bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6190Dynamic stress CTP with a whole-heart coverage scanner in addition to cCTA and FFRCT
Authors: Baggiano A , Guglielmo M , Muscogiuri G , Fusini L , Del Torto A , Andreini D , Mushtaq S , Conte E , Annoni A , Formenti A , Mancini E , Guaricci A I , Bartorelli A L , Pepi M , Pontone G 
Published: October 2019

Abstract

Background
Recently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experience used technology that was associated with high radiation exposure.

Purpose
The aim of the study is to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus FFR computed tomography derived (FFRCT) by using a whole-heart coverage CT scanner as compared to invasive coronary angiography (ICA) plus clinically indicate invasive fractional flow reserve (FFR).

Methods
Eighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner. FFRCT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant CAD in a vessel-based model of cCTA alone, cCTA+FFRCT, cCTA+CTP or cCTA+FFRCT+CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured.

Results
The prevalence of obstructive CAD and functionally significant CAD were 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFRCT and cCTA+CTP, were 83% and 66%, 86% and 75%, 73% and 86%, respectively. Both the addition of FFRCT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared to cCTA alone (0.826, p<0.05). The sequential strategy of cCTA+FFRCT+CTP showed the highest AUC (0.919, p<0.05) as compared to all other strategies. The mean ED for cCTA and stress CTP was 2.8±1.2 and 5.3±0.7 mSv, respectively.

Conclusions
The addition of dynamic stress CTP on top of cCTA and FFRCT provides additional diagnostic accuracy with acceptable radiation exposure.
P6203Intramyocellular lipid saturation as a new metabolic biomarker
Authors: Mezincescu A M , Ahearn T , Rudd A E , Cheyne L , Scally C , Horgan G , Philip S , Delibegovic M , Lobley G , Thies F , Gray S , Henning A , Dawson D K 
Published: October 2019

Abstract

Background
Endurance trained athletic healthy volunteers (Athl-HV) and type 2 diabetes patients (T2D) have higher levels of lipids in their skeletal myocytes compared to healthy controls. Despite apparently similar metabolic storage, they are at opposite ends of insulin sensitivity and cardio-metabolic risk.

Purpose
We investigated if the degree of saturation of the IntraMyoCellular Lipids (IMCL) will differentiate Athl-HV from T2D; and explored if an exercise intervention will induce changes in the IMCL saturation.

Methods
Male, age matched Athl-HV and T2D were enrolled (n=25/group). Athl-HV had ≥5 years endurance training, T2D were sedentary. Subjects were studied at baseline and after an exercise intervention (4 week deconditioning in Athl-HV and supervised bike training at ≥65% of peakVO2, 5 hours/week x 8 weeks in T2D). All subjects underwent cardio-pulmonary exercise testing (CPET), blood sampling for insulin sensitivity (QUICKI*) and single voxel 1H-magnetic resonance spectroscopy (1H-MRS) of the right vastus lateralis. 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression and analysed in LCModel. We derived fractional lipid mass (fLM) and fractions of saturated (fSL) and unsaturated (fUL) lipids. Data were analysed by t tests, shown as mean±SEM, statistical significance p<0.05.

Results
CPET and insulin sensitivity are presented in Table 1. T2D had higher fLM in the skeletal muscle compared to Athl-HV, at baseline (p=0.003) and after the exercise intervention (p=0.009), Figure 1A. At baseline, T2D had a different phenotype with a lower fSL and higher fUL compared to Athl-HV (82±3 vs 88±1% and 18±3 vs 12±1%, p=0.02 for both). Whilst deconditioning did not attract any significant changes in either fSL or fUL in Athl-HV (88±1 to 86±1% and 12±1 to 14±1, p=0.2), in contrast, with exercise training T2D significantly increased fSL (82±3 to 88±1%) and decreased their fUL (18±3 to 12±1%) (both p=0.01). Figure 1B and 1C.
CPET and insulin sensitivity results Athl-HV Baseline Athl-HV Deconditioning p value T2D Baseline T2D After Training p value VO2 peak, (mL/kg/min) 45.0±0.9† 41.7±0.9‡ <0.0001 23.6±0.6† 30.3±0.6‡ <0.0001 QUICKI* 0.346±0.002† 0.343±0.003‡ 0.2 0.308±0.004† 0.317±0.004‡ 0.02 *QUICKI: Quantitative Insulin Sensitivity Check Index; †Athl-HV vs T2D at baseline p≤0.001, ‡Athl-HV vs T2D after exercise intervention p≤0.001.
Figure 1

Conclusion
We demonstrate for the first time, in vivo, significant differences in the IMCL amount and saturation between Athl-HV and T2D. IMCL saturation was changed by exercise training in T2D to mirror the phenotype seen in Athl-HV uncovering a new, independent biomarker of improved cardio-metabolic health.

Acknowledgement/Funding
British Heart Foundation Project Grant no. PG/15/88/31780
P6209Relationship between skin autofluorescence levels and clinical outcomes in heart failure patients undergoing cardiac rehabilitation
Authors: Kunimoto M , Shimada K , Yokoyama M , Honzawa A , Yamada M , Matsubara T , Fukao K , Kadoguchi T , Fujiwara K , Miyazaki T , Yamamoto T , Takahashi T , Fujiwara T , Amano A , Daida H 
Published: October 2019

Abstract

Background
Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear.

Purpose
The purpose of this study was to investigate the prognostic value of SAF levels in patients with HF who underwent CR.

Methods
This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. The major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2018.

Results
Patients' mean age was 68.1 years, and 61% were males. Patients were divided into two groups according to the median SAF levels (high and low SAF groups). Patients in the high SAF group were significantly older, had a higher prevalence of chronic kidney disease, and histories of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a median follow-up period of 623 days, 25 patients experienced all-cause mortality and 34 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P<0.05), whereas when patients were divided into two groups according to the median hemoglobin A1c level, no significant between-group difference was observed for the incidence of MACE (Figure). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (hazard ratio: 1.74, 95% confidence interval: 1.12–2.65, P<0.05).
Figure 1

Conclusion
SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who undergo CR.
P6214How to improve long-term prevention in young patients after myocardial infarction - the IPP-Y study
Authors: Wienbergen H , Retzlaff T , Erdmann J , Michel S , Mata Marin L A , Wettwer T , Schmucker J , Osteresch R , Munz M , Fach A , Hambrecht R 
Published: October 2019

Abstract

Background
Patients who experienced myocardial infarction (MI) at a young age are of special medical and socioeconomic interest; cardiovascular risk factor control to prevent recurrent events is crucial in this specific cohort.

Objectives
The purpose of the study was to evaluate long-term risk factor control in young MI-patients in clinical practice and investigate the effects of a modern intensive prevention program in a prospective randomized trial. In a genetic substudy it was analyzed if prevention effects were depending on individual genetic risk.

Methods
Patients who had MI at age of ≤45 years were revisited after a mean period of 5.7±4.0 years to evaluate long-term risk factor control. Furthermore a 12-months intensive prevention program in young MI-patients (IPP-Y), coordinated by non-physician prevention assistants and including personal teachings, telephone contacts, clinical and telemetric control of risk factors, was compared to usual care in a randomized trial. Primary endpoint of the randomized trial was prevention success, defined as improvement of one of the risk factors smoking, LDL cholesterol or physical inactivity without deterioration of the others. As the opposite prevention failure was defined as deterioration of one of the risk factors without improvement of the others. Genetic risk was assessed by polygenetic risk scores, based on 163 SNPs.

Results
Only a minority of the 277 young patients after MI achieved guideline-recommended risk factor targets at long-term follow-up visits: mean body mass index was 29.9±5.1 kg/m2, just 14.8% had a body mass index <25 kg/m2. More than one third (38.3%) were persistent or recurrent smokers. Mean LDL cholesterol level was 94±38 mg/dl, only 27.1% of the patients achieved LDL cholesterol levels <70 mg/dl.
However, the long-term prevention program IPP-Y led to a higher rate of the primary endpoint prevention success (IPP-Y: 49% vs. UC: 27%, p<0.05) and a lower rate of prevention failure (IPP-Y: 15% vs. UC: 38%, p<0.05) compared to usual care after 12 months (see figure). Telemetric control of risk factors as part of the prevention program was used by 71.4% of the patients.
In the genetic subanalysis prevention effects were found in both, patients with high genetic risk as well as patients with low genetic risk assessed by polygenetic risk scores (p=0.79 high vs. low genetic risk).
Effects of IPP-Y during 12 months

Conclusions
To our knowledge this is the first study on young patients with MI that demonstrates insufficient long-term risk factor control in clinical practice and significant effects of an intensive prevention program. Prevention effects were independent from individual genetic risk.

Acknowledgement/Funding
This work was supported by the Stiftung Bremer Herzen, Bremen, Germany and the Stiftung Bremer Wertpapierbörse, Bremen, Germany
P6225Uric acid visit-by-visit variability is an independent risk factor of CHD - and all-cause mortality
Authors: Goldbourt U 
Published: October 2019

Abstract

Variability of serum uric acid (SUA) has been seldom examined in connection with long-term morbidity and mortality. We present results from a study of male civil servants and municipal employees, estimating associations of visit-by-visit variability of SUA with long-term all-cause as well as cause-specific mortality.

Patients and methods
There were 10,059 men, aged 40–65, tenured civil servants and municipal employees in the territories of the three most populated urban areas. Of these, 8822 participated in three extensive examinations in 1963, 1965 and 1968 and underwent assessment of diabetes and coronary morbidity status. We conducted analysis examining whether the standard deviations of Z-scores of SUA (SUA-Z), across the three study visits, predicted fatal outcomes. SUA-Z was defined as the difference between the individual SUA and the mean of SUA, divided by the standard deviation (SD) for the pertinent examination, namely separately for the 1963, 1965 and 1968 means and SD. Hazard ratios (HR) associated with the SD of SUA-Z were calculated for 18-yr stroke and CHD mortality (1968 to 1986) and the 18-yr all-cause mortality associated with quartiles of the above variability. The lowest quartile served as the referent, adjusting for age. A subsequent model adjusted additionally for the baseline value of SUA as well as for baseline frequency of diabetes mellitus and coronary heart disease (CHD)

Results
Multivariate analysis of 18-yr CHD mortality (1968–1986, 906 deaths among 8822 men) yielded a significant association with the 1963–1968 SD of SUA-Z with age adjusted HR of CD mortality of 0.99, 1.12 and 1.43 for quartiles 2 to 4 respectively (P using Mantel trend test=0.0002). Further adjustment for baseline prevalence of diabetes and CHD somewhat decreased the above HR estimates to 0.98, 1.04 and 1.29, respectively, with a HR=1.15 (95% CI, 1.07–1.23) per 1 mg/Dl increment of the 1963 SUA serum level.
The results for the 18-yr all-cause mortality (2836 deaths, 1968–1986) strongly indicated increasing age-adjusted mortality risk with increasing SD of SUA-Z: HRs= 1.08 (95% CI,0.97–1.21), 1.15 (1.03–1.28), and 1.37 (1.23–1.51). No association was observed between the SD of SUA-Z and 18 years stroke mortality. Sensitivity analysis, incorporating the last (1968) SUA levels assessed, rather than the 1963 ones, yielded virtually identical HRs.

Conclusion
In this cohort of tenured male workers, with diverse occupation, higher variability of SUA measurement taken in 1963–5-8 were clearly predictive of 18-year CHD and all-cause mortality, above and beyond the SUA levels proper.
P6266Circulating microparticules of patients with coronary artery disease up-regulate the expression of sodium-glucose cotransporters 1 and 2 in coronary artery endothelial cells: role of angiotensin II
Authors: Park S , Belcastro E , Hasan H , Bruckert C , Marchandot B , Kibler M , Toti F , Auger C , Jesel L , Ohlmann P , Morel O , Schini-Kerth V 
Published: October 2019

Abstract

Introduction
Circulating microparticles (MPs) from patients with coronary artery diseases (CAD) have been shown to promote endothelial senescence and dysfunction involving the pro-oxidant local angiotensin system. Sodium-glucose cotransporters (SGLTs)2 inhibitors decreased the risk of cardiovascular disease in patients with type 2 diabetes and this effect appears to be independent of glycemic control. Moreover, high glucose and H2O2 have been shown to cause a redox-sensitive upregulation of SGLT1 and 2 in coronary artery endothelial cells (ECs).

Aim
Therefore, this study examined whether angiotensin II (Ang II, a potent NADPH oxidase-dependent inducer of oxidative stress) and CAD MPs stimulate SGLT1 and 2 expression in ECs, and assessed their role in the induction of endothelial dysfunction.

Methods
ECs were isolated from porcine coronary arteries. The protein expression level was assessed by Western blot analysis and immunocytochemical staining, oxidative stress using dihydroethidium staining, and senescence by senescence-associated beta-galactosidase activity (SA-beta-gal activity). Circulating CAD MPs were collected from blood samples of patients (61–79 year) with established cardiovascular disease.

Results
Control ECs expressed low levels of SGLT1 and SGLT2 proteins. Exposure of ECs to Ang II caused a time- and concentration-dependent increase in the protein level of SGLT1 and SGLT2 with a significant increase observed at concentrations as low as 10 nM. Exposure of ECs to CAD MPs (10 nM PhtdSer eq) from 3/5 patients increased the SGLT1 and SGLT2 protein level. An increased SGLT1 and SGLT2 immunofluorescence signal was also observed in response to Ang II and H2O2. Ang II increased the level of oxidative stress, SA-beta-gal activity, senescence markers (p53, p21 and p16), VCAM-1, MCP-1, tissue factor (TF) and the local angiotensin system (ACE, AT1R), and down-regulated that of eNOS. CAD MPs from 4/5 patients decreased eNOS level and from 5/5 patients increased VCAM-1 level. All the Ang II-induced effects were prevented by the dual SGLT1/2 inhibitor LX-4211 and the selective SGLT2 inhibitor, empagliflozin.

Conclusions
The present findings indicate that CAD MPs and Ang II upregulate the expression of SGLT1 and SGLT2 protein levels in ECs, and that they promote endothelial dysfunction. They further suggest that inhibition of SGLT1 and/or SGLT2 might be an attractive strategy to protect the arterial wall and, hence, the development of cardiovascular diseases.

Acknowledgement/Funding
Unrestricted research grant from Boehringer Ingelheim Pharma GmbH & Co. KG
P6270Empagliflozin reduces the total burden of first and recurrent hospitalisations in patients with type 2 diabetes and established cardiovascular disease
Authors: McGuire D , Zinman B , Inzucchi S E , Anker S D , Wanner C , Kaspers S , Von Eynatten M , Johansen O.-E , Elsasser U , Pocock S , Fitchett D , Jamal W , Hantel S , Lund S S 
Published: October 2019

Abstract

Background and aims
The EMPA-REG OUTCOME trial included patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular (CV) disease. Empagliflozin reduced the risk of 3-point major adverse CV events (MACE; composite of CV death, myocardial infarction [MI], or stroke) by 14%, CV death by 38% and hospitalisation for heart failure (HF) by 35% vs placebo in analyses of time to first event. We assessed the effect of empagliflozin on all-cause hospitalisation in post-hoc analyses of all (first and recurrent) events.

Materials and methods
Patients were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care. We assessed the effects of empagliflozin pooled vs placebo on first event of all-cause hospitalisation using Cox regression and all (first and recurrent) events of all-cause hospitalisation using a negative binomial model.

Results
A total of 7020 patients were treated (4687 empagliflozin; 2333 placebo, mean [SD] age 63 [9] years, 71% male, 47% with history of MI, 23% with history of stroke, 10% with HF). In this analysis, 1725/4687 (36.8%) empagliflozin patients and 925/2333 (39.6%) placebo patients experienced an event leading to hospitalisation. The adjusted hazard ratio (HR; 95% CI) vs placebo for first all-cause hospitalisation using the Cox regression model was 0.89 (0.82, 0.96; p=0.0033; Figure); In analyses of all (first and recurrent) hospitalisation events, there were 3168 events in the empagliflozin group and 1863 in the placebo group. The adjusted event rate ratio (95% CI) vs placebo was 0.83 (0.76, 0.91; p<0.0001; Figure).

Conclusion
In the EMPA-REG OUTCOME trial, risk reductions with empagliflozin were seen in both first and all hospitalisation events and were numerically more favourable in analyses of all events vs analyses of first events. These analyses expand on the favourable CV effects of empagliflozin by also showing a reduction in the total burden of hospitalisation events in patients with T2D and established CV disease.

Acknowledgement/Funding
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
P6284The antioxidant MitoQ protects against intestinal disturbances in the experimental autoimmune model of myocarditis
Authors: Gallardo I , Gutierrez B , Hernandez M , Cabero I , Alvarez Y , Simon I , Munoz J C , San Roman J A , Cachofeiro V , Nieto Callejo M L 
Published: October 2019

Abstract

Purpose
Myocarditis and dilated cardiomyopathy represent the acute and chronic phases of an inflammatory disease of the myocardium, for which no standardized treatment is currently available in clinical practice. Myocardial fibrosis an oxidative stress are pathogenic factors associated with these processes. However, new research has found that gut health can be linked to some cardiac conditions. Thus, in this study we investigated whether intestinal disturbances are present in myocarditis, using a murine experimental autoimmune model (EAM) that mimics human myocarditis, as well as the potential beneficial effect of treatment with the mitochondrial antioxidant, MitoQ.

Methods and results
EAM was induced in BALB/c mice with a myocardiogenic peptide and mice were treated with MitoQ (50 mg/kg/day, i.p). On day 21 (acute phase), we assessed signs of heart injury (e.g. hypertrophy, fibrosis, oxidative stress) and parameters related to gut damage such as accumulation of reactive oxigen species (superoxide anion: O2·−), inflammation (IL-1β, IL-33, TNFα), microbial translocation (sCD14; intestinal fatty acid binding protein, I-FABP) and mucins in serum and/or intestine. MitoQ teatment significantly reduced the high heart weight/body weight ratio (HW/BW) of EAM mice, a characteristic hallmark of cardiac hyperthropy. Histological analysis of hearts showed presence of fibrosis (Sirius Red stain) and high O2·− levels (DHE stain) in EAM mice whereas these effects were not detectable in cardiac tissue from healthy or MitoQ-treated EAM mice. In addition, the enhanced O2·− ions (DHE stain) and mucin loss (Alcian Blu/PAS stain) found in colon, ileum, jejunum and duodenum sections from EAM mice were attenuated by MitoQ treatment. The systemic markers associated to intestinal barrier disruption, sCD14 and I-FABP, were found strongly increased in serum from EAM mice, and MitoQ prevents this rise. The beneficial MitoQ effects were also associated with a decrease in the pro-inflammatory cytokines TNFα, IL-33 and IL-1β, both in serum and colonic tissue of treated-EAM mice, as well as a reduction of the myeloperoxidase activity in colon, compared with untreated EAM mice.

Conclusion
Our data show that in addition to the heart, the intestinal tissue is also damaged in the preclinical model of experimental autoimmune myocarditis, and that MitoQ treatment could reverse this profile. Since there are systemic markers released from the intestine, therapeutic strategies targeting to prevent the intestinal oxidative stress and its associated gut barrier dysfunction, could contribute to the amelioration of the disease.

Acknowledgement/Funding
SAF2016-81063; CIBERCV