scholarly journals Acute and chronic cholinergic activity in the inflammatory and lipid regulation of epicardial stromal cells from patients with and without atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Couselo Seijas ◽  
X Fu ◽  
J.N Lopez-Cano ◽  
A Rozados-Luis ◽  
A.L Fernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Stromal Cells ◽  
Lipid Accumulation ◽  
Plasma Levels ◽  
Calcium Mobilization ◽  
Public Institution ◽  
Epicardial Fat ◽  
Funding Source ◽  
Cholinergic Activity

Abstract Aims Acetylcholine (ACh) released modulation by botulinum toxin injection into epicardial fat diminish atrial fibrillation (AF) recurrence. These results suggest an interaction between autonomic imbalance and epicardial fat as risk factors of AF. Our aim was to study the inflammatory and lipid profile of epicardial stroma from AF patients and their regulation by high cholinergic activity. Methods and results We performed in vitro assays with primary cultures from paired subcutaneous and epicardial stromal cells from 33 patients. We analysed ACh effect on gene expression, intracellular calcium mobilization and neutrophil migration. Plasma protein regulation by parasympathetic denervation was performed in vagotomised rats. Acute ACh treatment up-regulated MCP1 levels on epicardial stromal cells and suggested a neutrophil infiltration enhancement. Patients with AF had a greater FABP4 gene expression (1.54±0.01 vs 1.47±0.01, p=0.005). Its plasma levels were pronouncedly declined on vagotomised rats (2.02±0.21 ng/mL vs 0.65±0.23 ng/mL, p<0.001). Additionally, chronic ACh treatment improved lipid accumulation within epicardial stromal cells (60.50% [22.82–85.13] vs 13.85% [6.17–23.16], p<0.001). Conclusions Acute ACh activity up-regulates MCP1 and calcium mobilization on epicardial stromal cells. Longer ACh treatment enhanced lipid accumulation. In this line, epicardial stroma from patients with permanent AF contains higher FABP4 expression levels. Thus, modulate cholinergic activity might reduce FABP4 since vagus nerve denervation is associated with a sharply decrease in FABP4 plasma levels. FABP4 in human AF and vagotomised rats Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Carlos III Health Institute; Health Research Institute of Santiago de Compostela

scholarly journals The safety of catheter ablation of atrial fibrillation in elderly patients -analysis of the nationwide database in Japan, JROAD-DPC-

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Yokoyama ◽  
K Miyamoto ◽  
M Nakai ◽  
Y Sumita ◽  
N Ueda ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Elderly Patients ◽  
Complication Rate ◽  
Safety Data ◽  
Public Institution ◽  
Funding Source ◽  
Chads2 Score ◽  
Aged Patients ◽  
Nationwide Database

Abstract Background “Age” is one of the major concerns and determinants of the indications for catheter ablation (CA) of atrial fibrillation (AF). There are little safety data on CA of AF according to the age. This study aimed to assess the safety of CA in elderly patients undergoing CA of AF. Methods and results We investigated the complication rate of CA of AF for the different age groups (<60 years, 60–65, 65–70, 70–75, 75–80, 80–85, and ≥85) by a nationwide database (Japanese Registry Of All cardiac and vascular Diseases [JROAD]-DPC). The JROAD-DPC included 73,296 patients (65±11 years, 52,883 men) who underwent CA of AF from 516 hospitals in Japan. Aged patients had more comorbidities and a significantly increased CHADS2 score and higher rate of female according to a higher age. The overall complication rate was 2.6% and in-hospital mortality was 0.05%. By comparing each age group, complications occurred more frequently in higher aged groups. A multivariate adjusted hazard ratio revealed an increased age was independently and significantly associated with the overall complications (odds ratio was 1.25, 1.35, 1.72, 1.86, 2.76 and 3.13 respectively; reference <60 years). Conclusions The frequency of complications was significantly higher according to a higher age. We should take note of the indications and procedure for CA of AF in aged patients. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Intramural Research Fund 17 (Kusano) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center

Reliable detection of atrial fibrillation with a medical wearable under inpatient conditions (CoMMoD-A-fib)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Jacobsen ◽  
T.A Dembek ◽  
A.P Ziakos ◽  
G Kobbe ◽  
M Kollmann ◽  
...  
Keyword(s):  
Neural Network ◽  
Atrial Fibrillation ◽  
Deep Neural Network ◽  
Sampling Rate ◽  
Public Institution ◽  
Funding Source ◽  
Upper Arm ◽  
Recording Time ◽  
Reduced Ejection Fraction ◽  
Non Invasive

Abstract Background Atrial fibrillation (A-fib) is the most common arrhythmia; however, detection of A-fib is a challenge due to irregular occurrence. Purpose Evaluating feasibility and performance of a non-invasive medical wearable for detection of A-fib. Methods In the CoMMoD-A-fib trial admitted patients with a high risk for A-fib carried the wearable and an ECG Holter (control) in parallel over a period of 24 hours under not physically restricted conditions. The wearable with a tight-fit upper arm band employs a photoplethysmography (PPG) technology enabling a high sampling rate. Different algorithms (including a deep neural network) were applied to 5 min PPG datasets for detection of A-fib. Proportion of monitoring time automatically interpretable by algorithms (= interpretable time) was analyzed for influencing factors. Results In 102 inpatients (age 71.0±11.9 years; 52% male) 2306 hours of parallel recording time could be obtained; 1781 hours (77.2%) of these were automatically interpretable by an algorithm analyzing PPG derived intervals. Detection of A-Fib was possible with a sensitivity of 92.7% and specificity of 92.4% (AUC 0.96). Also during physical activity, detection of A-fib was sufficiently possible (sensitivity 90.1% and specificity 91.2%). Usage of the deep neural network improved detection of A-fib further (sensitivity 95.4% and specificity 96.2%). A higher prevalence of heart failure with reduced ejection fraction was observed in patients with a low interpretable time (p=0.080). Conclusion Detection of A-fib by means of an upper arm non-invasive medical wearable with a high resolution is reliably possible under inpatient conditions. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Internal grant program (PhD and Dr. rer. nat. Program Biomedicine) of the Faculty of Health at Witten/Herdecke University, Germany. HELIOS Kliniken GmbH (Grant-ID 047476), Germany

The role of epicardial fat tissue in atrial fibrillation onset in patients with hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tarzimanova ◽  
V.I Podzolkov ◽  
M.V Pisarev ◽  
R.G Gataulin ◽  
K.A Oganesian
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Concentration ◽  
Sinus Rhythm ◽  
Epicardial Fat ◽  
Funding Source ◽  
Fat Tissue ◽  
Hypertensive Patients ◽  
Group I ◽  
Epicardial Fat Tissue ◽  
Group Ii

Abstract Aim To study the influence of epicardial fat tissue (EFT) on atrial fibrillation (AF) occurrence in hypertensive patients. Materials and methods The study included 195 patients with hypertension aged from 38 to 72 years (mean age was 61.5±1.8 years). All patients were divided into two groups: group I included 95 hypertensive patients with paroxysmal AF; 100 patients with hypertension in sinus rhythm were enrolled into group II. Echocardiography was performed to evaluate the thickness of EFT in a parasternal long-axis view. The EFT volume was assessed with computed tomography (CT) scan. The plasma concentration of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-9 (MMP-9) was measured to evaluate the myocardial fibrosis process. Results There was no significant difference between the studied groups of patients in body mass index: 34.43±1.2 kg/m2 in group I vs 31.97±1.67 kg/m2 in the group II. Waist circumference was significantly higher in group I in comparison with the group II patients: 118.9±3.3 cm vs 110.2±1.4 cm, respectively (p=0.038). EFT thickness was significantly higher in patients with paroxysmal AF (11.6±0.8 mm) in comparison with the patients in sinus rhythm (8.6±0.4 mm) (p<0.001). In group I patients a significant increase of EFT volume (4.6±0.4) in comparison with II group (3.5±0.25) (p=0.002) was noted. A significant positive correlation was revealed in hypertensive patients with paroxysmal AF between EFT volume and left atrial (LA) volume (r=0.7, p=0.022). Also, the plasma concentrations of TIMP-1 and MMP-1 were significantly higher in patients with paroxysmal AF and hypertension. There was a strong positive correlation between EFT volume and plasma concentration of TIMP-1 (r=0.72; p=0.01) and between the EFT volume and the LA volume (r=0.7, p=0.022) in group I patients. Multivariate regression analysis revealed the significant influence of increased EFT thickness more than 10 mm (prevalence ratio (PR) 4.1; 95% CI 1.1; 15.6) and EFT volume more than 6 ml (PR 3.7; 95% CI 1.0; 14.2) on AF occurrence. Conclusion Increased EFT thickness (more than 10 mm) and EFT volume (more than 6 ml) are predictors of AF onset in hypertensive patients. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The complex subject of the Department

scholarly journals Non-invasive mid-term ECG monitoring for the detection of atrial fibrillation in an outpatient population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Cai ◽  
K.K Yeo ◽  
P Wong ◽  
C.K Ching
Keyword(s):  
Atrial Fibrillation ◽  
Public Institution ◽  
First Episode ◽  
Prior History ◽  
Funding Source ◽  
Monitoring Device ◽  
Ecg Monitoring ◽  
Non Invasive ◽  
Increased Risk ◽  
The Mean

Abstract Background Atrial fibrillation (AF) is a common arrhythmia with significant morbidity due to an increased risk of ischemic stroke. Outpatient electrocardiogram (ECG) monitoring is an integral part of the diagnosis of AF. Conventional 24 hour Holter monitoring can be cumbersome and often fails to diagnose patients with paroxysmal AF. Spyder ECG is a non-invasive ECG monitoring device that allows wireless transmission of ECG information for analysis. It is small and comfortable, allowing for easy application for the screening and detection of AF over a mid-term duration. Purpose This study aims to evaluate the incidence of AF in patients with no prior AF and CHADsVASC score of at least 1 with the use of the Spyder ECG mid-term ECG monitoring device. Methods Patients aged 21 to 85 years old with no prior history of AF and CHADsVASC score of at least 1 were recruited from outpatient clinics of 3 large tertiary hospitals in Singapore from December 2016 to April 2019. Patients wore the Spyder ECG device for up to 2 weeks, during which continuous ECG information was uploaded onto a central cloud database and analysed. Results There were 363 patients recruited. The mean age was 61±10.0 years and 65.1% were male. There were 80.3% Chinese, 11.6% Malay, 7.5% Indian and 20.6% of other races. 68.3% of the patients were non-smokers and 74.0% of them were non-alcohol drinkers. The mean BMI of 25.5±4.7 kg/m2. The patient population had significant co-morbidities. 76.3% of the patients had hypertension, 69.4% of them had hyperlipidemia and 40.5% of them had diabetes mellitus. 10.0% of them had congestive cardiac failure and 56.7% had ischaemic heart disease. 11.3% of patients had a previous stroke and 20.4% had a prior myocardial infarction. 7.8% of the patients had asthma, 5.8% of them had thyroid disease and 9.9% of them had chronic kidney disease. They were monitored for a mean of 5.4±2.9 days each. There were 15 (4.1%) patients in whom AF was detected. The patients with AF wore the device for a mean of 5.7±2.0 SD days. The mean burden of AF was 9.0% of monitored time. 46.7% of the patients with AF had detection of AF on the first day, 26.7% on the second day, 13.3% on the third day and 13.3% on the seventh day. The mean duration of the first episode of AF was 251±325 minutes. 7 out of 15 (46.7%) of patients had first episodes of AF lasting less than 10 minutes. Conclusion Continuous mid-term ECG monitoring was able to detect AF in 15 (4.1%) of a population of 363 patients with no prior AF and CHADsVASC score of at least one, monitored for a mean of 5.4 days. Most episodes (53.3%) of AF were detected after the first day of ECG monitoring. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Duke-NUS Medical School Singapore

scholarly journals Effects of catheter ablation on left atrial performance in different types of atrial fibrillation: a strain study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Katbeh ◽  
T De Potter ◽  
P Geelen ◽  
E Stefanidis ◽  
K Iliodromitis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Time Course ◽  
Public Institution ◽  
P Value ◽  
Funding Source ◽  
Functional Changes ◽  
Af Recurrence

Abstract Background Atrial structural and functional changes may develop as a result of catheter ablation (CA) in patients with paroxysmal and persistent atrial fibrillation (AF). However, the relation between AF recurrence and atrial performance following CA is still under debate. Our aim is to describe the long-term effects of CA on LA remodeling and its correlates to the maintenance of sinus rhythm (SR). Methods We prospectively enrolled 178 consecutive patients (age: 63±9 years, 35% females) with paroxysmal AF undergoing first-CA (67%) or redo-CA (22%), and 20 individuals (11%) with long-standing persistent AF (PAF) undergoing first CA. All patients underwent comprehensive transthoracic echocardiography at baseline and at 12-month follow-up, including the assessment of reservoir and contractile strain (LAS) using two dimensional speckle tracking echocardiography in all three apical views. The study population was divided in two sub-groups according to AF recurrence during follow-up. Results During one-year follow-up, 144 (81%) patients maintained SR whereas 34 (19%) patients had AF recurrence [first-CA group 16 (13%), redo-CA group 8 (20%) and PAF group 10 (50%)]. Improvement of LAS was observed only in patients with paroxysmal and long-standing persistent AF who underwent the first CA and who remained in SR (Figure 1A, 1C). In contrast, recurrent AF was associated with absence of LAS improvement (Figure 1A, 1C). Different time course of LA performance was observed in the redo-CA group, i.e. LAS remained unchanged from baseline regardless of long-term maintenance of SR (Figure 1B). Moreover, at follow-up, no significant differences in LAS between redo-CA patients with SR versus AF were observed. Of note, in patients with long-standing persistent AF and SR, follow-up LAS increased to values observed in the redo-CA group. Conclusion LA performance following CA is strongly affected by complex interplay between extent of atrial electro-structural remodeling and CA procedure. Repeated wide CA might affects negatively LA compliance and contractility despite SR restoration. Figure 1. Reservoir and contractile LAS at Baseline and 12-month follow-up in the First-CA (1A), the Redo-CA (1B) and the long-standing persistent AF (1C) groups in patients who maintained SR versus patients who had AF recurrence. *p value <0.05 (baseline vs. follow-up). Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Association of biomarkers of inflammation with hospitalization for heart failure and death in patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.P Benz ◽  
S Aeschbacher ◽  
P Krisai ◽  
S Blum ◽  
P Meyre ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Incidence Rates ◽  
Adverse Outcomes ◽  
Funding Source ◽  
All Cause Mortality ◽  
Hs Crp ◽  
Multivariable Adjustment ◽  
Inflammation Score

Abstract Background Hospitalization for heart failure and death are among the most common adverse clinical outcomes in patients with atrial fibrillation (AF). The underlying mechanisms are poorly understood. Purpose We hypothesised that inflammation, quantified by plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6), is independently associated with hospitalization for heart failure and death in a large, contemporary cohort of AF patients. Methods Patients with established AF and 65 years of age or older were enrolled in two large, prospective, multicentre cohort studies in Switzerland. Plasma levels of high-sensitivity (hs) CRP and IL-6 were measured from frozen EDTA plasma samples obtained at baseline. Using these two biomarkers, we calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). We constructed multivariable Cox proportional hazards models to quantify the associations of hs-CRP, IL-6 and the inflammation score with time to first hospitalization for heart failure and time to all-cause mortality, respectively. Results A total of 3,784 patients with AF (median age 72 years, 28% women, 24% with a prior history of heart failure and 84% anticoagulation use at baseline) were followed for a median (interquartile range [IQR]) of 4.0 (2.9–5.1) years. The median (IQR) plasma levels of hs-CRP and IL-6 at baseline were 1.64 (0.81–3.69) mg/L and 3.42 (2.14–5.60) pg/mL, respectively. The incidence rates of hospitalization for heart failure and death were 3.04 and 2.80 per 100 person-years, respectively. After multivariable adjustment, both biomarkers were significantly associated with the risk of hospitalization for heart failure (per increase in 1 standard deviation [SD], adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] 1.11–1.34 for log-transformed hs-CRP, and aHR 1.48, 95% CI 1.35–1.62 for log-transformed IL-6) and death (per increase in 1 SD, aHR 1.40, 95% CI 1.27–1.54 for log-transformed hs-CRP, and aHR 1.67, 95% CI 1.53–1.81 for log-transformed IL-6). Incidence rates of hospitalization for heart failure increased from 1.34 to 7.31 per 100 person-years across categories of the inflammation score (Figure 1). A strong relationship persisted after multivariable adjustment. Similar findings were observed for all-cause mortality. Conclusions Inflammation is a strong predictor of hospitalization for heart failure and death in patients with AF. Targeting inflammation may be a promising treatment strategy to improve outcomes in these patients at high risk for adverse outcomes. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation

Left atrial dysfunction and dyssynchrony in paroxysmal atrial fibrillation: data from the akershus cardiac examination 1950 study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.G Solberg ◽  
E.N Aagaard ◽  
T Berge ◽  
P.S Roenningen ◽  
S Enger ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Ventricular ◽  
Public Institution ◽  
Left Ventricular Ejection ◽  
Chronic Obstructive ◽  
Funding Source ◽  
Obstructive Pulmonary Disease ◽  
Ventricular Ejection Fraction ◽  
Healthy Group

Abstract Background Left atrial (LA) strain measurements by speckle tracking echocardiography (STE) are predictive markers of cardiovascular morbidity, including atrial fibrillation (AF). LA mechanical dispersion (LA MD) is a new parameter derived from STE. A reduction of LA strain is considered to reflect LA dysfunction, while increased LA MD may reflect LA dyssynchrony. Purpose To assess LA dysfunction and dyssynchrony, as measured by STE, in patients with paroxysmal AF (pAF). Methods A subset of 616 participants in the Akershus Cardiac Examination 1950 Study were divided into three groups: (1) A healthy group (n=179) defined by excluding AF, coronary artery disease, stroke, hypertension, chronic obstructive pulmonary disease, body mass index >30, left ventricular ejection fraction <50%, transmitral E/e' >14 or E/A >2.0, (2) A non-healthy group (n=350) of participants without pAF, but with any of the above conditions, (3) A group with pAF, but in sinus rhythm at examination (n=87). LA reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct), as well as LA MD were assessed by STE. MD was defined as the standard deviation (SD) of time from ECG R to peak atrial longitudinal strain (SD-TPS), and corrected by RR-interval (SD-TPS/RR), expressing LA MD as a percentage of the cardiac cycle. Comparisons were made by Mann-Whitney U-test due to non-normal distributions. Results Mean age was 63.5±0.5 years and 46.6% were women. LASr, LAScd and LASct were significantly lower, and LA MD significantly higher in the pAF group compared to the healthy and non-healthy groups (Table; Figure). Conclusion The present study has demonstrated LA dysfunction and dyssynchrony in patients with pAF, which may reflect LA remodeling and increased fibrosis. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority

Pulmonary vein isolation procedure may be associated with intracranial artery microembolism and increased risk of acute neurological incidents

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lasek-Bal ◽  
P Puz ◽  
J Wieczorek ◽  
S Nowak ◽  
A.M Wnuk-Wojnar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Middle Cerebral Artery ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Cerebral Artery ◽  
Public Institution ◽  
Funding Source ◽  
Radiological Investigation ◽  
Cerebral Microembolism

Abstract Background Atrial fibrillation ablation can be associated with the microembolism detected in intracranial arteries and risk of acute neurological incidents. Purpose The aims of this study were a quantitative and a qualitative evaluation of microembolic signals (MES) during pulmonary vein isolation (PVI) and establishing the potential significance of MES for damage of brain assessed in radiological investigation and neurological state of patients. Methods To the prospective project we qualified patients with atrial fibrillation undergoing percutaneous pulmonary vein isolation (radiofrequency ablation / balloon cryoablation) with ultrasound monitoring of microembolisms in right middle cerebral artery. Baseline and up to 12 months post pulmonary vein isolation the neurological examination and brain MRI were performed in all participants. Results The study enrolled 80 patients at a mean age of 58 years. Microembolisms during the monitoring of the flow in the right middle cerebral artery were recorded in 61 (76.3%) patients in the amount of 51–489 (mean 239). Most often the microembolic signals were registered during the trans-septal puncture and the stage of ablation. In 89%, microembolisms were gaseous. Mean score on Fazekas scale for the whole group before ablation: 0.87±0.7 (0–3, med. 1); after: 0.93±0.71. In 3 (4.3%) patients the lesions worsened during the follow-up period. None of the patients revealed a cardiovascular event during the follow-up period and no changes were observed in the neurological status. Conclusions The majority of cerebral microembolism generated during PVI are gaseous in nature. The cerebral microembolism associated with PVI probably result from the technical aspects of the procedure and do not cause neither the permanent brain damage in the radiological investigation nor neurological deficit. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice, Poland - statutory work

Gene expression profiling and enrichment functional analyses to compare coronary microvessels and cardiomyocytes in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Pisano ◽  
L Le Pera ◽  
M Lombardi ◽  
F Ferre ◽  
R Carletti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Analysis ◽  
Hypertrophic Cardiomyopathy ◽  
Interventricular Septum ◽  
Functional Enrichment ◽  
Public Institution ◽  
Cardiomyocyte Hypertrophy ◽  
Coronary Microvascular Dysfunction ◽  
Funding Source ◽  
Rna Seq

Abstract Background Hypertrophic cardiomyopathy (HCM) is characterized by severe alterations of cardiac architecture and function involving cardiomyocytes (CM) and coronary microvessels (MV). Coronary microvascular dysfunction, cardiomyocyte hypertrophy and disarray, sarcomeric alterations and interstitial fibrosis are HCM features. The transcriptome profile associated with coronary MV and CM in HCM patients is presently unknown. Purpose Aim of this study was to improve knowledge of the molecular and biological pahways involved in HCM. To this purpose, the gene expression profile of coronary MV and CM was investigated. Methods Interventricular septum myectomies from patients with obstructive HCM and donors' hearts (CTR) were collected. Coronary MV (HCM=20, CTR=6) and CM (HCM=10, CTR=5) were laser capture microdissected. RNA-seq was performed by Illumina Nextseq 500, with 76 nt long single-reads. Adapter trimming and quality filtering of the sequenced reads were performed before alignment to the human reference genome. Univocally mapped reads estimated gene expression/sample. Normalized expressed gene levels were quantified. Statistical tests compared HCM and CTR to identify differentially expressed genes (DEG), i.e. up- and down-expressed genes in CM and MV samples. Functional enrichment analysis was performed. Biological categories, i.e. KEGG and Reactome pathways, Gene Ontology terms, protein domains in InterPro database, putative interactors collected in the Intact database and protein annotations in UniProt were considered for inter group comparison of DEGs. Results Transcriptome analysis identified 392 genes significantly up-regulated and 514 down-regulated in CM samples of HCM vs. CTR, while in MV 681 genes were up-regulated and 815 down-regulated. Although some DEGs were shared between MV and CM (26 and 146 are up- and down-expressed in both sample types), the majority of DEGs displayed a sample-specific pattern. A comparative functional analysis of DEGs highlighted some statistically enriched biological categories including an enrichment of phosphoproteins, with down-expressed genes both in CM (490) and MV (314). Other biological categories annotated as “ubiquitin-like protein conjugation” or “acetylation” in Uniprot database were enriched in down-regulated genes, both in MV and CM. Interestingly, “ribosomal protein” and “ribonucleoprotein” categories resulted as enriched up-regulated DEGs in MV. Conversely, the “citrullination” category was specifically present in annotations associated to down-regulated DEGs in MV from HCM compared to CTR. Conclusions Our preliminary results support the suitability of RNA-seq analysis to assess: i. the transcriptome profiles and pathways associated to coronary MV and CM; ii. the possible relationship/interplay of MV and CM profiles and HCM disease. The enrichment functional analysis provides preliminary data on candidate DEGs and target proteins for in vitro studies on HCM-related mechanisms. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Ministry of Health

Risk factors for silent and symptomatic atrial fibrillation in an elderly population screening programme:a report from the noninvasive monitoring for early detection of atrial fibrillation (NOMED-AF)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mitrega ◽  
B Sredniawa ◽  
J Stokwiszewski ◽  
A Sokal ◽  
J Boidol ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
General Population ◽  
Population Sample ◽  
Population Based ◽  
Public Institution ◽  
Elderly Subjects ◽  
Funding Source ◽  
Cross Sectional ◽  
Independent Risk Factors

Abstract Background It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited. Aim To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor. Methods The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression. Results The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF. Conclusions AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)

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