bluuebunny/crossref_metadata_2025 huggingface dataset:
P3427Prognostic performance of echocardiography, electrocardiogram, albuminuria, plasma proBNP and hs-TnI in patients with type 2 diabetes
Authors: Busch N , Jensen M T , Goetze J P , Biering-Soerensen T , Fritz-Hansen T , Andersen H U , Gislason G , Vilsboell T , Rossing P , Joergensen P G
Published: October 2019

Background

A range of diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), plasma measurement of high sensitivity troponin T (hs-TnI) and pro-brain natriuretic peptide (proBNP) have been suggested as cardiovascular (CV) risk predictors in patients with type 2 diabetes. In this study we examined prognostic yield from these risk markers.

Methods

A total of 1,030 out-patients followed at a large secondary care diabetes clinic were recruited. Echocardiography was considered feasible in patients in sinus rhythm with adequate image quality (n=886). Abnormal echocardiography was defined as a left ventricular ejection fraction (LVEF) <50%; a ratio of early diastolic mitral inflow velocity to early diastolic septal annular velocity (E/e'septal) ≥15; increased left ventricular mass index (>95 g/m2 for women and >115 g/m2 for men) or left atrial volume index >34 ml/m2. ECG was performed in 983 patients and was considered abnormal in the presence of abnormal Q-waves; ST-T segment deviation or bundle branch block. We measured urine albumin (n=1,009) and proBNP/hs-TnI (n=933). The end-point of CV event was a composite of CV death and hospitalization with myocardial infarction/revascularization, stroke, peripheral artery disease or heart failure.

Results

The median follow-up was 4.7 years (interquartile range: 4.0 to 5.3) and 174 patients suffered an CVD event. All markers except hs-TnI were significantly (p<0.001) associated with the composite outcome: Abnormal echocardiogram: Hazard ratio (95% confidence interval): 2.39 (1.69–3.37); albuminuria 2.01 (1.47–2.76); abnormal ECG 2.35 (1.72–3.21); log2(proBNP) 1.60 (1.47–1.75) and hs-TnI 1.05 (0.92–1.19). The findings persisted after adjusting for clinical variables, but after adjusting for the other markers, only log2(proBNP) remained associated with the composite outcome (1.50 (0.20–1.73), p<0.001), figure. Measured by C-index model performance was highest with proBNP (0.70 (0.65–0.75)) and similar to clinical variables (0.71 (0.67–0.76)). Combining risk markers only resulted in very limited increase in C-index (echocardiogram, albuminuria, ECG and proBNP: 0.71 (0.66–0.76)).

Uni- and multivariables

Conclusions

This study identifies proBNP measurement in plasma over echocardiography, ECG and albuminuria for risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.
P3430Classification of pronounced subclinical atherosclerosis: deep learning approach of carotid intima media ultrasound images is superior to clinical risk factors
Authors: Nyman E , Karlsson M , Naslund U , Gronlund C
Published: October 2019

Background

Carotid ultrasound measurements of subclinical atherosclerosis is extensively used in the research field of cardiovascular disease. Increased intima media thickness (IMT) and plaque detection have predictive value for cardiovascular events when added to traditional risk factors. However, among studies different protocols for measuring IMT (projections, mean or max values and sites) are used and methodological difficulties of plaque detection, together result in conflicting results. Recently, Deep Learning image driven classification methods, has been successfully applied in several medical imaging applications. Here we hypothesize that ultrasound image texture of the intima media complex accurately reflects the disease burden without the need to measure IMT values or detect plaques.

Purpose

To evaluate classification accuracy of ultrasound based deep learning approach of the intima media complex image compared to traditional risk factors for participants with no vs pronounced subclinical atherosclerosis.

Methods

Subjects from the VIPVIZA study (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention, n: 3532, 40, 50 and 60 year old, 53% women) were selected for analysis. Bilateral carotid ultrasound examinations were performed according to a standardized protocol. Subjects were categorized in two groups as 1) pronounced subclinical atherosclerosis (n: 401) – bilateral plaques and estimated vascular age 10 years older, or 2) No subclinical atherosclerosis (n: 592) – no plaques and estimated ordinary vascular age. Traditional risk factors for the participants were estimated by the SCORE risk chart. A 1-cm wide region of the distal common carotid artery intima media complex was automatically segmented from the original B-mode images. The images were fed to a Deep Learning model, convolution neural network (CNN), trained using transfer learning model with 60% training data set and 40% evaluation data set. Classification performance was quantified using accuracy of ROC analysis.

Results

The mean age was 58 and 56 years in groups 1 and 2, respectively (with 43% and 56% women, respectively). The mean SCORE was 1.74 in group 1 and 1.09 in group 2. Classification based on SCORE had an area under the curve of 0.69 with an accuracy of 38%. The Deep learning approach had an area under the curve of 0.89 with an accuracy of 78%.

Intima media image based classification

Conclusion

The results shows that ultrasound image texture of the intima media with Deep Learning approach can be used to detect pronounced disease without explicit measurement of IMT values or detection of plaques. With hard end-points, the approach could be used for risk stratification of subclinical atherosclerosis.

Acknowledgement/Funding

Västerbotten County Council, Swedish Research Council, Heart and Lung Foundation, Carl Bennet Ltd, Sweden.
P3431Machine learning applied to energy waveform ECG for prediction of subclinical myocardial dysfunction
Authors: Potter E , Liu Y , Teo S , Inouye M , Marwick T H
Published: October 2019

Background

Energy waveform (ew) ECG used continuous wavelet transforms (CWT) to create time-frequency energy characterisations. Although ewECG changes reflect myocardial disease, the optimal measures for prediction of subclinical left ventricular dysfunction (sLVD) are unclear.

Aim

Using machine learning, we investigated whether ewECG could predict sLVD in community subjects at risk of heart failure (HF).

Methods

Asymptomatic community subjects aged ≥65 yrs. with ≥1 non-ischaemic risk factor for HF underwent clinical evaluation, MyoVista (HeartSciences, Southlake, TX) ewECG and echocardiographic evaluation. sLVD was defined as systolic (global longitudinal strain, GLS≤16%) or diastolic (E/e' ≥15, E/e'>10 with left atrial enlargement, or impaired relaxation with other changes). A gradient boosting algorithm (supervised machine learning) with regularisation was implemented to predict sLVD using 362 ewECG features. The performance was assessed by precision, recall, F measure, precision-recall (PR) curve and receiver operating characteristic (ROC) curve. Feature importance was inspected by information gain node splitting.

Results

Of 97 subjects (age 71 (68–73) yrs., 53% female) 56 (58%) had sLVD. For prediction of sLVD, ewECG showed areas under PR and ROC curves of 0.86 and 0.8 respectively. The feature of greatest importance, with twice the importance of the second was a CWT frequency related to depolarisation.

Baseline characteristics Hypertension (%) 83 (86) Diabetes Mellitus (%) 34 (36) Atrial Fibrillation (%) 8 (8) BMI (IQR) 31 (27–34) LVMi (SD) 73 (23) Ejection fraction (SD) 60 (6) GLS (SD) 18 (3) E/e' (IQR) 8 (7–10) LAVi (IQR) 33 (28–40) IQR, Interquartile range; BMI, body mass index; LVMi, left ventricular mass index; GLS, global longitudinal strain; LAVi, left atrial volume index.

Prediction model performance

Conclusion

ewECG shows good predictive performance for sLVD in elderly subjects at risk of HF. HF prevention strategies incorporating ewECG to select individuals for echocardiographic evaluation should be considered.

Acknowledgement/Funding

Baker Heart and Diabetes Institute
P3440Can pre-operative echocardiography predict RV failure post-LVAD implantation in children?
Authors: Cardoso B , Heads-Baister A , Johnson A , Wake J , Chila T , Simpson E , Hasan A , O'sullivan J , Reinhardt Z , Khushnood A
Published: October 2019

Background

One of the most frequent complications of left ventricular assist device (LVAD) implantation is the development of right ventricular (RV) failure, which occurs in 10%-40% of patients. It is, therefore, essential to identify which LVAD candidates are at risk for RV failure and will require additional RV mechanical support with a biventricular assist device (BiVAD). However, the echocardiographic assessment of the RV is challenging due to its complex geometry and marked load dependence of its function indices. To our knowledge, there is no published evidence regarding which specific RV echocardiographic parameters should inform this decision in the paediatric population.

Aims

We sought to determine which pre-operative RV echocardiographic parameters best correlate with the need for a BiVAD, as opposed to LVAD alone, in a paediatric population undergoing VAD insertion at a tertiary care institution.

Methods

Retrospective review of the pre-operative echocardiograms of children (<18 years) with dilated cardiomyopathy undergoing elective VAD implantation at our institution, from November 2007 to December 2018. Preoperative quantitative and qualitative RV echocardiographic parameters described in the literature to be associated with RV failure after LVAD implantation in adults were collected. Moreover, qualitative RV function was independently assessed by three echocardiographers, blinded to the outcome of the patients.

Results

89 patients were included, 39 (43.8%) males, median age = 1.7 years (IQR = 6.9), median weight = 11.6 kg (IQR = 13.8). 49 (55.1%) patients had an LVAD implanted, whereas 40 (44.9%) were deemed to need biventricular support. 45 (50.6%) patients received an EXCOR Berlin Heart, 16 (18%) a HeartWare HVAD and 28 (31.4%) a Levitronix Centrimag device. Requirement of BiVAD support was significantly more common in patients with moderate to severe RV impairment, as per expert assessment (OR = 2.864; 95% CI: 1.188–6.903, p=0.018), and tricuspid regurgitation > grade III (OR = 3.154; 95% CI: 1.124–8.850, p=0.025). All the other parameters collected – tricuspid annular plane systolic excursion (TAPSE), tricuspid regurgitant jet velocity, tricuspid regurgitation duration corrected for heart rate, RV tissue Doppler indices, RV fractional area change, and RV/LV diameter ratio– were not significantly different among groups.

Conclusions

In our paediatric population, expert assessment of RV function and degree of tricuspid regurgitation were strong predictors of RV failure among patients undergoing LVAD implantation, allowing for pre-emptive RVAD implantation and improving patient outcomes.
P3452Differential implication of gender on future thromboembolic risk in patients with and without atrial fibrillation
Authors: Choi K.-J , Cho M S , Do U , Kim J , Nam G B , Kim Y H
Published: October 2019

Background

Gender difference in stroke risk by the presence of atrial fibrillation was not well evaluated.

Purpose

We hypothesized that the gender showed different impacts on future thromboembolic risk in patients with and without atrial fibrillation.

Methods

The study population comprised of 26,226 patients (mean 56.3 years old, 52.6% male) with (n=3147, 12.0%) or without (n=23079, 88.0%) atrial fibrillation who underwent cardiac evaluations consisted of electrocardiography, echocardiography, and holter monitoring in our center. The main study outcomes were thromboembolic events defined as composite of ischemic stroke and systemic embolism.

Results

During mean follow-up period of 2.8 years, thromboembolic event occurred in 610 patients (2.3%). In the overall population, the 3-year rate of thromboembolic event of female patients was lower than males (2.2% vs. 2.8%, P=0.011). However, when the population was divided according to the presence of AF, females showed higher rate of thromboembolic events in those with AF (6.7% vs 3.1%, P<0.001), whereas lower rate in those without AF (1.7% vs. 2.7%, P<0.001, P for interaction between gender and AF <0.001). After multivariable adjustment, female gender was at higher risk of future thromboembolic events in those with AF (HR 1.61, 95% CI 1.13–2.29, P<0.001), whereas at lower risk in those without AF (HR 0.75, 95% CI 0.62–0.91, P=0.003). The interaction between gender and AF was significant in those who had one or more components of CHA2DS2-VASc score other than gender (CHA2DS2-VA score ≥1, P for interaction = 0.001), but not in those without (P for interaction = 0.196)

Conclusion

Female gender demonstrated differential thromboembolic risk according to the presence of AF.

Acknowledgement/Funding

None
P3455Trends, untilization of therapies and outcomes of females with history of breast cancer admitted for STEMI
Authors: Mastoris I , Shah Z , Vuddanda V , Mohammed M , Haglund N , Sauer A , Porter C
Published: October 2019

Background

Real world experience of treatment of female patient with history of breast cancer suffering from STEMI is lacking

Purpose

To study the trends, utilization of therapies and outcomes of STEMI in females with history of breast cancer from a large, national, multicenter US database.

Methods

We analyzed Nationwide Inpatient Sample from years 2007 to 2014 to identify all females with primary discharge diagnosis of STEMI and secondary diagnosis of breast cancer. We then analyzed the use of various therapies and outcomes.

Results

Of 476,462 females with STEMI hospitalizations, 17, 357 (3.65%) had history of breast cancer. In this patient cohort the mean age was 75.81±11.82 years and 85% were Caucasians, hypertension, diabetes mellitus, chronic kidney disease and peripheral vascular disease was present in 29.5%, 70.3%, 12.4% and 8.3% respectively. 50% of the patients underwent percutaneous coronary intervention (PCI) and 3% underwent coronary artery bypass surgery (CABG). Intra-aortic balloon pump was used in 5.2% and percutaneous LVAD (PLVAD) in 0.5%. 15.3% patients developed cardiogenic shock (CS) and 6.2% had ventricular fibrillation/cardiac arrest (Vfib/CA). The in-hospital mortality was 12.3%.

Comparison of female patients for STEMI with and without history of breast cancer Group Patients No Age (mean) PCI CABG IABP PLVAD CS Vfib/CA Mortality STEMI / Breast cancer − 495,105 69±14 54% 4.5% 6.5% 3% 9.42% 8.1% 9.7% STEMI / Breast cancer + 17,357 75.8±11.8* 50%* 3%* 5.2%* 0.5%* 15.3%* 6.2%* 12.3%* *P<0.05.

Conclusion

The STEMI/breast cancer cohort is significantly older with underutilization of PCI, CABG, and mechanical circulatory support. This population exhibits higher mortality rates.

Acknowledgement/Funding

None
P3457Oxidative stress and left ventricular remodeling in postmenopausal women
Authors: Lareva N , Govorin A , Luzina E
Published: October 2019

Purpose

To asses the level of oxidative stress in postmenopausal women in dependence of LV structural and functional changes and its filling parameters.

Methods

203 postmenopausal women were included in the investigation: 142 women with surgical menopause (average age 44,3±5,4 years, menopause duration 3,8±2,4 years); and 61 women with natural menopause (average age 46,2±4,7 years, menopause duration 4,3±2,1 years). All patients underwent general clinical examination, menopausal index evaluation, ambulatory blood pressure (BP) monitoring (Cardiotens-01, Meditech, Hungary), echocardiographic examination with systolic and diastolic left ventricular (LV) function assessment. We also measured erythrocyte thiobarbituric acid reactive substances (TBARs), ultimate products of lipid peroxidation (Shiff bases), catalase activity and plasma general antioxidant activity. Control group consisted of 35 healthy menstruating women (mean age 39,2±4,2). Statistical methods such as Cruskell-Walles criteria and χ2 test were used.

Results

Only 39 postmenopausal women (19,2%) had normal LV geometry; 89 pts (43,8%) demonstrated LV concentric hypertrophy, 57 pts (28,1%) – concentric remodeling and 18 women (8,9%) –eccentric hypertrophy. All postmenopausal women showed signs of activation of oxidative stress while reducing the power of antioxidant protection systems, however, these changes were most pronounced in groups of patients with eccentric and especially concentric LV hypertrophy

Nobody of included postmenopausal women had LV systolic function failure. Presence of LV diastolic function disturbance was the same in the patients with surgical and natural menopause (54,1% (33 pts) and 59,1% (84 pts), respectively, p=0,231) and did not depend on BP level: 59,1% (52 pts) in hypertensive and 56,5% (65 pts) in normotensive women, p=0,118. We detected that Shiff bases level in postmenopausal women with diastolic dysfunction was increased in 1,5 times in comparison with healthy menstruating women and in 1,3 times in comparison with those postmenopausal women who had no diastolic function disturbance (p<0,01). The level of erythrocyte TBARs in this group was increased in 1,3 and 1,2 times respectively (p<0,05). Erythrocyte catalase activity and plasma general antioxidant activity were decreased in all postmenopausal women in comparison with healthy ones (p<0,01). The presence of LV diastolic dysfunction correlated positively with erythrocyte Shiff bases level (τ=0,47, p<0,01) and negatively – with erythrocyte catalase activity and plasma general antioxidant activity (τ=−0,35 and τ=−0,35, p<0,01 respectively)

Conclusions

Thus, oxidative stress may play important role in left ventricular remodeling and diastolic dysfunction formation in postmenopausal women.
P3460Structural and functional changes of vascular wall in women of perimenopausal period with long-term menopausal hormone therapy
Authors: Tolstov S N , Salov I A , Rebrov A P
Published: October 2019

Introduction

Features of changes in the vascular wall in women of the menopausal period are not sufficiently illuminated. Most of the studies evaluating the effect of menopausal hormonal therapy (MHT) on the structural and functional state of the vascular wall were limited to the time frame from several months to 1–3 years, which distinguishes them from our study.

Purpose

To evaluate structural and functional changes in the vascular wall in women of early postmenopausal period with prolonged use of low doses of MHT 1 mg of 17β-estradiol (E2) and 2 mg drospirenone (DRSP).

Methods

The study included 162 women in the early postmenopausal period with climacteric syndrome were divided into 2 groups: the main group of 84 women assigned MHT 1 mg E2 /2 mg DRSP, control group of 78 women who did not receive MHT. Duration of follow-up 5,2 (4,8; 5,7) years. Explored pulse wave velocity (PWV). Bbrachial blood pressure was measured non-invasively over the 24 h with an electronic, oscillometric, automated device (BPLab) with the assessment of 24-h central arterial pressure (CAP), aortic augmentation index (AIx), arterial stiffness index (ASI); ambulatory arterial stiffness index (AASI). Endothelium-dependent vasodilation (EDV) of the brachial artery was evaluated.

Results

In women of the main group PWV made up 7.19±1.7 m/s initial and 7.53±1.3 m/s to the end of the study (p>0.05); in the control group - 7,21±1.8 m/s and 7.95±1.9 m/s (p<0.001). In the women of the main group by the end of the study a decrease in the CAP was noted from 38.4±6.2 to 35.3±4.1 mm Hg. (p<0.001), in the women of the control group there were no changes of 41.4±9.6 and 40.9±9.8 mm Hg. (p<0.001 between women of both groups at the end of the study). In women of the control group, a significant increase in AIx was found from 31.0 (20.0; 35.0)% initially to 33.0 (29.0; 37.0)% by the end of the study (p<0.05) and no changes in women of the main group – 27.0 (20.0; 35.0)% and 28.0 (20.0; 33.0)%. Multidirectional changes ASI were revealed: a decrease in women of the main group from 132.0 (121.0; 142.0) to 127.0 (115.5; 137.0) cu and an increase from 133.0 (111.0; 155.0) to 148.0 (134.2; 171.0) cu in women of the control group (p<0.01 between women of both groups at the end of the study).

By the end of the study, there was a decrease in AASI in women of the main group from 0.379 (0.320; 0.463) to 0.264 (0.203; 0.329) cu (p<0.001) and the absence of changes AASI value in women of the control group – 0.360 (0.283; 0.471) and 0.370 (0.310; 0.476) cu. In women of the main group, an increase in the brachial artery EDV was found from 8.6±7.4% initially to 11.1±6.8% by the end of the study (p<0.05) and no change in women in the control group −7.3±5.6% and 6.2±5.0%.

Conclusion

In women in early postmenopause with prolonged MHT of 1 mg E2/2 mg DRSP positive changes in the structural and functional state of the vascular wall were established.
P3471Anti-inflammatory effects of direct oral anticoagulants in patients with non-valvular atrial fibrillation: insights from 2216 patients in the DIRECT registry
Authors: Hamanaka Y , Sotomi Y , Hirata A , Hirayama A , Higuchi Y
Published: October 2019

Background

Several previous studies reported anti-inflammatory effect of direct oral anticoagulant (DOAC). However, it was limited to basic pathological data with small sample size. Real-world large clinical data is still scarce.

Methods

We conducted a single-center prospective observational registry of NVAF patients treated with DOACs: the DIRECT registry (UMINehz745.034333283). All patients with nonvalvular atrial fibrillation (NVAF) (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from June 2011 to November 2017 were enrolled (71.6±10.8 years, 36.4% female, follow-up duration: 407.2±388.3 days). High sensitive C-reactive protein (hsCRP) test was performed before (within 3 months from the start) and after the start of DOAC prescription (6±3 months after the start). Patients with a hsCRP value >1.00 mg/dL were excluded from the analysis due to possibility of other systemic inflammatory conditions. The present post-hoc study of the DIRECT registry assessed anti-inflammatory effect of DOAC. Pre-hsCRP and post-hsCRP were compared by Wilcoxon Signed Ranks test.

Results

A total of 1,855 patients were analyzed in the present study (71.0±10.7 years, 677/1,855 (36%) females). In the overall cohort, hsCRP significantly decreased after the start of DOAC prescription (pre median 0.08 interquartile range [0.04–0.17] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001). The significant reduction of hsCRP was consistent across all DOACs (p=0.301) [dabigatran (N=562), pre 0.08 [0.04–0.1625] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001: rivaroxaban (N=457), pre 0.07 [0.04–0.16] mg/dL vs. post 0.07 [0.03–0.125] mg/dL, p<0.001: apixaban (N=494), pre 0.09 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001: edoxaban (N=342), pre 0.08 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001].

Conclusions

The present study of DIRECT registry suggested anti-inflammatory effect of DOAC presented as a significant reduction of hsCRP. Although further investigation would be warranted to evaluate the clinical significance of the suppressed systemic inflammation, the recent favorable clinical data of DOACs might be attributed to the present finding.
P3472Modifications of renal function in atrial fibrillation patients treated with different oral anticoagulants: a multicentre cohort study
Authors: Pastori D , Lip G Y H , Sciacqua A , Perticone F , Melillo F , Godino C , Marcucci R , Berteotti M , Violi F , Pignatelli P
Published: October 2019

Background

A decline of estimated glomerular filtration rate (eGFR) has been described in atrial fibrillation (AF) patients on Vitamin K antagonists (VKAs). Few real-world data on the modifications of eGFR in AF patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) do exist.

Purpose

To evaluate changes of renal function in AF patients treated with VKAs or NOACs.

Methods

Multicentre prospective cohort study including 1,667 patients with non-valvular AF from 5 clinical centres of Internal Medicine and Cardiology in Italy.

Renal endpoints were: 1) median annual decline of eGFR; 2) transition to eGFR <50 ml/min/1.73 m2; 3) eGFR class worsening according to KDIGO 2012 classification. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up.

Results

Median age was 73.7±9.1 years and 43.3% were women. 743 patients were on VKAs and 924 on NOACs (Dabigatran, Rivaroxaban e Apixaban). Median annual eGFR decline was −2,11 (Interquartile Range [IQR] −5,68/−0,62] in patients on VKAs, −0,27 [IQR −9,00/4,54] with Dabigatran (p<0.001 vs. VKAs), −1,21 [IQR −9,98/4,02] with Rivaroxaban (p=0.004 vs. VKAs) and −1,32 [IQR −8,7/3,99] with Apixaban (p=0.003, vs. VKAs). Use of Dabigatran and Apixaban was associated to a lower transition to eGFR <50 mL/min/1.73 m2, compared to VKAs: adjusted Odds Ratio (aOR) 0.492, 95% Confidence Interval (CI) 0.298–0.813, p=0.006 for Dabigatran; aOR 0.449, 95% CI 0.276–0.728, p=0.001 for Apixaban). Regarding the eGFR class worsening, Dabigatran (aOR 0.70, 95% CI 0.503–0.975, p=0.035), Rivaroxaban (aOR 0.591, 95% CI 0.423–0.825, p=0.002), and Apixaban (aOR 0.591, 95% CI 0.429–0.815, p=0.001) were all associated to a lower rate of eGFR class worsening compared to VKAs.

Forest plot

Conclusions

In this prospective multicentre cohort study, NOACs use was associated with a lower decline of renal function compared to VKAs. Patients on Dabigatran showed the lowest annual rate of eGFR decline and those on Apixaban and Rivaroxaban a lower eGFR class worsening.

Acknowledgement/Funding

None
P3474Relationship between international normalized ratio variability, quality of anticoagulation control and outcomes in patients with atrial fibrillation: an AFFIRM post-hoc analysis
Authors: Proietti M , Romiti G F , Olshansky B , Lip G Y H
Published: October 2019

Introduction

Quality of anticoagulation control is essential to ensure better clinical outcomes in patients with atrial fibrillation (AF). Time in therapeutic range (TTR) is recommended as a measure of the quality of anticoagulation control. The International normalized ratio (INR) variability has been suggested as an alternative index, even though large independent validations for this index are still lacking.

Purpose

To provide validation of clinical usefulness of INR variability as a measure of the quality of anticoagulation control in a large cohort of AF patients.

Methods

Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial were analysed. INR variability was defined as the standard deviation (SD) of mean INR values [INR-SD] recorded throughout the follow-up observation for each patient. All patients with available INR values were included in the analysis. Stroke, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes.

Results

Among the original 4060 patients, a total of 3185 (78.4%) were available for analysis. Mean (SD) INR-SD was 0.58 (0.25). According to INR-SD patients were categorized into four quartiles. Mean (SD) CHA2DS2-VASc score was increased (p=0.040), with no difference in proportions of CHA2DS2-VASc ≥2 (p=0.582) between the subgroups. A significant inverse correlation was found between INR-SD and TTR (Spearman's Rho: −0.536, p<0.001). Continuous INR-SD, after multiple adjustments, was inversely associated with TTR (standardized beta: −0.451, p<0.001) and directly associated with SAMe-TT2R2score (standardized beta: 0.084, p<0.001). A fully adjusted Cox multivariate regression analysis found that INR-SD was directly associated with increased risk of stroke, major bleeding and all-cause death (Table). An INR-SD ≥0.85 was directly associated with all the study outcomes, on multivariate analysis (Table).

Cox Regression Analysis INR-SD INR-SD ≥0.85 HR (95% CI) HR (95%) Stroke 2.52 (1.34–4.67) 1.62 (1.00–2.63) Major Bleeding 2.43 (1.49–3.96) 1.61 (1.10–2.36) CV Death 1.50 (0.87–2.59) 1.54 (1.07–2.24) All-Cause Death 1.79 (1.21–2.66) 1.55 (1.17–2.05) CI = Confidence Interval; CV = Cardiovascular; HR = Hazard Ratio; INR-SD = International Normalized Ratio Standard Deviation.

Conclusions

INR variability, expressed as INR-SD, was significantly correlated and associated with TTR. Both continuous INR-SD and INR-SD ≥0.85 were significantly associated with a higher risk of all study adverse outcomes.

Acknowledgement/Funding

None
P3478Glucose-dependent insulinotropic peptide is essential for maintenance of cardiac lipid metabolism via FGF21-dependent pathway
Authors: Remina Y , Kureishi Bando Y , Ozaki R , Kamihara T , Nishimura K , Murohara T
Published: October 2019

Background/Introduction

Incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are secreted from the small intestine and emerged as important participants in glucose homeostasis that involves in the pathogenesis of type 2 diabetes (T2D). stimulate glucose-dependent insulin biosynthesis. Emerging data suggest important extrapancreatic functions for GLP-1 on cardiovascular system. However, limited evidence has been emerged whether GIP may play any pathophysiological role in heart. GIP promotes insulin secretion leading to augment insulin-induced lipogenesis. Recent research has highlighted the relevance of the GIP/GIPR axis in principal insulin-sensitive organs such as adipose tissue. Heart is another insulin-sensitive organ in which insulin promotes hypertrophy of myocardium presumably via activation of Akt pathway. In T2DM, ectopic accumulation of lipid and fat to myocardium that is known as “cardiac steatosis”; however, it remains uncertain whether the GIP/insulin axis may modulate cardiac steatosis observed in T2DM.

Purpose

To elucidate that physiological GIP may play a regulatory role in cardiac pathophysiology.

Methods

We employed mouse model of GIPR deficiency (GIPR-KO) that was generated by lacking the GIPR gene (GIPR), by replacing exons 4 and 5 of GIPR with the PGK-neo cassette. Cardiac evaluation of GIPR-KO was performed at the age of 6 week-old (w/o), 10 w/o, 23 w/o, and 53 w/o.

Results

GIPR deficient mice (GIPR-KO) exhibited normoglycemia, but their circulating free acid level and ketone level were elevated. Interestingly, GIPR-KO at younger age (6-week-old and 10-week old) exhibited normal left-ventricular (LV) function, however, older mice aged older than 20-week-old exhibited significant systolic left-ventricular dysfunction (FS (%) 55.2±1.9 for Wild-type, 32.1±2.6 for 23-w/o-GIPR-KO, 28.5±2.6 for 56-w/o-GIPR-KO, P<0.01). Histological analysis revealed that cardiomyocyte size was decreased and capillary density was increased in GIPR-KO. Interestingly, TUNEL staining revealed that there was no increase in cardiac apoptosis in GIPR-KO. In contrast, GIPR-KO exhibited increase in cardiac fibrosis (Picro-sirius staining) and oxidative stress (DHE staining). Myocardial triglyceride accumulation was decreased in GIPR-KO heart. QPCR analysis revealed GIPR-KO heart exhibited increase in BNP level and decline in fibroblast growth factor 21 (FGF-21), an hormonal activator for energy expenditure in adipocyte. GIP augmented FGF-21 expression in cardiomyocytes via PPARalfa.

Conclusion

Loss of GIP signaling caused impaired fatty acid metabolism in heart via impairment of FGF21 pathway and oxidative stress, leading to an age-dependent progression of cardiac dysfunction.
P3529Prognostic impact of cohabitation status in hospitalized patients with acute heart failure
Authors: Kenichiro Y , Oguri M , Takahara K , Takahashi H , Ishii H , Murohara T
Published: October 2019

Background

The prevalence of heart failure (HF) in the elderly is steadily increasing, therefore, the prudent care and treatment according to individual's characteristics, comorbidities, or prognosis, should be prerequisite. Although cohabitations status in each elderly patient is different, an association of this condition with long-term prognosis remains to be identified definitively in Japan.

Purpose

The purpose of the present study was to examine the prognostic impact of cohabitation status on 3-year mortality among hospitalized acute HF patients.

Methods

The study population comprised a total of 817 individuals who were hospitalized for acute HF between November 2009 and December 2015, and was followed up for 3 years. We classified patients into three groups (cohabitation with spouse, cohabitation with another generation, and living alone). We evaluated relative predictive values between these three groups for 3-year mortality by Cox regression model.

Results

The median age was 79 (interquartile range 70–85) years, and 55.7% of the subjects were male. Median length of hospital stay was 16 (interquartile range 11–23) days. The distribution of three groups was cohabitation with spouse (50.9%), cohabitation with another generation (28.5%), and living alone (20.6%). The overall rate of 3-year mortality was 32.2% (n=263), 31.5% (n=131) in cohabitation with spouse, 38.2% (n=89) in cohabitation with another generation, and 25.6% (n=43) in living alone. Cohabitation with another generation was significantly related to the occurrence of 3-year mortality by univariate analysis (P<0.001). Age (84 years vs. 77 years), the frequency of female (69.1% vs. 33.4%), left ventricular ejection fraction (52.7% vs. 47.5%) were significantly greater, whereas body mass index (21.2 vs. 22.6), smoking status (27.0% vs. 53.4%), ischemic etiology (27.5% vs. 35.6%), and the prevalence of type 2 diabetes mellitus (32.2% vs. 41.4%) and atrial fibrillation (20.6% vs. 29.8%) were significantly (P<0.05) smaller in cohabitation with another generation than others. The ratio of home return and optimal medical therapy were similar between the 2 groups. Cohabitation with another generation was associated with higher relative risk of 3-year mortality than living alone [Hazard Ratio (HR) 1.65; 95% Confidence Interval (CI) 1.15–2.38, P=0.007], or cohabitation with spouse (HR 1.46; 95% CI 1.12–1.92, P=0.006). Multivariable Cox regression model, with adjustment for age, albumin, brain natriuretic peptide, and prior HF hospitalization, revealed that cohabitation with another generation was no longer significant.

Conclusion

Our present results suggest that cohabitation status affected on long-term prognosis in patients with HF, especially cohabitation with another generation posed as worst predictor. We should pay more attention to social factors including cohabitation status in the clinical practice.
P3548Noninvasive estimation of left ventricular diastolic function in patients with hypertension and normal ejection fraction using 3-dimensional speckle tracking echocardiography
Authors: Minatoguchi S , Tanaka R , Yoshizane T , Deguchi T , Sato H , Ono K , Nagaya M , Miwa H , Iwama M , Noda T , Watanabe S , Kawasaki M , Okura H
Published: October 2019

Background

Left ventricular (LV) relaxation (eTau) and pulmonary capillary wedge pressure (ePCWP) were reported to be estimated by speckle tracking echocardiography (STE). LV camber stiffness (e-c stiffness) may be estimated with the use of 2 diastolic pressure-volume coordinates. The minimum diastolic pressure (mP) is reported to have a strong correlation with Tau.

Purpose

We sought to examine the impact of hypertension on LV diastolic function and LA properties and to elucidate the feature of hypertensive heart failure with preserved EF (HFpEF).

Methods

The e', E/e', Tau, PCWP, LVEDP, LV stiffness, LAV, LA emptying function (LAEF) and LA strain were examined in 53 controls (age 66±11), 136 hypertensive patients (HTN) with normal EF (69±11) and 39 HFpEF (77±14). ePCWP and estimated EDP (eEDP) was calculated as previously reported. Tau was calculated as isovolumic relaxation time/(ln 0.9 x systolic blood pressure − ln PCWP). Myocardial stiffness (e-m stiffness) was estimated as LVED stress/LV strain. LV c-stiffness was calculated as LV pressure change (from mP to EDP) obtained by catheterization divided by LV volume change. Estimated LV c-stiffness (e-c-stiffness) was noninvasively obtained using e-mP and e-EDP. The eTau, eEDP and e-mP by STE were validated by catheterization (n=126).

Results

The mP had a good correlation with Tau (r=0.70, p<0.01). The eTau, eEDP and e-mP by STE had a good correlation with those by catheterization (r=0.75, 0.63 and 0.70, p<0.01). Multivariate analysis revealed that ePCWP and LA strain were independent predictors of HFpEF.

LV diastoric function Variables Control HTN HFpEF LVEF, % 68±6 68±8 63±9*+ LV longitudinal strain x (s–1) 19.1±3.0 16.8±4.3* 14.5±5.1*+ E/e' 9.2±2.6 11.6±4.5* 15.9±7.9*+ eTau, ms 35±12 48±17* 59±17*+ ePCWP, mmHg 7.3±2.7 8.3±4.3 15.0±4.4*+ eLVEDP, mmHg 9.4±2.2 10.4±3.5 15.9±3.7*+ LV e-myocardial stiffness, kdynes/cm 0.56±0.25 0.69±0.56 1.27±0.71*+ LV e-chamber stiffness, mmHg/ml 0.19±0.06 0.20±0.08 0.36±0.19*+ Maximum LAVI, ml/m2 42±15 50±21* 68±17*+ Total LAEF, % 55±7 51±11 36±12*+ LA peak strain 41±15 40±17 19±8*+ *p<0.05 vs Control, +p<0.05 vs HTN.

Conclusion

We demonstrated that LV diastolic function in HTN may be accurately and noninvasively evaluated by STE.
P3571Genes polymorphism and renal dysfunction formation in arterial hypertension patients with high adherence to treatment
Authors: Koziolova N , Chernyavina A
Published: October 2019

Objective

To evaluate the contribution of gene polymorphism to the formation of renal dysfunction in patients with hypertension with high adherence to treatment.

Methods and materials

88 working-aged subjects with non-complicated arterial hypertension (average age 48,65±7,24 yrs). All patients underwent evaluation of genotype for markers AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met. To assess the glomerular function, cystatin C was measured in serum by ELISA, and serum level of NGAL was determined by ELISA to assess the function of the tubules.Depending on genotype peculiarities the following groups were formed: 1) 39 patients who had polymorphism of AGT Thr174Met in homozygous and 49 subjects without one; 2) 62 subjects who had polymorphism of GNB3 C825T in heterozygous and 26 subjects without one; 3) 52 subjects with polymorphism of MTHFR C677T in heterozygous and 36 subjects without one; 4) 48 subjects with polymorphism of MTRR Ile22Met in heterozygous and 40 subjects without one.

Results

Patients in the groups did not differ in sex, age, risk factors, comorbidities, concomitant medications, BP level, lipid spectrum. In the groups with the presence of the genes GNB3 and MTHFR polymorphism in the heterozygous form, the level of NGAL was significantly higher than in the groups with normal genotypes: 1.67±0.86 ng/ml versus 1.2±0.87 pg/ml (p=0.022), 1.49±0.61 pg/ml versus 1.21±0.56 ng/ml (p=0.034), respectively. At the same time, in these groups, the level of cystatin C was not significantly different. The AGT gene polymorphism groups differed significantly in cystatin C (p<0.001), but did not differ in the level of NGAL. In the group with the presence of the MTRR gene polymorphism, the level of cystatin C and the level of NGAL were significantly higher (p=0.042 and p=0.004, respectively). The correlation analysis revealed a moderate direct interconnections between cystatin C levels and the presence of the AGT gene polymorphism (r=0.46; p=0.017) and MTRR (r=0.33; p=0.039), as well as between the NGAL level and the presence of the GNB3 gene polymorphism (r=0.42; p=0.031), MTHFR (r=0.39; p=0.023) and MTRR (r=0.43; p=0.007).

Conclusions

In working-aged patients with uncomplicated hypertension with high adherence to treatment, the formation of renal dysfunction with a primary glomerular lesion is associated with the presence of polymorphism of the AGT gene in the heterozygous form. Formation of renal dysfunction with predominant tubular lesion is associated with the presence of GBN3 and MTHFR genes polymorphism of in the heterozygous form. And the formation of renal dysfunction with the damage of both glomeruli and tubules is associated with the presence of the MTRR gene polymorphism of the in the heterozygous form.
P3581Periinterventional cocoa flavanol supplementation prevents functional and structural damage to the arterial wall after transradial catheter intervention
Authors: Grone M , Ophoff M , Heiss C , Kelm M , Sansone R
Published: October 2019

Background

The transradial approach is commonly preferred over the femoral approach for coronary angiography to reduce vascular complications like bleeding, aneurysm formation and all-cause mortality ensuring early ambulation after coronary procedures. However, there is growing evidence that damage to the radial artery endothelium elicits intimal hyperplasia, vascular remodeling and might ultimately lead to total vessel occlusion.

Objective

Our study aimed to investigate the effects of dietary flavanol intervention on (a) early endothelial functional recovery and (b) late structural changes i.e. intimal hyperplasia after mechanical vascular wall injury in the human forearm model during coronary angiography.

Methods

Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change, Fdc), intima-media thickness (IMT), luminal and external arterial diameter at the site of intervention and the contralateral control artery were measured in 38 male patients (19 flavanol intervention, 19 placebo control) undergoing transradial coronary angiography (TCA) at baseline, after 7 days of 450mg flavanol supplementation BID, directly after TCA and 6 months after TCA. Circulating levels of endothelial microparticle (EMP) subpopulations CD31+/41-, CD62e+and CD144+were analyzed simultaneously as a surrogate for endothelial functional integrity and activation.

Results

One week of flavanol supplementation, not placebo, significantly increased RA-FMD (8.88±2.03% vs. 11.17±2.89%, p<0.01 in flavanol and 8.64±1.87% vs. 8.32±1.63%, p=n.s. in placebo). RA-FMD significantly decreased in the intervention artery directly after TCA, which was partly mitigated by flavanol supplementation (delta to baseline: −2.61±0.82% in flavanol vs. −4.91±0.63% in placebo, p=0.034). TCA induced significant intimal hyperplasia in the radial artery (0.36±0.02mm vs. 0.44±0.04mm, p<0.01) in placebo, but not in the flavanol group (0.36±0.02mm vs. 0.37±0.02mm, p=n.s.) after 6 month. One week of flavanol supplementation increased Fdc (1.94±0.99 vs. 3.07±1.31, p<0.01). No changes occurred in the placebo group (1.99±1.29 vs. 1.96±1.17, p=n.s.). On the contralateral arm, the decrease in RA-FMD was blunted by flavanols (delta to baseline: +0.42±1.05% in flavanol vs. −0.61±1.55% in placebo) along with decreased circulating levels of EMPs.

Conclusions

TCA impairs endothelial function (RA-FMD), vascular physicomechanics (Fdc) and induces intimal hyperplasia (IMT). Periinterventional flavanol supplementation blunts the acute decreases in endothelial function and physicomechanics and prevents chronic negative vascular remodeling.
P3583Optimal procedural strategy to improve clinical outcome in primary percutaneous coronary intervention
Authors: Park Y J , Lee J H , Park B E , Kim H N , Jang S Y , Bae M H , Yang D H , Park H S , Cho Y , Chae S C
Published: October 2019

Background

Current guideline recommends potent antiplatelet agents and transradial intervention. However, it is uncertain whether routine use of IVUS, thrombus aspiration and glycoprotein IIB-IIIA inhibitor is beneficial for improving clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI).

Purpose

The aim of this study was to investigate optimal procedural strategy to improve clinical outcome.

Methods

A total of 6,046 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI were analyzed from the Korean Acute Myocardial Infarction Registry (KAMIR) – National Institute of Health (NIH) database. MACCEs were defined as a composition of all cause death, non-fatal MI, repeat revascularizations including repeated percutaneous coronary intervention and coronary bypass grafting, cerebrovascular accident and rehospitalizations. This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.

Results

During the primary PCI, potent antiplatelet agents such as prasugrel and ticagrelor were used in 2342 (38.4%). PCI was performed through transradial approach in 1490 (25.2%). Thrombus aspiration and intravascular ultrasound (IVUS) examination was done in 2204 (36.1%) and 1079 (18.1%), respectively. Glycoprotein IIB-IIIA inhibitor was administered in 1295 (21.7%). Among them, potent antiplatelet agents, transradial intervention, IVUS, and thrombus aspiration significantly reduced MACCEs at 1 year. Glycoprotein IIB-IIIA inhibitor was not effective to improved clinical outcome. In Cox-proportional hazards model, potent antiplatelet agents (hazard ratio 0.82, 95% confidence interval 0.67–0.99; p=0.045) and transradial intervention (hazard ratio 0.61, 95% confidence interval 0.47–0.78; p<0.001) was an independent predictor of MACCEs after adjusting for confounding variables. Combined use of potent antiplatelet agents and transradial intervention (hazard ratio 0.54; 95% confidence interval 0.37–0.80; p=0.002) substantially reduced MACCEs at 1 year.

Conclusion

Among evidence based procedures during the primary PCI, combined use of potent antiplatelet agents and transradial intervention was optimal procedural strategy to improve clinical outcome.
P3604Gender difference in Low-BMI patients with acute myocardial infarction makes an impact on mid-term outcomes
Authors: Yoshioka G , Shibata Y , Node K , Kuriyama N , Watanabe N , Koiwaya H , Ogata K , Goriki Y , Shinzato K
Published: October 2019

Background/Introduction

There are some reports about impact of low body-mass-index (BMI) on patients with acute myocardial infarction (MI), suggesting an obesity paradox. However, the differential impact of gender between low-BMI and mid-term outcome remains unclear.

Purpose

To evaluate the differential impact of gender between low-BMI patients with acute MI and mid-term outcome.

Methods

We evaluated 3038 consecutive patients with acute MI in Miyazaki medical association hospital. Patients were stratified low-BMI group (BMI≤20) from other-BMI group (BMI>20), and compared. BMI was measured at admission of acute MI. Primary outcome was cardiac death. We also analyzed each gender, using Kaplan-meier curve with long-rank test.

Result

Among all patients, low-BMI patient was 8.6%. Median follow-up was 1085 days, and cardiac death was significantly higher rate in low-BMI group (14.5% vs 7.7%, p<0.001). Male patient with low-BMI was significantly higher event rate, compared with other-BMI group (11.0% vs 5.5%, p<0.001). However, female patient group had no significant difference of outcomes between low-BMI and other-BMI (12.6% vs 10.3%, p=0.315). Event rate is shown in the Figure.

Gender

Conclusions

Low BMI was associated with mid-term outcomes in acute MI patients. Impact of low-BMI on mid-term outcome seems to be gender dependent in acute MI patients.