bluuebunny/crossref_metadata_2025_split huggingface dataset:
P315In-vivo and vitro mitochondrial transfer from adipose-derived mesenchymal stem cell to ischemic cardiomyocyte
Authors: Mori D , Miyagawa S , Kawamura T , Hata H , Ueno T , Toda K , Kuratani T , Kurata H , Nishida H , Sawa Y 
Published: October 2019

Abstract

Background
Although transplantation of human Adipose-derived Mesenchymal stem cell (hADSC) shows efficacy in the treatment of ischemic cardiomyopathy, its therapeutic mechanisms have not been fully elucidated. It has been already reported that mitochondria transfer to recipient cells have impact on resistance to injury and tissue regeneration, however this phenomenon has not been elucidated in the damaged heart. Therefore, we hypothesized that ADSC transfer own mitochondria to cardiomyocytes in-vivo and in-vitro under ischemic condition, resulting in the functional recovery of cardiomyocyte.

Method and result
Transplantation of hADSC (group A) to the heart surface or sham operation (group C) was performed in rats that were subjected to LAD ligation 2 weeks prior to the treatment (n=10 each). The number of transplant cell was 1x106/body. Three days after transplantation, transferred hADSCs' mitochondria were observed in recipient cardiomyocytes histologically (Figure). Quantitative PCR analysis revealed that mitochondrial genome of recipient myocytes increased over time. The cardiac function assessed with echocardiography was significantly better in group A. Furthermore, live-imaging of hADSC transplantation revealed the suspected transfer of mitochondria to beating heart.
In-vitro, the co-culture of rat cardiomyocytes (rCM) and hADSC was observed with time-lapse photography and demonstrated mitochondrial transfer under the hypoxic condition. The measuring the oxygen consumption rate (OCR) of these cells showed that OCR of rCM was reinforced by co-culture with hADSC conspicuously.
Figure 1

Conclusion
Mitochondrial transfer from hADSC to rCM was suggested in-vivo and in-vitro ischemic condition and suspected to be related to functional recovery of ischemic cardiomyocyte.
P318Exosomes mediate myocardial regeneration of cardiac progenitor cells in a swine model of dilated cardiomyopathy
Authors: Hirai K , Goto T , Ousaka D , Ohtsuki S , Oh H 
Published: October 2019

Abstract

Introduction
Stem cell therapy has been shown to improve cardiac function. The mechanisms of therapeutic efficacy are considered the secretion of paracrine factors but the details are still unknown.

Hypothesis
Exosomes are extracellular vesicles containing bioactive substances such as proteins, messenger RNAs and micro RNAs. We hypothesized that exosomes may be the main paracrine factors to mediate therapeutic efficacy of cardiosphere-derived cells (CDCs).

Methods
Farm pigs (30 kg, n=10) were treated by intracoronary administration of 10,000 microspheres (100–300 μm) into three vessels. Two weeks later, 9.0×106 CDCs pretreated by exosome inhibitor (EI; 20μM of GW4869) or DMSO as controls were selectively infused into three coronary arteries. Evaluation of ejection fraction (EF) was performed before cell infusion and 1 month after protocol treatment.

Results
Pigs developed diffuse hypokinetic heart failure (baseline EF 37.1%±2.1%) and randomly assigned into two groups (CDCs with EI: n=5, CDCs with DMSO: n=5). No serious adverse events were found during the CDCs infusion. Significant improvement of EF was observed in CDCs with DMSO group (37.1%±2.1% to 42.5%±3.0%; P=0.01), whereas no change was found in CDCs with EI group (37.1%±2.4% to 36.2%±2.9%; P=0.58). Myocardial fibrosis stained by picrosirius red was significantly reduced in CDCs with DMSO group compared with CDCs with EI group (9.5±3.6% versus 17.3±5.3%; P<0.01).

Conclusions
We confirmed the therapeutic efficacy of CDCs and these effects were mainly mediated by exosomes.
P319Proliferative induced cardiomyocyte precursor cells obtained by direct reprogramming and transcriptional selection
Authors: Bachamanda Somesh D , Klose K , Juerchott K , Krueger U , Kunkel D , Kurtz A , Falk V , Gossen M , Stamm C 
Published: October 2019

Abstract

Objective
Enriched populations of proliferative induced cardiomyocyte precursors (iCMPs) generated from cardiac fibroblasts (CF) could represent a potential population for use in therapeutic application. We developed a protocol for generation of iCMPs from cardiac fibroblasts by genetic reprogramming followed by transcriptional selection and induced maturation.

Methods
Cardiac fibroblasts were reprogrammed into induced cardiomyocyte precursor cells (iCMPs) via transduction with cardiomyogenesis-related transcription factors Gata4, Mef2c, TBX5 and Myocd. Pure population of iCMPs were obtained by molecular beacons (MB) based selection of MYH6/7 expression. The transcriptome was profiled by RNA sequencing. For maturation iCMPs were treated with 5'-azacytidine and cultured in medium containing ascorbic acid and TGFβ1. The cells were monitored regularly for formation of sarcomere structures, cardiac marker expression and contractions. iCMPs were transplanted into MI mice and monitored for 6 weeks. At the end of 6 weeks, the mice were sacrificed and hearts were explanted and cryopreserved to examine the heart structure and scare size. Cardiac function was monitored by echocardiography.

Results
iCMPs expressed troponin T, α-actinin and myosin heavy chain (MHC) protein observed by immunocytology. These iCMPs could robustly proliferative and maintain a stable phenotype. Global transcriptome analysis revealed that the iCMP gene expression profile is unique from those of the parental CFs and adult CMs. With Gene Ontology (GO) analysis, we found that iCMPs show upregulation of genes associated with cardiac development, differentiation and morphogenesis while they showed downregulation of genes associated to cell-proliferation in comparison to their parental CFs. Evaluation of selected gene sets showed downregulation of non-myocyte genes, upregulation of transcription factors and upregulation of certain functional and structural genes like ion channel genes and contractile genes. Maturation studies showed that iCMPs gradually changed morphology after stimulation with 5-Aza, as seen in immunofluorescence staining. Cells expressing cTnT showed formation of sarcomeric striations. In vivo translational studies showed reduction of heart function in control groups treated with PBS or CF whereas the iCMPs group showed an improvement in function, reflected by left ventricular ejection fraction and fractional shortening as evaluated by echocardiography. Additionally we noticed an improvement in left ventricular wall thickness at diastole in mice transplanted with iCMPs.

Conclusions
Gene expression pattern suggests that these iCMPs represent an intermediate state of cardiogenic population that can be expanded to yield therapeutic cell doses. When transplanted to mouse hearts following myocardial infarction, they improved cardiac function.
P320Heart failure with mid-range (HFmrEF) or recovered (HFrecEF) ejection fraction: differential determinants of transition
Authors: De Maria R , Macera F , Gorini M , Battistoni I , Iacoviello M , Iacovoni A , Palmieri V , Pasqualucci D , Leonardi G , Pagnoni N , Montagna L , Floresta M , Midi P , Pulignano G , Mortara A 
Published: October 2019

Abstract

Background
Heart failure with mid-range ejection fraction (HFmrEF) has been identified as a multi-faceted phenotype that may encompass both patients with mild disease or those who from previous HFrEF recover EF (HFrecEF)

Purpose
To describe clinical characteristics and factors associated with phenotype transition at follow-up.

Methods
From 2009 to 2016, 1194 patients with baseline EF<50% and a second echocardiographic determination during clinically stability at a median of 6 months were enrolled in the IN-CHF Registry. Based on EF at enrollment, 335 (28%) had HFmrEF and 859 (72%) had HFrEF. We compared baseline clinical characteristics and predictors associated with follow-up reclassification to HFmrEF or full EF recovery

Results
When compared to HFrEF patients, those with HFmrEF had less often an ischemic etiology, advanced symptoms and a HF admission in the previous year. No other differences were found in clinical characteristics and drug therapy (Table).
At a median follow-up of 6 months, 30% of HFrEF patients improved EF by 14 (9) units: 21% showed partial EF recovery (transition to HFmrEF) and 9% had full EF recovery. Conversely among HFmrEF patients 22% improved EF, by 9 (5) units, to full recovery, and 18% deteriorated by 1.5 (5.5) units sloping to HFrEF.
By multivariable logistic regression analysis, variables associated with EF recovery at 6-month follow-up differed between baseline phenotypes. Within HFrEF, ischemic etiology (OR 0.46, 95% CI 0.33–0.64) and NYHA class III-IV symptoms (OR 0.57, 95% CI 0.38–0.68) were associated with a lower likelihood of EF recovery, while a history of HF<6 month correlated with a higher likelihood of EF recovery (OR 2.44, 95% CI 1.76–3.39). Within HFmrEF, while ischemic etiology (OR 0.66, 95% CI 0.19–0.68) was also associated with a lower likelihood of EF recovery, a history of atrial fibrillation at enrollment correlated with higher likelihood of EF recovery (OR 2.66, 95% CI 1.37–5.17) by 6 month-follow-up.
At a median follow-up of 36+28 months mortality was 4.6% vs 6.9% in HFrecEF vs non-recovered patients (log rank p=0.08).
Baseline characteristics HFrEF vs HFmrEF

Conclusions
HFmrEF patients showed a less severe clinical picture than HFrEF patients, but had EF recovery less often. EF improvement is negatively associated with ischemic etiology in both phenotypes, and positively associated with atrial fibrillation in HFmrEF and a short history of HF in HFrEF.
P323Haemodynamic implications of mitral regurgitation in heart failure with preserved ejection fraction
Authors: Tamargo Delpon M A , Masaru O , Reddy Y N , Pislaru S , Egbe A , Borlaug B A 
Published: October 2019

Abstract

Background
Mild to moderate mitral regurgitation (MR) is a common finding in heart failure with preserved ejection fraction (HFpEF). MR is often considered to be an innocent bystander, yet little data is available regarding its implications.

Aim
Determine the pathophysiologic correlates of MR in HFpEF

Methods
We retrospectively studied 280 patients with invasively proven HFpEF. MR was absent (None or trivial) in 163 subjects (Non-MR-HFpEF), and present in 117 (MR-HFpEF; 78 mild and 39 moderate MR). 247 subjects also underwent invasive cardiopulmonary exercise testing.

Results
At rest, MR-HFpEF subjects displayed higher pulmonary artery pressures (PAP), PCWP, and pulmonary vascular resistance (PVR; Table). During exercise, PAP and PCWP were not significantly different among groups, but MR-HFpEF displayed reduced ability to enhance cardiac output (CO) in response to heightened metabolic demand (oxygen consumption, VO2; Figure).
Baseline characteristics and haemodynamic characterization at baseline and peak exercise Baseline characteristics Non-MR-HFpEF (N=163) MR-HFpEF (N=117) p value Age 66±11 71±10 0.0002 Female (%) 56 69 0.02 AFib (%) 13 38 <0.0001 Nt proBNP 192 [66, 557] 870 [401, 2135] <0.0001 E/E' 12.3±5.5 15.6±7.2 0.0006 LVEF (%) 64±6 62±6 0.0001 RV fractional area change (%) 51±9 47±10 0.0001 Mean PA (mmHg) 25±7 28±9 0.001 Mean PCWP (mmHg) 15±5 17±6 0.0002 PVR (Woods) 2.0±1.1 2.5±1.4 0.015 CO (L/min) 5.5±1.6 4.8±1.3 0.12 Peak exercise hemodynamics Non-MR-HFpEF (N=152) MR-HFpEF (N=95) p value Mean PA (mmHg 45±10 46.5±10 0.07 Mean PCWP (mmHg) 32±6 31±6 0.6 PVR (Woods) 1.8±1.6 2.7±2.4 0.002 CO (L/min) 9.1±3 7.2±3 0.01 P value adjusted for age, gender and BMI.
CO change in response to VO2 increase

Conclusion
The presence of even mild MR in HFpEF is associated with more adverse hemodynamics, greater pulmonary vascular dysfunction and impaired CO reserve with exercise. Further study is required to better understand the natural history and treatment for MR in HFpEF.

Acknowledgement/Funding
None
P335Prevalence of transthyretin cardiac amyloidosis in a community-based heart failure population
Authors: Lindmark K , Pilebro B , Solekrans L , Wixner J , Anan I , Suhr O , Lindqvist P 
Published: October 2019

Abstract

Introduction
Cardiac wild type (wt) transthyretin (ATTR) amyloidos causes hypertrophic, restrictive cardiomyopathy in older patients and is generally considered underdiagnosed. However, its prevalence remains poorly investigated. Scintigraphy using bone tracers, e.g. Tc-PYP and Tc-DPD, is a highly sensitive and specific method for detection of cardiac ATTR and has revolutionised diagnostics The aim of this study was to describe the prevalence of wtATTR amyloidosis in our heart failure population.

Methods
Our University Hospital is the sole provider of specialised heart care in an area with around 150 000 inhabitants, 37 600 of which are older than 60 years. Medical records for all living patients in the area with a diagnosis of heart failure, hypertensive heart disease or cardiomyopathy between 2010 and May 2018 were scrutinized (n=2237). 95% of these patients had an echocardiographic exam available for re-evaluation. All patients withseptal thickness >14 mm who had no previous DPD scintigraphy or genetic diagnosis of sarcomeric hypertophic cardiomyopathy were offered DPD scintigraphy (n=131). Eight patients died prior to and 38 patients declined work up, mainly due to old age.
A DPD uptake of grade 2 or higher was considered diagnostic in absence of signs of AL amyloidosis.

Results
Adding up patients found during the screening effort and those with an already known diagnosis of wtATTR amyloidosis, 26 patients had wtATTR. Their men age was 84 years and 90% were male.

Conclusions
The study gives us an estimated prevalence of disease warranting specialized heart failure treatment of 1/1500 in the population older than 60 years. Cardiac wtATTR amyloidosis is common in patients with heart failure and increased LV wall thickness, especially among the older male patients. Therefore we recommend a liberal use of bone scintigraphy in this group.
P343Comparison of Focal Impulse and Rotor Modulation Ablation (FIRM) only versus second-generation cyroballoon ablation in patients with paroxysmal atrial fibrillation
Authors: Tilz R , Lyan E , Heeger C , Fink T , Liosis S , Brueggemann B , Meyer-Sarai R , Sano M , An D , Eitel C , Vogler J 
Published: October 2019

Abstract

Background
Rotors have been postulated to be a major driver of atrial fibrillation (AF). Initial studies demonstrated, that focal impulse and rotor modulation (FIRM) might be an effective therapy for the treatment of paroxysmal AF (PAF). However, data about FIRM-guided ablation strategies without PVI is sparse.

Objective
To compare the safety and efficacy of FIRM-guided catheter ablation (without PVI; FIRM arm) and second generation cryoballoon (CB2, CB2 arm) based PVI in patients with paroxysmal atrial fibrillation (PAF) and de-novo catheter ablation of AF.

Methods
In this retrospective single-center study patients with PAF undergoing de-novo ablation of PAF between February 2016 and January 2017 were enrolled. Patients treated with FIRM-guided AF ablation as a standalone therapy without PVI were included and compared with patients undergoing CB2 based PVI. All patients in the FIRM arm were part of the randomized multicenter FIRMAP AF trial (results of this trial will be presented at this meeting). In patients undergoing FIRM-guided ablation, 3D electroanatomical mapping of both atria was performed. Rotor mapping using FIRM technology was conducted in spontaneous or induced AF. The procedural endpoint was the elimination of all rotors and focal impulses; no PVI was performed in those patients. In the CB2 arm, CB based PVI with the procedural endpoint of isolation of all veins was performed. Procedural data and arrhythmia-free survival after 12 months were compared.

Results
FIRM-guided and CB2 based AF ablation was performed in 22 and 86 patients, respectively. Follow up was completed in 20 and 79 patients LA diameter differed between groups. Otherwise, baseline characteristics did not differ between the FIRM group (mean age 60±11 years, 59.1% males) and the CB2 group (mean age 62±13, 62.4% male).
Arrhythmia-free survival including a 90-day blanking period was 25.0% (15/20) in the FIRM group and 86.1% (11/79) in the CB2 PVI group (p=0.000; Figure 1). Procedure duration was significantly longer in the FIRM group (152 [120; 176] minutes) compared to the CB2 PVI group (122 [110; 145] minutes) (p=0.031), whereas radiation dose was lower in the FIRM group (1266 [1027; 2281] cGy·cm2 vs. 3020 [1677; 4215] cGy·cm2). Adverse events (groin complications) occurred in 1 patient (1.2%) in the CB2 PVI group and 5 patients (22.7%) in the FIRM group.
Figure 1. Kaplan-Meier-survival curve dem

Conclusion
De novo ablation of PAF using a FIRM-guided AF ablation only (without PVI) is associated with poor arrhythmia-free survival after 12 months compared to CB2 PVI. These results underline the importance of PVI as the first-line approach in catheter ablation of AF.
P346More procedural complications in female patients undergoing pulmonary vein ablation in atrium fibrillation: results from 12,430 patients in the Netherlands Heart Registry
Authors: Mol D , Houterman S , De Jong J S , De Groot J R 
Published: October 2019

Abstract

Introduction
Pulmonary vein isolation (PVI) has become a cornerstone of the treatment of atrial fibrillation (AF). Several technologies have been developed to improve procedural and long-term outcomes. Depending on type of AF and rhythm recording used, 1-year freedom of AF varies between 55–82%. However, severe complications are reported in 1–3%.

Purpose
To describe procedural complications of PVI with either single tip radiofrequency ablation (STRF), multi electrode phased RF ablation (PVAC) or cryoballoon (CB).

Methods
Data was extracted from the Netherlands Heart Registry in which 14 Dutch heart centres participate. Procedural complications in patients treated with the 3 different ablation modalities (STRF, PVAC and CB ablation) were compared. Complications included: pericardial tamponade, persistent phrenic nerve palsy (PNP) beyond 24hrs, thromboembolic events, vascular- and bleeding complications. Patient characteristics: gender, age, BMI, CHA2DS2 -VASc, type of AF and previous left atrium ablation were assessed in a univariate and multivariate regression model.

Results
In total, 12,430 patients were included (STRF n=5,106, PVAC n=2,341, CB n=4,983) between January 2013 and December 2017, of whom, 69% were male, 74% had a history of paroxysmal AF, 24% persistent AF and 2% longstanding persistent AF. The incidence of complications within 30 days was 3.6%. Pericardial tamponade requiring intervention, occurred more frequently in the STRF group (STRF: 0.8% vs PVAC 0.3% vs CB 0.3% p= <0.01). PNP was present in 0.1% of patients after STRF ablation, in 0.2% of patients after PVAC ablation and in 1.5% of patients treated with CB ablation (p= <0.001). Thromboembolic events were observed in 0.4% with no statistical difference between the 3 modalities. Patients treated with STRF had more vascular complications (STRF 1.7% vs PVAC 1.2% vs CB 1.3% p= <0.001). In the PVAC and CB group there were significant less bleeding complications (STRF: 1.1% vs PVAC: 0.5% vs CB: 0.7% p=0.01). Female patients and patients with a higher CHA2DS2-VASc had an increased risk for pericardial tamponade, vascular- and bleeding complications (figure) with adjusted odds ratios for female patients of 2.97 (95% CI 1.77–5.00), 2.24 (95% CI 1.41–3.56) and 2.84 (95% CI 1.88–4.28) respectively.
Univariate analysis

Conclusion
PVI was associated with a complication rate of 3.6%. Compared to PVAC and CB ablation, patients treated with STRF ablation more often developed a pericardial tamponade and vascular- and bleeding complications. PNP occurred most frequent in patients undergoing CB ablation. Female gender and CHA2DS2-VASc were independent predictors for pericardial tamponade, vascular- and bleeding complications.
P581Electronic health records (EHRs) data validation in atherosclerotic/cardiovascular clinical phenotypes
Authors: Cruz N , Serrano M , Lopez A , Medrano I H , Lozano J , Coll B 
Published: October 2019

Abstract

Background
Research efforts to develop strategies to effectively identify patients and reduce the burden of cardiovascular diseases is essential for the future of the health system. Most research studies have used only coded parts of electronic health records (EHRs) for case-detection obtaining missed data cases, reducing study quality and in some case bias findings. Incorporating information from free-text into case-detection through Big Data and Artificial Intelligence techniques improves research quality. Savana has developed EHRead, a powerful technology that applies Natural Language Processing, Machine Learning and Deep Learning, to analyse and automatically extracts highly valuable medical information from unstructured free text contained in the EHR to support research and practice.

Purpose
We aimed to validate the linguistic accuracy performance of Savana, in terms of Precision (P), Recall (R) and overall performance (F-Score) in the cardiovascular domain since this is one of the most prevalent disease in the general population. This means validating the extent to which the Savana system identifies mentions to atherosclerotic/cardiovascular clinical phenotypes in EHRs.

Methods
The project was conducted in 3 Spanish sites and the system was validated using a corpus that consisted of 739 EHRs, including the emergency, medical and discharge records, written in free text. These EHRs were randomly selected from the total number of clinical documents generated during the period of 2012–2017 and were fully anonymized to comply with legal and ethical requirements. Two physicians per site reviewed records (randomly selected) and annotated all direct references to atherosclerotic/cardiovascular clinical phenotypes, following the annotation guidelines previously developed. A third physician adjudicated discordant annotations. Savana's performance was automatically calculated using as validation resource the gold standard created by the experts.

Results
We found good levels of performance achieved by Savana in the identification of mentions to atherosclerotic/cardiovascular clinical phenotypes, yielding an overall P, R, and F-score of 0.97, 0.92, and 0.94, respectively. We also found that going through all the EHRs and identifying the mentions to atherosclerotic/cardiovascular clinical phenotypes, the expert spent ∼ 60h while Savana ∼ 36 min.

Conclusion(s)
Innovative techniques to identify atherosclerotic/cardiovascular clinical phenotypes could be used to support real world data research and clinical practice. Overall Savana showed a high performance, comparable with those obtained by an expert physician annotator doing the same task. Additionally, a significant reduction of time in using automatic information extraction system was achieved.