximal test.

Methods

Four groups of subjects [128 healthy controls (73 M), 44 asymptomatic hypertensive (HT) patients (26 M), 67 adult cardiac congenital heart disease (ACHD) patients (44 M) and 35 Heart Failure with preserved Ejection Fraction (HFpEF) (10M) patients] were recruited after informed consent. All subjects underwent clinical assessment, resting ECG, blood pressure and spirometry prior to a treadmill CPEX to volitional exhaustion and a respiratory exchange ratio (RER) of at least 1.1 using the same testing protocol. Peak VO2 (ml/min) was recorded from the last 5s of the maximal test (RER=1.1) and OUES was calculated from complete (RER=1.1) and truncated (RER=0.9) gas exchange data. The linear relationships between absolute peak VO2 and OUES from complete and truncated gas exchange data were assessed using Pearson's correlation coefficient. Subsequently, the two correlations obtained in each patient group were compared. Statistical significance was set at p<0.01.

Results

Mean and 95% confidence intervals of the peak VO2 for males and females in each decile of life examined in the 4 subject groups are shown in the Figure. Peak VO2 values achieved in each of the patient groups were significantly lower when matched for age and sex compared to healthy participants (HT p=0.006, ACHD patients p<0.001 and HFpEF patients p<0.001).

In all 4 groups there was a good correlation between absolute peak VO2 and the OUES at RER 1.1 (healthy volunteers r=0.910, p<0.001, HT r=0.899, p<0.001, ACHD r=0.816, p<0.001 and HFpEF r=0.846, p<0.001). Correlations were inferior for absolute peak VO2 and OUES at RER 0.9 (healthy volunteers r=0.74, p<0.001, HT r=0.780, p<0.001, ACHD r=0.651, p<0.001 and HFpEF r=0.817, p<0.001). Correlations between absolute peak VO2 vs OUES at RER of 1.1 and 0.9 were significantly different only for healthy controls (p=0.001, Z-score = −4.649), but not for HT (p=0.05, Z-score = −1.909), ACHD (p=0.04, Z-score = −2.080) or HFpEF (p=0.7, Z-score = −0.377) patients.

Conclusion

Our data support the use of submaximal OUES at an RER of 0.9 as a surrogate marker for absolute peak VO2 obtained at an RER of 1.1, especially in patients, in whom it can often be difficult to achieve maximal exercise.

Funding Acknowledgement

Type of funding sources: None.
Clinical validation of an artificial intelligence algorithm offering cross-platform detection of atrial fibrillation using smart device electrocardiograms
Authors: Mannhart D , Lefebvre B , Gardella C , Henry C , Serban T , Knecht S , Kuehne M , Sticherling C , Badertscher P
Published: October 2022

Introduction

Multiple smart devices capable of “screening” for atrial fibrillation (AF) based on single-lead electrocardiogram (SL ECG) are presently available. Manufacturers' algorithm capabilities and accuracy for the automated detection of AF vary. Reliable artificial intelligence (AI) algorithms would be valuable to assist physicians with managing the large amount of data. We aimed to assess the clinical value of applying a smart device agnostic AI-based algorithm for the detection of AF from five different smart devices (four smartwatches, one handheld device) and compared the results to the cardiologist-interpreted 12-lead ECG in a real world cohort of patients.

Methods

This is a prospective, observational study enrolling patients presenting to a cardiology service at a tertiary referral center. Patients were prescribed a 12-lead ECG, followed by five consecutive smart device recordings from five different manufacturers. SL ECGs were exported as PDF files from the devices and analyzed by a deep neural network (DNN) based platform which allows automated AI assisted cardiac rhythm interpretation.

Results

We prospectively enrolled 157 patients (32% female, median age 66 years). AF was present in 48 patients (31%) at time of recording, as documented by the 12-lead ECG. Accuracy for the detection of AF by the DNN-based algorithm was 96.6% for the Apple Watch 6, 95.2% for the AliveCor Kardia Mobile, 96.0% for the Fitbit Sense, 95.7% for the Samsung Galaxy Watch 3 and 93.8% for the Withings Scanwatch, respectively (Figure 1, left). While diagnostic accuracy of the DNN-based algorithm was similar compared to each manufacturer's individual algorithm, the proportion of SL ECGs with a conclusive diagnosis was significantly higher for all smart devices when using the DNN-based algorithm, p<0.001 (Figure 1, right). As complementary analysis, we assessed sensitivity and specificity detection capabilities in both algorithms (Figure 2).

Conclusion

In this clinical validation, a DNN-based algorithm reported significantly more conclusive diagnoses for each smart device compared to the manufacturers' algorithms, whilst showing similarly high accuracy in the detection of AF compared to the cardiologist-interpreted standard 12-lead ECG. Given further validation, SL ECG assisted rhythm interpretation through a cross-platform AI-algorithm presents a promising clinical value for AF detection and offers a possible solution for managing the data surge for smart device-acquired ECGs.

Funding Acknowledgement

Type of funding sources: None.
Right heart catherisation – a virtual reality
Authors: Brown M , Krishnananthan N , Paul V
Published: October 2022

Introduction

Right heart catheterisation (RHC) is the gold standard for assessing patients with pulmonary hypertension. Doctors require training in this procedure in a safe and friendly environment with minimal risk to patients. Due to the Covid pandemic, formal RHC teaching workshops were cancelled in our country, so we sought to develop a Virtual Reality Right Heart Catheterisation (VRRHC) training program to fulfil this area of need without the need for face to face contact. The aim was to improve training, competency and confidence in this technique with improved diagnostic skills and reduction of procedural errors.

Method

We approached a health technology company to design a VRRHC training module based on our current RHC simulation workshops. Phase 1 required virtual insertion of RHC via the right internal jugular vein using micro-puncture, double Seldinger technique under ultrasound guidance, followed by insertion of the RHC to the right atrium, right ventricle and pulmonary artery with pulmonary artery occlusion using real time pressure tracings and fluoroscopy. Thermodilution cardiac outputs and chamber saturations were also performed.

The proprietary platform technology was delivered via a laptop and VR headset. Clinicians perform the VRRHC with imaging, monitoring and haptic feedback with the collection of real time performance tracking allowing user data (e.g. failed steps and proficiency scores) to be captured and subsequently visualised in the learning management system.

We collected analytics and data on user engagement, experience and retention, targeted learning outcomes and learning curve, reduction in operating costs, reduction in procedure times due to higher proficiency, early diagnosis of pulmonary hypertension, reduced complications, improved interpretation and diagnosis.

Results

The program was launched in October 2021. Preliminary data shows a learning curve is associated with both using VR (10–15 minutes) and the RHC procedure itself. Initial time to completion of the RHC was 30–40 mins, reducing to 20–30 minutes with experience and 15 minutes in experts. Completion rates increase with experience from 40–50% to 100% and error rates reduce with frequency of completion.

Conclusion

A Virtual Reality Right Heart Catheter training program is safe, feasible and non-invasive. Increased experience results in increased completion rates, reduced procedure time and reduced errors. Using this program will potentially have beneficial effects on doctor training, outcomes, patient safety and health economics with no risk to a real patient.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen Pharmaceuticals
Implementation of a clinical trial recruitment support system based on fast healthcare interoperability resources (FHIR) in a cardiology department
Authors: Scherer C , Endres S , Orban M , Kaeaeb S , Massberg S , Winter A , Loebe M
Published: October 2022

Background

Clinical Trial Recruitment Support Systems can booster patient inclusion of clinical trials by automatically analyzing eligibility criteria based on electronic health records. However, missing interoperability has hindered introduction of those systems on a broader scale.

Purpose

Our aim was to develop a recruitment support system based on FHIR R4 and evaluate its usage and features in a cardiology department.

Methods/Implementation

Clinical conditions, anamnesis, examinations, allergies, medication, laboratory data and echocardiography results were imported as FHIR resources. Trial study nurses and physicians were enabled to add new and edit trial information and input inclusion and exclusion criteria using a web-browser user interface in the hospital intranet. All information were recorded on the server side as the FHIR resources “ResearchStudy” and “Group”. Eligibility criteria linked by the logical operation “OR” were represented by using multiple FHIR Group resources for enrollment. On the client side, eligibility criteria were transformed to a tree-like structure (see Figure 1). Upon user demand, all hospitalized and ambulatory patients in the cardiology department were instantly screened for trial eligibility using the FHIR eligibility criteria on the existing patients' FHIR resources. Furthermore, study personal was able to manually edit trial status (i.e. ineligible, on-study, ...) of patients, which was implemented using the FHIR resource “ResearchSubject”.

Results

This implementation of a CTRSS based on FHIR R4 was evaluated in clinical practice: Beginning from 1st April 2021 the application was used as an additional patient screening tool for the four trials CLOSURE-AF, FAIR-HF2, SPRIRIT-HF and TORCH-PLUS of the German Centre for Cardiovascular Research. As the COVID-19 pandemic is prohibiting any proper comparison of patient inclusion rates, efficacy of the recruitment support system was tested by comparing the numbers of patients identified by the recruitment support system and enrolled in a trial to the actual number of enrolled patients irrespective of the screening method from 1st April 2021 to 23rd November 2021. The system was able to identify 52 of 55 patients included in those four clinical trials.

Conclusion

Use of FHIR for defining eligibility criteria of clinical trials may facilitate interoperability and allow automatic screening for eligible patients at multiple sites of different healthcare providers in the future. Upcoming changes in FHIR should allow easier description of “OR”-linked eligibility criteria.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft
Wearable device for continuously blood pressure monitoring enable atrial fibrillation risk
Authors: Guo Y , Zhang H
Published: October 2022

Background

The epidemiological data have linked atrial fibrillation (AF) risk with hypertension.

The surging wearable devices allow noninvasive beat-by-beat blood pressure monitoring.

Objective

The present study aimed to investigate dynamic changes on blood pressure with wearable blood pressure monitors and its-related risk for AF occurrence.

Methods

In the mobile Atrial Fibrillation Application (mAFA II) programme, the subjects used the photoplethysmography (PPG)-based smart devices to detect the AF episodes. They simultaneously freely decided whether to take the wearables to monitor their blood pressure.

Results

There were 25388 subjects (mean age ± standard deviation, SD, 48±12 years old, 90.4% male) who received simultaneously blood pressure and cardiac rhythm monitoring with the wearables between Jan 1, 2022 and March 19, 2022. The monitored time (median, interquartile) were 6 (12–18) days and the number of measurements of blood pressure were 16 (3–56).

The 8830 subjects (34.8%, 8830/25388) monitored with average 24-hour BP >130/80 mm Hg and 945 subjects (10%, 945/8830) with pulse differential over 60 mmHg.

The extreme-dippers blood pressure and reverse-dippers blood pressure were in 8563 subjects (33.7%, 8563/25388) and 7018 subjects (27.6%, 7018/25388), respectively.

There were 498 subjects (58±12 years, 89% male) who identified with AF. After adjusting age, gender, diabetes, obstructive sleep apnea, heart failure, coronary artery disease, and hyperthyroidism, the average 24-hour BP >130/80 mm Hg (Odd ratio, OR, 95% confidential interval, CI, 1.38, 1.12–1.69, p=0.002), the reverse-dippers blood pressure (OR, 95% CI, 1.29, 1.07–1.56, p=0.008) and pulse differential over 60 mmHg (OR, 95% CI, 1.76,1.17–2.64, p=0.006) independently predicted the risk of AF.

Conclusion

Wearable devices with beat-by-beat monitoring demonstrated that not only high average 24-hour BP, but also reverse-dippers blood pressure and pulse differential over 60 mmHg increased AF susceptibility, which informing the clinical application of personalized “upstream risk control” of AF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China
Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation
Authors: Ahmed F Z , Sammut-Powell C , Martin G P , Callan P , Cunnington C , Kale M , Gerritse B , Lanctin D , Soken N , Campbell N G , Taylor J K
Published: October 2022

Background

Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations.

The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses “high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined.

Purpose

To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates.

Methods

A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights.

Results

Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively.

196 high risk transmissions prompted telephone assessment, with successful contact in 182; of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results.

Conclusions

This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Medtronic
Endothelial dysfunction in the post-COVID-19 period: a meta-analysis
Authors: Theofilis P , Oikonomou E , Lampsas S , Siasos G , Tsioufis K , Tousoulis D
Published: October 2022

Background

Coronavirus disease (COVID)-19 is an entity characterized by a cytokine storm and profound endotheliitis. Although several reports have pointed to the presence of endothelial dysfunction in the acute phase, data is accumulating regarding a possible prolonged adverse effect of COVID-19 on endothelial function.

Purpose

This systematic review and meta-analysis aims to evaluate the degree of endothelial impairment, assessed by flow-mediated dilation (FMD) of the brachial artery, in individuals recovering from COVID-19.

Methods

We conducted a systematic literature search for studies assessing FMD between in patients post-COVID-19 and controls. Exclusion criteria consisted of the absence of a control group, measurement of FMD only during the acute phase of the disease, and not reporting FMD in % change. Effect sizes were pooled via random-effect model and the results are expressed as uncorrected standardized mean difference (SMD), using the Cohen's d as the effect size metric, with 95% confidence intervals (CI). Between-study heterogeneity was assessed through the calculation of I2. Subgroup analysis according to follow-up duration and the presence of cardiovascular risk factor-matched controls was also carried out.

Results

Database search identified 51 studies. Following the application of the exclusion criteria, 7 studies were included in the meta-analysis (post-COVID-19: 342 subjects, Control: 273 subjects). Compared to controls, patients post-COVID-19 had significantly lower FMD% values (SMD: −1.06, 95% CI: −1.74 to −0.38, p<0.01, I2: 86%) (Figure 1). Results remained unaffected after exclusion of any single study using the leave-one-out method. Subgroup analysis revealed no significant differences in FMD between post-COVID-19 patients and controls according to follow-up duration or the presence of cardiovascular risk factor-matched control group.

Conclusion

Flow-mediated dilation of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in post-COVID-19 subjects compared to non-infected controls. This finding may be an alarming sign towards a higher risk of incident cardiovascular events.

Funding Acknowledgement

Type of funding sources: None.