bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3814An analysis of Medicare reimbursement rates in cardiology from 2000 to 2018
Authors: Bhatt S , Haglin J , Tseng A S , Mishark K 
Published: October 2019

Abstract

Background
There is a paucity of data regarding financial trends for procedural reimbursement in the field of cardiology. A comprehensive understanding of such trends is important as continued progress is made to advance agreeable reimbursement models in cardiology while maintaining quality of care.

Purpose
To evaluate monetary trends in Medicare reimbursement rates for 10 commonly utilized cardiology procedures from 2000 to 2018.

Methods
Reimbursement data was extracted using The Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services of the 10 included Current Procedural Terminology (CPT) codes in cardiology. The utilized CPT codes included each of the top two most frequently billed codes in the echocardiology, catheterization, pacemaker, electrophysiology, and device integrations divisions of our local cardiology department during the 2017 calendar year. All monetary data for each code was adjusted for inflation to 2018 US dollars (USD) utilizing changes to the United States consumer price index (CPI). If the code was redefined throughout the study period, the correct replacement code was utilized for each year as defined by the procedure. The R-squared and both the average annual and the total percentage change in reimbursement were calculated based on these adjusted trends for all included procedures.

Results
After adjusting for inflation, the average reimbursement for all procedures decreased by 38.2% from 2000 to 2018. The greatest mean decrease was observed in transthoracic echocardiogram (−64.4%). The only procedure with an increased adjusted reimbursement rate throughout the study period was biopsy of heart lining (+60.4%). From 2000 to 2018, the adjusted reimbursement rate for all included procedures decreased by an average of 2.8% each year, with an average R-squared value of 0.81, indicating a stable decline throughout the study period.

Conclusion
This is the first study to evaluate trends in procedural Medicare reimbursement for cardiology. When adjusted for inflation, Medicare reimbursement for included procedures has steadily decreased from 2000 to 2018. Increased awareness and consideration of these trends will be important for policy-makers, hospitals, and surgeons in order to assure continued access to meaningful cardiology care both at the local and global level.
P3817Predictors of controlled CD4 count and blood pressure in an integrated chronic disease management model in a rural South African setting
Authors: Ameh S , Klipstein-Grobusch K , Kahn K , Tollman S , Gomez-Olive F X 
Published: October 2019

Abstract

Background
South Africa is undergoing an epidemiological transition with a dual burden of chronic communicable and non-communicable diseases. A pilot integrated chronic disease management (ICDM) model was initiated in 2011 by the National Department of Health in selected primary health care (PHC) facilities. The aim of the ICDM model is to leverage an established HIV treatment programme for non-communicable diseases (NCDs) for better health outcomes of patients with chronic diseases.

Purpose
This study determined predictors of controlled CD4 count and blood pressure (BP) in hypertension and HIV patients receiving antihypertension medication and antiretroviral drugs, respectively in PHC facilities in the Bushbuckridge sub-district of Mpumalanga province, South Africa.

Methods
This was a panel study to assess the effectiveness of the ICDM model in controlling patients' CD4 count and BP. Patients ≥18 years were recruited through a three-step sampling process into the ICDM model facilities (n=435) and comparison facilities (n=443) in the Bushbuckridge sub-district. Health outcome data (BP and CD4 counts) for each patient were retrieved from health facility records over 30 months (January 2011 to June 2013). Control of BP and CD4 counts were defined as BP <140/90 mmHg and CD4 counts >350 cells/mm3, respectively. Multilevel logistic regression analyses were conducted to determine predictors of controlled CD4 count and controlled hypertension. Data were analysed using Stata 14 statistical software.

Results
The odds of controlling CD4 count were increased by reception of care at the ICDM model facilities (OR=4.05, 95% CI: 2.77–5.92), but decreased by male gender (OR=0.52, 95% CI: 0.34–0.80). The odds of controlling hypertension were higher with increasing age: 40–49 years (OR=6.02, 95% CI: 2.07–17.57); 50–59 years (OR=23.17, 95% CI: 7.46–72.16); ≥60 years (OR=77.48, 95% CI: 25.03–82.26), but decreased by male gender (OR=0.38, 95% CI: 0.21–0.69).

Conclusion
Application of the ICDM model appeared effective in controlling patients' CD4 counts, but not their BP; hence, the HIV programme should be more extensively leveraged for hypertension treatment in health facilities in the study setting. Health education programmes to improve HIV treatment outcomes should focus on males. Hypertension educational programmes should target younger males in the study setting.

Acknowledgement/Funding
Fogarty International Centre of the National Institutes of Health under the Award number D43 TW008330
P3819Machine learning for predicting early left ventricular abnormalities in the general population
Authors: Kuznetsova T , Cauwenberghs N , Haddad F , Alonso-Betanzos A , Vens C 
Published: October 2019

Abstract

Background
Current heart failure guidelines emphasize the importance of timely detection of subclinical left ventricular (LV) remodelling and dysfunction for more precise risk stratification of asymptomatic subjects. Both LV diastolic dysfunction (LVDD) and LV hypertrophy (LVH) as assessed by echocardiography are known independent prognostic markers of future cardiovascular events in the community. However, selective screening strategies of individuals at risk who would benefit most from in-depth cardiac phenotyping are lacking.

Purpose
We assess the utility of several Machine Learning (ML) classifiers built on clinical and biochemical features for detecting subclinical LV abnormalities.

Methods
We included 1407 participants (mean age, 51 years, 51% women) randomly recruited from the general population. We used echocardiographic parameters reflecting LV diastolic function and structure to define LV abnormalities (LVDD, n=239; LVH, n=135). After that four supervised ML algorithms (Random Forest (RF), Gradient Boosting (GD), Stochastic Gradient Descent (SGD) and Support Vector Machines (SV)) were built based on routine clinical, hemodynamic and laboratory data (features; n=61) to categorize LVDD and LVH (two prediction tasks). We applied a 10-fold stratified cross-validation set-up.

Results
ML classifiers exhibited a high area under the ROC (AUC) for predicting LVDD with values between 88.5% and 93.1% (Figure, left panel). Age, BMI, different components of blood pressure, antihypertensive treatment, routine biomarkers such as serum electrolytes, creatinine, blood sugar, leptin, uric acid, lipid profile, as well as blood cell counts were the top selected features for predicting LVDD. Prediction AUC of ML algorithms for detection of LVH was somewhat lower than for LVDD and ranged from 72.5% to 78.7% (Figure, right panel). The top selected features for LVH classifier were similar to those of LVDD, but also included social class, serum gamma-glutamyl transferase, fasting insulin, plasma renin activity and cortisol.
ROC curves (sensitivity-1-specificity)

Conclusions
ML algorithms combining routinely measured clinical and laboratory data have shown high accuracy of LVDD and LVH prediction. These ML classifiers might be useful to preselect individuals at risk for further in depth echocardiographic examination, monitoring and implementation of preventive strategies in order to delay transition to disease symptoms.
P3827Low dose of quinidine is effective to normalize the slow inactivation in mutant Kv4.3 channel identified in an early repolarization syndrome patient
Authors: Takayama K , Ding W G , Matsuura H , Horie M , Ohno S 
Published: October 2019

Abstract

Background
Early repolarization syndrome (ERS) is characterized by J-point elevation in the ECG and ventricular fibrillation (VF). Several mutations in genes encoding cardiac ion channels have been reported as the causes for ERS. For the treatment of ERS, clinical studies have shown that quinidine is effective for the suppression of electrical storm. However, the mechanism or the optimal concentration for quinidine to suppress the electrical storm has not been elucidated yet.

Purpose
The aim of the present study is to clarify pharmacological effect of quinidine on mutant Kv4.3 channel by electrophysiological analysis and to establish theoretically effective treatment for ERS.

Methods
A KCND3 mutation, p.G306A, identified heterozygously in a 12-year-old boy was examined by whole-cell patch-clamp methods using CHO cells. We performed functional analysis of the Kv4.3 channels encoded by KCND3 of wild-type (WT), heterozygous (WT/G306A), or homozygous (G306A) mutants. Pharmacological normalizing effects of quinidine to the WT and mutant channels were investigated by loading test in various concentration. The sensitivity of quinidine was evaluated in terms of the concentration of the clinical course and the loading test.

Results
The patient suffered VF while sleeping or under sedation. Significant J-point elevations in multiple leads were recorded and he was diagnosed as ERS. Quinidine administration in the serum concentration of 1.2 to 3.1 μM was effective to stop his VF storm. Mutant Kv4.3 currents showed significantly slow inactivation time course (Fig 1), which meant that the mutation caused the gain-of-function channel. Quinidine loading to the mutant Kv4.3 normalized the inactivation time course in concentration-dependent manner (Fig 2, 3). In the loading concentration of 1 μM, the peak currents were not changed regardless of the voltage (Fig 4). The optimal serum concentration of quinidine in clinical use as multi-ion-channels blocker is 6 to 15 μM and the concentration was higher than that of the patient to stop the VF storm. The electrophysiological analysis showed that the low dose loading of quinidine was effective to prevent the gain-of function change of mutant Kv4.3 channels.
Electrophysiological analysis

Conclusions
We showed the pharmacological mechanism of quinidine against the mutant Kv4.3 channels identified in an ERS patient. Even the low concentration of quinidine was effective to normalize the slow inactivation, gain-of-function, in mutant Kv4.3 channels. Our data would be helpful to confirm the optimal concentration of quinidine for ERS patients to avoid adverse effect.
P3832Dantrolene reduces CaMKII-mediated arrhythmogenesis
Authors: Mustroph J , Pabel S , Stehle T , Lebek S , Neef S , Maier L S , Sossalla S 
Published: October 2019

Abstract

Rationale
In atrial and ventricular rhythm disorders, an increased diastolic sarcoplasmatic reticulum (SR) calcium leak can induce a depolarizing transient inward current, serving as a trigger for cellular arrhythmias. Dantrolene has been shown to also stabilize the cardiac ryanodine receptor. However, the detailed mechanism of the mode of action remains unknown. This study aims to investigate the effects of dantrolene on calcium/calmodulin-dependent kinase II (CaMKII) mediated arrhythmogenesis.

Methods and results
Right atrial cardiomyocytes (CM) were isolated from patients with atrial fibrillation. To investigate SR Ca2+ leak, measurements of diastolic SR Ca2+ sparks were performed by confocal microscopy using Fluo-4 AM. Dantrolene (10 μmol/l) potently reduced Ca2+-spark-frequency (CaSpF) by 90±26% (p<0.05, n=21 cells dantrolene vs. 19 cells control) leading to a reduction of the calculated diastolic SR-Ca2+-leak by 91±31% (p<0.05, n=21 vs. 19). Interestingly, CaMKII-inhibition using Autocamtide-2-Related Inhibitory Peptide (AIP) did not further reduced SR Ca2+ leak compared to dantrolene alone in human cardiomyocytes. This observation may suggest (secondary) inhibitory effects of dantrolene on CaMKII. To elucidate the role of CaMKII in dantrolene-mediated antiarrhythmic effects, we investigated atrial CM from mice overexpressing CaMKII (TG) and respective wildtype controls (WT). CaSpF and SR Ca2+ leak were reduced by dantrolene in both TG and WT mice (p<0.005, TG: dantrolene vs. vehicle n=132 vs 127 cells (9 mice); WT: dantrolene vs. vehicle n=61 vs 61 cells (5 mice)). However, proarrhythmogenic Ca2+ waves were only significantly reduced by dantrolene in TG mice (p<0.05, TG: dantrolene vs. vehicle 10.8% vs. 26.2%, n=154 vs 164 cells). Correspondingly, the incidence of delayed afterdepolarizations (DADs) in TG cells was significantly diminished by dantrolene (p<0.05, TG: dantrolene vs. vehicle 1/14 vs. 9/15 cells, n=5 mice). In contrast, DADs were not reduced by dantrolene in WT cells without increased CaMKII activity (p=n.s., WT: dantrolene vs vehicle 3/16 vs 2/13 cells, n=5 mice). In preliminary in vivo experiments, intraperitoneal injection of 40 mg/kg body weight dantrolene reduced the inducibility of arrhythmias by ventricular burst stimulation in CaMKII TG mice compared to vehicle (dantrolene 0/2 mice vs. vehicle 2/2 mice, p<0.05 Chi-Square).

Conclusion
Dantrolene beneficially altered Ca2+ homeostasis in human AF CM and murine CM. Dantrolene seems to exert its antiarrhythmic potential in a CaMKII-dependent manner. Thus, dantrolene as an already clinically approved compound might be a potential antiarrhythmic drug that merits clinical investigation.

Acknowledgement/Funding
Deutsche Forschungsgemeinschaft (MA 1981/5-1 and 7-1 to LSM). Marga und Walter Boll-Stiftung (SS).
P3844Percutaneous coronary intervention in the age of frailty
Authors: Bergami M , Manfrini O , Cenko E , Kedev S , Vavlukis M , Vasiljevic Z , Zdravkovic M , Scarpone M , Milicic D , Badimon L , Bugiardini R 
Published: October 2019

Abstract

Background
Although guidelines from the European Society of Cardiology and American Heart Association/American College of Cardiology recommend early percutaneous coronary intervention (PCI) in all patients with non-ST-elevation myocardial infarction/ unstable angina (NSTE-ACS), in day-to-day practice persists uncertainty as to whether to follow guidelines in patients aged 75 years or older. Indeed, recommendations are based on large randomized trials where patients aged 75 years or older are under-represented.

Purpose
We aimed to investigate whether patients aged 75 years or older would benefit from an early invasive strategy versus a conservative strategy. We also analyzed the factors associated with the choice of an early PCI in this population.

Methods
The research was conducted on the population of the International Survey of Acute Coronary Syndromes (ISACS-TC) registry. The study population consisted of 6826 eligible patients with NSTE-ACS. Of these patients, 1496 were 75 years old or older and were included in the analysis. The primary outcome measure was 30-day mortality. Key secondary outcomes were bleeding complications during the index hospitalization. Multivariate logistic regression analyses were conducted to establish outcomes and factors associated with outcomes. We evaluated specific ranges of ages: 75–79 years, 80–84 years, and 85 years or over. Further, data were sorted by sex and diabetes mellitus status.

Results
The mean age of our study population was 80.0 (interquartile range: 77–82) years old. Elderly patients treated with early PCI and medical therapy were significantly younger than those treated with only medical therapy were (78.9 vs 80.5, p<0.001), with each one-year increase in age corresponding to a 7% reduction in likelihood of receiving invasive treatment (OR 0.93, 95% CI 0.91–0.96). Crude 30-day mortality was significantly lower in the overall invasively managed population (5.4% vs 13.1%, p<0.001). After multivariable logistic adjustment for demographic and clinical features, early PCI was associated with lower mortality (OR 0.47, 95% CI 0.30–0.76). No significant differences in outcomes were observed between sexes (interaction, p=0.54) or by the presence of diabetes mellitus (interaction, p=0.61). In addition, no differences were seen among age groups (75–79 vs 80–84, interaction p=0.47; group 80–84 vs ≥85, interaction p=0.69). In early PCI, the group between 75–79 years had 5 (1.6%) major and 5 (1.6%) minor bleeding complications whereas the older groups had 1 (1.1%) and 1 (2.7%) major and 3 (3.2%) and 2 (5.4%) minor bleeding complications for patients aged 80–84 and ≥85, respectively.

Conclusions
In the real-life clinical setting, early PCI is a safe and efficacious treatment option in very elderly patients presenting with NSTE-ACS. Revascularization is better than medical therapy whatever the age is.
P4139Prediction of atrial fibrillation in embolic stroke of unknown source
Authors: Range F T , Peters D P , Zeus T , Jander S , Mueller P , Kelm M 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) is one of the leading cardiogenic causes for embolic stroke of unknown source (ESUS). Its incidence is growing with patients' age. Detection and rule out of AF is complex and cumbersome. The best method is an implantable loop recorder (ILR). In patients elder than 60 years, incidence of AF is reported incongruently and reliable patient characteristics that can predict a low or high risk for AF are scarce.

Purpose
This study reports real life incidences of AF in a group of patients undergoing ILR after ESUS. It aims to depict age dependency of AF and to identify potential confounding factors.

Methods
In a single center study, we analysed 111 patients (age=62±13 years, nmale=65) who received an ILR in our centre following ESUS. Patient characteristics, brain imaging, hemodynamic monitoring, blood pressure, electrocardiography, holter ecg and echocardiography data from the initial hospital stay and ILR follow-up over a mean of 460 days were analysed. Primary endpoint was the recording of AF during follow-up.

Results
AF was detected in 23% of all patients. Patients with AF were significantly elder than those without AF (p=0.01). Incidence of AF was in Patients <60y: 14%, 60–69y: 13%, 70–79y: 45%, >80y: 67%. We observed a significant difference in AF incidence comparing patients younger and elder than 70 years (p=0.034).
Both, CHADS-Vasc (p=0.036) and HATCH-scores (p=0.018) were higher in the AF group while the simple CHADS2 Score missed significance (p=0.068). PQ duration was longer in AF patients (p=0.022) and baseline heart rate at admission was lower (p=0.027). NIHSS scores were lower in the AF group at admission (2.97 vs. 4.10; p=0.049) but due to less neurological improvement in the AF group, this difference faded until dismission (1.09 vs 1.79 p=ns).

Conclusions
In our real life ILR group following ESUS, strongest predictor of AF was age. Pivot point rather was at 70 than at 60 years of age.
P4144Pericyte-specific deletion of ninjurin1 induces abnormal vasa vasorum formation and persistent inflammation and enhances intimal hyperplasia of injured vasculature
Authors: Horiuchi K , Minoshima A , Kabara M , Kano K , Tomita Y , Yoshida Y , Hayasaka T , Takehara N , Hasebe N , Kawabe J 
Published: October 2019

Abstract

Introduction
Atherosclerosis is fundamental pathological condition inducing severe ischemic diseases such as ischemic heart disease and stroke. New concept has been proposed that adventitial abnormalities including enhanced malformation of adventitial microvessel, vasa vasorum are associated with development and vulnerability of atherosclerotic plaque. However, the role of vasa vasorum malformation in vascular remodelling has not been fully clarified. We recently reported that Ninjurin1 (Ninj1) is critical adhesion molecule to associate pericytes (PCs) with endothelial (EC) tubes to form stabilized mature neovessels. The purpose of this study is to examine if formation of adventitial microvessels affects the vascular remodelling of injured vessels using PCs-specific Ninj1 deletion mouse model.

Methods and results
Deletion of Ninj1 gene in NG2-positive PCs was induced by tamoxifen (Tam)-treated NG2-CreER/Ninj1loxp mice (Ninj1KO, n=9). Tam-treated-NG2-CreER (n=4) or Tam-nontreated NG2-CreER/Ninj1loxp (n=5) mice were used as Control (Ct1 and Ct2 respectively). Femoral arteries were injured by insertion of coiled wire. After 4 weeks of surgery, blood vessels were stained by venous injection of FITC-lectin. Isolated femoral arteries were fixed with paraformaldehyde and decolorized with CUBIC reagent. Wire-mediated vessel injury induced intimal hyperplasia, as assessed by intima/media (I/M) ratio and accordingly grew microvessels in adventitia. Intimal hyperplasia in Ninj1KO were significantly enhanced compared to Controls. Although there was no significant difference in total length of adventitial microvessels among three groups, extravasation of FITC-lectin from adventitial microvessels were significantly enhanced in Ninj1KO. The number of infiltrated macrophages in adventitia were increased in Ninj1KO.

Conclusion
Deletion of Ninj1 in PCs contributes to formation of immature microvessels in adventitia of injured vasculature and to adventitial microbleeding, and subsequently enhances intimal hyperplasia. Ninj1 is an attractive target to normalize microvessels for anti-atherosclerotic therapy.
P4160Safety and efficacy of triple combination therapy with parenteral prostanoids in patients with Eisenmenger physiology
Authors: D'Alto M , Balint O H , Giannakoulas G , Romeo E , Argiento P , Farro A , Russo M G , Sarubbi B , Skoro-Sajer N , Gatzoulis M A , Dimopoulos K 
Published: October 2019

Abstract

Aim
While combination therapy is currently strongly advocated for idiopathic pulmonary arterial hypertension (PAH) patients, evidence to support its use in patients with PAH related to congenital heart disease (CHD), especially patients with Eisenmenger syndrome, is lacking. We evaluated the efficacy and safety of sequential triple combination therapy with parenteral prostanoids after failure of double oral therapy in patients with PAH-CHD and Eisenmenger physiology.

Methods
This is an international, multicentre, retrospective cohort study conducted in adult patients with Eisenmenger physiology on double oral PAH therapy in whom intravenous or subcutaneous prostanoid treatment was added due to clinical deterioration or failure to reach the treatment goals. Clinical status, 6-minute walk test distance (6MWD), biomarkers and haemodynamics were assessed at baseline and during the follow-up.

Results
A total 28 patients with Eisenmenger syndrome (6 [21%] male, age 37.6±14.3 years) were included. A post-tricuspid shunt was present in 16 (57%), 86% of whom had a ventricular septal defect. The majority (89%) were treated with subcutaneous treprostinil. At 27±14 months follow-up, WHO functional class improved in 18 (64%), remained unchanged in 8 (29%), and deteriorated in 2 (7%) patients. There was also an increase in 6MWD (mean 339±145 versus 233±140m, p=0.0001, fig 1A) and a reduction in NT-proBNP levels (median 1125 [123–5882] versus 3087 [234–7428] pg/mL, p<0.0001, fig 1B). On follow-up cardiac catheterization, an improvement in right atrial pressure (8±2 versus 11±5 mmHg, p=0.01), mean pulmonary artery pressure (68±12 versus 72±17 mmHg, p=0.005), cardiac index (2.3±0.3 versus 2.0±0.5 l/min/m2, p=0.005, fig 1C), and pulmonary vascular resistance (17±7 versus 21±10, p=0.008, fig 1D), was observed compared to baseline. No patients discontinued treatment. Five (18%) patients died during follow up.
Figure 1

Conclusions
Triple combination therapy with subcutaneous treprostinil or endovenous epoprostenol in patients with Eisenmenger syndrome is safe and well tolerated at 2 years follow-up, resulting in a significant improvement in clinical status, exercise tolerance and haemodynamics.