bluuebunny/crossref_metadata_2025_split huggingface dataset:
4302Machine-learning integration of complex echocardiographic patterns and clinical parameters from cohorts and trials
Authors: Cikes M , Sanchez Martinez S , Claggett B , Solomon S D , Bijnens B 
Published: October 2019

Abstract

Introduction
Contemporary machine learning (ML) allows comparing individuals based on a wide range of heterogenous data. We aimed to use similarity-based unsupervised ML to integrate clinical variables and complex imaging patterns from a population-based cohort (Atherosclerosis Risk in Communities study - ARIC) with a HFPEF (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist - TOPCAT) as well as a HFREF (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy - MADIT-CRT) clinical trial and to predict the outcome of the patients based on their location in the derived ML universe, rather than on their original cohort.

Methods
An unsupervised ML for dimensionality reduction algorithm (multiple kernel learning) was trained using 2123 subjects enrolled in ARIC. The algorithm positioned them based on similarities in longitudinal strain patterns of 12 LV regions and an LV volume curve, together with 17 clinical parameters (age, sex, myocardial infarct, QRS width, prior HF, LVEDVi, LAVi, race, heart rate, SBP, BP meds, diabetes, smoking status, BMI, GLS, LVMi, LVEF). Using the same descriptors, 105 untreated TOPCAT and 429 untreated MADIT-CRT patients were projected onto the learned space (upper-left figure). A k-means algorithm was subsequently used to partition the resulting space into 3 clusters (broadly speaking, the number of expected clinical categories: controls (ARIC), HFPEFs (TOPCAT) and HFREFs (MADIT-CRT) (upper-right figure). Finally, cluster-wise event rates (composite of death or HF hospitalization) were computed for the combination of the two trials (bottom-left figure) and only considering subjects from ARIC (bottom-right figure).

Results
The visualisation of the low-dimensional space (upper-left figure) showed a clear aggregation of individuals according to the study, highlighting their different clinical and deformation properties. The individuals located around the MADIT-CRT patients (predominantly in cluster 3) showed the highest event rate (26.6%, similar to the MADIT-CRT event rate 25.4%) while those around the majority of the ARIC cohort showed the lowest rates (5.3%, similar to the ARIC event rate 5.7%). The MADIT-CRT-like ARIC individuals showed a much higher event-rate compared to the one expected from the cohort (21.1% vs 5.7%).
Figure 1

Conclusion
Our results serve as a proof-of-concept that unsupervised ML based analysis of complex clinical and imaging data can be used to integrate patient-based data, including complex echocardiographic data, to project individuals onto a multi-dimensional space with event rates that track with multidimensional location.

Acknowledgement/Funding
ARIC and TOPCAT were funded by the National Heart, Lung and Blood Institute, MADIT-CRT by Boston Scientific
4308Lung ultrasound guided dry-weight probing reduces left and right atrial dimensions and left ventricular filling pressures in hemodialysis patients with hypertension
Authors: Loutradis C , Papadopoulos C E , Sachpekidis V , Pagourelias E , Ekart R , Krunic B , Toumpourleka M , Tsouchnikas I , Vassilikos V , Papagianni A , Zoccali C , Sarafidis P A 
Published: October 2019

Abstract

Introduction and purpose
Left ventricular hypertrophy and dysfunction is tightly associated with adverse outcome in hemodialysis. Hypertension and increased preload due to hypervolemia are major factors for these cardiac anomalies in hemodialysis. This study examined the effect of lung-ultrasound-guided dry-weight reduction on echocardiographic indices of left and right cardiac size, systolic and diastolic function in hypertensive hemodialysis patients.

Methods
This pilot, single-blind trial randomised 71 clinically euvolemic hypertensive hemodialysis patients in an active group (n=35), following a strategy for dry-weight reduction guided by the total number of US-B lines (US-B lines score) prior to a mid-week dialysis session, and a control group (n=36), following standard-of-care treatment. Among others, patients underwent two-dimensional and tissue-Doppler echocardiographic (TDI) at baseline and after 8-weeks.

Results
Overall, 19 (54.3%) patients in the active and 5 (13.9%) in the control group had UF intensification (p<0.001) during follow-up (US-B lines 5.3±12.5 vs +2.2±7.6, p<0.001, dry-weight: −0.71±1.39 vs +0.51±0.98 kg, p<0.001). Inferior vena cava diameter was reduced to a greater extend in the active compared to control group (−0.43±4.00 vs 0.71±4.82, p=0.033) at study-end. Reductions in LA and RA sizing parameters were greater in the active group (LA Surface: −1.09±4.61 vs 0.93±3.06 cm2, p=0.034; RA surface: −1.56±6.17 vs 0.47±2.31, p=0.024; LAVi: −2.43±13.14 vs 2.95±9.42 ml/m2, p=0.052). Reductions in LV end-diastolic diameter and volume were marginally greater in the active group. LV filling pressures significantly decreased in the active compared to the control group (E/e' LV: −0.38±3.14 vs 1.36±3.54, p=0.034; DT: 35.43±85.25 vs −18.44±50.69, p=0.002). Systolic function indices were unchanged in both groups. In multivariate analysis, US-B lines reduction was a powerful predictor (OR: 4.542, 95% CI: 1.266–16.292, p=0.020) of E/e' LV ratio decrease, among various factors examined.

Conclusions
A lung-ultrasound-guided strategy for dry-weight reduction can effectively reduce cardiac chambers dimensions and LV filling pressures without changing systolic performance during an 8-week follow-up in hypertensive hemodialysis patients.
4309Structural or functional left sided heart disease found on echocardiographic screening is associated with a higher risk of death in patients with end stage renal disease receiving haemodialysis
Authors: Axelsson Raja A , Lange Nielsen T , Plesner L L , Warming P E , Ersboll M , Dalsgaard M , Schou M , Rydahl C , Brandi L , Iversen K 
Published: October 2019

Abstract

Introduction
Cardiovascular disease is the leading cause of death in patients with end-stage renal disease on haemodialysis. Guidelines recommend echocardiography in all incident patients on dialysis and every three years, or when considered for kidney transplantation. The prognostic value of significant valve disease or reduced systolic function detected by echocardiographic screening is however not clear.

Purpose
We aimed to test the hypothesis that structural heart disease in an unselected, contemporary population of patients on maintenance dialysis is associated to a higher risk of death.

Methods
Adult chronic haemodialysis patients in two large dialysis centers had transthoracic echocardiography performed immediately prior to dialysis and were followed prospectively. Significant structural or functional left sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%.

Results
Among the 247 included patients (66 [IQR 64–67] years of age, 68% male), 54 (22%) had significant structural or functional left sided heart disease. An LVEF ≤40% was observed in 31 patients (13%). Severe or moderate aortic stenosis was present in 4 (2%) and 16 (7%) patients respectively, moderate mitral regurgitation in 4 (2%) patients and mitral stenosis in one (0.4%) patient. In more than half of the patients (56%), significant structural or functional left sided heart disease was not recognized prior to the study. After 2.8 years of follow-up, all-cause mortality was 52% for patients with significant heart disease and 32% for patients without significant structural heart disease (hazard ratio [HR] 1.95 (95% CI 1.25–3.06) (Figure). On multivariable adjusted Cox proportional hazard analysis, including age, sex, ischemic heart disease, diabetes, hypertension and time on dialysis, structural heart disease was an independent predictor of mortality with a HR of 1.60 (95% CI 1.01–2.55) along with age (HR per year 1.05 [95% CI 1.03–1.07]).
Kaplan-Meier estimate of survival

Conclusion
Left ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage renal failure on haemodialysis and are associated with a higher risk of death.
4332Benefit of sinus rhythm restoration in acute decompensated heart failure patients with atrial tachyarrhythmia treated with landiolol
Authors: Sakai M , Suzuki A , Shiga T , Tanaka Y , Kouno E , Osada A , Matsuura J , Hayashi N , Matsui Y , Hagiwara N 
Published: October 2019

Abstract

Background
Atrial tachyarrhythmias (ATA), such as atrial fibrillation / atrial tachycardia are frequently observed in patients with acute decompensated heart failure (ADHF). Because ATA leads to clinical deterioration and worsen HF, the conversion and prevention of ATA is important of ADHF with ATA. Landiolol, an ultrashort-acting intravenous beta-1 blocker, was developed and has been used for the treatment of ATA.

Purpose
We evaluated the acute effect of landiolol treatment on heart rate or blood pressure (BP), also the rates and benefits of sinus rhythm (SR) restoration among AHF patients with ATA treated with landiolol.

Methods
We studied 67 consecutive HF patients with ATA (age: 67±12 years, 36 male) treated with landiolol from 2015 to December 2017 at our University Hospital. They were compared with 50 paired subjects, matched for gender, age and baseline BP who developed HF with ATA from HIJ-HF 2 study (consisted of HF patients hospitalized between 2013 and 2014).

Results
At the start of landiolol treatment, mean left ventricular ejection fraction (LVEF) was 41±14%. The median maintenance dose of landiolol was 3.0 (1.0–12.0) μ/kg/min and the median treatment duration of landiolol was 5 (1–24) days. After 6 hours from administration of landiolol, mean HR decreased significantly from 140±18 to 100±21 bpm (p<0.05), whereas BP was not difference during landiolol treatment. Sinus rhythm was restored spontaneously in 15 (22%), and by electrical or pharmacological cardioversion in 5 (7%) during a treatment with intravenous landiolol. Furthermore, sinus rhythm was restored in 22 patients using additional rhythm control treatment, such as amiodarone or catheter ablation after intravenous landiolol treatement. Eight patients experienced in-hospital death. Forty-one (69%) of 59 patients discharged alive were in SR. During the follow-up period of 16±12 months, 4 patients died and 12 patients experienced rehospitalization due to worsening HF after hospital discharge. There was a significant higher rate of death or HF rehospitalization in patients without SR restoration than patients with SR restoration (44% vs. 20%, p<0.05) (Figure A). Compared with 50 paired subjects from HIJ-HF 2 study, those who treated with landiolol developed a significant higher rate of SR restoration (68% vs. 20%, p<0.05) (Figure B).
Figure 1

Conclusion
This study demonstrated that landiolol treatment was effective for both rate control and conversion to sinus rhythm in ADHF patient with ATA. We should consider that the benefits of rhythm control in ADHF patients with ATA during and after landiolol treatment.
P3094Feasibility and prognostic value of vasodilator stress perfusion CMR in elderly patients > 75 years without known CAD
Authors: Pezel T , Kinnel M , Hovasse T , Garot P , Unterseeh T , Champagne S , Louvard Y , Morice M C , Sanguineti F , Garot J 
Published: October 2019

Abstract

Background
The World's ageing population with a life expectancy that is steadily increasing raises the question of the benefit of screening for coronary artery disease (CAD) in very old patients with high risk of CAD. Current guidelines discourage the performance of stress testing in asymptomatic elderly.

Purpose
To assess the prognostic value of vasodilator stress perfusion cardiac magnetic resonance (CMR) in elderly patients aged >75 years without previous known CAD.

Material
Consecutive elderly patients >75 years without known CAD referred for vasodilator stress perfusion CMR were followed for major adverse cardiovascular events (MACE) defined as cardiac death, non-fatal myocardial infarction or stroke. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indexes.

Results
Of 754 elderly high risk patients (82.0±3.9 years, 48.4% men), 747 (99%) completed the CMR protocol, and among those 659 (88.2%) completed the follow-up (median follow-up 5.7±2.5 years). Reasons for failure to complete CMR included claustrophobia (n=3), declining participation (n=2) and intolerance to stress agent (n=2). Stress CMR was well tolerated without occurrence of death or severe disabling adverse event. Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (5.5% vs. 9.9% for those with ischemia and vs. 6.9% for those with ischemia and/or LGE). In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, the absence of inducible ischemia was an independent predictor of a lower incidence of MACE at follow-up (hazard ratio 0.46; 95% confidence interval: 0.34 to 0.62; p<0.001) (Figure 1A) and all-cause mortality (hazard ratio 0.67; 95% confidence interval: 0.45 to 0.97; p=0.037).
When patients with early coronary revascularization (within 30 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE. Using Kaplan-Meier analyses, the presence of myocardial ischemia identified the occurrence of future CV events (p<0.001). Moreover, the absence of inducible ischemia was a predictor of a lower incidence of MACE less significant in men than in women (p<0.01) (Figure 1B).

Conclusion
Stress CMR is safe and has discriminative prognostic value in very elderly patients, with a very low negative event rate in patients without ischemia or infarction. Among elderly patients without known CAD, the presence of myocardial ischemia on vasodilator stress CMR was predictive of future CV event or death.
P3108Microcirculation injury is involved in anthracycline-induced cardiac toxicity
Authors: Galan C , Vilchez-Tschischke J P , Lobo-Gonzalez M , Lopez G J , Gavilan M , De Molina-Iracheta A , Perez-Martinez C , Villena-Gutierrez R , Oliver E , Fernandez-Jimenez R , Pizarro G , Fuster V , Sanchez-Gonzalez J , Ibanez B 
Published: October 2019

Abstract

Background/Introduction
Cardiotoxicity (CT) is a major concern for cancer patients receiving anthracyclines. While the effect of anthracyclines on cardiomyocytes is well established, its impact on myocardial microcirculation has not been characterized.

Purpose
To evaluate the effect of low and high cumulative doses of doxorubicin (doxo) on anatomical and functional vasculature status evaluated by serial invasive Coronary Flow Reserve (CFR) and Cardiac Magnetic Resonance (CMR)-based quantitative perfusion in a large animal model.

Methods
Large-white male pigs (n=15, 30 kg) were distributed in 2 doxo regimes: Group 1) high cumulative dose (5 biweekly intracoronary (i.c) injections of 0.45 mg/kg of doxo) followed-up until week 16 (a time when severe left ventricular systolic dysfunction is present) and then sacrificed (N=5); Group 2) low cumulative dose of doxo (3 biweekly i.c. doses) followed-up until week 16 and then sacrificed (N=5)). Group 3) pigs sacrificed at 6 weeks (2 weeks after third doxo dose), N=5. Invasive catheter-based CFR was evaluated after i.c papaverine (0.5 mg/kg) while CMR quantitative rest perfusion maps were obtained after intravenous injection of gadolinium. CFR and CMR were performed before doxo, and at 0, 2, 4, 6 and 16 weeks thereafter. Cardiac vessels were evaluated ex vivo with trichrome staining. Statistical analysis was performed using one-way ANOVA with multiple pairwise comparisons (vs. baseline) and Bonferroni corrected p-value.

Results
CFR and CMR-quantitative myocardial perfusion were non-significantly reduced after 3 doxo doses despite myocardial vasculature was overtly injured on histology at this timepoint. Animals receiving 5 doxo doses suffered a progressive deterioration of CFR and CMR-perfusion until week 16 (1.41±0.23 vs 3.71±0.94 at baseline [p=0.014] and 65.4±18.2 ml/100g/min vs 154.9±56.3 ml/100g/min at baseline [p=0.046], respectively). At 16 weeks histology revealed extensive microvascular damage with media layer involvement and perivascular fibrosis. Pigs receiving 3 doxo doses showed less pronounced CFR reduction on long-term follow-up (3.13±0.82 vs 3.69±1.57 at baseline [p>0.05] but overt CMR-perfusion reduction (138.3±11.9 vs 197.8±37.1 at baseline [p=0.045]). On histology, damage of vasculature including arterioles was evidenced to a lesser extent than in the high cumulative doxo dose group with mild microvascular disruption and smooth muscle vacuolization.

Conclusions
Doxorubicin results in a progressive damage of the myocardial microcirculation. Even low cumulative doxo doses (resulting in no overt left ventricular dysfunction) results in vascular damage. The microcirculation status may serve as an early marker of doxorubicin cardiotoxicity.
P3116New role of EPAC1 in Anthracycline-induced cardiotoxicity and anticancer therapy
Authors: Belhadef A , Ribeiro M , Mazevet M , Laudette M , Crozatier B , Lezoualc'h F , Benitah J.-P , Gomez A.-M , Lemaire C , Morel E 
Published: October 2019

Abstract

Introduction
Doxorubicin (Dox) is an anthracycline commonly used to treat many types of cancer; unfortunately this chemotherapeutic agent induces many side effects such as cardiotoxicity leading to dilated cardiomyopathy (DCM). The cardiotoxicity of Dox has been related to reactive oxygen species generation, DNA intercalation, topoisomerase II inhibition and bioenergetics alterations leading to cardiomyocyte death.

Objective
Nowadays the challenge is to find new treatment options aiming at reducing Dox cardiotoxicity. Epac (exchange protein directly activated by cAMP) signaling could be worth investigating as Epac activates small G proteins which are known to be involved in Dox-induced cardiotoxicity.

Methods
We investigated the time/dose-dependent Dox effect on Epac signaling in both in vivo mice model (C57Bl63/ Knock-out Epac1 mice, iv injections, 12mg/kg cumulative dose) and in vitro (primary culture of neonatal rat cardiomyocytes (NRVM, 24h, Dox 1μM).

Results
In vivo, Dox-treated mice developed a DCM associated with Ca2+ homeostasis dysfunction (increase of Ca2+ waves and Ca2+ leaks). In vitro, as measured by flow cytometry and western blot, Dox (1μM) induced DNA damages and cell death in NRVM. This cell death is associated with apoptotic features including mitochondrial membrane permeabilization, caspase activation and cell size reduction. The inhibition of Epac1 (ESI09, CE3F4) decreased Dox-induced DNA damage, loss of mitochondrial membrane potential, apoptosis and finally cardiomyocyte death. Moreover, in vivo, Epac1 KO mice were protected against Dox-induced cardiotoxicity by unaltered cardiac function (no DCM) and calcium homeostasis at 15 weeks post-treatment.

Conclusion
Inhibition of Epac1 could be a valuable therapeutic strategy to limit Dox-induced cardiomyopathy during cancer chemotherapy. Indeed, preliminary data show also that preventing Dox-induced cardiotoxicity, the inhibition of Epac1 can also potentiate cancerous cells death.

Acknowledgement/Funding
Labex Lermit (ANR 0033), Torino and Inserm
P3130Relation between serum levels of long acting penicillin and the inflammatory markers: High sensitivity C-reactive protein and interleukin-6 in patients with chronic rheumatic heart disease
Authors: A Rifaie O , Hamza M A , Amin S M , Yousef M A 
Published: October 2019

Abstract

Background
There is evidence of a chronic inflammatory state in patients with chronic rheumatic valvular heart disease (RhD) as shown by high serum levels of high sensitivity C-reactive protein (CRP) and interleukin-6 (IL6). Despite the efficacy of long acting penicillin (LAP) in secondary prevention of rheumatic fever, its effect on this inflammatory state is still unknown

Objective
We sought to study the effect of (LAP) on the inflammatory markers, (CRP) and (IL-6), in patients with chronic rheumatic heart disease.

Methods
Eighty patients having (RhD) patients coming to our university hospitals outpatient clinic for rheumatic fever secondary prophylaxis by regular administration of (LAP) were enrolled in. the study. Patients were divided into to 3 groups: Group A; 70 patients with (RhD) already on prophylactic (LAP), Group B; 10 patients with (RhD) who have not yet started prophylactic (LAP), Group C; control group of 10 healthy individuals not known to have (RhD). Serum levels of (LAP), (IL6) and (CRP) were measured for the three groups.

Results
. Group A had significantly lower (IL6) levels than group B (25.22±33.50 vs. 126.1±33.76ng/ml, respectively, p<0.0001). (IL6) levels were significantly lower in control subjects compared to patients in group B (3.600±2.319, 25.22±33.50 ng/ml respectively, p<0.0001). However, IL6 levels in the control group were lower but non-significantly different compared to Group A . (CRP) level was lower in group A than group B (8419±4935 vs. 14400±3375mg/dl respectively, p=0.0002). (CRP) levels were significantly lower in control subjects compared to patients in group A and group B. (IL6) values were positively correlated with (CRP) values (r=0.6387, p<0.0001).
(CRP) level negatively correlated with Long acting penicillin level (r=−0.5277, p<0.0001). (IL-6) level negatively correlated with (LAP) level (r=−0.4401, p<0.0001). There was a highly significant difference between (LAP) level in compliant and non-compliant patients (1.045±1.270 vs. 0.0785±0.1057ng/ml, respectively, p value <0.0001).
There was also a highly significant difference between (CRP) level in compliant and non-compliant patients (7640±4558 vs. 13090±4717 mg/dl, respectively, p value 0.005).Moreover, there was a significant difference between (IL-6) levels in compliant and non-compliant patients (21.53±32.70 vs. 47.40±30.91 ng/ml, respectively, p value 0.03).

Conclusion
Serum (LAP) has a strong negative correlation with (IL-6) and (CRP) levels. Regular administration of (LAP) strongly ameliorates the inflammatory state seen in patients with (RhD).