bluuebunny/crossref_metadata_2025 huggingface dataset:
3256Long-term safety of stereotactic body radiotherapy for ablation of ventricular tachycardia: a multicentric study
Authors: Cvek J , Knybel L , Neuwirth R , Jiravsky O , Sramko M , Peichel P , Januska J , Resova K , Kautzner J
Published: October 2019

Background

Contemporary stereotactic body radiotherapy (SBRT) enables to accurately concentrate high radiation doses to small volumes of myocardial tissue. There is a rising interest in using SBRT to modify arrhythmogenic substrate in patients with previously failed radiofrequency catheter ablation. However, data on the safety of SBRT for the treatment of VT are lacking.

Purpose

This study evaluated the long-term safety of SBRT for the treatment of VT.

Methods

SBRT was performed in patients with structural heart disease and failed catheter ablation for VT. The critical part of the VT substrate was identified by electroanatomic mapping (EAM) using a combination of voltage mapping, pace mapping, and activation mapping; and it was marked on a contrast-enhanced computer tomography study as a target for radioablation. SBRT was performed using a radiosurgery system with real-time motion tracking using the tip of the electrode of an indwelling defibrillator as a fiducial marker. A total radiation dose of 25 Gy was delivered to the ablation target in a single session during free breathing. Radiation-induced toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Results

Between 2014 and 2018, 18 patients from two electrophysiology centres underwent SBRT for recurrent, drug-resistant VT after previously failed catheter ablation (17 male, 1 female; mean age 63±9 years; 14 ischemic cardiopathy, 3 dilated cardiopathy, 1 fibroma). The mean volume of the ablation target was 34±17 ml, and the mean duration of the therapy was 78±14 minutes. No patient exhibited acute (up to 3 months) elevation of troponin, pericardial effusion, or a decrease in left ventricular ejection fraction from baseline. Four patients developed acute mild nausea, which waned after antiemetic drugs. Two patients gradually developed significant progression of mitral regurgitation after SBRT. One of the patients was treated medically (grade 3 toxicity), but the other had to undergo mitral valve replacement (grade 4 toxicity). No other cardiac or pulmonary radiation related toxicity was observed during a median follow-up of 23 months. Three patients died at 54, 43, and 18 month after SBRT. None of the deaths was related to VT recurrence or complication of SBRT.

CARTO, Radiation dose and Survival

Conclusions

This is the largest series of patients who underwent EAM-guided SBRT for VT as a bailout therapy after previously failed radiofrequency catheter ablation. Our preliminary data indicate the feasibility and safety of the procedure. To further investigate long-term safety and efficacy of SBRT for VT, we initiated a prospective multicentric study (NCT03819504).

Acknowledgement/Funding

Supported by RVO-FNOs/2014
3269Impact of type 2 diabetes on incidence and phenotype of heart failure in patients with atrial fibrillation
Authors: Polovina M , Milinkovic I , Krljanac G , Veljic I , Petrovic-Djordjevic I , Djikic D , Simic J , Pavlovic A , Kovacevic V , Asanin M , Seferovic P M
Published: October 2019

Background

Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised.

Purpose

In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up.

Methods

We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF.

Results

Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%).

Conclusions

T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.
3284Quantification of macrophage presence and identification of thin-cap fibroatheroma by optical coherence tomography image: histopathological validation study
Authors: Fujii K , Kawakami R , Imanaka T , Shibutani H , Kawai K , Hirota S , Shiojima I
Published: October 2019

Background

Intracoronary optical coherence tomography (OCT) is thought to be capable of identifying a vulnerable, rupture-prone plaque based on the presence of a thin-cap fibroatheroma (TCFA). Moreover, recent studies have reported that OCT may be able to identify macrophage infiltration of the fibrous cap, a key characteristic of vulnerable plaque.

Purpose

This study evaluated the accuracy of OCT image for characterizing TCFA and identifying macrophage infiltration in comparison with histopathology.

Methods

A total of 924 focal plaques in 206 coronary arteries from 78 autopsy hearts were examined to compare OCT and histological images. By histology, 16 plaques (1.7%) were classified as TCFAsthat contained a large necrotic core covered by a thin (<65μm) fibrous-cap. Correlating OCT-histological sections were identified and OCT-derived tissue property indexes named normalized standard deviation (NSD) and signal attenuation ratio were applied on the fibrous-cap to identify inflamed fibrous-cap defined as a macrophage percentage >10% by histology.

Results

With histology as standard, the sensitivity, specificity, and negative-predictive-value of TCFAs were extremely high (more than 90%). However, the positive-predictive-value of TCFAs was only 32%, which indicated a high proportion of false-positives. Most false-positive diagnoses of OCT for TCFAs contained large amounts of foam cell accumulations on luminal surface without necrotic core. Twelve of 16 fibrous-caps were considered as inflamed and the remaining 4 were non-inflamed on histology. However, no significant difference in NSD and signal attenuation ratio were identified between them. There was moderate correlation of the fibrous-cap thickness between OCT and histology (r2 = 0.41 and p<0.01).

Conclusions

OCT is a promising intracoronary imaging modality for differentiating tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identifying TCFA. However, it is still challenging to precisely identify inflammation, fibrous-cap thickness, and necrotic core in the native coronary artery. Therefore, careful interpretation is required to assess coronary vulnerable plaque by OCT.

Acknowledgement/Funding

None
3300MiR-126-3P and MiR-223-3p in Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty, The Prague-18 Genetic Sub-study
Authors: Hromadka M , Motovska Z , Karpisek M , Hlinomaz O , Miklik R , Tousek F , Jarkovsky J , Rokyta R , Krepelkova I , Izakova J , Widimsky P
Published: October 2019

Background

Balancing the intensity and duration of antiplatelet therapy according to thrombotic risk is a fundamental need in order to optimize therapy effectiveness and safety. Incorporation of new predictors in thrombotic risk stratification is therefore of a crucial importance for antiplatelet therapy net clinical benefit.

Purpose

The present analysis aimed to evaluate the relation of miR-126-3p and miR-223-3p, new markers of platelet activation, in order to facilitate prediction of recurrent thrombotic events after acute myocardial infarction (AMI).

Method

The analysis included 598 patients (age median 62 years, men 77.8%) randomized in the Prague-18 study (ticagrelor vs. prasugrel in AIM treated with primary PCI). During the study follow up, 40.6% of patients switched to clopidogrel. Determination of miR was evaluated 24 hours after admission; miR-126-3p and miR-223-3p were normalized by miR-423-3p and miR-150-5p. Quantitative determination of selected miRNAs was performed with a novel microRNA immunoassay method.

Selected miRNAs were compared with key efficacy endpoints (cardiovascular death, nonfatal MI and stroke), stent thrombosis and all hemorrhagic events, and analysed using univariate and multivariate logistic regressions.

Results

Increased values of miR-223-3p were significantly related to the occurrence of combined ischemic endpoint within 30 days [OR (95% CI) 15.739 (2.066; 119.932) p=0.008] and within one year [3.175 (1.40; 7.186) p=0.006]. Decreased ratio of miR-126-3P/miR-223-3p was significantly related to the occurrence of combined ischemic endpoint within 30 days [0.137 (0.031; 0.609) p=0.009] and one year [0.372 (0.169; 0.819) p=0.014]. MiRNAs were identified as independent predictors even after adjustment for confounding clinical predictors (Study arm, Switch to Clopidogrel, Age, Men, BMI, Smoking, History of Hyperlipidemia, Hypertension, DM, MI, PCI, CABG, Chronic heart failure, Chronic renal failure, Peripheral arterial disease, LBBB, RBBB, TIMI <3 after PCI, Number of diseased vessels >1, Stem disease, Suboptimal of failure of PCI, Time to hospital). Adjusted ORs (95% CI) are 11.828 (1.472; 98.011), p=0.022 and 2.394 (1.021; 5.610), p=0.045 for increased value of miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively; 0.151 (0.030; 0.757), p=0.022 and 0.407 (0.179; 0.925), p=0.032 for decreased ratio of miR-126–3P/miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively. No association between miRNA and bleeding complications was identified.

Conclusion

The miR-223-3p and miR-126-3p to miR-223-3p ratio are strong independent predictors of thrombotic ischemic events and can be used to stratify patients post AMI.
3306Endothelial cell senescence accelerates atherosclerosis by enhancing monocyte recruitment via hyper-reactivity to inflammatory stimuli
Authors: Honda S , Ikeda K , Hoshino A , Urata R , Yagi S , Emoto N , Matoba S
Published: October 2019

Background

Ageing is a significant risk factor for atherosclerotic diseases. Vascular senescence has been considered to play an important role in the progression of atherosclerosis; however, it remains unclear whether endothelial cell (EC) senescence is causally involved in the pathogenesis of atherosclerosis.

Purpose

The purpose of this study is to elucidate a causative role of senescent EC in the progression of atherosclerosis.

Methods

Telomeric repeat-binding factor 2 (TRF2) plays a central role in telomere maintenance and protection against end-to-end fusion of chromosome. We previously reported that overexpression of TRF2-dominant negative mutant (TRF2DN) induced premature senescence in EC. We recently generated EC-specific progeroid mice by overexpressing TRF2DN specifically in EC (TRF2DN-Tg), and then generated ApoE-KO/TRF2DN-Tg mice to analyze a role of EC senescence in atherosclerosis. These mice were fed with a high cholesterol-diet, and atherosclerosis was assessed by en face analysis of whole aorta and histological analysis of aortic sinus. In vitro studies to analyze the underlying mechanisms were performed using replicative senescent HUVECs.

Results

En face analysis of aorta revealed that atherosclerotic lesions were significantly increased in ApoE-KO/TRF2DN-Tg mice comparing with that in ApoE-KO mice at as early as 2 weeks after high-cholesterol diet. Histological analysis of aortic sinus also exhibited accelerated atherosclerosis in ApoE-KO/TRF2DN-Tg mice in association with increased macrophage infiltration. Mechanistically, we found that the induction of adhesion molecules such as VCAM-1, ICAM-1, and E-selectin in response to low-grade inflammatory stimuli was substantially augmented in senescent ECs comparing with that in young ECs. As a result, monocyte adhesion was significantly enhanced in senescent ECs. Of note, eNOS inhibition did not affect the hyper-reactivity of senescent EC to inflammation, while antagonizing NF-kB abolished it. Nuclear translocation of NF-kB in response to inflammation was not different between young and senescent ECs, suggesting that NF-kB transcriptional activity might be enhanced in senescent ECs.

Conclusion

We revealed a causative role of EC senescence in the progression of atherosclerosis in vivo using unique EC-specific progeroid mice. Our findings revealed that EC senescence is a bona fide risk for atherosclerosis, and thus senescent ECs are attracting pharmacotherapeutic targets for the prevention and/or treatment of atherosclerotic disease in elderly population.
3310Platelet complement C3 deposition predicts platelet hyperactivity in patients with type II diabetes
Authors: Berger M , Maxeiner S , Lysaja K M , Baldia P , Wessel L , Marx N , Schuett K M
Published: October 2019

Introduction

Atherothrombotic disease is associated with significant morbidity and mortality. Diabetes greatly increases the prothrombotic risk of individuals by factors that remain ill defined. Recently, increased plasma levels of complement C3 were associated with prothrombotic alterations in coagulation in patients with diabetes. The aim of this project was to evaluate the role of complement C3 on platelets in patients with type 2 diabetes.

Methods

Patients with type 2 diabetes (N=20) and controls (N=22) were included in the present study and assessed for platelet complement C3 deposition and expression of complement regulating proteins (e.g. CD35, CD55, CD59 and Factor H).

Results

Complement C3 was present on the surface of unstimulated platelets and significantly increased upon platelet activation (C3: 194±10 vs. C3-activated: 778±51 p=0.0001). Expression of complement C3 correlated significantly with platelet expression of CD35 and CD55, that are known to impair C3 breakdown, suggesting a key function in regulation of platelet complement deposition of these proteins (CD35 R2=0.374, p=0.001; CD55 R2 = 0.121 p=0.026). Interestingly, in patients with type 2 diabetes complement C3 deposition predicted platelet hyperactivity measured by P-selectin expression in an univariate analysis while this was not the case in control patients (Diabetes: std. β: 0.527; p=0.013 Controls: std.β 0.087 p=0.740). Using a multivariate approach complement C3 deposition remained a predictor for platelet hyperactivity after correction for dual antiplatelet therapy (DAPT), Aspirin treatment, BMI, age and basal platelet activity in patients with type II diabetes (Diabetes: std. β 0.490 p=0.049 Control: std. β −0.152 p=0.612). Since there was no quantitative difference in complement C3 deposition between the patient groups we hypothesised that a difference in complement activation might explain the differential effects of C3 deposition in these patient groups (Control: 186±54 vs. Diabetes: 202±76 p=0.422). Indeed, presence of the complement C3 metabolite iC3b, which is liberated by complement C3 activation, correlated significantly with HbA1c (R20.174; p=0.015) suggesting an increased complement activation in patients with diabetes. To test whether complement C3 activity influences platelet activity, we preincubated platelets with the complement activator cobra venom factor (CVF) or complement inhibitor CP40 (C3 inhibitor) and Eculizumab (C5 Inhibitor). While additive complement activation showed no effect on platelet activity (p=0.87), complement inhibition by either CP40 and Eculizumab led to a significant reduction in platelet activity (CP40% Inhibition: 15.81% ± 2.42 p=0.0006 Eculizumab % Inhibition: 31,71% ± 7.89, p=0.007).

Conclusion

Our data suggests that complement C3 deposition in patients with type 2 diabetes predicts platelet hyperactivity and these effects might be due to increased complement activation.
3328Relationship between streptococcal infective endocarditis and pre-neoplastic colorectal lesions
Authors: Vilardell P , Moral S , Bosch D , Morales M , Frigola J M , Albert X , Robles R , Kassem H , Aboal J , Brugada R
Published: October 2019

Background

Colorectal cancer is associated with infective endocarditis (IE), due to specific gut pathogens like streptococcus Gallolyticus that use the tumor presence as a point of blood entry. However, the association between streptococcal IE and pre-cancerous lesions such as dysplastic adenomas is unknown.

Objectives

To determine the association with pre-neoplastic colorectal lesions and streptococcal IE.

Methods

Two hundred eighty consecutive patients with IE were included retrospectively in a protocol of clinical, microbiological and imaging follow-up, between January 2008 and December 2018. Pre-cancerous lesions were divided as high and low-grade dysplasia based on World Health Organization criteria. Colorectal cancer was defined as the presence of malignant cell beyond the muscularis mucosa.

Results

Fifty patients (18%) presented neoplastic or pre-neoplastic lesions, and 26 of them (52%) were colorectal: 10 (38%) colorectal cancer and 16 (62%) precancerous lesions (12% high degree (n=2); 88% low degree (n=14)). Both, colorectal cancer (20% vs 5%; p=0.03) and pre-neoplastic lesions (44% vs 3%; p<0.05) were associated with higher incidence of streptococcus Gallolyticus IE (Figure 1). Additionally, 42% (n=11) of colorectal lesions were diagnosed in the IE event. No significant differences were found about cardiac surgery and in-hospital mortality in these patients.

Figure 1. Relationship between S. Gallolyticus IE and colorectal lesions. (a) Statistical significance between colorectal cancer and S. Gallolyticus IE. (b) Statistical significance between pre-neoplastic colorectal lesions and S. Gallolyticus IE.

Conclusions

Pre-cancerous colorectal lesions are also associated with streptococcus Gallolyticus IE, even low-grade lesions. Hence, it is necessary to rule out occult neoplastic and also pre-neoplastic colorectal lesions with colonoscopy in these patients.
4077Sex-specific aging effects on iliofemoral and carotid atherosclerotic plaque composition in vascular surgery patients
Authors: De Bakker M , Van Koeverden I D , Timmerman N , De Kleijn D P V , De Borst G J , Pasterkamp G , Boersma H , Den Ruijter H M
Published: October 2019

Introduction

Knowledge on factors that influence atherosclerotic plaque composition may allow improved risk stratification and treatment selection in iliofemoral and carotid atherosclerotic disease, since outcomes of different treatment strategies are influenced by the type of underlying lesions. The sex- and age-related differences in iliofemoral atherosclerotic plaque composition is largely unknown. Unravelling the intertwined relation between sex, age and plaque composition might provide important implications for the treatment of peripheral artery disease.

Purpose

We aimed to elucidate the associations between sex, age and plaque composition in a histopathological analysis of plaque specimens of patients undergoing iliofemoral endarterectomy. Given the systemic nature of atherosclerosis, analyses are replicated in atherosclerotic plaque specimens obtained from patients undergoing carotid surgery.

Methods

Peripheral atherosclerotic plaques of 790 patients who underwent iliofemoral endarterectomy were harvested between 2002 and 2014. A cohort of patients (n=2006) who underwent carotid endarterectomy was used to replicate analyses on sex-specific aging effects in plaques from a different vascular bed. The atherosclerotic plaques were semi-quantitatively analyzed for the presence of lipid cores, plaque calcifications, plaque hemorrhages and collagen, macrophage and smooth muscle cell content, and quantitatively for microvessel density. Patients were stratified by age tertiles and by sex.

Results

Men had a higher prevalence of lipid cores (25.7% versus 20.5%, odds ratio [OR] 1.62 and 95% confidence interval [CI] 1.06–2.45, P=0.025) and plaque hemorrhage (54.3% versus 42.9%, OR 1.62 and 95% CI 1.16–2.54, P=0.004) when compared to women. Women showed an increase in plaque calcifications, plaque hemorrhage and a decrease in macrophages with increasing age (figure panel B, D, E), whereas men only showed a decrease in collagen content (figure panel C). These sex-specific aging effects were replicated in plaques obtained from the carotid arteries.

s

Conclusion

Atherosclerotic iliofemoral plaques derived from men display more rupture-prone characteristics compared to women. However, advanced age was more often associated with an increase in the presence of vulnerable plaque characteristics in women as compared to men in both the iliofemoral and carotid atherosclerotic plaque.
4096Additive effects of exercise training upon cognitive function in regular red wine consumers compared to abstainers
Authors: Nishiyama M , Campane L Z , Nucci M P , Zuben M V , Trombetta I C , Rondon E , Negrao C E , Junior E A , Laurindo F R M , Da Luz P L
Published: October 2019

Background

Although regular red wine (RW) consumption and physical exercise (PE) exert cardiovascular protection a possible aditive effect of both is unknown, especially regarding cognition.

Purpose

To investigate the effects of supervised PE upon cognitive function in regular RW consumers compared to abstainers (Abs)

Methods

Cognitive function was assessed by functional Cerebral Magnetic Resonance Image (fMRI) through Stroop Color Word test (Stroop) for executive function and 2-back for working memory as well as neuropsychological tests (trails A, B and Stroop1). Seventy three healthy males, aged 59±5.9 (SD) years were divided into 4 groups: 37 Abs (17 with PE, 20 without) and 36 RW drinkers (17 with PE, 19 without) and then were randomized in the pre-PE phase, either to supervised PE for 3 months, 3x week/1h duration or no PE. Cardiopulmonary exercise test (CET) was performed before and after interventions. Plasma lipids and glucose also were measured.

Results

Drinkers ingested 19.8±10.3 (SD) gr of ethanol/day as RW for an average of 26.1±15.7 years and did not change their habits during the study period. In pre-PE phase RW drinkers showed lower execution times than Abs in neurophsychological tests (trails A and B and Stroop1) and higher accuracy in the 2-back test in fMRI (p<0.05 for both). Furthermore, in post intervention phase, RW consumers with PE showed a trend towards improvement in executive function (Stroop: % accuracy 92.5±9.2 vs 95.6±5.0, p=0.05) and reduction in execution time (21.9±6 vs 19±3.4; p=0.049) as well as in neuropsychological Stroop-2 (p<0.05).In parallel there were no changes in activated cerebral áreas in either group after PE. However, there was a negative correlation between peak VO2 and activated brain areas by fMRI (Expert Analysis Tool based on the Generalized Linear Model; p<0.05) in both Abs and drinkers.

In contrast, there were no significant changes in any cognition test among abstainers regardless of PE; also there were no changes in metabolic profile. PE induced significant increments in peak VO2 in all PE groups (p<0.05).

fMRI BOLD sign during 2-back test

Conclusion

Physical exercise induced further improvement in executive function and working memory in long term RW drinkers, while no effects occurred in abstainers. Such effect was correlated with global fitness, as assessed by peak VO2.

Acknowledgement/Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo; Banco Bradesco SA
4101Identification of genetic variants associated with the cardiovascular disease risk factor, low aerobic fitness - The HUNT study
Authors: Bye A , Ryeng E , Silva J J , Moreira J B , Stensvold D , Wisloff U
Published: October 2019

Background: Low maximal oxygen uptake (VO2max) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. Although physical activity is a major determinant of VO2maxlevel, genetics contribution is estimated to be ∼50%.

Methods

We performed a genetic association study on 123.545 single-nucleotide polymorphisms (SNPs) and directly measured VO2max in 3470 individuals (exploration cohort). The candidate SNPs were subsequently analyzed in a separate cohort of 718 individuals (validation cohort), in addition to 7 wild-card SNPs previously associated with VO2max, but not included on the chip used in the exploration cohort. Sub-analyses were performed for each gender. In silico analysis and genotype-phenotype databases were used to predict physiological function of the SNPs.

Results

In the exploration cohort, 42 SNPs were associated with VO2max (p<5.0×10–4). Six of the candidate SNPs were also found to be associated with VO2max in the validation cohort (p<0.05, either in men, women or both), in addition to three wild-card SNPs. By using these nine SNPs we created a genetic score for inborn VO2max-level. Together, these nine SNPs explained ∼8% of the variation in VO2max, and discriminate individuals with inborn high versus low VO2max based on simultaneous carriage of multiple favorable alleles. The cumulative number of favorable SNPs correlated negatively with the presence of several CVDrisk factors, e.g. waist-circumference, visceral fat, fat %, cholesterol levels and BMI. In silico analysis indicated that several of the SNPs influence gene expression across multiple organs, including adipose tissue, skeletal muscle and heart.

Conclusion

We identified six novel genetic variants associated with VO2max, and validated three SNPs previously associated with fitness related traits.

Acknowledgement/Funding

K.G. Jebsen Foundation, the Norwegian Health Association, the Liaison Committee between the Central Norway Regional Health Authority (RHA) and NTNU
4328Short-term effects of dapagliflozin versus canagliflozin on acute decompensated heart failure in patients with type 2 diabetes
Authors: Nakagaito M , Joho S , Ushijima R , Nakamura M , Hirai T , Kinugawa K
Published: October 2019

Background

The CANVAS program and DECLERE-TIMI 58 reported that SGLT2i had been demonstrated to reduce hospitalization for heart failure (HF) in type 2 diabetic mellitus (T2DM) patients with high cardiovascular disease risk. However, it remains unclear whether the effectiveness of SGLT2i on acute decompensated HF is also observed in T2DM patients irrespective of acting types of SGLT2i.

Methods

In this single center, open-label, prospective study, fifty-eight T2DM patients hospitalized due to decompensated HF were enrolled (mean age 73 years, HbA1c 7.2%). After treatment for HF, 5mg/day of dapagliflozin (n=24, from February 2016 to February 2017) or 100mg/day of canagliflozin (n=34, from March 2017 to July 2018) was administered and clinical parameters about HF and T2DM were followed for 7 days. Statistical comparison of parameters between groups taking dapagliflozin or canagliflozin was performed using the two-way repeated measures analysis of variance (MANOVA).

Results

In both groups, urine glucose excretion increased significantly after administration of SGLT2i. Fasting blood glucose level tended to be decreased in both groups. Urine volume increased significantly one day after administration of SGLT2i, and returned to the baseline after one week in both groups. Interestingly, urine volume one day after administration of SGLT2i tended to increase more in the group taking canagliflozin than in the group taking dapagliflozin (interaction P value = 0.088). Importantly, plasma BNP levels and Nt-proBNP levels were decreased significantly in both groups.

Parameters before and after treatment Baseline Day 7 (Day 1) P value Interaction P value Fasting blood glucose, mg/dL All 137±57 122±51 0.013 0.900 Dapa 144±64 133±53 0.089 Cana 128±64 118±40 0.069 log BNP All 5.31±1.11 4.91±1.09 <0.001 0.102 Dapa 5.48±1.04 4.94±1.00 <0.001 Cana 5.20±1.15 4.89±1.16 <0.001 log Nt-proBNP All 7.25±1.35 6.96±1.41 <0.001 0.735 Dapa 7.54±1.16 7.22±1.25 0.048 Cana 7.04±1.45 6.79±1.50 0.005 Urine volume (Day 1), mL/24h All 1218±523 1584±614 <0.001 0.088 Dapa 1261±564 1486±568 0.038 Cana 1186±498 1654±644 <0.001 Urine volume (Day 7), mL/24h All 1218±523 1305±408 0.128 0.428 Dapa 1261±564 1295±468 0.700 Cana 1186±498 1313±367 0.097 Urine glucose, g/24h All 1.6±5.5 23.7±23.5 <0.001 0.330 Dapa 1.7±6.8 20.3±21.7 <0.001 Cana 1.5±4.6 26.0±24.7 <0.001

Conclusion

SGLT2i are useful for correcting volume overload and recovering from the decompensated state in HF patients with T2DM irrespective of acting types of SGLT2i.
P3111Empagliflozin, a SGLT2 inhibitor, attenuates endothelial dysfunction and atherogenesis by inhibiting inflammatory responses in the vasculature and adipose tissue in diabetic apolipoprotein E-deficient
Authors: Ganbaatar B , Fukuda D , Yagi S , Kusunose K , Yamada H , Soeki T , Sata M
Published: October 2019

Background

Inflammation and oxidative stress associated with hyperglycemia are major causes of vascular dysfunction and cardiovascular complications in diabetes. Recent studies reported that cardioprotective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors, however underlying mechanisms are still obscure.

Purpose

The aim of this study was to investigate whether empagliflozin attenuates atherogenesis and endothelial dysfunction in diabetic apolipoprotein E-deficient (ApoE−/−) mice and investigated underlying mechanisms.

Methods

ApoE−/− mice were injected with streptozotocin (75 mg/kg) for 3 consecutive days. One week after last injection, a western type diet and administration of empagliflozin (20 mg/kg/day) or vehicle via oral gavage were started. Atherosclerotic plaque area was examined by en face Sudan IV staining. Lipid deposition and inflammatory features of atherosclerotic plaques was examined on lesions in the aortic root by immunohistochemical analysis. Vascular function was assessed by isometric tension recording. mRNA or protein expression level was examined by quantitative RT-PCR (qPCR) or western blot analysis, respectively. In in vitro experiments, murine macrophage cell line, RAW264.7, was used.

Results

Treatment with empagliflozin for 12 weeks significantly decreased atherosclerotic plaque size in the aortic arch compared with untreated group (p<0.01). Empagliflozin reduced blood glucose (p<0.001) and plasma lipid levels. Results of histological analyses revealed that empagliflozin decreased lipid deposition, macrophage accumulation, and the expression of inflammatory molecules in the aortic root. Empagliflozin treatment for 8 weeks significantly attenuated endothelial dysfunction as determined by vascular response to acetylcholine. qPCR results demonstrated that empagliflozin reduced the expression of inflammatory molecules such as MCP-1 (p<0.05), ICAM-1 (p<0.05) and Nox-2 (p<0.05), a major NADPH oxidase subunit, in the aorta compared with the untreated group. Furthermore, empagliflozin significantly mitigated the expression of these inflammatory molecules in fat tissues around the aortic arch as determined by qPCR. In in vitro studies, methylglyoxal (MGO), a precursor of AGEs, increased the expression of inflammatory molecules (e.g., MCP-1, IL-1b and TNF-a (p<0.05, respectively)) in RAW264.7 cells. MGO also significantly induced activation of JNK and p38 MAP kinase (p<0.001, respectively) in this cell-type.

Conclusions

Empagliflozin attenuated endothelial dysfunction and atherogenesis in diabetic ApoE−/− mice. Reduction of inflammation in the vasculature and peri-vascular adipose tissues may have a role as underlying mechanisms at least partially.
P3344Research network in Africa (RNA): observatory of hospitalizations in cardiology departments in 14 African countries (FEBRUARY Study: 2016, 2017 and 2018)
Authors: Kingue S , Kouam Kouam C , Suliman A , Antignac M , Empana J P , Jolis N , Traore A , Toure I A , Damorou J M , Sidy Ali A , Ikama S M , Niakara A , Balde D , Jouven X , Diop I B
Published: October 2019

Background

Epidemiological transition in the developing world has resulted in a shift from infectious to non-communicable diseases as leading causes of morbidity and mortality, cardiovascular (CV) disease (CVD) is the first cause of death in Africa. However, data regarding the characteristic of patients with CVD are scarce, especially in Sub-Saharan Africa.

Purpose

We built an observatory recording the characteristics of all patients admitted to hospital in CV departments and hospital care components in Sub-Saharan Africa (FEBRUARY Study).

Methods

We conducted a transversal and longitudinal study in CV departments of 29 hospitals from 14 African countries. FEBRUARY study was designed by a multidisciplinary collaborative team of epidemiologists, pharmacists and cardiologists from Africa and France. This ongoing observatory included all patients admitted in hospitalization during the month of February every year since 2016 and will continue every year. Data including socio-demographic and clinical characteristics, causes of admission, clinical, biological, complementary examinations, treatments, length of stay and discharge diagnosis were collected by the investigating physicians.

Results

Overall 2680 patients were admitted to hospital in February 2016 (n=736), 2017 (n=967), and 2018 (n=987) in CV departments from 14 countries: Benin, Burkina Faso, Burundi, Cameroon, Congo, Côte d'Ivoire, Gabon, Guinea, Mali, Niger, Dem. Rep of The Congo, Senegal, Togo and Sudan (figure). Men represented 58,8%. Mean age of age was 54 years and Women 52 years. The mean length of stay was 9 days, and death rate 10,1%. The main cause of admission was cardiac failure (40,3%) followed by acute coronary syndrome (10.1%) and stroke (9,3%). Among CV risk factors, high blood pressure, sedentary behavior, diabetes, active tobacco consumption and dyslipidemia were present in 46%, 19%, 13%, 11% and 6% of patients, respectively.

In a longitudinal analysis, hospital admission due coronary syndrome increased from 7% in 2016 to 10.5% in 2018 (p for trend = 0.03). Length of hospital stay and rate of hospital death remain stable.

Hospitalizations by country (FEBRUARY)

Conclusion

The FEBRUARY observatory is an important tool to describe cardiovascular characteristics of patients in transversal analysis, but also the longitudinal evolution over the coming years in Sub-Saharan Africa.
P3345Stroke and death in atrial fibrillation patients newly treated by oral anticoagulants in France: a national cohort study 2012–2016
Authors: Gabet A , Chatignoux E , Bejot Y , Olie V
Published: October 2019

Background

Introduction of new oral anticoagulants (OAC) lead to an increase in atrial fibrillation (AF) patients treated with those drugs. Few epidemiological data on outcomes are available in France or abroad in this population. There is an important need to follow up patients newly diagnosed for AF and treated by OAC, and estimate stroke and mortality outcomes at national level in unselected patients' population. The French “Système national des données de santé” (SNDS) gathered enough medical information on the overall French population, with complete follow-up until patient's death.

Purpose

The objective of this study was to analyze stroke and death outcomes and their determinants in a cohort of AF patients newly treated by OAC in France between 2012 and 2016.

Methods

All AF patients aged over 20 years old, residing in France, and newly treated by OAC between 2012 and 2016 were included in a cohort. The date of OAC delivery was considered as the inclusion date. Patients were followed till 31 of December 2017. Main outcomes studied were the first hospitalisation for stroke or death. We used a Fine and Gray regression model to estimate subdistribution hazard ratio (SHR) for stroke. Cox regression models were used to compute cause-specific hazard ratios (CSHR) for stroke and death respectively. Analyses were adjusted for main confounders.

Results

The total number of patients enrolled in the study for the period 2012–2016 was 662,298. Mean age at inclusion was 74.9 years old. Women accounted for 47.8% of the study population. Globally, 3.8% of patients experienced stroke after initiation of OAC and 13.9% of patients died over the study period with 1.1% of death occurring after a stroke. The median follow-up for stroke or death events was 1094 days, 1208 days for stroke and 1123 days for death. Incidence rates of stroke or death reached 53.3 [53.0–53.6] per 1,000 person-year and, 11.3 [11.2–11.5] and 44.0 [43.7–44.3] for stroke and death respectively. Advanced age, history of stroke, acute coronary syndrome (ACS), chronic kidney disease (CKD), treated hypertension, diabetes and to be included during the first year of the study period were associated with an increase in the subdistribution hazard of stroke. Significant differences were found by age group such as an increase in SHR for stroke in women aged over 85 years compared to men of the same age. Cause-specific analyzes gave similar results for stroke. History of heart failure, ACS, CKD, hemorrhages, treated hypertension and diabetes were associated with increased hazard of death. On the contrary, female sex was associated with a significant decrease in the hazard of death only.

Conclusion

Stroke incidence and mortality rate in AF patients newly treated by OAC were high. Several factors were associated with increased hazard of stroke and death but differed according to patient's age.
P3352Telemedicine transcends national boundaries in quest of creating a behemoth ami program
Authors: Mehta S , Botelho R , Fernandez F , Feres F , Abizaid A , Cade J , Perin M , Prudente M , Cavalcanti R , Dusilek C , Frauenfelder A , Matheus C , Pinto G , Mazzini J , Quintero S
Published: October 2019

Background

The Latin America Telemedicine Infarct Network (LATIN) has exploited the remarkable competence of telemedicine for remote guidance. In doing so, LATIN created a mammoth population-based AMI network that employed experts located several hundred miles away to guide the reperfusion strategies for almost 800,000 screened patients. In this pioneering project, telemedicine was initially utilized to guide AMI management within national confines. We speculated whether LATIN telemedicine navigation could outstrip countrywide borders.

Purpose

To maximally harness the vast possibilities of telemedicine for improving AMI care.

Methods

During its pilot phase, LATIN began as a hub and spoke, AMI system in Colombia where 20 spokes (small community health centers and rural clinics) were configured with 3 hubs that could perform Primary PCI. These sites were linked through web-based connectivity. Expert cardiologists, located 50–250 miles away in Bogota, Colombia, used sophisticated telemedicine platforms for urgent EKG diagnosis and teleconsultation of the entire AMI process. Based upon the duration of chest pain and travel time to the hub, these experts guided patients through guideline-based strategies of thrombolysis, pharmaco invasive management or primary PCI. Efficiency of the telemedicine process was measured with the new metric of time to telemedicine diagnosis (TTD). Cloud computing, GPS navigation, and numerous business intelligent tools were gradually incorporated into LATIN telemedicine. As systems became more scalable, the program was expanded to Brazil, where LATIN flourished. Over the last 18 months, LATIN telemedicine capabilities have been pressed across national boundaries. Presently, all 82 LATIN centers in Mexico are guided by experts located in Bogota, Colombia and the 7 Argentina centers channeled through Santiago, Chile.

Results

784,947 patients were screened for AMI at 350 LATIN centers (Brazil 143, Colombia 118, Mexico 82, Argentina 7). Navigation pathways are depicted in the attached figure. TTD remains extremely low in all four countries, and comparable efficiency and tele-accuracy have been achieved. With expanded geographic reach, 8,448 (1.08%) patients were diagnosed with STEMI and 3,911 (46.3%) urgently reperfused, including 3,049 (78%) with Primary PCI. Time to TTD ranged between 2.8 to 5.8 minutes, with a mean of 3.5 min. Tele-accuracy was 98.5%, D2B 51 min, and in-hospital mortality 5.2%. Various other comparative metrics for the 4 countries are being gathered and will be available at the time of presentation.

Conclusions

LATIN demonstrates the robust ability of telemedicine to transcend national boundaries to guide AMI management. This strategy can be adopted in under-developed countries in Asia and Africa to provide an umbrella of AMI care for the millions of disadvantaged patients.
P3368Mitral annulus disjunction retrospective assessment by transthoracic and transoesophageal echocardiography in a large cohort of patients with mitral valve prolapse and significant mitral regurgitation
Authors: Mantegazza V , Tamborini G , Gripari P , Ghulam Ali S , Volpato V , Italiano G , Fusini L , Muratori M , Pepi M
Published: October 2019

Background

The separation between the atrial wall-mitral valve junction and the left ventricular attachment (mitral annulus disjunction, MAD) is a recently discovered feature associated with Barlow's disease (BD). Correlations between MAD and morpho-functional alterations of the mitral valve (MV) apparatus have been described and different prevalence rates of MAD have been reported by several authors, analysing small sample size populations of patients with mixomatous MV prolapse (MVP).

Purpose

Aims of the study were 1) to estimate the prevalence and to assess MAD in a large cohort of patients with MVP (either BD or fibroelastic deficiency, FED) and significant mitral regurgitation with indication for surgical correction conforming to guidelines; 2) identification of any correlation between MAD and the MV anatomy, MVP aetiology and general characteristics of the study population.

Methods

A total of 979 patients presenting at our Centre from 2007 and 2018 with MVP and moderate-to-severe or severe mitral regurgitation were enrolled in the study. All patients underwent pre-operative transthoracic echocardiography (TTE) and 792 also intraoperative transoesophageal echocardiography (TOE). All recorded images and clips were saved in a central archive and were retrospectively analysed. MAD was defined as any distance observed between the atrial wall-MV junction and the left ventricular wall; it was evaluated in all available views and measured at end-systole.

Results

The overall population included 630 patients (64.4%) affected by BD and 349 (35.6%) with FED. Assessing off-line images from TTE and/or TOE, MAD was identified in 161 (16.4%) patients, respectively 21% and 8% in the BD and FED subgroups. Maximal MAD distance measured 6.6±2.2 mm at TTE and 6.7 mm ± 2.2 mm at TOE. Comparing MVP patients with and without MAD, it emerged that MAD was associated with younger age (60±14 vs 64±13 years, p<0.001) and slightly lower BMI (23.9±3.6 vs 24.5±3.6 kg/cm2, p=0.045). As concerns the MV apparatus, the presence of MAD showed a median larger MV annulus (medio-lateral diameter 41.0 [37.0–44.0] vs 39.0 [36.0–42.0] mm, p=0.001; antero-posterior diameter 38.0 [34.0–41.0] vs 36.0 [33.0–40.0] mm, p=0.001), greater incidence of bileaflet MVP (47.8% vs 25.9%, p<0.001) and mixomatous aetiology (82.0% vs 60.9%, p<0.001) and a lower prevalence of chordal rupture (61.5% vs 75.7%, p<0.001).

Conclusion

MAD significantly correlates with specific anatomical MV characteristics. Its prevalence results to be lower than reported in previous studies performed in different clinical contexts. In MVP population with surgical indication, MAD is clearly associated to BD, but it is also observed in a minority of patients with FED

Acknowledgement/Funding

None
P3372Prediction of outcome in functional mitral regurgitation using the average pixel intensity method
Authors: Kamoen V , El Haddad M , De Buyzere M , De Backer T , Timmermans F
Published: October 2019

Background

Functional mitral regurgitation (FMR) is a frequent finding in patients with systolic heart failure. However, the echocardiographic grading of MR is challenging and different severity cut-offs are recommended by international guidelines. We developed and validated a novel echocardiographic parameter to grade MR, the average pixel intensity (API) method, based on pixel intensity analysis of the continuous wave Doppler signal.

Purpose

In this study, we assessed the long-term predictive value of the API method on clinical endpoints in FMR.

Methods

Transthoracic echocardiography was performed in consecutive heart failure patients with reduced EF (HF-REF) (n=221). MR was assessed using the API method, vena contracta width (VCW), effective regurgitant orifice area (PISA-EROA) and regurgitant volume (PISA-RV). The primary clinical events were major adverse cardiac events (MACE: cardiovascular mortality, mitral valve surgery, percutaneous mitral intervention or heart failure hospitalization).

Results

The API method was feasible in 97% of all FMR patients, which was significantly higher than parameters such as VCW, PISA-EROA and PISA-RV. 84 patients (37%) had one or more clinical events during the follow-up period (cardiovascular mortality (20%), mitral valve surgery (5%), percutaneous mitral intervention (5%), heart failure hospitalization (16%) or heart transplantation (2%)). Based on ROC curves, an API cut-off of 121 au was defined as “severe” MVP-MR with an overall better sensitivity and specificity than current guideline-recommended parameters. On multivariate analysis, MR graded with API was independently predictive for clinical events, whereas PISA-based methods were not independent. In addition, pulmonary pressures and NYHA class were powerful independent predictors of clinical outcome in FMR on multivariate analysis.

Conclusions

The API method better predicts clinical events and outcome in FMR compared to established grading methods. Therefore, the API method may be considered for grading FMR severity in clinical practice.