bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCSK9 inhibition with alirocumab decreases plasma lipoprotein(a) concentration by a dual kinetic mechanism of action
Authors: Ying Q , Pang J , Chan D C , Barrett P H R , Watts G F 
Published: October 2021

Abstract

Background
Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle, covalently bound to apolipoprotein(a) [apo(a)]. Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, decrease plasma Lp(a) levels and risk of atherosclerotic cardiovascular disease (ASCVD). The kinetic mechanism for lowering Lp(a) by PCSK9 inhibitors may differ according to pre-treatment apo(a) levels.

Purpose
We investigated the effect of alirocumab on Lp(a) metabolism in 21 long-term statin-treated patients [Lp(a) &gt;0.5 g/L in all] with moderate-high (n=10) and high (n=11) apo(a) concentrations according to a cutoff of median apo(a) levels of 145 nmol/L.

Methods
Apo(a) kinetics were studied before and after 12-week treatment with alirocumab (150 mg subcutaneously fortnightly). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling.

Results
The plasma concentration and PR of apo(a) were significantly higher in patients with high apo(a) than in patients with moderate-high apo(a) levels (273±30 nmol/L vs 130±4.7 nmol/L and 6.0±0.69 nmol/kg/day vs 2.6±0.15 nmol/kg/day, respectively; P&lt;0.001). The FCR of apo(a) was not significantly different between two groups (0.48±0.02 pools/day vs 0.45±0.01 pools/day, P&gt;0.05). In patients with moderate-high apo(a) levels, alirocumab significantly lowered plasma apo(a) levels (−17%, P&lt;0.01) and increased the FCR of apo(a) (+26%, P&lt;0.001), but did not alter apo(a) PR. In contrast, alirocumab significantly lowered plasma apo(a) concentrations (−31%, P&lt;0.001) via a dual mechanism that increased apo(a) FCR (+31%, P&lt;0.001) and lowered PR (−9%, P&lt;0.05) in patients with high apo(a) levels. The reductions in apo(a) concentration and PR with alirocumab in the high apo(a) group remained significant after adjusting for background statin when compared with patients with moderate-high apo(a) levels (P&lt;0.05).

Conclusions
In statin-treated patients with elevated Lp(a), alirocumab may lower elevated plasma Lp(a) concentrations by a dual mechanism of increasing the catabolism and decreasing the production of Lp(a) particles, specifically in patients with relatively high apo(a) concentrations.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This independent research was funded by an Investigator Initiated Study Concept Research Grant from Regeneron Pharmaceuticals and Sanofi (Protocol No. LPS 14508). Figure 1Figure 2
The prevalence and safety of direct oral anticoagulants in patients with non-atrial fibrillation associated intra-cardiac thrombus
Authors: Kanwal A , Zulty M , Rao S , Young R 
Published: October 2021

Abstract

Background
The standard of care in management of intra-cardiac thrombus has been the use of vitamin K antagonists (VKAs). The emergence and use of direct oral anticoagulants (DOACs) in other conditions has led to the consideration of their use in patients with intra-cardiac thrombus. Thus far, case-reports have provided the majority of data regarding the efficacy of DOACs in this population.

Purpose
The aim of this observational study was to investigate the safety and efficacy of DOACs in intracardiac thrombus not associated with atrial fibrillation, compared to the current standard of care, VKAs.

Methods
An observational study was conducted between 10 hospitals in our region. The study was conducted between 2013 and 2019 in patients with a diagnosis of intracardiac thrombus. All left and right, atrial and ventricular thrombi were included. Patients with atrial fibrillation were excluded. Patient information was collected from the hospital electronic record. The primary endpoints were clinically significant bleeding requiring transfusion and thromboembolic events, excluding myocardial infarction.

Results
1153 patients had a diagnosis of intracardiac thrombus. 878 out of 1153 patients were discharged on warfarin and 275 were discharged on a DOAC. In the warfarin population 73 of 878 patients (8.3%) had clinically significant bleeding events compared to 21 of 275 patients (7.6%) in the DOAC population (p=0.801). The median ages were 60.5 and 58 respectively. The median time period to a bleeding event was 151 and 198 days respectively. In the warfarin population, 116 of 878 patients (13.2%) had thromboembolic disease versus 34 of 275 patients (12.4%) in the DOAC arm (p=0.759). The median ages were 62 and 62.5 respectively. The median time period to a thromboembolic event was 114 and 184 days respectively. In the warfarin arm, 3 patients had systemic thromboembolism and 113 patients had embolic strokes. In the DOAC arm, 2 patients had systemic thromboembolism, 32 patients had embolic strokes.

Conclusion
The data from this study suggests that DOACs may be a feasible alternative to warfarin in patients with intracardiac thrombus. There was no statistically significant difference in the rates of clinically significant bleeding or in incidence of thromboembolic disease. To our knowledge, this is the largest observational study to date on this topic. Randomized controlled trials are needed to fully establish the efficacy of DOACs in this patient population.

Funding Acknowledgement
Type of funding sources: None. Table 1
Edoxaban treatment in real-world practice is highly concordant with ESC atrial fibrillation guidelines: results from the non-interventional global ETNA-AF program
Authors: Morrone D , Chen C , Dinshaw L , Jiang W , Kim Y.-H , Kirchhof P , Koretsune Y , Pecen L , Reimitz P.-E , Wang C.-C , Yamashita T , Unverdorben M , De Caterina R 
Published: October 2021

Abstract

Background
The ESC atrial fibrillation management guidelines recommend a risk-based approach to oral anticoagulant (OAC) therapy. How clinical practice aligns with these recommendations is of interest.

Purpose
To analyse real world data from Global ETNA-AF program in patient groups stratified by stroke and bleeding risk scores according to ESC guidelines.

Methods
Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Baseline characteristics and clinical event data at 2-year follow-up were analysed in 4 subgroups defined by CHA2DS2-VASc score (≥3 for female / ≥2 for male [OAC recommended] vs 2 for female / 1 for male [OAC should be considered]) and HAS-BLED score (≥3 [Bleeding risk high] vs &lt;3 [Bleeding risk low]) (Table 1).

Results
Of 27,616 patients included in this analysis, 23,152 (83.8%) were in the “OAC recommended” category and 3,539 (12.8%) were in the “OAC should be considered” category. Only 3.3% of patients did not meet ESC guideline criteria for OAC initiation. Among patients with high bleeding risk, 98% were in the “OAC recommended” category. A similar distribution was observed across regions (Table 2). The recommended edoxaban dose was used in the vast majority (&gt;80%) of patients across all risk stratification subgroups. In the “OAC recommended” category, patients with high bleeding risk had higher rates of thromboembolic, bleeding, and death events than those with low bleeding risk.

Conclusion
Data from routine clinical practice in Global ETNA-AF demonstrate high concordance of edoxaban treatment with ESC guidelines. Edoxaban dose is consistent with label recommendation in the vast majority (&gt;80%) of patients. Clinical event rates were generally low across all risk groups, including acceptable bleeding rates in anticoagulated patients with high bleeding risk.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Subgroups as per ESC guidelinesTable 2. Patient characteristics & events
Protective mechanisms of betablockers for coronary artery disease are by distal vasoconstriction and slower speed: a study by angiographic assessment and artificial intelligence program
Authors: Duong H , Nguyen T , Ho D , Le M , Thai M 
Published: October 2021

Abstract

Background
Patients with coronary artery disease (CAD) were protected with betablockers (BB) for lower mortality and lower rate of new myocardial infarction. What are the protective mechanisms? In prior studies, our hypothesis was that damage to the intima of the coronary arteries was caused by cavitation or rupture of bubbles which was seen frequently in industrial pipes. The bubbles ruptured when they flew in areas of different pressures among the layers and segments of the coronary flows. How did BB change the dynamic of coronary flow?

Methods
After percutaneous coronary interventions (PCI) patients were started on BB. Later, when there was indication, the patient underwent another angiogram. The diameter of the distal LAD was measured and compared between the two angiograms. The distance reached the coronary flow after 0.6seconds was calculated in both angiograms and compared. In the reviewing protocol, the coronary angiograms were done with the contrast injected until the index coronary artery was completely opacified. As the injection of contrast stopped, the blood in white color moved in and displaced the contrast in black color. The morphologies, movements, directions, and interactions of the blood flow in white color above a black background were reviewed frame by frame by investigators analyzing flow dynamics. At the same time, the artificial intelligence (AI) program has 2 models (build on Python), The model 1 was built based on U-net and Densenet-121 for vessel segmentation. Model 2 was used for classification of stagnant flow or normal, the model 2 was trained based on the convolutional neural network with the dataset selected from model 1 results.

Results
In total, 50 patients were included with a total of 50 pairs of angiograms. In 80% patients, the diameter of the distal segment of the LAD was 20% smaller in BB compared with before BB (p≤0.05). In 75%, the speed of the coronary after BB was lower (p&lt;0.05), A lower speed guaranteed laminar flow and less chance for cavitation. The above data was confirmed by the AI programs.

Conclusion
BB improved the coronary flow by decreasing the diameter of the arteries so decreased the turbulent flow and promoted laminar flow. BB also decreased the speed of the flow so decreased the chance for cavitation. Both decreased the possibility of ACS.

Funding Acknowledgement
Type of funding sources: None. Artery with centerlineMeasuring the diameter of the artery by
Analysis of telephone demand in a heart failure unit: something more than a simple call
Authors: Luna M , Cruzado Alvarez C , Perez Cabeza A I , Robles Mezcua A , Martinez Carmona J D , Diaz Exposito A , Gomez Doblas J J , Jimenez Rubio C , Morcillo Hidalgo L , Garcia Pinilla J M 
Published: October 2021

Abstract

Introduction
Specific care programs for HF patients significantly reduce readmissions, which is why they are recommended in clinical practice guidelines with the highest level of evidence. Telephone assistance is a service offered to patients within these programs.

Purpose
The main objective was to evaluate the most frequent reasons for consultation and the ability to resolve them after the call.

Methods
This is a descriptive, retrospective study of all the telephone consultations registered between June 2020 and January 2021. The calls are attended by the HF consultation nurse, commenting with Cardiology on those that imply changes in the pharmacological treatment.
Sociodemographic and clinical variables, reasons for the call and their frequency were collected. Categorical variables were expressed as percentages and quantitative variables as means ± standard deviation.

Results
During the analyzed period, 1.608 consultations were attended, 494 were telephone calls, which represents 31% of the overall activity of the nursing consultation. 423 consultations were analyzed, 55.7% (235) reactive, and 44.3% (187) proactive. 72.5% of the patients were under follow-up by the nurse, compared to 27.5% who had completed drug titration.
The mean age was 65 (± 12.3) years, 65.6% were men, 98.4% had a caregiver, 77% of the patients had an LVEF &lt;40%, Charlson modified mean 4.7 (± 3.6) and 92.3% were on treatment with beta-blockers, 89.1% with ACE inhibitors/ARBs/ARNI and 82.3% with MRA. The mean number of drugs per patient was 8.6 (± 3).
Reasons for the reactive calls were in 46% of the cases the consultation of symptoms, 20% to consult doubts about the treatment or procedures, 16% for problems related to the prescription of pharmacological treatment and 14% for the appointment management.
Reasons for proactive calls were 40% for symptoms control, 30.5% for appointment management, 27.3% for drug titration and 2.1% related to other causes.
When the reason for consultation was the appearance of symptoms, the mean number of calls required was 1.4 (± 0.8), 77.6% of the calls were solved through the telephone, 16.4% required a face-to-face visit in the nursing consultation and 2.7% were referred to the emergency room. Queries related to doubts, problems with the prescription or appointment management were solved in a single telephone consultation.

Conclusions
The most common telephone request when the patient made the call was the worsening of HF symptoms. The telephone consultation is presented as an effective tool in these cases, by favoring the accessibility of patients and avoiding unnecessary trips to the health center.

Funding Acknowledgement
Type of funding sources: None. Table 1. Descriptive details of patientsTable 2. Call reasons
Using a machine learning algorithm to detect depressed ejection fraction from a single-lead ECG
Authors: Guo L , Le L , Kieu S , Tiwari U , Currie C , Shenthar J , Padmanabhan D , Pressman G , Maidens J , Saltman A 
Published: October 2021

Abstract

Background
Multiple studies demonstrate the benefit of intervention for left ventricular ejection fraction (LVEF) below 40%, so the development of a low ejection fraction algorithm to detect LVEF below 40% can aid in early screening of initial asymptomatic Heart Failure with reduced Ejection Fraction (HFrEF).

Objective
To demonstrate the performance of a low ejection fraction algorithm using single-lead ECG data to detect LVEF below 40%.

Methods
We collected 1325 single-lead ECG recordings (15s duration) at various chest positions using an electronic stethoscope from 197 patients. We analyzed these ECG recordings using a deep neural network model trained on individual leads extracted from a 12-lead ECG to discriminate left ventricular ejection fractions (EFs) above or below different thresholds. We compared the model output to ejection fraction measured using echocardiograms.

Results
Across all recordings from all patients, we obtained an AUROC of 0.89, with a sensitivity of 88% and specificity of 74% using a model output threshold of 0.35 (Figure 1). The AUROC of recordings taken at different orientations and stances ranged from 0.85 to 0.92 (Table 1), with a sensitivity of at least 78% and specificity of at least 66% at any orientation.

Conclusion
Using a single lead ECG measured by an electronic stethoscope and a deep neural network model, we were able to detect depressed ejection fraction (≤40%) with a sensitivity of 88% and specificity of 74%. This work demonstrates the utility of a low-cost electronic stethoscope and machine learning for early screening and detection of depressed left ventricular ejection fraction.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Eko Health
Cost burden and cost-effective analysis of the nationwide implementation of the Quality in Acute Stroke Care protocol in Australia
Authors: Marquina C M , Ademi Z A , Zomer E Z , Ofori-Asenso R O A , Tate R T , Liew D L 
Published: October 2021

Abstract

Background
The Quality in Acute Stroke Care (QASC) protocol is a multidisciplinary approach to implement evidence-based treatment after acute stroke that reduces death and disability.

Aim
This study sought to evaluate the cost-effectiveness of implementing the QASC protocol across Australia, from a healthcare and a societal perspective.

Methods
A decision-analytic model was constructed to reflect one-year outcomes post-stroke, aligned with the stroke severity categories of the modified Rankin scale (mRS). Decision analysis compared outcomes following implementation of the QASC protocol versus no implementation. Population data were extracted from Australian databases and data inputs regarding stroke incidence, costs, and utilities were drawn from published sources. The analysis assumed a progressive uptake and efficacy of the QASC protocol over five years. Health benefits and costs were discounted by 5% annually. The cost of each year lived by an Australian, from a societal perspective, was based on the Australian Government's “value of statistical life year” (AUD 213,000).

Results
Over five years, the model predicted 263,722 strokes among the Australian population. The implementation of the QASC protocol was predicted to prevent 1,154 deaths and yield a gain of 876 years of life (0.003 per stroke), and 3,180 quality-adjusted life years (QALYs) (0.012 per stroke). There was an estimated net saving of AUD 65.2 million in healthcare costs (AUD 247 per stroke) and AUD 251.7 million in societal costs (AUD 955 per stroke).

Conclusions
Implementation of the QASC protocol in Australia represents both a dominant (cost-saving) strategy, from a healthcare and a societal perspective.

Funding Acknowledgement
Type of funding sources: None. Decision treePSA
Activation of GPER limits adverse changes to Ca2+ signalling and arrhythmogenic activity in cardiomyocytes of ovariectomised guinea pigs
Authors: Francis A J , Firth J M , Gorelik J , MacLeod K T 
Published: October 2021

Abstract

Background
Post-menopausal women have an enhanced risk of developing cardiovascular disease and disturbances of cardiac rhythm, generally attributed to declining oestrogen levels during menopause. In an animal model that mimics menopause, the long-term withdrawal of oestrogen dysregulated Ca2+ signalling and increased the formation of a pro-arrhythmic substrate. Selective targeting of the membrane bound G-protein coupled oestrogen receptor 1 (GPER) eliminated such arrhythmogenic activity associated with the loss of oestrogen.

Purpose
We aim to assess the “cardioprotective” role of GPER in response to oestrogen withdrawal.

Methods
Ovariectomy (OVx) or sham surgeries were conducted on female guinea pigs. Left ventricular cardiomyocytes were isolated 150-days post-operatively for experimental use. GPER expression was quantified by western blot. Myocytes were incubated in solutions containing GPER agonist G-1 for &gt;2h before recording some electrophysiological and Ca2+ regulatory parameters.

Results
GPER expression was 32% higher in OVx. OVx cardiomyocytes had prolonged action potential duration (APD) compared with sham and in the presence of G-1, APD90 shortened by 12% and 22% in sham and OVx, respectively. G-1 reduced early after depolarisation (EAD) formation by &gt;99% in OVx. OVx cells had larger sarcoplasmic reticulum (SR) Ca2+ content (by 13%), compared with sham. While G-1 had little effect on SR content, it reduced Ca2+ transient amplitude (by 40%), SR fractional release (by 11%) and sarcomere shortening (by 29%) in OVx cells. The frequency of occurrence of spontaneous Ca2+ waves evoked by periods of rapid stimulation reduced by 40% and wave-free survival time prolonged in OVx cells incubated with G-1.

Conclusions
In the hearts of an animal species whose electrophysiology and intracellular Ca2+ regulation is akin to humans, we show that following oestrogen deficiency, GPER expression increased and its activation induces negative inotropic responses in cardiomyocytes. It limits the adverse changes to Ca2+ signalling and induces anti-arrhythmogenic behaviours in OVx.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation
The role of obesity in structural and functional characteristics of left cardiac chambers
Authors: Trofimova E , Bogdanova A , Konstantinova E , Bogdanov A , Gilyarov M 
Published: October 2021

Abstract

Purpose of study
To evaluate the role of obesity in structural and functional characteristics of left cardiac chambers according to the echocardiographic study.

Materials and methods
The retrospective analysis of 1760 echocardiographic studies in patients 30–65 years old with hyperlipoproteinemia IIa and IIb types was evaluated. The body mass index (BMI) of the patients varied from normal to morbid obesity.

Results
The achieved results showed positive correlation between structural and functional heart characteristics and BMI. Anteroposterior size and BMI reliable correlated (KK=0,70, p&lt;0,05). In obese patients the thickness of left ventricular wall increased in 20% (1,25±0,15sm), compared to 1,0±0,19sm in patients with normal weight. The thickness of interventricular wall raised from 1,02±0,15sm to 1,23±0,14sm. End-diastolic volume in obese patients was higher than in normal weight patients (70±16 and 123±32,3sm3). End-systolic volume of left ventricle grows to 45% (from 30±8,5 to 54,3±20,5sm3). Impact volume in patients with obesity increased from 52±9,8 ml to 68,4±15,0ml. In patients with BMI 25–39.9kg/m2 the left ventricle mass myocardium index raised in 10%, and in patients with BMI over 40kg/m2 – more than 20%.
Concentric remodeling of left ventricle was found in 28,18% women and 43,39% men with normal BMI, in 30,76% women and 34,12% men with obesity, and in 15,9% women and 15,26% men with morbid obesity.
Concentric hypertrophy of left ventricle wall was diagnosed in 10% women and 10,74% men with normal BMI, in 33,38% women and 32,4% men with obesity and in 59,36% women and 54,82% men with morbid obesity.
Eccentric hypertrophy of left ventricle wall was diagnosed in 4,61% women and 2,89% men with normal BMI, in 9,42% women and 16,74% men with obesity and in 14,87% women and 25,9% men with morbid obesity. The proportion of women with normal LV geometry decreased more than 6 times as obesity progressed, proportion of men decreased by 9 times.

Conclusions
Thus, the typical presentation of structural and functional changes in the left heart chambers of obesity is the combination of concentric hypertrophy and/or remodeling of LV myocardium, diastolic LV dysfunction and dilatation of the left atrium. All these changes are the basis for the formation of dilated cardiopathy in obesity.

Funding Acknowledgement
Type of funding sources: None.