bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2553Combined with ticagrelor, 50 mg aspirin daily can reduce bleeding events without increasing ischaemic risk compared with 75–100 mg aspirin daily in coronary artery disease patients
Authors: Li J 
Published: October 2019

Abstract

Aim
To investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin than that recommended by guidelines.

Methods
Hospitalized patients received ticagrelor (90 mg twice daily) plus aspirin (50–100 mg/day) for up to 12 months. The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared among the groups treated with 50 mg and 75–100 mg aspirin.

Results
MACE risk was not significantly different between the two groups (OR=0.829, 95% CI: 0.279–2.461, P=0.736). However, 75–100 mg aspirin was associated with a greater risk of bleeding events (OR=1.524, 95% CI: 1.082–2.146, P=0.016), particularly mild and moderate bleeding events (OR=1.480, 95% CI: 1.047–2.092, P=0.026). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR=1.850, 95% CI: 1.025–3.339, P=0.041), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR=4.565, 95% CI: 1.081–19.270, P=0.039).
MACEs and bleeding events within 1 year Endpoint 75–100 mg (n=744) 50 mg (n=188) Unadjusted (95% CI) P value Adjusted# (95% CI) P value MACEs 18 (2.4) 4 (2.1) 0.876 (0.296–2.588) * 0.876 0.829 (0.279–2.461)* 0.736 Bleeding 311 (41.8) 60 (31.9) 1.532 (1.091–2.152)** 0.014 1.524 (1.082–2.146)** 0.016 Severe bleeding 14 (1.9) 2 (1.1) 1.784 (0.402–7.916)** 0.447 1.807 (0.405–8.069)** 0.438 Mild bleeding 297 (39.9) 58 (30.8) 1.489 (1.057–2.098)** 0.023 1.480 (1.047–2.092)** 0.026 #Adjusted for age, sex, LDL-C, hs-CRP, diabetes mellitus, hypertension, hyperlipidaemia and MI history. *Hazard ratio (high vs low); **Odds ratio (high vs low).

Conclusion
Among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75–100 mg aspirin daily.

Acknowledgement/Funding
The study was supported by AstraZeneca's fund for the TIFU study (ESR-15-11199).
P2555Efficacy and safety of oral anticoagulant versus antiplatelet therapy for secondary prevention of cardiovascular disease in patients without atrial fibrillation
Authors: Ricci F , Ianni U , Forcucci F , Fedorowski A , Zimarino M , Gallina S , Renda G 
Published: October 2019

Abstract

Background
Anticoagulation is the mainstay of prevention of arterial thromboembolism in patients with atrial fibrillation, but it could be effective also in secondary prevention of patients who are in sinus rhythm.

Purpose
We performed this meta-analysis to determine relative efficacy and safety of oral anticoagulant therapy (OAC) as compared with antiplatelet therapy (APT) in patients with prevalent cerebro-cardiovascular disease without atrial fibrillation.

Methods
Our systematic review of the literature published through January 31st, 2019 sought all phase III randomized controlled trials which compare OAC with APT in patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, and major bleeding, assessed at the longest available follow-up. We used random-effects models to estimate summary relative risk reduction (RRR) and 95% confidence intervals (95% CI).

Results
We identified a total of 9 randomized controlled trials including a total of 34,912 patients (ASA, n=17,726; adjusted-dose warfarin, n=4,460; rivaroxaban, n=12726), with a mean follow-up of 2.2 years. When compared with antiplatelet therapy, OAC was associated with reduced risk of ischemic stroke (RRR 38%, 95% CI: 1; 47; P=0.04; I2=72%) and myocardial infarction (RRR 13%, 95% CI: 0,23; P=0.05, I2=0%), but increased risk of major bleeding (RRR −52%, 95% CI: −129; −1; P=0.04; I2=76%). Compared to antiplatelet treatment, OAC did not significantly affect the risk of all-cause death (RRR 1%, 95% CI: −9; 10; P=0.86; I2=12%).

Conclusions
In sinus rhythm patients with prevalent cardiovascular disease, OAC reduces risk of ischemic stroke and myocardial infarction, but significantly increases risk of major bleeding. The choice of antithrombotic treatment does not appear to influence all-cause mortality.
P2564Levosimendan shortens action potential duration, decreases alternans threshold and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts
Authors: Hsieh Y C , Li C H , Liao Y C , Lin J C , Weng C J , Lin S F , Huang J L , Wu T J 
Published: October 2019

Abstract

Background
Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VA) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). The calcium sensitizer levosimendan has been reported to shorten APD by enhancing ATP-sensitive K current. We hypothesize that levosimendan might shorten the already prolonged APD during TH, decreasing SDA threshold, and prevent the occurrence of VA.

Methods
Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induced SDA phenomenon. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s using the shortest PCL that achieved 1:1 ventricular capture.

Results
Levosimendan shortened the ventricular APD (at PCL 300 ms, from 229±9 ms to 211±18 ms, p=0.02) and decrease the SDA threshold (from 327±88 ms to 311±68 ms, p=0.001) during TH. The VF inducibility was decreased by levosimendan from 39±30% at 30°C to 14±12% after levosimendan infusion. In control hearts, the APD (p=0.75), SDA threshold (p=ns) and VF inducibility (p=0.12) were not changed by vehicle during TH.

Conclusions
Levosimendan protects the hearts against VA during TH by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to prevent VA during TH.
P2567First experience of non-invasive and invasive activation maps merge in carto system for topical diagnosis of focal arrhythmias
Authors: Budanova M , Chmelevsky M , Zubarev S , Potyagaylo D , Parreira L , Adragao P 
Published: October 2019

Abstract

Background
Correct preoperative topical diagnostics of atrial and ventricular arrhythmias allows for operation time reduction by facilitating the ablation target localization, especially in case of several ectopic sources.

Purpose
To implement a non-invasive electrocardiographic imaging (ECGI) technique in CARTO system for aiming at topical diagnostics of focal arrhythmias improving.

Methods
Twelve patients (m/f – 10/2, age (min–max) – 50,5 (32–71)) with focal arrhythmias underwent ECGI in combination with CT or MR imaging. Two subjects had atrial premature contractions (PAC), while ten patients suffered from ventricular premature contractions (PVC) with indications for ablation. Before the ablation procedure Carto LAT mapping was performed in all patients. Using ECGI epi-/endocardial polygonal models of the heart were created, isopotential and activation maps were calculated, uploaded into the Carto system and merged with the CARTO FAM models (Figure 1).

Results
For six patients with PVC and two patients with PAC, earliest activation zones (EAZs) anatomical locations obtained by invasive and non-invasive methods were the same (RVOT septum, RVOT lateral-anterior and RV lateral-basal walls, right aortic cusp, LVOT, coronary sinus (CS), CS ostium, RA posterior wall), and arrhythmias ablation was successful. Two patients featured coherent EAZs (RV lateral-basal wall and RVOT septum) but a negative ablation outcome. In one patient, EAZs were situated in different anatomical regions: CARTO showed the PVC EAZ in RV septum, whereas Amycard system identified endocardial surface of lateral-basal RV wall. In this patient, PVC was ablated partially. For another patient with MRI late enhancement area in LV lateral wall the EAZs were in the same LV segment but with mismatch in epi/endocardial surface.

Conclusion
Non-invasive and invasive activation maps merge can improve localization of ablation targets in focal arrhythmias, potentially increasing effectiveness of the EP procedure and reducing operation time.
P2568Larger vectorcardiographic QRS area is associated with increased risk of heart failure development among left bundle branch block patients: a register-based cohort study
Authors: Andersen D , Petersen L , Kragholm K , Graff C , Soerensen P , Nielsen J , Pietersen A , Soegaard P , Atwater B , Torp-Pedersen C , Polcwiartek C 
Published: October 2019

Abstract

Background
QRS morphology including left bundle branch block (LBBB) and duration remain the most widely used surrogate markers in the 12-lead electrocardiogram (ECG) for assessing ventricular dyssynchrony and predicting future burden of heart failure (HF) and cardiovascular mortality. However, the vectorcardiographic QRS area has recently been proposed and evidence suggest that this marker may more accurately predict HF development.

Purpose
The aim of this study was to investigate the association between vectorcardiographic QRS area and risk of HF development in LBBB patients.

Methods
From 2001–2015, the Copenhagen General Practitioners' Laboratory was used to identify patients with a first-time LBBB ECG (QRS>120 ms; LBBB morphology), from which QRS area was derived using the Kors transformation method and grouped into quartiles. Outcome was a composite of HF diagnosis, redeemed prescriptions of loop diuretics, or death from HF. Death from other causes was accounted for as a competing risk.

Results
We included a total of 2843 LBBB patients who were free of heart failure (median age, 70 years; female, 58%; ischemic heart disease, 9%). QRS area quartiles comprised Q1, 67–158 μVs; Q2, 159–189 μVs; Q3, 190–228 μVs; and Q4, 229–739 μVs. During 6-month, 1-year, and 5-year follow-up, 9%, 12%, and 28% of patients reached the combined HF endpoint, and 1%, 2%, and 8% of patients died from other causes, respectively (Figure 1). After multivariable adjustment, the highest QRS area quartile, Q4, was associated with increased HF risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.35–2.00) compared with the lowest quartile, Q1. We did not observe any significant increase in HF risk for remaining quartiles (Q2 or Q3 vs. Q1).
Figure 1

Conclusions
Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (229–739 μVs) is associated with increased risk of developing the incident, combined HF endpoint. This indicates that the QRS area derived using the Kors method may serve as a valuable prognostic marker when assessing risk of HF in patients with LBBB.
P2571Differentiation of iPS-derived cardiac mesoderm cells into cardiomyocytes using inducible shRNA technology
Authors: Garcia Duran A , Nazari-Shafti T , Kurtz A , Falk V , Gossen M , Stamm C 
Published: October 2019

Abstract

Introduction
The development of robust and scalable cardiomyocyte differentiation protocols from human pluripotent stem cells (hPSCs) offers the opportunity to derive large number of autologous cardiomyocytes for cell therapy. However, human induced pluripotent stem cells-derived cardiomyocytes (hiPSCs-CM) do not proliferate, are susceptible to ischemia and poorly retained in the recipient myocardium. In addition, arrhythmias are a severe side effect of cell therapy with hiPSC-CM, probably due to their immature phenotype. Based on previous observations in our lab, we speculate that the heart environment might be an important factor to enable full maturation and in situ coupling of the implanted cells in vivo. We therefore speculate that transplantation of robust, proliferative, partially committed, non-tumorigenic cardiac mesoderm cells and subsequent differentiation in situ may overcome these limitations.

Purpose
We seek to engineer hiPSC-derived cardiac mesoderm cells for implantation in the failing myocardium that, once they have settled, consolidated, and proliferated in situ, can be selectively induced to mature into cardiomyocytes.

Methods
Wnt signalling induces mesoderm lineage differentiation of hiPSCs and inhibits further maturation towards CM. To induce Wnt signalling inhibition, we designed a customized biomimetic shRNA targeting the Wnt agonist β-catenin fused to a fluorescent reported protein controlled by a Tet-ON promoter. This transgene was transferred to the safe harbour locus AAVS1 of the OPTI-OX hiPS cell line constitutively expressing the reverse tetracycline transactivator protein (rtTA) in the ROSA26 locus. In this configuration, gene expression can be activated in trans upon doxycycline administration.

Results
We studied the kinetics of gene expression activation on the engineered undifferentiated hiPSCs and observed that a maximal reduction of 80–90% β-catenin correlating with reporter expression was achieved upon a 4-day treatment with doxycycline. Importantly, this activation could be fully reverted 6 days upon withdrawal. Furthermore, in vitro differentiation of cardiac mesoderm cells into cardiomyocytes was enhanced upon doxycycline administration as compared to the untreated cells as assessed by the upregulation of cardiomyocyte specific genes and the increased percentage of cTNT+ cells.

Conclusion
An inducible system for targeted β-catenin downregulation by shRNA allows for significant, sustained, and reversible Wnt signalling modulation, which is sufficient to induce cardiomyocyte differentiation of cardiac mesoderm cells in vitro. This technology may be implemented to differentiate the transplanted cells in the failing myocardium, opening new prospects to overcome the current limitations of hiPSC-based cardiac cell therapy.

Acknowledgement/Funding
BMBF funding (FKZ 13GW0098, FKZ 13GW0099) DFG funding through the BSRT GSC 203
P2573Modelling the duchenne muscular dystrophy-induced dilated cardiomyopathy using patient-specific induced pluripotent stem cells-derived cardiomyocytes
Authors: Souidi M , Sleiman Y , Moreau A , Amedro P , Meyer P , Rivier F , Lacampagne A , Meli A 
Published: October 2019

Abstract

Introduction
Duchenne Muscular Dystrophy (DMD) is a X-linked degenerative pathology with a prevalence of 1/3500 boys due to absence of functional dystrophin in muscles. In a late stage of DMD, patients developed a dilated cardiomyopathy (DCM) which can lead to heart failure and premature death.
In the past, we showed that DMD (mdx) mice exhibit a perturbation of the intracellular calcium homeostasis correlated to a pathological remodelling of the calcium ryanodine receptor channel (RyR2) leading to DCM with aging. However, mouse model does not represent a pertinent prototype to study DMD. Human pluripotent stem-cell derived-cardiomyocytes (hiPSC-CMs) are a pertinent tool to model patient-specific inherited cardiac diseases and screen pharmacological drugs in a Petri dish.

Objective
Based on the clinical history of DMD patients in the local Hospital, our main objective is to model DMD-induced DCM using hiPSC-CMs and compare the functional and molecular features with the clinical echocardiography. To that, we hypothesize that hiPSC-CMs are a powerful technology to model in vitro DCM and to better understand the pathophysiological mechanisms underlying DCM.

Methods
3 blood samples from DMD patients with different DCM degrees of severity and 3 from healthy control (HC) were collected, reprogrammed in hiPSC and differentiated into cardiomyocytes.

Results
Our preliminary data indicate that DMD hiPSC-CMs present an abnormal intracellular calcium homeostasis characterized by the presence of leaky diastolic calcium events compared to HC hiPSC-CMs suggesting a RyR2 dysfunction. In DMD hiPSC-CMs, we also observe alterations in the contractile properties and a perturbation of the mitochondrial respiration.

Conclusion
Our results support the fact that DMD-inducing DCM can be modelled in the dish using patient-specific hiPSC-CMs. Such modelling may provide a better understanding of the pathophysiological mechanisms and the pharmacological treatment of the DMD-induced DCM.
P2606Analysis of myocardial work: a potential new tool for a better assessment of left ventricular function
Authors: Rimbas R C , Chitroceanu A M , Luchian M L , Visoiu S I , Mihaila-Baldea S , Magda L S , Memis H , Lungeanu-Juravle L , Velcea A , Balinisteanu A , Andronic A A , Vinereanu D 
Published: October 2019

Abstract

Background
Left ventricular (LV) deformation is dependent on mechanical load and does not reflect directly the myocardial energy consumption. Thus, measurement of global and regional myocardial work might be alternative and complementary methods for the assessment of myocardial function. However, there is no data regarding myocardial work changes during the heart failure continuum, from normal to diastolic dysfunction (DD), and to heart failure with preserved ejection fraction (HFpEF).

Methods
We assessed 80 subjects by 2D conventional and speckle tracking echocardiography (2DSTE): 25 patients with DD, 30 with HFpEF, and 25 normal, control subjects. We measured NTproBNP, LV ejection fraction (EF), and E/E' ratio. We used a new approach to calculate myocardial work, during mechanical systole and isovolumetric relaxation, by 2DSTE: global constructive work (GCW), as the “positive” work of the heart; global wasted work (GWW), as the “negative” work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. Similarly, a regional, segmental analysis was performed (18 segments model) (Figure 1).

Results
GCW increases in patients with DD, probably as a compensatory mechanism to preserve LV function against an increased after load, and decreases back to the normal values in HFpEF, while GWE significantly decreases from normal subjects to patients with DD, and then further in patients with HFpEF (table). Meanwhile, GWW increases from normal subjects to patients with DD, and then further in patients with HFpEF. As expected, GWI does not change significantly. By segmental analysis, first segment affected in terms of myocardial work is basal antero-septal segment, with low WE and higher WW (figure), probably due to the flat shape (based on the Laplace law), with a compensatory increased CW in the apical segments. NTproBNP level and E/E' ratio correlated only with GWW (r=0.4, p=0.013).
Comparative global myocardial work Group LVEF (%) E/E' NTproBNP (pg/ml) GWI (mmHg%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls 58±6 7.3±2.4 – 2102±303 95.5±1.8 2295±279 87.9±39.6 DD 57±8 7.7±2.4 36±25 2296±431 94.8±2.3 2550±463 108±50 HFpEF 63±7 10.3±3.1 349±418 2074±485 93.5±2.5 2300±535 125±51 P (Anova) 0.004 <0.001 <0.001 0.12 0.008 0.05 0.019
Figure 1. Myocardial Work

Conclusion
Myocardial work efficiency decreases and wasted work increases in parallel with the severity of LV dysfunction. The first myocardial segment affected is basal antero-septal. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better assessment of LV function in patients with DD or HFpEF.

Acknowledgement/Funding
This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III
P2611The prognostic value of serum magnesium levels in patients with heart failure with preserved left ventricular ejection fraction
Authors: Nishihara T , Sueta D , Yamamoto E , Fujisue K , Usuku H , Oike F , Takae M , Takashio S , Sakamoto K , Kaikita K , Tsujita K 
Published: October 2019

Abstract

Background
In heart failure (HF) patients, various factors, such as hyperactivity of the renin-angiotensin system, influence of drug therapy such as loop and thiazide diuretics, undernutrition and others, can causes hypokalemia and hypomagnesemia. Although serum magnesium (Mg) levels are closely associated with the prognosis of HF patients, the clinical significance of serum Mg levels in cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood.

Purpose
We examined the relationship between serum Mg and future HF-related events in patients with HFpEF.

Methods
This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to our university hospital between January 2007 and September 2013 and followed them for 4 years or until occurrence of HF-related events. We defined lower serum Mg as <2.0 mg/dL (=0.8 mmol/L) and higher serum Mg as ≥2.0 mg/dL based on recent clinical evidences and compared their clinical characteristics and prognosis.

Results
The mean serum Mg level was 2.12 mg/dL (median, 2.1 mg/dL; interquartile range, 2.0–2.28 mg/dL). The follow-up period was 0–50 months (median, 47.3 months) and 48 HF-related events (10.6%) were recorded. The frequency of HF-related events was significantly higher in the lower serum Mg group compared with the higher serum Mg group (n=16, 17.4% vs. n=32, 8.9%; P=0.018). There were no significant differences between groups in the use of all drugs (loop diuretics, mineralcorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, β-blockers, statins and Mg preparations). The lower serum Mg group (n=92) showed significantly higher prevalence of diabetes mellitus (DM), uric acid levels and B-type natriuretic peptide (BNP)levels compared with the higher serum Mg group (n=360). Kaplan-Meier curve revealed a significantly higher probability of HF-related events in the lower serum Mg group compared with the higher serum Mg group (log-rank test, P=0.012, Figure). Multivariate Cox proportional hazard analysis revealed that the lower serum Mg group had significantly and independently higher probabilities of HF-related events compared with those in the higher serum Mg group (hazard ratio: 2.37, 95% confidence intervals: 1.27–4.41, P=0.007). We reclassified the risk of a HF-related events after adding the lower serum Mg to the prognostic factors (age, previous hospitalization for HF, DM, ln-BNP); the continuous net reclassification improvement was 29.0% (p=0.041).

Conclusion
We first demonstrated that serum Mg was significantly correlated with the occurrence of future HF-related events in HFpEF patients. Lower serum Mg is able to successfully predict future HF-related events, and management of serum Mg in HFpEF patients is thus important.

Acknowledgement/Funding
None