bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence in echocardiography diagnostics – detection of takotsubo syndrome
Authors: Di Vece D , Laumer F , Schwyzer M , Burkholz R , Corinzia L , Cammann V.L , Citro R , Bax J , Ghadri J.R , Buhmann J.M , Templin C 
Published: November 2020

Abstract

Background
Machine learning allows classifying diseases based only on raw echocardiographic imaging data and is therefore a landmark in the development of computer-assisted decision support systems in echocardiography.

Purpose
The present study sought to determine the value of deep (machine) learning systems for automatic discrimination of takotsubo syndrome and acute myocardial infarction.

Methods
Apical 2- and 4-chamber echocardiographic views of 110 patients with takotsubo syndrome and 110 patients with acute myocardial infarction were used in the development, training and validation of a deep learning approach, i.e. a convolutional autoencoder (CAE) for feature extraction followed by classical machine learning models for classification of the diseases.

Results
The deep learning model achieved an area under the receiver operating curve (AUC) of 0.801 with an overall accuracy of 74.5% for 5-fold cross validation evaluated on a clinically relevant dataset. In comparison, experienced cardiologists achieved AUCs in the range 0.678–0.740 and an average accuracy of 64.5% on the same dataset.

Conclusions
A real-time system for fully automated interpretation of echocardiographic videos was established and trained to differentiate takotsubo syndrome from acute myocardial infarction. The framework provides insight into the algorithms' decision process for physicians and yields new and valuable information on the manifestation of disease patterns in echocardiographic data. While our system was superior to cardiologists in echocardiography-based disease classification, further studies should be conducted in a larger patient population to prove its clinical application.

Funding Acknowledgement
Type of funding source: None
Selective beta-3 adrenergic receptor blockade increases contractility of human ventricular trabeculae from HFrEF donors
Authors: Nguyen N , Page G , Abi-Gerges N , Miller P.E , Adams J.W 
Published: November 2020

Abstract

Background
Alterations of the beta-adrenergic system have been extensively described in the setting of heart failure (HF). Upregulation of beta-3 adrenergic receptor (β3-AdrR) expression in human failing hearts depresses myocardial contractility and, during an acute decompensation event, can be considered a maladaptive compensatory mechanism that exacerbates cardiac dysfunction. APD418 is a selective β3-AdrR antagonist currently in development for patients who have acute heart failure with reduced ejection fraction (HFrEF). APD418 is designed to improve myocardial contractility by selectively antagonizing the β3-AdrR and thereby avoiding the cAMP/Ca2+ signaling pathway stimulated by current inotropes.

Purpose
This study evaluated the effect of a selective β3-AdrR antagonist (APD418) on contractile responses in explanted human ventricular trabeculae obtained from normal and HFrEF hearts.

Methods
Left ventricular trabeculae from normal and HFrEF donors were electrically stimulated (1 Hz) ex-vivo to analyze force generated during contractions. First, BRL37344, a selective β3-AdrR agonist, was applied at increasing concentrations (0.01–10 μM) to confirm β3-AdrR mediated negative inotropy in human myocardial tissue. To test the effect of a selective β3-AdrR antagonist on contractile force, myocardial tissue was pre-treated with APD418 or vehicle for 5 minutes, followed by treatment with non-selective β-AdrR agonists isoproterenol (10 nM) or norepinephrine (5 μM).

Results
In heart tissue from normal donors, the β3-AdrR agonist BRL37344 did not affect contractile function at 0.01 and 0.1 μM. However, in heart tissue from HFrEF donors, BRL37344 induced a significant decrease in contractility at 0.01, 0.1 and 1 μM (85.9±1.8% with 0.1 μM BRL37344 vs 104.1±2.9% with vehicle). Selective blockade of β3-AdrR with APD418 had no effect on force of contraction induced by norepinephrine in cardiac tissue from normal donors. In contrast, APD418 potentiated the force of contraction induced by either isoproterenol (49.1±20.6% increase with 0.1 μM APD418 compared to baseline) or norepinephrine (26.5±4.9% increase with 0.01 μM APD418 compared to baseline) in cardiac tissue from HFrEF patients.

Conclusion
This is, to our knowledge, the first evidence showing that selective blockade of β3-AdrR increases contractility of human ventricular trabeculae from HFrEF donors and suggests that further studies evaluating the therapeutic benefit of APD418 in patients with HFrEF are warranted.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Arena Pharmaceuticals
Temporary assist devices in France 2014–2018: intra-aortic balloon pump: is the technique really outdated?
Authors: Roubille F , Akodad M , Delmas C , Bonnefoy-Cudraz E , Huet F , Leclercq F , Gaudard P , Rouviere P , Gandet T , Duflos C , Delseny D , Battistella P , Agullo A , Aguilhon S , Puymirat E 
Published: November 2020

Abstract

Aims
Intra-aortic balloon pump (IABP) utilization was expected to be quickly abandoned following the IABP-shock trial and its class III, level B of recommendation in the 2016 ESC guidelines. The aim of this study was to evaluate the use of IABP compared to other mechanical support devices in a nationwide approach.

Methods
We conducted a retrospective study based on the French national hospital discharge database. All patients implanted by an assist device either by IABP, extracorporeal membrane oxygenation (ECMO) or IMPELLA® from 2014 to 2018 (2 years before/2 years after the 2016 guidelines) were included. The primary endpoint was the incidence of IABP implantation over the years. Secondary endpoints were incidence of total assist devices implantations, ECMO and IMPELLA® implantation.

Results
From 2014 to 2018, a total of 18,872 patients benefited from mechanical support by IABP (n=6,637, 35.2%), ECMO (n=11,833, 62.7%) or IMPELLA® (n=402, 2.1%) in France. The incidence of total mechanical support implantations (ECMO and IABP) was constant over the years. IABP implantation decreased progressively from 1,725 implantations in 2014 to 976 in 2018 (−44%). By contrast, ECMO implantation increased progressively from 1,919 implantations in 2014 to 2,715 implantations in 2018 (+42%). IMPELLA® implantations remained stable over the years from 63 (1.7%) implantations in 2014 to 83 (2.1%) in 2018.

Conclusion
In this nationwide real-life study, despite a significant decline in IABP implantations over the years since the ESC guidelines, this device remained used in clinical practice with around 1,000 implantations in 2018. The size of the centers is not strictly correlated with this use, suggesting differential uses depending of the local background.

Funding Acknowledgement
Type of funding source: None
Mechanical circulatory support with impella in patients with non-acute myocardial infarction related cardiogenic shock
Authors: Haurand J , Bueter S , Jung C , Kelm M , Westenfeld R , Horn P 
Published: November 2020

Abstract

Background
Percutaneous left ventricular assist devices such as the Impella pump, are used to hemodynamically stabilize patients with cardiogenic shock (CS) caused by acute myocardial infarction (AMI) until cardiac function has recovered after revascularization. Whether Impella mechanical circulatory support (MCS) is effective in stabilizing patients with CS not caused by AMI has so far not been thoroughly investigated.

Purpose
The aim of this study is to analyze whether MCS with Impella is effective to stabilize patients with non-AMI related CS compared to patients with AMI related CS.

Method
We retrospectively analyzed 106 patients with CS and Impella support in the years from 2011 to 2018. Efficacy to stabilize the patient was assessed by laboratory values such as lactate, hemodynamic parameters and clinical scores. The difference in mortality was calculated with the Log-Rank-Test, comparing Kaplan-Meier curves.

Results
36 patients suffered from non-AMI CS and in 70 patients CS was caused by AMI. Regarding the clinical scores and hemodynamic parameters, both groups were severely ill, with no significant difference in APACHE II score, with a mean score of 17.9 in the non-AMI group compared to 20.5 in the AMI-group (p=0.103), the SOFA score (mean score of 6.3 in non-AMI group vs 6.8 in AMI group, p=0.467) and cardiac index (mean CI of 1.9 l/min/m2 in non-AMI group vs 2.2 l/min/m2 in AMI group, p=0.176). There was a comparable mean decrease in lactate levels in both groups 48 hours after initiation of MCS, from initially 4.1 mmol/l to 1.7 mmol/l (p&lt;0.001) in the non-AMI group and from initially 3.6 mmol/l to 2.2 mmol/l (p=0.025) in the AMI group. The non-ACS group exhibited a trend of lower mortality compared to the AMI group, with 47% in the non-AMI group and 57% in the AMI group (p=0.067). In multivariate analysis, age, lactate levels, cardiopulmonary resuscitation, low platelets and higher doses of inotropes and vasopressors were independent predictors for mortality. An upgrade to LVAD was performed for 22% of the non-AMI group and for 6% of the AMI group (p=0.020).

Conclusion
Impella support is effective to hemodynamically stabilize patients with non-AMI related CS. Therefore, MCS can be used as bridge to recovery or enables further treatment options as upgrade to longterm mechanical support devices.

Funding Acknowledgement
Type of funding source: None
Intra-aortic balloon pump as a bridge therapy to heart transplant in refractory heart failure
Authors: Boros G.A.B , Bellini V.S.C , Fatori D , Bernoche C , Macatrao-Costa M.F , Lopes L.N.G.D , Bacal F , Hueb W , Kopel L , Lage S.G 
Published: November 2020

Abstract

Background
The role of intra-aortic balloon pump (IABP) in advanced heart failure (HF) treatment is still under debate. Some heart transplant (HTx) candidates on the waiting list require mechanical support, and IABP may be the simple and most available device.

Purpose
Describe the impact of IABP treatment in advanced HF patients who underwent HTx.

Methods
We retrospectively analysis patients who underwent HTx from a single center intensive care unit (ICU), between 2009 and 2018, to evaluate the use of IABP as bridge therapy. Selection included decompensated chronic HF patients that required intensive care with optimized intravenous drugs before IABP placement. Exclusion criteria were acute myocardial infarction or cardiac surgery 90 days prior to admission, and implant of ventricular assist device before HTx.

Results
We included 134 HF patients with IABP therapy before HTx. Insertion site was exclusively femoral. Mean time of IABP onset to HTx were 26±21 days, and hospital admission to HTx 65±45 days. The main cardiomyopathy etiology was Chagas Disease (46%) and mean LVEF was 23±6% (TABLE 1). Clinical and laboratory data were compared before and 96 hours after IABP therapy. Mean central venous oxygen saturation (SvO2) increased from 49.7±14.6% to 67.4±11.3% (p&lt;0.001), creatinine decreased from 1.77±0.9 mg/dL to 1.40±0.6 mg/dL (p&lt;0.001), and urine output increased from 1552±886 mL/24h to 2189±1029 mL/24h (p&lt;0.001). These differences were sustained or improved until the day before HTx (FIGURE 1). After 96 hours dobutamine was maintained in 98% of patients, nitroprusside increased from 56% to 67%, milrinone decreased from 26% to 20%, and norepinephrine decreased from 18% to 3%. Significant IABP complications were few (5.2%; n=7: 3 infections, 2 major bleeding, 2 arterial injury).

Conclusion
In this single center ICU sample, IABP improved hemodynamic status and renal function in refractory HF patients waiting for HTx. IABP can be a reasonable, available and effective bridging therapy.
Figure 1

Funding Acknowledgement
Type of funding source: None
Coronary flow velocity reserve predicts adverse outcome in patients with angina and no obstructive coronary artery disease
Authors: Schroder J , Michelsen M.M , Mygind N.D , Frestad D , Suhrs H.E , Bove K.B , Aziz A , Hansen H.S , Hansen P.R , Gustafsson I , Kastrup J , Prescott E 
Published: November 2020

Abstract

Background
Many patients with angina do not have obstructive coronary artery disease (CAD) when evaluated with coronary angiography. It is unknown whether echocardiographic coronary flow velocity reserve (CFVR) predicts an adverse outcome in these subjects. Previous CFVR studies have included heterogeneous patient subtypes both with and without CAD.

Purpose
To assess whether reduced CFVR predicts adverse outcome in women with angina and no CAD.

Methods
We evaluated 1853 women with angina and a coronary angiogram without stenosis. Exclusion criteria were previous myocardial infarction, coronary revascularisation, heart failure or valvular disease. Coronary microvascular function was assessed by echocardiographic CFVR. All patients were followed up for major adverse cardiovascular events.

Results
CFVR was obtained in 1681 patients (91%), median CFVR was 2.33 (IQR 2.00–2.74). During a median follow-up of 4.48 years, 96 adverse events occurred (acute myocardial infarction: 25; heart failure: 21; revascularisation: 8; stroke: 32; cardiovascular death: 10). In univariate Cox regression, CFVR (hazard ratio [HR] 2.04 [95% CI 1.39–2.94] per unit decrease in CFVR; p&lt;0.001), hypertension (HR 2.29 [95% CI 1.46–3.59]; p&lt;0.001) and diabetes (HR 2.13 [95% CI 1.31–3.45]; p=0.002) were associated with adverse outcome. These associations remained in age-adjusted multivariable regression. Exploratory analyses identified CFVR=2.24 as the optimal discriminating threshold. Stratification according to reduced CFVR and hypertension identified subgroups with better, intermediate and worse outcome (Figure 1). Outcome analyses excluding stroke yielded similar results.

Conclusion
Impaired CFVR predicts adverse outcome in women with angina and no CAD. Integrating CFVR and hypertension identifies high-risk patients.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The Danish Heart Foundation
Distinct circulating cytokine levels in patients with angiography-proven coronary artery disease compared to disease-free controls
Authors: Maaniitty E , Sinisilta S , Jalkanen J , Hollmen M , Biancari F , Gunn J , Jalkanen S , Airaksinen K.E.J , Kiviniemi T.O 
Published: November 2020

Abstract

Background
Systemic inflammation has a critical role in the development of coronary artery disease (CAD). Identification of inflammatory pathways may provide a platform for novel therapeutic approaches.

Purpose
We sought to determine whether there are differences in circulating cytokine profiles between patients with CAD and disease-free controls.

Methods
Study population consisted of 458 patients who underwent diagnostic invasive coronary angiography for clinical indications. Altogether 312 patients had angiographically significant CAD whereas 146 had no angiographically-detected coronary atherosclerosis. We measured the serum concentrations of 48 circulating cytokines.

Results
Patients with CAD had increased levels of interleukin-1 receptor antagonist (IL-1-RA), interleukin-2 receptor alpha (IL-2Rα), IL-3, IL-4, IL-6, IL-9, IL-10, IL-16, IL-17, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), macrophage inflammatory protein-1-beta (MIP-1-β), tumor necrosis factor-alpha (TNF-α), TNF-β, cutaneous T-cell-attracting chemokine (CTACK), growth regulated oncogene alpha (GRO-α), hepatocyte growth factor (HGF), interferon alpha-2 (IFNα-2), leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), monokine induced by gamma interferon (MIG), beta-nerve growth factor (β-NGF), stem cell factor (SCF) and stromal cell-derived factor 1 alfa (SDF1α). On a logistic multivariate regression model adjusted with age, sex, hypertension and treatment for diabetes, increased levels of IL-4 (p=0.027, OR 1.090), IL-9 (p=0.000, OR 1.013), IL-17 (p=0.011, OR 1.005), CTACK (p=0.008, OR 1.001), MIP-1-β (p=0.004, OR 1.006), GRO-α (p=0.008, OR 1.004), TNF-α (p=0.019, OR 1.011) were independently associated with atherosclerosis.

Conclusions
Patients with CAD have distinct circulating cytokine profiles compared to disease-free controls. Based on these findings, certain cytokines may have a pivotal role in the development of atherosclerotic cardiovascular disease and cytokine-mediated pathway appear as a promising target for cardiovascular drug development.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Helsinki, Finland; The Finnish Foundation for Cardiovascular Research, Helsinki, Finland
Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention
Authors: He C , Lin K , Chen H , He H , Yang J , Zhang S , Guo Y , Chen J 
Published: November 2020

Abstract

Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention.

Objective
Contrast-induced nephropathy (CIN) remains a common complication of coronary procedure and increases poor outcomes, especially in patients with heart failure. Plasma volume expansion relates to worsening prognosis of heart failure. We hypothesised that calculated plasma volume status (PVS) might provide predictive utility for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention (PCI).

Methods
We enrolled 441 patients with heart failure undergoing PCI from 2012 to 2018. Pre-procedural PVS was calculated by comparing actual plasma volume (aPV) derived from the Hakim formula to ideal plasma volume (iPV). CIN was defined as an absolute SCr increase ≥0.5 mg/dl within 72h of contrast medium exposure. We assessed the association between PVS and risk of contrast-induced nephropathy in patients with heart failure undergoing elective PCI.

Results
In 441 patients, 28 (6.3%) patients developed CIN. The median pre-procedural PVS was −0.02 (−0.09–0.05). The best cutoff value of PVS for predicting CIN was 0.04 with 64.5% sensitivity and 75.5% specificity according to the ROC analysis (C statistic = 0.718; 95% CI: 0.674–0.760),of which predictive value is similar to NT-proBNP (C statistics 0.721 vs. 0.773, P=0.355). After adjusting for potential confounding risk factors, multivariable analysis demonstrated that PVS &gt;0.04 (OR=3.142, 95% CI: 1.185–8.332, P&lt;0.05) and NT-proBNP &gt;4518pg/ml (OR=7.591, 95% CI: 2.886–19.968, P&lt;0.05)were strong independent predictors of CIN.

Conclusion
Pre-procedural PVS is an independent risk factor for predicting CIN markedly, of which predictive value is comparable to BNP and also independent of BNP. The best cutoff point of PVS for predicting CIN was 0.04.
ROC for PVS and NT-proBNP to predict CIN

Funding Acknowledgement
Type of funding source: None
Association of Lipoprotein(a) levels with intrinsic and on-clopidogrel platelet reactivity
Authors: Kille A , Nuehrenberg T , Valina C.M , Neumann F.J , Hochholzer W 
Published: November 2020

Abstract

Background
Lipoprotein(a) [Lp(a)] is an independent, genetic, and causal risk factor for premature cardiovascular disease (CVD). Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its structural similarity to plasminogen. So far, the potential association of Lp(a) with platelet activation and reactivity has not been well established in larger clinical cohorts.

Methods
This secondary analysis of the EXCELSIOR study analyzed intrinsic platelet reactivity before loading with clopidogrel 600mg and on-treatment platelet reactivity tested 24 hours following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry as final aggregation after 5 min following stimulation with 5μM ADP. Platelet reactivity was also assessed by flow cytometry (expression of CD62P and PAC1) following stimulation with ADP and TRAP. Levels of Lp(a) on admission of each patient were immediately measured from fresh samples in a central laboratory.

Results
The present analysis included 2046 patients. Levels of Lp(a) ranged between 0 and 332 mg/dl. Results for intrinsic (p=0.80) and on-clopidogrel platelet reactivity (p=0.81) did not differ between quartiles of Lp(a) levels (Figure). Flow cytometry analyses confirmed these findings.

Conclusion
The present data do not support the hypothesis of an interaction of Lp(a) with platelet function. This finding might be important to define the safety of evolving therapeutic options for lowering Lp(a).

Funding Acknowledgement
Type of funding source: None
The prognostic impact of coronary calcium score in low risk patients presenting with chest pain; a 6-year follow-up single center study
Authors: Thalamus J , Gibbs C.C , Topper M.E , Oestvold C , Heldal K , Solli J.D , Motswakadikgwa T , Tobiasson K.A , Aasegard H , Hysing J , Haugaa K.H 
Published: November 2020

Abstract

Background
Evaluation and risk stratification of patients with chest pain is a frequent task in cardiology. Coronary artery calcium is an established risk marker and is in wide clinical use. However, less is known about the long-term prognostic implications of coronary calcium score values in low risk individuals.

Purpose
We wanted to investigate the long-term outcome related to coronary artery calcium score (CAC).

Methods
We included patients who were examined with coronary CT angiography or GT SPECT from August 2011 to August 2015. The coronary calcium score percentile was calculated using the MESA Coronary Artery Calcium (CAC) Score Reference Values web tool. We excluded patients already stratified as high risk due to previous myocardial infarction or coronary revascularization. The primary endpoint was a composite of 5 point MACE (death, myocardial infarction, PCI, CABG and stroke) and was extracted from the electronic medical records. We censored follow up on the 31st December 2018.

Results
We included 1975 patients (958 (48.5%) male, age 60.3±12.0). The average CAC was 288±701. After median follow up of 6.0 (5.3–6.5 IQR) years, 372 patients fulfilled a primary endpoint. Event rate increased significantly with higher percentiles of CAC score (log rank 0.001, Figure 1). A total of 687 patients had a CAC score of 0. In this group we observed only 21 events during 6 years follow up, giving an annual event rate of 0.6%. Annual event rate in the patients with CAC percentile 1–75 was 3.2% and in the patients with CAC percentile 75–99 annual event rate was 5.6%. Death occurred in 10% of patients in the two upper percentiles compared to only 2% in the lowest percentile (p&lt;0.001)

Conclusion
Our findings support that CAC is a powerful predictor of coronary artery events. Furthermore, our study confirms excellent long term prognosis regarding cardiac events in patients with 0 CAC, which is helpful in risk stratification of patients with chest pain.
Figure 1

Funding Acknowledgement
Type of funding source: None