bluuebunny/crossref_metadata_2025 huggingface dataset:
Causation of potential drug to drug interactions alerts, alert overrides, and adverse drug events in critical cardiac patients
Authors: Mohamed Ariff A , Nalliah S N , Abdul Hadi H A H , Win N T W , Thoulath M I T , Aktifanus A T J , Mutaya S M M , Yusof A K M
Published: October 2022

Background

Drug-drug interactions (DDIs) leading to adverse drug events (ADEs) are of special interest because they represent preventable medication errors. Preventable ADE can result in errors involving the manifestation of adverse patient outcomes. Given the high complexity of critically ill cardiac patients, it is important to learn how Clinical Drug Decision Support System (CDDSS) affects outcomes in this population and the number of alerts that are likely to be safely suppressed.

Purpose

Identify adverse DDIs that are clinically detected and review the appropriateness of the doctor's actions to the potential DDIs (PDDIs) alert. Study Design: This is a prospective observational study conducted at a critical cardiac care unit (CCU) in a selected tertiary cardiac center for a duration of six months.

Methods

Physicians treating critically ill cardiac patients were presented with PDDIs data which were acquired from two commercially available CDDSS. The relationship between the decision to prescribe and factors hypothesized to affect physicians' decisions was examined.

Results

Evaluation of 709 patient medication profiles were conducted, resulting in 521 assessed patient profiles having had one or more PDDIs with 87% of them being influenced by polypharmacy. Ninety-one patients (17.5%) were associated with one or more adverse DDIs. Of the total 3284 potential DDIs alerts, 95.5% of the alerts were overridden. Preventable ADE as an outcome of inappropriate override has resulted in 83.1%. (236/284) of adverse DDIs. Whereas appropriate overrides as an outcome of clinically irrelevant ADE were 16.9% (48/284).

Conclusion

Poor preventive actions taken by the doctors caused drug-related harm to the patients despite having CDDSS in place. This suggests that CDDSS is an important application to minimize the harm associated with adverse DDIs by alerting physicians of potentially unsafe situations.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): International Medical UniversityNational Heart Institute
Activation of the HeartLogic algorithm on top of heart failure care: a multicenter propensity-matched cohort analysis
Authors: Feijen M , Beles M , Than Y Z , Cordon A , Dupont M , Treskes R W , Caputo M , Mullens W , Van Bokstal K , Auricchio A , Egorova A D , Maes E , Beeres S L M A , Heggermont W A
Published: October 2022

Background

Hospitalization for decompensated heart failure may be prevented by early detection of fluid retention. The multisensory HeartLogic™ algorithm, incorporated in a cardiac implantable electronic device (CIED) aims to detect impending fluid retention and thereby enables timely adjustment of medical therapy. However, it is to be investigated whether HeartLogic™ provides clinical benefit compared to heart failure care with conventional telemonitoring. This analysis investigates the effects of activating HeartLogic™ on top of heart failure care with telemonitoring on the number of episodes with fluid retention and heart failure related hospitalizations.

Methods

Heart failure patients with a CIED were recruited from the outpatient clinics of four European cardiology departments. All patients were included from January 2017 until December 2020, and followed-up for 365 days. Patients with a CIED and an activated HeartLogic™ algorithm were compared to a 1:1 propensity score-based matched control group consisting of patients with CIED on routine telemonitoring. Data of all episodes of (impending) fluid retention with ≥2 signs and symptoms of congestion were included for analyses.

Results

Data of 127 patients with an activated HeartLogic™ algorithm were adequately matched with 127 heart failure patients with a CIED on routine telemonitoring. Median age was 68 [59–75], majority of patients were male (80%), 46% had an ischemic etiology of heart failure. Total follow-up consisted of 254 patient years. During follow up, 77 (61%) individual patients with HeartLogic™ experienced an episode of fluid retention, compared to 85 (67%) induvial patients on routine telemonitoring. Patients with an activated HeartLogic™ algorithm had 1.62±1.78 events of fluid retention per patient year (PPY) compared to 2.61±3.71 events PPY in patients on routine telemonitoring, p<0.01 (Figure 1). Hospitalization for fluid retention occurred in 7 (6%) HeartLogic™ patients (0.06±0.27 hospitalizations PPY) compared to 13 (10%) patients on routine telemonitoring (0.15±0.45 PPY), p=0.07 (Figure 2A). Mean length of hospitalization in days PPY was 0.29±1.46 in patients with HeartLogic™ and 1.59±6.30 in patients on routine telemonitoring, p=0.02 (Figure 2B).

Conclusion

In a real-world multicenter heart failure population, activation of the HeartLogic™ algorithm was associated with a lower number of episodes of fluid retention per patient and a shorter duration of hospitalization for congestive heart failure.

Funding Acknowledgement

Type of funding sources: None.
The effectiveness of a telemedical program for COVID-19 positive high-risk patients in domestic isolation
Authors: Brunelli L , Poelzl L , Hirsch J , Engler C , Naegele F , Egelseer-Bruendl T , Scheffauer T , Rassel C , Schmit C , Nawabi F , Luckner-Hornischer A , Bauer A , Poelzl G
Published: October 2022

Background

For almost two years, the Covid-19 pandemic has posed an enormous challenge to healthcare systems. Recurrent waves of disease brought the health systems to the limit of their resilience.

Purpose

The Tele-Covid telemedicine care program was installed in December 2020 to monitor high-risk patients in home isolation. Close monitoring allows early detection of disease deterioration and timely intensification of therapy, ideally avoiding intensive care. Conversely, if the course of the disease is stable, unnecessary hospitalisation can be avoided, thus reducing the burden on the healthcare system.

Methods

Patient acquisition was performed in collaboration with the local public health service and primary care physicians. Covid-19 positive high-risk patients (age >65 years and/or severe comorbidities) from the greater Innsbruck area were fitted with an ear sensor-based home monitoring system. The ear sensor measures SpO2, respiratory rate, body temperature and heart rate. The monitoring team (25 medical students supervised by 6 physicians) provided continuous monitoring of vital signs (24/7).

After validation of the measurements, the collected parameters were evaluated using a specially developed risk score. If a defined risk score was exceeded, the patient was contacted by telephone. The combination of the clinical condition and the risk score determined the further course of action: (a) wait and see, (b) notify the primary care physician, or (c) refer for inpatient admission.

The program was active from December 2020 to March 2022. In Summer 2021, the program was temporarily paused due to the epidemiological situation.

Results

A total of 132 patients (59.8% women) were monitored. The median age was 74 years (IQR: [67.3–80.8]). 91 patients (68.9%) had at least one relevant comorbidity. During the monitoring period, hospitalisation was required in 20 patients (15.2%), 3 of whom were transferred to the intensive care unit. Of the hospitalised patients, 3 (15%) patients died. During the same monitoring period, the Austrian Ministry of Health reported a mortality rate of 20.5% of all hospitalised patients in Austria aged 70–79 years. Subjectively, the patients felt safe due to close monitoring.

Conclusion

The Tele-Covid program is the successful implementation of a remote monitoring system in a pandemic situation. In the future, a broad application of the program is feasible.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Region of the Tyrol
Clinical relevance of the single-lead ECG of the Apple Watch
Authors: Pepplinkhuizen S , Hoeksema W F , Van Der Stuijt W , Smeding L , Wilde A A M , Knops R E
Published: October 2022

Introduction

The Apple Watch (AW) is one of the first commercially available wearable with built-in electrocardiogram (ECG) electrodes to perform a single-lead ECG to detect atrial fibrillation (AF). The AW ECG application showed to have a high rate of unclassifiable notifications. The interpretation of the single-lead ECG by a physician can possibly reduce the total of unclassifiable notifications and contribute to the overall accuracy to detect AF.

Methods

This was a prospective, non-randomized, single center observational study to evaluate the accuracy and interrater agreement of the single-lead ECG of the AW. Patients scheduled for cardioversion for atrial fibrillation were asked for participation. The AW series 6 was used with WatchiOS 7.2 or 7.3 and ECG algorithm version 2.0. A single-lead ECG was obtained pre-conversion and, when cardioversion was successful, post-conversion. All single-lead ECGs and 12-lead ECGs were adjudicated by two physicians, agreement was reached by consensus. The AW single-lead ECG notification was compared to the physicians “gold-standard” interpretation of the 12-lead ECG. Sensitivity and specificity of the AW single-lead ECG and Kappa coefficient were calculated.

Results

In total, 74 patients were included. Mean age was 67.1±12.3 years and 20.3% were female. In total 65 AF and 64 sinus rhythm (SR) single-lead ECG measurements were obtained. Of these measurements, 27.9% (36/129) showed an unclassifiable notification. The AW ECG notification showed a sensitivity of 93.5% to detect AF and a specificity of 100% to detect SR (K= 0.94). After adjudication of the unclassifiable notifications by two independent physicians 1.6% (2/129) of the measurements remained unclassifiable. When including the by the physicians adjudicated unclassifiable recordings the sensitivity to diagnose AF was 89.2% and the specificity to detect SR was 93.8% (K=0.83). The adjudication of all single-lead ECGs by the two physicians showed a sensitivity of 90.6% to detect AF and specificity of 95.2% to detect SR (K= 0.83) (Table 1). All SR and AF notification by the AW were similarly adjudicated by the two physicians. The kappa coefficient for interrater agreement between both physicians was 0.69 for all single-lead ECGs and 0.58 for unclassifiable notifications specific.

Conclusion

Unclassifiable notifications of the AW can be reduced by physicians interpretation of the single-lead ECG, however the interrater agreement is only moderate. The physicians interpretation of the single-lead ECGs did not increase the accuracy to detect AF and the clinical relevance of the single-lead ECG, in addition to the AW notification, should therefore be questioned.

Funding Acknowledgement

Type of funding sources: None.
Telemedical monitoring and coaching improves survival and hospitalisation rates in heart failure
Authors: Knoll K , Rosner S , Trenkwalder T , Lennerz C , Dittrich D , Kloss C , Doerr M , Schunkert H , Reinhard W
Published: October 2022

Aims

To investigate the effectiveness of a combined telemonitoring and telecoaching programme for chronic heart failure patients at high risk for hospitalisation compared to usual care in a real life setting. The applied telehealth programme consisted of regular individualised telecoaching sessions as well as daily remote telemonitoring of heart failure signs and symptoms.

Methods

Between January 2018 and September 2020, 6,065 heart failure patients were enrolled in a combined telehealth programme and retrospectively compared to a propensity matched usual care group (n=6,065). All participants were members of a statutory health insurance. Median follow-up was 442 days (IQR 309–681). Endpoints were all cause mortality, number and duration of hospitalisations.

Results

After 1 year the combined telecoaching and telemonitoring programme significantly reduced all-cause mortality probability compared to usual care (11.0 vs. 5.8%, p<0.001). The corresponding number-needed to treat to prevent one death in one year was 19.3. In addition, the number of hospitalisations for heart failure (17.9 vs. 21.8 per 100 patient years, p<0.001) and all cause hospitalisations (129.0 vs. 133.2, p=0.015), as well as their duration (2.0 vs. 2.6 days per year p<0.001, and 12.0 vs. 13.4 days per year p>0.001, respectivel y) were significantly lower in the telehealth group than in the usual care group.

Conclusion

In ambulatory heart failure patients at high risk for hospitalisation, a combined telemonitoring and telecoaching programme led to a reduction of heart failure hospitalisations and all-cause mortality compared to standard care.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Health Care Systems GmbH (HCSG), Pullach i. Isartal
Efficacy of controlvit as a complementary strategy in reducing hospitalizations in patients with heart failure. Randomized clinical trial
Authors: Achury D M , Garcia A G , Marino A M , Bohorquez W B , Gonzalez R G
Published: October 2022

Introduction

In patients with heart failure, the main cause of hospital admissions is due to episodes of decompensation, which are associated with an increase in the costs and resources needed for care; they have a negative impact on the quality of life and prognosis of the disease. Therefore, it is necessary to design, evaluate and implement alternatives to achieve efficient follow-up and monitoring, improving adherence to treatment and helping identify decompensation episodes that facilitate their early treatment, so new hospital admissions can be avoided. For this reason, the use of information and communication technologies (apps) is emerging as an excellent strategy for the possibility of improving coverage, real-time monitoring and timeliness of care. ControlVit® is an electronic application that allows permanent, real-time monitoring of biomedical measurements for early detection of complications.

Objective

To determine the efficacy of ControlVit® as a complementary strategy in reducing hospital admissions in patients in a heart failure program.

Methodology

A randomized, placebo-controlled, open-label clinical trial was conducted, (n=140), included patients with heart failure under controlled clinical follow-up in a structured heart failure program, into NYHA FC II–IV, capable of handling smartphones and with permanent internet connectivity. All patients were provided with educational elements, a scale and a blood pressure monitor to enter clinical data and a symptom questionnaire necessary for follow-up. The patients were randomized to 2 groups: intervention: use of ControlVit® vs. placebo, with a 6-month follow-up. The primary outcome was the difference in readmissions for heart failure between the 2 groups. Patients on the waiting list for heart transplantation or use of ventricular assist devices were excluded. All participants signed informed consent and the protocol was approved by the institutional ethics committee.

Results

A total of 140 patients were included in the study (intervention = 71, placebo = 69), with an average age of 66 years, 71% were men, the main etiology of heart failure was ischemic (60%), the main comorbidities were arterial hypertension (44%), dyslipidemia (42%), hypothyroidism (38%), chronic kidney disease (38%), and diabetes mellitus (27%). During follow-up, there were 6 deaths (3 in each group) and 17 readmissions (3 in the intervention group and 14 in the control group). After adjustment for comorbidities, HR 0.72 CI95 (0.52; 0.92), p=0.0325 was found.

Conclusion

In patients with heart failure, ControlVit® is a useful and complementary tool for follow-up, which reduces hospital admissions due to episodes of decompensation.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): German Saldarriega award.Javeriana University
Healthcare utilization and costs associated with a diagnosis of incident atrial fibrillation
Authors: Deshmukh A D , Iglesias M I , Khanna R K , Beaulieu T B
Published: October 2022

Background

Atrial fibrillation (AF) is the most prevalent arrhythmia among adults worldwide and is associated with an increased risk of heart failure, stroke, and death. Prior studies have highlighted the healthcare burden associated with AF; however, contemporary data is lacking. As AF incidence and prevalence continue to increase due to the aging of the population, current estimates are needed for adequate healthcare resource allocation and policy decisions.

Purpose

The purpose of our study was to examine the healthcare utilization and cost burden associated with a diagnosis of incident AF in the United States (US).

Methods

Using the 2017–2020 Optum Clinformatics database, an administrative claims data of commercially insured individuals in the US, adult patients with an incident diagnosis of AF were identified. Adults with AF were matched on demographic and comorbid characteristics to those without AF using a propensity score greedy-matching algorithm with a 1:1 case to control ratio. Outcomes including medical services (inpatient admissions, emergency room [ER] visits, outpatients admissions, other services), utilization (all-cause, cardiovascular [CV]-related), and healthcare costs (sum of all medical services and prescription costs; adjusted for medical inflation and reported in 2021 US $) in the one-year post-incident diagnosis of AF were then compared among the matched cohort. Logistic and general linear modeling assessed healthcare utilization and cost outcomes.

Results

A total of 159,242 matched participants (79,621 AF cases and 79,621 non-AF controls) were identified. Among patients with AF, the mean age was 74 years, and 51% were females. Among the non-AF controls, the mean age was 73 years, and 50% were females. Patients with incident AF had significantly higher all-cause inpatient visits (relative risk [RR] 1.72; 95% confidence interval [CI]: 1.71–1.73), cardiovascular-related inpatient visits (RR 2.42; 95% CI: 2:41–2:44), as well as cardiovascular-related ER visits (RR: 2.36; 95% CI: 2:30–2:42) as compared to non-AF controls in the 1-year following diagnosis (Figure 1). The one-year mean total healthcare costs were $25,006 (95% CI $24,357-$26,912) higher among patients with AF as compared to non-AF controls ($63,031 vs $38,025, p<0.001).

Conclusion

Patients with AF had significantly higher medical services use than non-AF controls. The higher medical services utilization among the AF cohort translated into a considerably higher economic burden in this cohort. Timely management and treatment remain critical in alleviating the significant financial and health burden imposed by AF on patients, payers, and providers.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Johnson and Johnson
Long COVID syndrome: a case-control study
Authors: Xuereb R A , Gatt A , Vella K , Xuereb R G , Barbara C J , Fava S , Magri C J
Published: October 2022

Background

Cardiovascular complications are rapidly emerging as a major threat in COVID-19 infection. Nonetheless, the mechanisms underlying the disproportionate effect of SARS-CoV-2 infection on patients with cardiovascular comorbidities remain incompletely understood.

Purpose

To assess whether COVID-19 infection has an adverse clinical outcome at medium-term follow-up.

Methods

A case-control study was performed. Cases were subjects who were diagnosed with COVID-19 infection following nasopharyhngeal swabbing. Controls were age- and gender-matched subjects who were not found to be infected with COVID-19 following swabbing and were negative on testing for COVID-19 IgG antibodies. All participants were submitted a standardised questionnaire regarding past medical history. Baseline blood investigations were taken including N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin levels. High-sensitivity C-reactive protein (hsCRP) was taken as marker of inflammation and von Willebrand factor (vWF) was taken as marker of endothelial dysfunction.

Results

270 subjects were recruited, comprising 174 cases and 96 controls. Of the latter, 21 were found to be COVID-19 IgG positive and were excluded from the analysis. Hence, the study cohort comprised 174 cases and 75 controls. The mean age of the participants was 46.1±13.8 years. The median follow-up was of 173.5 days (IQR 129–193.25 days). There was no statistically significant difference in the baseline demographics between cases and controls with regards age, gender as well as cardiovascular risk factors and underlying medical conditions. Regarding symptomatology at follow-up, there was a statistically significant difference between the groups in deterioration in general condition (p<0.001), shortness of breath (SOB) (p=0.008), fatigue (p=0.044), arthralgia (p<0.001), abnormal taste (p<0.001) and anosmia (p<0.001), all being more frequent in subjects with prior COVID-19 infection. At follow-up, the blood investigations showed that only hsCRP was statistically significantly higher in the cases as compared to the controls (p=0.03, Figure 1). Correlation analysis consequently revealed a negative correlation in both troponin (p=0.013, r=−0.19) and vWF levels (p=0.026, r=−0.169) with time. Finally, the association between the cases experiencing dyspnoea and the blood investigations at follow-up was assessed. Multivariate analysis revealed that COVID-19 positive cases experiencing dyspnoea have significantly higher white cell count (WCC) (OR 1.22, 95% CI 1.02–1.46, p=0.029) and troponin levels (OR 1.15, 95% CI 1.02–1.29, p=0.015) and lower haemoglobin levels at follow-up (OR 0.66, 95% CI 0.5–0.86, p<0.002), Figure 2.

Conclusion

Patients previously infected with COVID-19 have persistent symptomatology at medium-term follow-up. The role of troponin, together with markers of inflammation and endothelial dysfunction at long-term follow-up merit further investigation.

Funding Acknowledgement

Type of funding sources: None.
Conflicts of interest among authors of the ESC guidelines for the diagnosis and treatment of acute and chronic heart failure between 2012 and 2021
Authors: Schneider B , Stoellberger C
Published: October 2022

Background

In 2011, the Institute of Medicine (IOM) published standards for developing trustworthy clinical practice guidelines recommending that “Whenever possible guideline development group members should not have conflicts of interest (COIs)... Members with COIs should represent not more than a minority of the guideline development group members. The chair or cochair should not be a person with COIs.”

Purpose

Aim of this study was to assess if the standards of the IOM have influenced the development of the heart failure guidelines of the European Society of Cardiology (ESC) published between 2012 and 2021.

Methods

From the ESC homepage, the declarations of COIs of task force members (TFM) and reviewers of the guidelines for the diagnosis and treatment of acute and chronic heart failure from 2012, 2016 and 2021 were retrieved. The number of COIs was assessed for each version of the guideline.

Results

Regarding the 2012 guidelines, 24/26 TFM (92%) indicated any COI (range 1–36). Overall, 249 COIs were reported (10.4±7.3 per member). 20/26 TFM (77%) received direct personal payments (8.0±6.6 COIs per member, range 1–28). The chairperson declared 8 COIs. Among the reviewers, 32/38 (84%) indicated any COI (8.1±5.9 COIs per reviewer, range 1–29).

Regarding the 2016 guidelines, 19/21 TFM (90%) indicated any COI (range 1–35). Overall, 250 COIs were reported (13.2±9.9 per member). 17/21 TFM (81%) received direct personal payments (10.4±7.4 COIs per member, range 1–28). The chairperson declared the second most COIs (n=33) and the co-chairperson the fourth most COIs (n=21). Among the reviewers, 67/87 (77%) indicated any COI (8.1±7.3 COIs per reviewer, range 1–31).

In 2021, 28/31 TFM (90%) indicated any COI (range 2–54). Overall, 391 COIs were reported (13.9±13.8 per member). 23/31 TFM (74%) received direct personal payments (9.7±7.5 COIs per member, range 1–29). The chairperson declared 5 COIs. Among the reviewers, 91/117 (78%) indicated any COI (4.8±4.3 COIs per reviewer, range 1–20).

Conclusion

Despite the recommendations of the IOM, the proportion of TFM and reviewers of the ESC heart failure guidelines with COIs remains high in 2021 (90% and 78%, respectively). Overall, the number of COIs of the TFM have increased from 2012 to 2021, and direct personal payments to the TFM remained at a high level. 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 sources: None.
Racial disparities in the contemporary utilization and outcomes of left atrial appendage occlusion in the United States
Authors: Lopez J , Karpel D , Obaed N , Mark J , Ramos F , Jazaerly M , Wahood W , Chait R
Published: October 2022

Background

Racial and socioeconomic disparities in the utilization of percutaneous structural heart disease interventions have been described in previous years, reflecting significant gaps. However, it is unclear if increased awareness has created meaningful changes in the utilization of left atrial appendage occlusion (LAAO) in underrepresented populations.

Purpose

We aim to further clarify current practices in the United States and answer questions to help guide further efforts in attenuating health disparities.

Methods

The National Inpatient Sample (NIS) was queried from 2016–2019 to identify all patients >65 years of age diagnosed with atrial fibrillation or atrial flutter who underwent left atrial appendage occlusion (LAAO) using the international classification of diseases, tenth revision clinical modification (ICD-10-CM) codes. We selected this age cutoff to minimize confounding bias from lack of insurance coverage as patients age 65 and older qualify for the Center of Medicare & Medicaid Services. We excluded patients with missing race information. In addition, we confined our analysis to patients of White, Black, and Hispanic ethnicity because the number of other races was insufficient for meaningful analysis. Multivariate linear and logistic regression analysis was performed to compare the odds of procedure utilization, in-hospital mortality, and significant periprocedural complications among study groups.

Results

We identified a total of 14,103,690 patients >65 years of age diagnosed with either atrial fibrillation or atrial flutter. Of those, 53,350 (0.38%) underwent LAAO. The mean age of the sample was 79±7.6 years. Compared to White patients, Black patients had lesser odds of undergoing LAAO when controlling for multiple confounders (AOR = 0.49, 95% CI 0.44–0.55, p<0.001). Among Hispanic patients, there was no statistically significant difference in the odds of undergoing LAAO compared to White patients. There was no statistically significant difference in mortality, vascular complications, non-home discharge, stroke, transient ischemic attack, pericardial tamponade, and length of stay in patients undergoing LAAO among different ethnicities.

Conclusions

Significant disparities, including procedure utilization and patient characteristics prior to the procedure, such as household income, still exist among Black patients compared to White patients undergoing the LAAO in the United States. Nevertheless, adjusted odds of in-hospital outcomes were similar among Black, Hispanic, and White patients. Further research is necessary to identify what mitigation strategies could be effective and what can be changed to close the remaining gap.

Funding Acknowledgement

Type of funding sources: None.
Counting the cost of progressive aortic valve stenosis: an international observational clinical cohort study
Authors: Stewart S , Afoakwah C , Playford D , Strom J B , Chan Y , Schuffham P , Strange G
Published: October 2022

Background

We sought, for the first time, to quantify the societal to healthcare burden associated with the entire spectrum of aortic stenosis (AS) - the most common cardiac valve disorder requiring clinical management.

Methods

In this observational clinical cohort study with individual data linkage to all-cause mortality, we examined the distribution of progressive stenosis in the native aortic valves of 98,565 men and 99,357 women aged ≥65 years within a multicentre cohort across 24 sites internationally. Individuals were grouped according to their peak aortic valve velocity on last electrocardiogram investigation: 1.0–1.99 m/s (no AS/reference groups) and then 0.5 m/s increments up to ≥4.0 m/s (severe AS). Sex-specific premature mortality and years of life-lost (YLL) during 5-year follow-up were calculated, along with willingness-to-pay (WTP) to regain quality-adjusted life-years (QALYs) and healthcare costs associated with concurrent heart failure (HF).

Results

Overall, 20,701 men (21.0%; 95% CI 20.8–21.3) and 18,576 women (18.7%; 95% CI 18.5–18.9) had AS at baseline. Five-year mortality in men and women with no AS was 38.6% and 36.8%, respectively. In both sexes, mortality rose from 46.8–49.0% to 59.5–65.7% in the least- to most-severe cases of AS. Premature mortality (53.5–59.1% in the no AS group) declined from 42.4–50.9% to 34.8–35.2% of all deaths. Per 1,000 individuals, AS in men and women was associated with 8 and 13 more premature deaths resulting in 36 and 62 more QALYs (societal cost of $AU1.54 and $AU2.68 million respectively) when compared to no AS. The additional 5-year cost of healthcare utilisation for the 25 and 35 more men and women with concurrent HF and AS was estimated to be $AU1.27 and $AU1.91 million, respectively.

Conclusions

The presence of any degree of aortic valve stenosis is associated with higher levels of premature mortality coupled with excess healthcare costs that impose a heavy societal burden. These findings indicate the need for proactive and cost-effective strategies to promptly detect this common condition.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Edwards LifeSciences: Investigator-initiated grant
Conflicts of interest among authors of the ESC guidelines for the management of atrial fibrillation between 2010 and 2020
Authors: Schneider B , Stoellberger C
Published: October 2022

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)... 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.”

Purpose

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 ESC atrial fibrillation guidelines 2010, 2016 and 2020 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, 17 of 25 TFM (68%) declared COIs. Overall, 148 COIs were reported (8.7±10.2 per member, range 1–44). The chairperson declared 11 COIs. 15 of 25 TFM (60%) received direct personal payments (5.9±7.3 COIs per member, range 1–30). Research contacts were reported by 13 TFM (52%). Among the guideline reviewers, 14/26 (54%) indicated any COI (5.1±3.3 per reviewer, range 2–14).

Regarding the 2016 guidelines, 14 of 17 TFM (82%) declared COIs. Overall, 182 COIs were reported (13.0±10.4 per member, range 1–32). The chairperson of the task force had the second most COIs (n=30). 14 of 17 TFM (82%) received direct personal payments (7.7±7.4 COIs per member, range 1–22). Research funding of the department was reported by 10 TFM (59%). Among the guideline reviewers, 63/79 (80%) reported any COI (7.5±6.8 per reviewer, range 1–34).

In 2020, 21 of 24 TFM (87%) indicated any COI. Overall, 140 COIs were reported (6.7±4.5 per member, range 1–20). The chairperson of the task force declared 5 COIs. 18 of 24 TFM (75%) received direct personal payments (4.1±3.1 COIs per member, range 1–10). Research funding of the department was reported by 13 TFM (56%). Among the guideline reviewers, 87/105 (83%) reported COIs.

Comparing the guidelines between 2010 and 2020, there is an increasing proportion of TFM with COIs (from 68% in 2010 to 87% in 2020), and the proportion of TFM receiving personal payment remains high (75% in 2020). In addition, more guideline reviewers reported COIs (54% in 2010 vs 83% in 2020). Overall, the number of COIs per TFM was slightly decreasing in 2020. Companies marketing direct oral anticoagulants were most frequently mentioned in the COI declarations of the TFM in 2016 and 2020.

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 sources: None.
Novel complex-valued deep learning applied to automatic classification of heart sounds
Authors: Jojoa M , Percybrooks W , Rodrigo D , Garcia-Zapirain B
Published: October 2022

Introduction

Cardiovascular disease (CVD) is a problem facing governments around the world. Early detection saves the healthcare system thousands of dollars by allowing prevention and avoiding costly treatments when the disease has progressed to advanced stages. According to the World Health Organization (WHO), cardiovascular diseases represent the leading cause of mortality worldwide (WHO, 2019). That is why, we have decided to develop novel artificial intelligence models for the detection of heart disease, with accuracies that allow us to put the obtained algorithms into production. The revolution of artificial intelligence allows the application Deep Learning techniques of two-dimensional images in the domain of both real numbers and complex value numbers, as classifiers of heart sounds, for the detection of normality or abnormality in the functioning of the heart.

Purpose

In the present work, we propose the comparison of a novel 2D convolutional neural network (CNN) algorithm in the domain of complex value numbers with its counterpart in the domain of real numbers for the automatic classification of heart sounds into normal or abnormal.

Material

The database we decided to use for our research is Pascal, which has audio files of cardiac activity, distributed in 351 normal sounds and 129 pathological sounds.

Methods

The following steps were applied to get the objectives of our work: 1) automatic segmentation of a single heartbeat, 2) conversion of the segmented sound into its associated image scalogram using the Hilbert transform, 3) classification of the sounds into normal and abnormal using the proposed algorithms, and 4) measurement and comparison of the results obtained by performing a two-tailed t-student hypothesis test and cross-validation.

Results

We present a comparative table between the two proposed models, finding that Accuracy, F1 Score, Precision and Recall metrics obtained using complex-valued convolution networks present significant improvements compared with the real valued one. The following table show us the obtained numbers.

For all cases, the t-student test shows us p-values less than 0.05%, giving statistical evidence that the means are significantly different between the two proposed models. Besides, in all cases, the performance of the Complex-valued model is better compared with the Real-valued one.

Conclusion

Complex-valued neural networks propose a significant advance around Deep learning, since they present a better performance than the traditional counterparts based on real numbers. This proposes an experimental basis for the construction of a new Deep learning paradigm, where information in another numerical domain, is better exploited with the help of mathematical transforms. The latter is a significant advance in health sciences, where the demand is higher, in terms of performance of the proposed models.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): eVIDA research Group
Ascertainment of aortic valve disease using administrative claims
Authors: Strom J , Xu J , Sun T , Song Y , Sevilla-Cazes J , Wadhera R , Yeh R
Published: October 2022

Background

Administrative claims may be useful for characterizing patients with aortic stenosis (AS) and aortic regurgitation (AR) and estimating disease prevalence. However, the accuracy of diagnostic codes for aortic valve disease has not been well studied.

Purpose

To evaluate the validity of International Classification of Diseases, 10th Revision (ICD-10) codes for identification of AS and AR.

Methods

Using a large, transthoracic echocardiographic (TTE) report dataset linked to Medicare Fee-for-service (FFS) claims, 2017–2018, the performance of candidate claims to ascertain AS/AR status using standard TTE definitions was evaluated. Recursive partitioning with 10-fold cross validation was used to build the optimal prediction tree for AS/AR status using all ICD-10 codes as candidate predictors. The optimal performing claims algorithm was tested against patient outcomes in a separate 100% sample of Medicare FFS inpatient and outpatient claims, 2017–2019.

Results

Of those included in the derivation dataset (N=5497, mean age 74.4±11.0 years, 49.7% female), any AS or AR was present in 24% and 38.8%, respectively. The code I35.0 was optimal for identification of any AS with a sensitivity and specificity for any AS of 53.1% and 94.8%, respectively (Table 1). Amongst those with an I35.0 code, 40.3% had severe AS. Claims were unable to distinguish disease severity (i.e. severe vs. non-severe) or subtypes (e.g. bicuspid or rheumatic AS), and were insensitive and nonspecific for AR of any severity. Among all Medicare beneficiaries who received an TTE (N=3,783,249), those with an I35.0 code, compared to those without, had a higher risk of all-cause mortality (HR 1.65, 95% CI 1.63–1.67), heart failure hospitalization (HR 2.17, 95% CI 2.11–2.24), and aortic valve replacement (HR 32.35, 95% CI 31.46–33.27) (Table 2).

Conclusions

Amongst those receiving TTE, the ICD-10 code I35.0 in any position was optimal for identification of AS and identified a population at significant greater risk of all-cause mortality, heart failure hospitalization, and receipt of aortic valve replacement. Though 40.3% of those with I35.0 had severe AS, claims were unable to distinguish disease severity of subtype. Claims may be feasibly used to identify those with AS who may be at risk for adverse valve-related cardiovascular events and require future treatment.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National, Heart, Lung, and Blood Institute
Development of a risk prediction score and equation for chronic kidney disease: a retrospective cohort study
Authors: Kawasoe S , Kubozono T , Ojima S , Kawabata T , Ikeda Y , Miyahara H , Tokushige K , Ohishi M
Published: October 2022

Background

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future onset of CKD using large-scale health checkup data.

Methods

This retrospective cohort study included 58,423 participants without baseline CKD who were randomly assigned to Derivation (n=38,948) and Validation cohorts (n=19,475) at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In the Derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to determine the risk of developing CKD after 5 years and applied them to the Validation cohort to assess their reproducibility.

Results

The risk prediction scores ranged from 0 to 16, consisting of the seven indicators, including age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR). From the receiver operating characteristic (ROC) curve predicting CKD incidence, the area under the curve (AUC) was 0.78. A score of ≥8 showed the highest Youden index in the Derivation cohort, with a sensitivity of 0.90 and specificity of 0.52. The CKD incidence gradually and constantly increased as the score increased from ≤6 to ≥14 (Figure). The risk prediction equation consisted of aforementioned seven indicators: 1/(1 + exp[−(9.4876 + 0.0311×age + 0.2400×sex + 0.3470×hypertension + 0.0893×dyslipidemia + 0.3444×diabetes + 0.0832×hyperuricemia + (−0.1980)×eGFR]). The median probability obtained from the Derivation cohort was 0.018 (interquartile range 0.002–0.084), and the AUC value of the ROC curve for the development of CKD after 5 years was 0.88, with a sensitivity of 0.84 and a specificity of 0.78 at a cutoff value of 0.077. The Validation cohort analysis yielded similar results.

Conclusion

We developed a clinically useful risk score and equation to predict the CKD incidence after 5 years in the general Japanese population. These models have reasonably high predictability and reproducibility.

Funding Acknowledgement

Type of funding sources: None.
High resolution single cell analysis of the developing human heart
Authors: Bayraktar S , Colzani M T , Davaapil H , Knight-Schrijver V R , Rericha P H , Lee J C M , He X L , Gambardella L , Sinha S
Published: October 2022

The human heart is composed of various cell types with distinct embryonic origins and functions. Having an understanding of the components of the developing heart at a molecular level should provide better insights into its function in health and disease. Current single cell studies of human fetal hearts are limited by low cell numbers and poor cell type resolution. Here, we aimed to increase the number of cells studied while adding a spatial resolution. We analysed human hearts aged between post conception weeks of 8 and 11, where apex and base in each were processed, providing spatial resolution on cells constituting the myocardium and the great vessels. Our analysis suggests 6 main cell types in the developing hearts with a total of 28 subtypes and provides a differential expression signature for similar cell types with different origins and anatomical locations, including the smooth muscle cells and endothelial cells of the myocardium and the great vessels. Through immunohistochemistry, we validated our findings on these subtypes, as well as on the cells that were less clearly described before, such sinoatrial node cells or resident macrophages. Cell to cell interaction analysis inferred distinct molecular crosstalk across subtypes, including the cells of the great vessels or the vessels of the myocardium. Our findings suggest a list of transcription factors that might be involved in governing the identity of these cells. Collectively, our analysis provides a better understanding of human heart development, and will inform studies into disease modelling and disease progression.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation
Prognostic implication of unrecognized myocardial infarction in patients with non-ST-segment-elevation acute coronary syndrome
Authors: Sayama K , Hoshino M , Kanaji Y , Sugiyama T , Misawa T , Hada M , Nagamine T , Nogami K , Teng Y , Ueno H , Matsuda K , Yonetsu T , Kakuta T
Published: October 2022

Background

Prognostic value of unrecognized non-infarct-related territory (non-IR) myocardial infarction (UMI) in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) remains to be elucidated.

Purpose

This study sought to evaluate the prevalence of non-IR UMI and its prognostic value in patients with first NSTE-ACS presentation.

Methods

This retrospective single-center analysis was conducted in patients with NSTE-ACS without prior history of coronary artery disease, who underwent uncomplicated urgent percutaneous coronary intervention (PCI) within 48 hours of admission between August 2014 and January 2018. All patients underwent postprocedural cardiac magnetic resonance imaging (CMR) within 30 days after PCI. Non-IR UMI was defined as the presence of non-IR delayed gadolinium enhancement with an ischemic distribution pattern. We investigated the association of non-IR UMI, other CMR findings and baseline clinical characteristics with major adverse cardiac events (MACE), defined as all-cause death, non-fatal myocardial infarction, ischemic stroke, late revascularization and hospitalization for congestive heart failure.

Results

A total of 168 NSTE-ACS patients were included (124 males (73.8%); 66±11 years). Non-IR UMI was detected in 28 patients (16.7%). During a median follow-up of 32 months (15–58), MACE occurred in 10 (35.7%) patients with non-IR UMI, and 20 (14.3%) patients without (P=0.013). Patients with MACE showed higher frequency of non-IR UMI in RCA territory and multi vessel disease, higher level of NT-proBNP at admission, higher Genisini score, and greater extent of UMI. Cox's proportional hazards analysis showed that the presence of non-IR UMI was an independent predictor of MACE (HR 2.34, 95% CI 1.02–5.37, P=0.045), after adjusting confounding factors, such as multi vessel disease and serum levels of NT-proBNP at admission. The discriminant efficacy (IDI and NRI) of predicting MACE was significantly improved when the presence of non-IR UMI added to the reference clinical risk model. Kaplan-Meier analysis revealed that patients with non-IR UMI were significantly associated with poor prognosis. (Figure 1).

Conclusions

In patients with NSTE-ACS undergoing urgent PCI, the prevalence of non-IR UMI was 16.7%. Non-IR UMI provided prognostic information independent of conventional risk factors.

Funding Acknowledgement

Type of funding sources: None.