bluuebunny/crossref_metadata_2025 huggingface dataset:
P5276A prospective pilot study to identify a myocarditis cohort who may safely resume sports activities 3 months after diagnosis
Authors: Patriki D , Baltensperger N , Cooper L T , Kissel C K , Kottwitz J , Lovrinovic M , Manka R , Scherff F , Schmied C , Tanner F C , Luescher T F , Heidecker B
Published: October 2019

Background

Sports activities may promote arrhythmias in the setting of acute myocarditis. International cardiovascular society recommendations to return to sports activities following acute myocarditis are based on expert consensus in the absence of prospective studies.

Purpose

We sought to identify patients who may safely resume sports activities 3 months after acute myocarditis.

Methods

We prospectively enrolled 27 patients with newly diagnosed myocarditis based on clinical parameters, elevated high sensitive troponin (TnT-hs) and cardiac magnetic resonance imaging (CMR) with mildly reduced or preserved LVEF. Follow-up examination included laboratory findings, electrocardiogram (ECG), 48-hour-Holter ECG, echocardiography, exercise stress testing and CMR. Cessation of physical activity was recommended for 3 months. All patients were followed for cardiac events for 12 months.

Results

Average age was 35 (19–80) years with 73% male patients. All patients performed 3- and 6-month follow-up with above mentioned diagnostic tests. Eight patients did not present for 12-month follow-up, but were contacted by phone. No cardiac events occurred within the interval of 12 months.

After 3 months, participants achieved an average of 92% of predicted maximum power on stress test. One case of non-sustained ventricular tachycardia was recorded during 48-hour-Holter ECG. Except for this case, all patients were allowed to resume physical exercise after 3 months. At 6- (n=26) and 12-month (n=19) follow-up no arrhythmias, recurrent myocarditis, worsening left ventricular ejection fraction (LVEF) or physical performance were recorded. TnT-hs, creatine kinase (CK), myoglobin (Mb), and C-reactive protein (CRP) normalized.

Conclusion

The risk of cardiac events and decreasing LVEF appears to be low after early resumption of exercise in asymptomatic patients who recover from acute myocarditis.

Acknowledgement/Funding

Forschungskredit of the University of Zurich,the Holcim Foundation, the Hartmann Müller Foundation, and the Walter and Gertrud Siegenthaler Foundation
P5286Cardiac magnetic resonance for quantification of absolute myocardial blood flow: comparison with [15O]H2O positron emission tomography
Authors: Everaars H , Van Diemen P A , Bom M J , Schumacher S P , Van De Ven P M , Raijmakers P G , Lammertsma A A , Hofman M B M , Van Der Geest R J , Gotte M J W , Van Rossum A C , Nijveldt R , Danad I , Driessen R S , Knaapen P
Published: October 2019

Background

Quantification of absolute myocardial perfusion using positron emission tomography (PET) augments diagnostic performance and aids risk stratification in patients with coronary artery disease (CAD). Similar to PET, cardiac magnetic resonance imaging (CMR) allows for quantification of absolute myocardial blood flow (MBF). To date, quantitative CMR perfusion has not been compared with [15O]H2O PET, which is considered to be the gold standard for quantification of MBF.

Purpose

The purpose of this study was to compare CMR measurements of absolute myocardial perfusion to those obtained using [15O]H2O PET.

Methods

Fifty-one patients with stable CAD underwent [15O]H2O PET followed by CMR within 7 days. Late gadolinium enhancement was used to rule out presence of scar tissue. CMR perfusion imaging was performed using a single bolus dual sequence technique. Myocardial perfusion was quantified for the three main vascular territories at rest and during vasodilator stress.

Results

Pooled CMR estimates of absolute MBF correlated well with PET (r=0.79; p<0.001) and showed good agreement (intraclass correlation coefficient [ICC]=0.78; p<0.001). However, rest and stress MBF correlated weakly (r=0.31; p<0.001 for rest MBF and r=0.35; p<0.001 for stress MBF, figure) and showed poor agreement between PET and CMR (ICC=0.24; p<0.001 for rest MBF and ICC=0.34; p<0.001 for stress MBF). Similarly, CMR derived coronary flow reserve (CFR) correlated weakly (r=0.28; p<0.001) and showed poor agreement with PET derived CFR (ICC=0.23; p<0.001). Nevertheless, for a cut-off value of 2.3 mL/min/g for stress MBF and 2.5 for CFR, CMR and PET were concordant in 116 (79%) vascular territories for stress MBF and 104 (75%) vascular territories for CFR.

Per vessel – CMR vs PET perfusion

Conclusions

Resting MBF, stress MBF and CFR measurements correlated poorly with [15O]H2O PET. Nevertheless, stress MBF and CFR were concordant between CMR and [15O]H2O PET in 79% and 75% of vascular territories, respectively.

Acknowledgement/Funding

None
P5287Influence of contrast and spatial resolution on myocardial strain results using feature tracking MRI
Authors: Von Knobelsdorff F , Schunke T , Reiter S , Scheck R , Hoefling B , Pilz G
Published: October 2019

Background

Feature tracking is a new post-processing algorithm for calculating myocardial strain from cardiac magnetic resonance (CMR) cine images. Quantification of myocardial deformation promises to detect myocardial abnormalities early in the course of disease. However, no uniform standards for image acquisition and processing are available.

Purpose

Analysing the influence of spatial resolution and contrast agent on quantitative myocardial strain results.

Methods

Seventy-five patients in sinus rhythm were prospectively enrolled and underwent a standardised CMR exam using a 1.5 Tesla scanner. For feature tracking analysis, steady-state free-precession (SSFP) cine images in long and short axes were acquired in 3 variants: 1. Native standard cine (spatial resolution 1.4x1.4x8mm3). 2. Native cine with lower spatial resolution (2.0x2.0x8mm3). 3. Standard cine equal to variant 1 but acquired 5 minutes after i.v.-administration of 0.2mmol/kg body weight gadoteracid. Group A consisted of 50 patients with normal left ventricular ejection fraction, no regional wall motion abnormality and no evidence of fibrosis based on Late Gadolinium Enhancement. Group B comprised 25 patients with evidence of infarct-like myocardial scar in the analyzed planes. Using dedicated feature tracking software, circumferential, longitudinal and radial strain were calculated as mean of the six midventricular myocardial segments for group A. For group B, the analysis focused on the infarcted segments.

Results

Figure 1 summarises the strain results, given as mean standard deviation. (The p-values stem from paired t-tests (group A) and Wilcoxon tests (group B), respectively. Significance is highlighted by *). In group A, circumferential and radial strain decreased significantly after Gadolinium administration, while longitudinal strain increased significantly with lower spatial resolution. In group B, circumferential, longitudinal and radial strain results of the infarcted segments increased significantly with lower spatial resolution, while Gadolinium had no statistically significant influence on strain results.

Figure 1

Conclusion

Quantitative myocardial strain results obtained by CMR feature tracking are significantly influenced by spatial resolution and Gadolinium administration. Standardised image acquisition seems fundamental for reliable and comparable CMR strain analysis.
P5288Slice position vulnerability in the basal and apical parts for right ventricular circumferential strain measurement with feature tracking cardiac magnetic resonance
Authors: Gleditsch J , Jervan O , Geier O , Tofteberg A , Ghanima W , Hopp E
Published: October 2019

Background

Strain is a more sensitive and precise parameter than ejection fraction (EF) for detection and characterization of subclinical left ventricular (LV) dysfunction and remodeling. Similar relationship is expected for right ventricle (RV); however RV functional parameters are less validated. Feature tracking strain analysis based on standard cardiac magnetic resonance (CMR) cine imaging is available for both ventricles. We experience a large slice-to-slice variation for RV global circumferential strain (GCS), possibly making the parameter vulnerable to minute position changes.

Purpose

To evaluate slice-to-slice differences in RV GCS for identification of the least variation region in a patient group without regional RV disease, in order to achieve a robust method for measurement.

Hypothesis

The slice-to-slice difference in peak GCS is lower in the mid-ventricular part of the RV than in the basal and apical parts.

Methods

50 patients 6–72 months after pulmonary embolism without other major cardiopulmonary disease were included; mean age 60 years (range: 18–75 years); 68% men.

Standard 2D cine CMR was obtained in longitudinal planes and in 10–12 consecutive 10 mm short axis planes for complete coverage of the RV. RV free wall and the inner contour of the septum were manually segmented on every end-diastolic and end-systolic slice from the pulmonary valve to the apex for feature tracking strain analysis.

Peak RV GCS for every short axis slice and GCS difference (absolute percentage points) between adjacent slices were calculated. RV EF and peak RV GLS from the 4-chamber image were measured for correlation to RV GCS. Wilcoxon signed rank test and Pearson correlation were performed. Confidence intervals of means are based on 1000 bootstrap samples.

Results

RV EF was 46.6% (95% CI: 44.3; 48.8), RV peak GLS was −17.6% (95% CI: −18.6; −16.6). RV mid-ventricular GCS was −10.9% (95% CI: −12.0; −9.9). RV peak GCS slice-to-slice difference was 6.8 absolute percentage points (95% CI: 6.0; 7.6) in the basal part, 2.7 (95% CI: 2.4; 3.0) in the mid-ventricular part and 4.6 (95% CI: 3.9; 5.3) apically. Difference was significantly lower in mid-ventricular (p<0.001) compared to both basal and apical.

RV EF correlated to RV peak GLS (r: −0.397, p=0.004) and mid-ventricular peak GCS (r: −0.356, p=0.01) but not to basal or apical peak GCS. RV peak GLS correlated to basal and mid-ventricular peak GCS (r: 0.313, p=0.03 and r: 0.301, p=0.03 respectively) but not to apical peak GCS.

Figure 1 shows slice-to-slice difference (expressed in absolute percentage points) in right ventricular peak GCS.

Conclusion

Slice-to-slice difference in RV peak GCS was significantly lower in the mid-ventricular region. Large differences in the basal and apical parts indicate that measurements largely depend on slice positioning.
P5298Influence of the changes in body fat on all-cause and cardiovascular mortality in a general population: a report from Ansan-Ansung cohort in the Korean genome environment study
Authors: Lee Y , Park H C , Shin J H , Lim Y H , Park J K , Shin J , Kim K S , Kim B K
Published: October 2019

Background

Paradoxical beneficial effects of obesity on all-cause and cardiovascular mortality have been reported in multiple cohort studies based on patients with cardiovascular disease as well as general populations. However, the association between the presence of obesity at baseline and the better survival rates could not be directly interpreted into the beneficial effect of gain in obesity or fatness on the mortality, which makes it difficult to provide any recommendation for the management of obesity. Therefore, we investigated the influence of the changes in body fat on all-cause and cardiovascular mortality in a general population.

Methods

A population-based cohort study has been conducted for 12 years (from 2001 to 2012). A total of 5,259 subjects in whom body compositions using a bio-impedance method were measured at least 2 times during the observational period were included. The causes of death was identified from the nation-wide database in KOSTAT. I20-I82 and R99 in the International Classification of Disease-10 codes were defined as a cardiovascular death. The subjects were evenly divided into 3 groups by the percentages of the changes in body fat (Δ%BF; decreased [Δ%BF <0.0%] vs. increased [Δ%BF 0.0–13.7%] vs. highly increased [Δ%BF ≥13.7%]). Inverse probability of treatment weighting was applied to balance the covariate differences among the groups.

Results

The age was 51.2±8.5 years and 51.6% was male. Median observation duration was 163 (the interquartile range: 157–168) months. The all-cause death and cardiovascular death occurred most frequently in the decreased Δ%BF group and least frequent in the highly increased Δ%BF group in both unweighted and weighted cohort. Multivariate Cox proportional hazard models showed that the risk of all-cause death was lower in the increased and highly increased Δ%BF groups (hazard ratio [HR] 0.61 [0.47–0.80] and 0.24 [0.17–0.34], respectively) and the risk of cardiovascular death was lower in the highly increased Δ%BF group (HR 0.20 [0.08–0.48]), compared to those in the decreased Δ%BF group after adjustment for all covariates including physical activities and the changes in muscle mass. The risk of all-cause death and cardiovascular death linearly decreased with increasing Δ%BF (HR 0.72 [0.67–0.77] and 0.70 [0.60–0.82], respectively).

Conclusion

The increase in body fat is associated with a lower risk of all-cause death and cardiovascular death in a middle-age general population, independently with physical activities and the changes in muscle mass.
P5299Epicardial obesity as a significant predictor of leptino and insulin resistance
Authors: Ott A , Chumakova G A
Published: October 2019

Leptino (LR) and insulin resistance (IR) are significant predictors of atherosclerosis, thrombosis, type 2 diabetes. The effect of epicardial obesity (EO) (as a type of visceral obesity) on the formation of LR and IR is studied.

Objective

To study the effect of EO on the formation of LR and IR among men with arterial hypertension (AH).

Materials and methods

The study included 130 men 49.5±4.3 years old, with AH of 1–3 degrees and the absence of clinical manifestations of coronary heart disease and atherosclerosis of other localizations, type 2 diabetes with a BMI of 20–35 kg /m2 and abdominal obesity according to WC ≥94 cm. Patients were divided into two groups depending on the thickness of epicardial adipose tissue (EAT), measured behind the free wall of the right ventricle by echocardiography. Group 1 consisted of 60 patients with epicardial obesity (EAT ≥7 mm), group 2 included 70 patients without epicardial obesity (EAT <7 mm). All subjects assessed indicators of LR and IR: measured levels of serum leptin (SL), soluble receptors for leptin (SLR), free leptin index (FLI), calculated as the ratio SL/SLR (as the only currently existing marker LR); IR was estimated by calculating the HOMA-IR index. IR was diagnosed with the generally accepted HOMA-IR index >2.7.

Results

When comparing LR indices in the studied groups, higher average values of SL, FLI were observed in the group with EO (EAT ≥7 mm) than in the group without EO (EAT <7 mm): (SL = 32.16 ng/ml (26.7; 37.62) versus SL = 14.92 ng/ml (11.62; 18.22), p=0.01, respectively); (FLI = 1.67 (0.47; 2.87) versus FLI = 0.37 (0.28; 0.46), p=0.01, respectively). Also in the EO group, higher indices of the HOMA-IR index were observed compared with the group without EO: (2.16 (1.62; 2.66) versus 1.35 (1.06; 1.64), p=0,01, respectively). When conducting the correlation analysis between FLI (as a marker of LR) and various obesity indicators (BMI, WC, EO) in the studied groups, a significant positive correlation relationship between FLI and EO was found in both the first and second groups (r=0.67, p=0.01; r=0.62, p=0.01, respectively). The IR index HOMA-IR also significantly positively correlated with EO in the group with a EAT ≥7 mm (r=0.68, p=0.01). BMI and WC did not correlate with FLI, IR in both groups 1 and 2 (p>0.05). In the EO group, 11 patients had IR with a HOMA-IR index >2.7. Using the linear regression analysis, the regression equation was obtained and the value of EO was calculated, from which the IR with HOMA-IR >2.7 started to be determined. This figure was 9.5 mm.

Conclusions

EO (EAT ≥7 mm) is a significant predictor of LR and IR, unlike the generally accepted criteria for obesity (BMI, WC). A EAT ≥9.5 mm can be a significant predictor of the development of type 2 diabetes, so these patients need additional examinations.
P5304Adipose tissue surrounding the kidney and its impact on coronary artery disease
Authors: Maimaituxun G , Fukuda D.A.I.J.U , Yagi S , Takao S , Yamada H , Soeki T , Wakatsuki T , Harada M , Sata M , Shimabukuro M
Published: October 2019

Background

Growing evidence suggests that visceral adipose tissue has systemic and local impact for the development of cardiovascular disease. Previously, we reported that epicardial adipose tissue, as one of visceral fat, was a risk factor for the development of coronary artery disease (CAD). However, the association between another visceral adiposity kidney fat and CAD remains unclear.

Purpose

In this study we aimed to clarify whether there exists link between adipose tissue surrounding the kidney and CAD among patients.

Method

The study population consisted of 201 consecutive patients who underwent 320-slice multi-detector computed tomography (MDCT) coronary angiography. Study subjects were divided into the CAD (≥1 coronary artery stenosis of ≥50%) and non-CAD groups. Adipose tissue surrounding the kidney were quantified by the computed tomography and peri-renal fat volumetric measurements were performed on axial views by manually placing the Region of Interest (ROI) on the renal fascia. The peri-renal fat area of each slice was summed and multiplied by the slice thickness and number of slices to determine the total peri-renal fat volume. Adipose tissue was determined as the density range was −190 to −30 Hounsfield unit. Peri-renal fat volume were indexed by body surface area (BSA).

Results

The mean age was higher in CAD group than those in non-CAD (66±11 vs. 71±10 years, p=0.005). The diabetes, hypertension and hyperlipidemia were significantly prevalent in CAD comparing to non-CAD group. BSA adjusted Peri-renal fat volume was significantly larger in CAD than those in non-CAD (43±27 vs. 60±39 ml/m2). Linear regression analysis showed that BSA adjusted peri-renal fat volume was significantly correlated with visceral fat area (VFA) (R=0.729, p<0.001). Multiple regression analysis for estimating CAD showed that BSA adjusted peri-renal fat volume was a predictor of CAD after adjusting for confounding factors which including age, gender, body mass index, smoking, hypertension, hyperlipidemia, diabetes and VFA (Adjusted R2=0.201, p<0.001); In addition, in the above traditional risk factors model even when the VFA was replaced by the eGFR<60 ml/min/1.73m2, the BSA adjusted peri-renal fat volume still keep a significance for predicting the CAD in the multivariate analysis (Adjusted R2=0.198, p<0.001).

Conclusion

Peri-renal fat volume might be a predictor of CAD. Kidney fat at least partially may contributes to the development of CAD by impaired kidney function.
P5307A consumer-direct digital health intervention for cardiovascular risk management in primary care: the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) randomised controlled trial
Authors: Redfern J , Usherwood T , Coorey G , Mulley J , Scaria A , Neubeck L , Hafiz N , Chow C , Peiris D
Published: October 2019

Background

Digital health interventions linked to electronic health records offer patients an innovative approach to support cardiovascular disease (CVD) risk management.

Purpose

Test the effectiveness of a consumer-directed digital health strategy on medication adherence and cardiovascular health outcomes in patients presenting to primary care who are at moderate to high risk of CVD.

Methods

Randomised controlled trial (RCT) with 12 month follow-up. Intervention group received an interactive digital health strategy for CVD management. The intervention was integrated with patient's electronic health record to enable automated population of risk factor and medication data (Figure). Control group received usual care. Primary outcome was the proportion of patients taking guideline-recommended BP and cholesterol-lowering medications on at least 80% of days (administrative data). Secondary outcomes included mean SBP, LDL-cholesterol, BMI and proportion meeting risk targets for physical activity, achieving smoking cessation, quality of life (EQ5D) and ehealth literacy (eHEALS).

Results

Intervention (n=486) and control (n=448) groups were well matched at baseline (Table). Mean age of participants was 67±8.1 years, 77% were male, 41% had existing CVD. At 12 months, there was no significant difference between the groups for medication days covered or mean cholesterol and BP (Table). However, there were significantly more patients in the intervention than control group who were physically active and had high ehealth literacy (Table).

Table 1. Primary and Secondary Outcomes Baseline 12 months Outcome Control (n=448) Intervention (n=486) Control (n=431) Intervention (n=460) p value* Taking BP and cholesterol medication on ≥80% of days, % 29.7 28.9 29.9 32.8 0.485 SBP (mmHg), mean±SD 139.0±16.6 137.3±15.9 136.3±16.1 136.4±17.6 0.921 LDL (mmol/L), mean±SD 2.6±1.0 2.6±1.0 2.5±0.9 2.4±1.0 0.240 BMI (kg/m2), mean±SD 29.7±5.1 29.9±5.7 29.4±5.0 29.7±5.7 0.508 Proportion achieving BP and LDL target, % 11.2 12.3 11.7 16.5 0.065 Physically active, % 84.0 85.4 79.7 87.0 0.016 Current smoker, % 12.9 13.0 12.0 8.1 0.087 eHEALS, mean±SD 27.0±6.4 27.0±6.4 26.4±7.5 28.3±6.3 0.002 *Comparing intervention and control at 12 month follow-up.

Conclusions

The integrated digital health strategy did not significantly impact on days of medication covered however, patients in the intervention had higher physical activity and ehealth literacy. The RCT highlights the importance of conducting robust research if we are to understand the potential value of digital health interventions.

Acknowledgement/Funding

This work was supported by a Project Grant from the National Health and Medical Research Council of Australia
P5309Age and gender distributions of coronary artery calcium in the Dutch adult population: preliminary results of the ImaLife study
Authors: Xia C , Rook M , Pelgrim G J , Van Bolhuis J N , Van Ooijen P M A , Vonder M , Oudkerk M , De Bock G H , Van Der Harst P , Vliegenthart R
Published: October 2019

Background

Coronary artery calcium (CAC) scoring is a promising tool for cardiovascular risk classification. Population-based reference values are important for the clinical interpretation of CAC scores.

Purpose

To establish standards of CAC distributions by age and gender in an unselected Dutch population, which can be used to determine reference values.

Methods

ImaLife (Imaging in Lifelines) is a computed tomography (CT) based substudy of the Lifelines cohort, with a primary aim to establish reference values of imaging biomarkers for early stages of coronary artery disease in adults (above 45 years old). In total, 12,000 participants will be enrolled from an unselected adult population in the northern Netherlands for CAC scoring with third generation dual-source CT. CAC is quantified with dedicated commercial software using the Agatston method.

Results

Included so far were 3,702 participants (57.5% females, mean age 54 years, range 45–82 years). CAC was present in 39.2% of participants, with a higher prevalence of CAC in men (55.3%) than in women (27.3%). CAC scores increased with increasing age in both genders. The percentiles of CAC scores by age and gender groups are summarized in the table.

Agatston CAC score percentiles by age and gender Percentiles Women – Age, years Men – Age, years 45–49 50–54 55–59 60–64 65∼ 45–49 50–54 55–59 60–64 65∼ N 505 634 719 260 10 355 473 543 185 18 25th 0 0 0 0 0 0 0 0 1 75 50th 0 0 0 0 4 0 1 6 22 556 75th 0 0 6 33 386 6 21 72 129 751 90th 4 26 77 120 1037 49 154 242 500 1803

Conclusion

This preliminary result presents CAC distribution by age and gender in a middle-aged unselected Dutch population. Compared with the Heinz Nixdorf Recall study, CAC scores in our cohort for both genders were lower in the 5-year age groups between 45 and 64 years. Based on the overall data, expected within 2 years, reference values of CAC for the Dutch population can be established.
P5310College students under stress have elevated cardiovascular risk factors associated to eating disorders
Authors: Saraiva J F K , Bellodi A C , Enumo S R , Machado W L , Fonseca H A , Saraiva D B , Avezum A
Published: October 2019

Background

High prevalence of cardiovascular diseases in the global adult population refers to the need for prevention. Tracking phenomenon studies have inferred that since childhood, risk and protection factors can be identified, thus supporting public health policies.

Purpose

To evaluate the prevalence of stress and the cardiovascular risk factor in Brazilian students.

Methods

A cross-sectional study was carried out in our city with 3,471 students, both sexes, from 7 to 13 years old, 51.7% of whom were non-Caucasian, aiming to analyze 31 variables: a) biological markers for cardiovascular risk (weight, height, waist circumference, systolic blood pressure, diastolic blood pressure, heart rate, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, use of medications); b) health-related behavioural variables (ingestion of fruits, vegetables, meats, fish, dairy products, sweets, sugary drinks, fast food, snacks, lunch at home or at school, daily study hours, physical activity at school and out of school, means of transport to go to school, screen time); c) emotional variables (perceived stress at school and at home); d) socio-demographic data (sex, age, ethnicity). Data were collected in schools and tabulated; Network analysis considered 16 composite variables.

Results

A total of 17.5% of obesity and 16.2% of overweight verified at the studied population. Children and adolescents, under stress, are shown to have higher cholesterol levels, followed by increased use of medications or supplements, and increased physical activity, higher ratios for boys and non-white ethnicity individuals. Eating lunch provided by the school and being a female served as a protective factor for cardiovascular risk.

Conclusion

Considering the already known impact of stress on children's physical and psychological development and cardiovascular risk, it is urgent to establish public policies aimed at preventing these conditions, which have been severely perceived in very young, non-white and resident of a periphery of metropolises individuals.
P5313The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and meta-analysis
Authors: Mazidi M , Mikhailidis D P , Dehghan A , Jozwiak J , Rysz J , Willet W C , Covic A , Sattar N , Banach M
Published: October 2019

Background

The reported relationship between coffee intake and renal function is poorly understood.

Purpose

By applying on two-sample Mendelian randomization (MR) and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function.

Methods

For the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from genome-wide association studies conducted on coffee intake (N=91,462) and kidney function (N=133,413). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, MR-RAPS, MR-PRESSO were applied. Random effects models and generic inverse variance methods were used for the meta-analysis.

Results

Finally, we included the data of 18,436 participants, 6.9% had prevalent CKD (based on eGFR). Caffeine intake for general population was 131.1±1.1 mg. The % of pts. with CKD, by caffeine quartile was 16.6% in Q1 (lowest), 13.9% in Q2, 12.2% in Q3 and 11.0% in Q4 (p<0.001). After adjustment, for increasing quartiles for caffeine consumption, mean urine albumin, albumin-creatinine ratio and eGFR did not change significantly (p>0.234). In fully adjusted logistic regression models, there was no significant difference in chances of CKD prevalence (p-trend=0.745) (Table). In the same line, results of MR showed no impact of coffee intake on CKD (IVW=β: −0.0191, SE: 0.069, p=0.781) (Figure), on eGFR (overall= IVW= β: −0.0005, SE: 0.005, p=0.926) both in diabetic (IVW= β: −0.006, SE: 0.009, p=0.478), and non-diabetic patients (IVW= β: −6.772, SE: 0.006, p=0.991). Results from the meta-analysis indicted that coffee consumption was not significantly associated with CKD (OR: 0.85, 95% CI 0.71–1.02, p=0.090, n=6 studies, I2=0.32). These findings were robust in sensitivity analyses.

Levels of CKD markers across caffeine Qs Characteristics Quartiles of Caffeine p-value First Second Third Fourth Number of participants (n) 4609 4611 4608 4608 Log Urine Albumin (mg/L) 2.20±0.02 2.16±0.02 2.19±0.02 2.17±0.02 0.239 Serum Creatinine (mg/dL) 0.89±0.003 0.90±0.004 0.91±0.002 0.88±0.003 0.234 Log ACR (mg/g) 2.14±0.02 2.10±0.02 2.11±0.02 2.16±0.02 0.352 eGFR (ml/min/1.73m2) 91.2±0.7 92.8±0.4 90.2±0.5 89.6±0.3 0.415

MR on the impact of coffee intake on CKD

Conclusions

By implementing on different strategies we have highlighted no significant association between coffee consumption with renal function and chance of CKD.

Acknowledgement/Funding

None
P5332Magic mirror on the wall, can we reach our LDL-C goal? Comparison of calculated LDL-C and direct measured LDL-C levels in atherogenic dyslipidemia condition
Authors: Reiber I , Mark L , Paragh G Y
Published: October 2019

Background

LDL-C represents the primary lipoprotein target for reducing cardiovascular risk. LDL-C can either be calculated or measured directly. Friedewald equation has certain limitations especially with high triglyceride and low LDL-C levels. Although a number of automated direct LDL-C assays are commercially available, non of them is considered to be equivalent to the “gold standard” of direct LDL-C, beta quantitation, a complex and expensive process that is unavailable in routine clinical practice. In atherogenic dyslipidemia condition (ADC) (triglycerides≥2.3 mmol/L and HDL-C<1.0 mmol/L) non-HDL-C and remnant cholesterol are proven additional risk factors.

Purpose

We compared one of the direct homogeneous assays with the widely used Friedewald's and the new Martin/Hopkins methods of estimation of LDL-C to see the differences in average LDL-C, remnant cholesterol and non-HDL-C levels and in availability of less than 1.8 mmol/L of LDL-C in atherogenic dyslipidemia condition.

Methods

We investigated 14 906 lipid profiles from fasting blood samples of Hungarian individuals with triglycerides <4.5 mmol/L. Total cholesterol (TC), HDL-C, triglycerides (TG) and direct LDL-C (D-LDL-C) were measured directly by the enzimatic assays. We also estimated calculated LDL-C by the Friedewald's formula (F-LDL-C) and by using the new Martin/Hopkins estimation (MH-LDL-C). We have now prepared first a variant of Martin/Hopkins table in mmol/L, in which the modified adjustable factors of 2.2 are included. We determined also non-HDL-C and remnant cholesterol (RC) as a difference of non-HDL-C and F-LDL-C (F-RC), MH-LDL-C (MH-RC), D-LDL-C (D-RC).

Results

In the investigated population 19.25% was F-LDL-C, 15.48% MH-LDL-C and 7.92% D-LDL-C below 1.8 mmol/L. ADC occurred at 8.12%. For ADC, when F-LDL-C<1.8 mmol/L (A), mean values for F-LDL-C, MH-LDL-C, D-LDL-C and non-HDL-C were 1.23±0.4; 1.65±0.39; 2.06±0.4 and 2.46±0.5 mmol/L respectively. These mean levels were 1.01±0.36; 1.4±0.3; 1.83±0.3 and 2.15±0.34 mmol/L for MH-LDL-C<1.8 mmol/L (B). For D-LDL-C<1.8 mmol/L (C), mean values were 0.79±0.35; 1.13±0.26; 1.54±0.19 and 1.83±0.25 mmol/L respectively. The average RC values (in mmol/L) for A were F-RC: 1.23±0.36; MH-RC: 0.81±0.18; D-RC: 0.4±0.17, for B 1.14±0.33; 0.74±0.14; 0.32±0.13, and for C 1.04±0.27; 0.70±0.1; 0.29±0.12 respectively.

Conclusions

The Friedewald equation tends to underestimate and the homogeneous enzimatic direct LDL-C assays to overestimate the LDL-C levels compared to the new, accurate, calculated LDL-C values in atherogenic dyslipidemia condition. Based on the data presented in our investigation we should like to propose that more realistic vasculo-protective lipid status can be attained if we calculate LDL-C using the Martin/Hopkins estimation.
P5369Alpha-V integrin regulates the contribution of PW1+ cells to cardiac fibrosis
Authors: Bouvet M , Claude O , Roux M , Mougenot N , Duval V , Nadaud S , Delacroix C , Perret C , Yaniz-Galende E , Lemitre M , Tregouet D A , Marazzi G , Silvestre J S , Sassoon D , Hulot J S
Published: October 2019

Background

Activated cardiac fibroblasts produce extracellular matrix proteins that accumulate during cardiac fibrosis. We have recently shown that PW1 is expressed in a subset of cardiac stromal cells and that cardiac PW1+ cells represent a cellular source of fibroblasts in the ischemic hearts.

Purpose

We aimed to further identify new cell surface markers expressed by cardiac PW1+ cells and to investigate their role in the fibrogenic behavior of these cells.

Methods and results

We first performed transcriptomic and proteomic profiling of FACS-isolated cardiac PW1+ from normal and ischemic hearts. RNA-sequencing output files were processed with bioinformatics algorithms to identify 378 specific cell-surface markers for cardiac PW1+ cells. By comparing these candidates with the proteomic profile, we then cross-identified 9 cell surface proteins primarily involved in cell motility, adhesion to the matrix, inflammatory response and response to wounding. One of these candidates (i.e., aV-integrin or CD51) was expressed in almost all cardiac PW1+ cells (93±1%), and was predominantly found in cells expressing PW1 in the myocardium. Cardiac PW1+ cells showed a predominant expression of aVβ1 complex which is known to mediate fibrosis through TGF-beta activation in a number of tissues. The transfer of isolated cardiac PW1+CD51+ cells into ischemic hearts was associated with fibrosis development. We further demonstrated that inhibition of aV-integrin in cardiac PW1+ cells reduces their profibrotic gene expression profile and their ability to differentiate into fibroblasts. Lastly, a pharmacological blockade of aV-integrin improved cardiac function and animal survival following myocardial infarction coupled with a reduced infarct size and fibrotic lesion.

Conclusions

These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of aV-integrin leads to reduced pathological outcomes following cardiac ischemia.

Acknowledgement/Funding

Fondation Leducq (grant 13CVD01, CardioStemNet project), Fédération Française de Cardiologie and Era-CVD (ANR-16-ECVD-0011-03, Clarify project)
P5379Modification with CREKA improves cell retention of myocardial ischemia reperfusion
Authors: Chen J , Song Y N , Huang Z Y
Published: October 2019

Background

Poor cell homing limits efficacy of cardiac cellular therapy. The cysteine–arginine–glutamic acid–lysine–alanine (CREKA) homing peptide binds with high specificity to fibrin which is involved in repair of tissue injury.

Purpose

We assessed if CREKA-modified stem cells had enhanced fibrin-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model.

Methods

CREKA-modified mesenchymal stem cells (CREKA-MSCs) were obtained via membrane fusion with CREKA-modified liposomes. The fibrin targeting ability of CREKA-MSCs was examined both in vitro and in vivo.

Results

Under both static and flow conditions in vitro, CREKA significantly enhanced MSCs binding ability to fibrin clots. CREKA-MSCs showed much more higher accumulation than unmodified MSCs in injured rat myocardium, colocalizing with fibrin and resulting in better cardiac function.

Stem cell-CREKA-fibrin targeting system

Conclusions

Modification of MSCs with the homing peptide CREKA favored their migration and retention in the infarcted area, resulting in better structural preservation and functional recovery. Fibrin is therefore a novel target for enhancing homing of transplanted cells to injured myocardium and the fibrin-targeting delivery system represents a generalizable platform technology for regenerative medicine.
P5381Lack of sirtuin 5 aggravates myocardial ischemia reperfusion injury
Authors: Witt C N , Koentges C , Pfeil K , Vogelbacher L , Pusdrowski T , Bode C , Zirlik A , Bugger H
Published: October 2019

Sirtuin 5 (SIRT5) is a mitochondrial NAD+-dependent protein deacylase which regulates the enzymatic activity of numerous mitochondrial proteins due to increased succinylation and malonylation, including enzymes of energy substrate oxidation and mitochondrial antioxidant enzymes. Since energy depletion and mitochondrial oxidative stress contribute to myocardial IR injury, it was our objective to evaluate the potential role of SIRT5 in IR injury. In regular Langendorff heart perfusions, 8 week-old cardiomyocyte-selective SIRT5−/− mice showed no difference in LV developed pressure or dp/dt max compared to wildtype mice. However, recovery of LV developed pressure and dp/dt max following 25 min of ischemia was lower by 34% and 20% in SIRT5−/− mice compared to WT mice, respectively. In contrast, postischemic recovery of cardiac function was not impaired and even improved in mice with cardiomyocyte-selective overexpression of SIRT5 compared to WT mice undergoing IR. Mitochondrial H2O2 generation was significantly increased in SIRT5−/− mice compared to WT mice following IR, and mitochondria-targeted antioxidant treatments (MnTBAP or SS-31) during heart perfusion completely normalized recovery of contractile parameters in SIRT5−/− mice following IR. In conclusion, SIRT5 is not required to maintain cardiac function under physiological conditions. However, lack of SIRT5 aggravates myocardial IR injury, likely by increasing mitochondrial oxidative stress. SIRT5 agonism may thus represent a potential therapeutic strategy to attenuate myocardial IR injury.
P5383Autologous adipose-derived stromal cell treatment for patients with refractory angina (MyStromalCell Trial) - 3-years follow-up results
Authors: Qayyum A A , Mathiasen A B , Helqvist S , Joergensen E , Haack-Soerensen M H , Ekblond A , Kastrup J
Published: October 2019

Background

Improvements in medical and interventional therapies have transformed ischemic heart disease into a chronic illness for lot of patients. The disease is in progress and by time patients suffer from cardiac symptoms, reduced work capacity and decline in quality of life. Stem cell therapy is investigated as a treatment option for these patients.

Purpose

In this study, long-term safety and efficacy of autologous intra-myocardial injections of adipose-derived stromal cells (ASCs) were studied in patients with refractory angina.

Methods

Sixty patients were double-blinded 2:1 randomised to ASC or saline injections and followed for three years. The patients had significant angina due to ≥1 coronary artery stenosis but preserved left ventricular ejection fraction. ASCs were obtained from abdomen, ex vivo culture expanded and VEGF-A165 stimulated before delivery into the ischemic myocardium.

Results

The cardiac symptoms, CCS and NYHA classification, were significantly reduced in the ASC group during the three years follow-up period (2.5±0.9 to 1.8±1.2, P=0.002 and 2.4±0.6 to 2.2±0.8, P=0.007, respectively). However, no significant change was observed in CCS or NYHA in the placebo group during the follow-up period (2.5±0.8 to 2.1±1.3, P=0.186 and 2.7±0.6 to 2.4±0.8, P=0.314, respectively).

Moreover, the number of weekly angina attacks reported was significantly reduced in the ASC group (P=0.017), but not in the placebo group (P=0.425).

For patients in the ASC group, the bicycle exercise time (383±30s to 370±44s, P=0.052) and the exercise performance in watt were un-changed (81±6 to 78±10, P=0.123), but the performance in METs was reduced significantly (4.2±0.3 to 4.0±0.4, P=0.027) during the follow-up period.

At the same time in the placebo group, there was a significant decline in bicycle exercise time (437±53s to 383±58s, P=0.001), the exercise performance measured in watt (87±12 watt to 80±12 watt, P=0.019) and in METs (4.5±0.4 to 4.1±0.4, P=0.002).

In both groups, significant improved quality-of-life, angina stability, angina frequency and physical limitation score was observed but not for overall satisfaction score.

Conclusion

Patients receiving ASCs had improved cardiac symptoms during the three years follow-up period, which was not the case for patients in the placebo group. Moreover, patients receiving ASCs had unchanged exercise capacity, in opposition to deterioration in the placebo group.

Acknowledgement/Funding

Arvid Nilssons Foundation; Rigshospitalets Research Foundation; Aase and Ejnar Danielsens Foundation
P5395Exercise-induced miR-17-3p Prevents Pathological Myocardial Dysfunction
Authors: Zhou Q , Xiao J
Published: October 2019

Background

Exercise is beneficial for pathological myocardial dysfunction and heart failure. We previously reported that miR-17-3p contributed to exercise-induced cardiac growth and protected against cardiac ischemia/reperfusion injury. However, if exercise-induced miR-17-3p can prevent pathological myocardial dysfunction is undetermined.

Purpose

To investigate if exercise-induced miR-17-3p can prevent pathological myocardial dysfunction.

Methods

The miR-17-3p expression was examined in phenylephrine (PE, 50μmol/L, 48 h) and angiotensin II (Ang II, 1μmol/L, 48 h) treated primary neonatal rat ventricular cardiomyocytes (NRCM), and the myocardium of thoracic aortic constriction (TAC, 4weeks) or angiotensin II (1.3 mg/kg/day, 4weeks) induced cardiac hypertrophy murine model. miR-17-3p transgenic mice were generated and subjected to TAC or Ang II to investigate the effect of miR-17-3p overexpression in attenuating pathological cardiac dysfunction by echocardiography. Cell area and hypertrophic genes were determined by Wheat Germ Agglutinin (WGA) staining and qRT-PCRs. In addition, cell area and hypertrophic genes (ANP, BNP, β-MHC) were determined by immunolabeling and qRT-PCR in NRCM after the transfection of miR-17-3p mimic or inhibitor. Furthermore, functional rescue assays were performed to identify phosphatase and tensin homolog (PTEN) as a target gene of miR-17-3p, and myocyte enhancer factor 2C (MEF2C) as an upstream regulator of miR-17-3p in pathological cardiac hypertrophy.

Results

The expression of miR-17-3p was significantly decreased in the heart from TAC or Ang II mouse model, and in PE or Ang II-induced cardiomyocyte hypertrophy model. miR-17-3p overexpression mice displayed improved cardiac function and reduced cardiac hypertrophy after TAC or Ang II treatment in vivo. miR-17-3p mimic significantly attenuated PE or Ang II-induced cardiomyocyte hypertrophy in vitro. Based on functional rescue experiments, PTEN was identified as a direct target of miR-17-3p that mediated its protective effects in cardiac hypertrophy. Moreover, MEF2C was identified as a negative upstream regulator of miR-17-3p involved in the control of cardiac hypertrophy.

Proposed mechanism of miR-17-3p

Conclusion

Exercise-induced miR-17-3p can prevent pathological myocardial dysfunction by targeting PTEN. MEF2C was an upstream regulator of miR-17-3p. Targeting MEF2C/miR-17-3p/ PTEN represents a novel therapeutic strategy for pathological myocardial dysfunction.

Acknowledgement/Funding

The grants from National Natural Science Foundation of China (81722008, 91639101 and 81570362 to JJ Xiao)
P5405Clinical and prognostic relevance of increased liver stiffness coupled with abnormal liver function tests in decompensated heart failure
Authors: Soloveva A , Bayarsaikhan M , Lukina O , Troitskaya E , Bondari S , Khruleva Y , Arisheva O , Garmash I , Villevalde S , Kobalava Z
Published: October 2019

Objective

Recent studies have demonstrated associations of either abnormal liver function tests (LFT) or liver stiffness (LS) increase with negative outcomes in decompensated heart failure (DHF). We aimed to assess incidence, clinical and prognostic relevance of combined increase of LS and LFT in DHF.

Methods

The study included 130 patients (73% male, 68±11 years [M±SD], myocardial infarction 49%, atrial fibrillation 63%, diabetes mellitus 39%, chronic kidney disease 24%, EF 39±14%, EF<40% 54%, NT-proBNP 3601 [1905; 6220] pg/ml, alcohol abuse 26.2%) hospitalized with DHF, in whom levels of alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TB) and LS (using transient elastography) were assessed in the first 48 hours of admission. Patients with previous liver disease or acute hepatitis were excluded. Higher then upper normal limit levels of either AST/ ALT/ TB were considered as LFT increase; LS >5.9 kPa – as abnormal. Outcomes were assessed by phone contacts in 1, 3, 6 and 12 months. Kruskal–Wallis test, Pearson's chi-squared test and Kaplan-Meier survival analysis were used. P<0.05 was considered significant.

Results

Median LS was 11.1 (6.8; 24.5) kPa, median ALT 20.1 (14.9; 30.7) U/l, AST 26 (20; 36.3) U/l, TB 19 (13.2; 27) μmol/l. LS and ALT, AST, TB increase occurred in 79.2 and 15.4, 13.1, 40.8% patients.

Based on combination of LS and LFT increase subjects were divided into 3 groups: without LS and LFT increase (G1, 16.2%), with only LS increase (G2, 33.1%) and both LS and LFT increase (G3, 46.1%). Isolated LFT increase was noted only in 6 (4.6%) patients.

G3 compared to G2 and G1 was characterized by lower EF (33±14 vs 41±13 and 45±11%, p<0.001) and inferior vena cava (IVC) collapsibility (23.3 vs 41.9 and 61.9%, p=0.003), higher IVC diameter (2.4 [2; 2.6] vs 2.2 [2; 2.4] and 2 [1.95; 2.2] cm, p<0.001), right ventricular diameter (3.5 [3.2; 3.9] vs 3.2 [3; 3.6] and 3 [2.9; 3.1] cm, p<0.001), pulmonary artery pressure (56 [45; 66] vs 50 [37; 65] and 40 [33; 49] mmHg, p=0.014), higher rate of tricuspid regurgitation (70 vs 44.2 and 28.6%, p=0.001). Groups did not differ by alcohol abuse rate (p=0.152).

Kaplan–Meier analysis of groups for all-cause death probability showed significant differences (figure): event-free survival for G3 vs G1 and G2 was 64.9 vs 81 and 95% (log rank p=0.011, χ2=6.5 for G3 vs G1; log rank p=0.081, χ2=3.1 for G3 vs G2). HF readmission probability was significantly higher in G3 vs G2 and G1: corresponding event-free survival was 50.9 vs 66.7 and 80% (log rank p=0.012, χ2=6.3 for G3 vs G1; log rank p=0.036, χ2=4.4 for G3 vs G2).

Conclusions

Combination of abnormal LFT and increased LS was observed in 46.1% of DHF patients and was associated with lower EF, more serious right-sided dysfunction and higher probability of negative long-term outcomes.