bluuebunny/crossref_metadata_2025 huggingface dataset:
P3378Differences in valve morphology and aortopathy between patients with bicuspid and tricuspid aortic valves: a Computed Tomography Study
Authors: Nassar M , Perlman G , Arow Z , Lessick J , Segev A , Assali A , Danenberg H , Goitein O , Vaknin-Assa H , Orvin K , Sabtan O , Finkelstein A , Banai S , Kornowski R , Hamdan A
Published: October 2019

Background

Transcatheter aortic valve implantation (TAVI) has been shown safe and feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of differences in valve morphology and aortic root dimensions in patients with BAV in comparison to patients with tricuspid aortic valve (TAV) is important for the spread of TAVI in patients with BAV.

Purpose

The present study evaluated the prevalence of BAV subtypes and the differences in valve morphology and aortic root dimensions between BAV and TAV in patients undergoing computed tomography (CT) before TAVI.

Methods

In five medical centers in Israel, 104 patients (69±13.5 years) with BAV and 105 patients (81±8.22 years) with TAV underwent CT angiography. BAV morphology was defined according to the number of commissures and raphe following Siever's classification. Functional BAV was defined as 3 cusps with focal fusion of 1, 2, or 3 commissures. Aortic root dimensions were measured at the level of the aortic annulus, sinus of Valsalva (SOV), sino-tubular junction (STJ), and ascending aorta (AA). Membranous septum (MS) length was measured in coronal view. The volume and agatston score of aortic valve calcification were evaluated.

Results

Type 0 account for 22% (23/104), type IA for 58% (60/104), Type IC for 9% (9/104), functional BAV for 11% (12/104). Type IB and II were not found in the studied population. As compared with TAV, patients with BAV have significantly larger aortic annulus area, SOV area, STJ area and AA Area; however, the ellipticity index of aortic annulus, SOV, STJ, and AA were similar. MS length was significantly smaller in patients with BAV compared to patients with TAV (6.4±2.3 mm vs. 8.1±2.7mm; retrospectively; P<0.001) and the volume of aortic valve calcifications was significantly higher in BAV compared to TAV patients: 2.3±1.6 ml3 vs. 1.4±1.2 ml3 retrospectively; P=0.003).

Conclusions

In Israel, patients with BAV showed more frequently type 1A BAV. BAV patients have larger aortic root dimensions than patients with TAV without difference in regard to the ellipticity index. MS length was smaller and the amount of aortic leaflet calcifications was higher in patients with BAV. These findings may have important impact on procedural outcome.
P3380Longitudinal assessment of coronary atherosclerosis according to baseline and changes of serum hemoglobin level
Authors: Won K.-B , Lee B K , Rizvi A , Hadamitzky M , Budoff M J , Leipsic J A , Berman D S , Min J K , Chang H.-J
Published: October 2019

Introduction

Little is known regarding the impact of serum hemoglobin level changes (Δ hemoglobin) on coronary plaque volume. This study evaluated the association between Δ hemoglobin and coronary plaque volume change (PVC) using serial coronary computed tomographic angiography (CCTA).

Methods

A total of 830 subjects (61±10 years, 51.9% male) who underwent serial CCTA with available hemoglobin levels were analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.5 to 4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were stratified into four groups based on the quartile of baseline hemoglobin levels. Annualized PVC was defined as total PVC divided by inter-scan period. Plaque progression (PP) was defined as plaque volume at follow-up minus plaque volume at index >0.

Results

Baseline total plaque volume (mm3) was not different among all groups (group I [lowest]: 34.1 (0.0–127.4) vs. group II: 28.8 (0.0–123.0) vs. group III: 49.9 (5.6–135.0) vs. group IV [highest]: 34.3 (0.0–130.7); p=0.235). During follow-up, Δ hemoglobin was related to annualized PVC (β:−0.114; p=0.001) and PP (odds ratio: 0.868; 95% confidence interval: 0.770–0.978; p=0.020). Multiple linear regression models showed that Δ hemoglobin significantly impacted on annualized PVC in only the composite of I and II groups.

Conclusion

Based on serial CCTA findings, Δ hemoglobin independently impacted on coronary PVC in individuals with low to normal baseline hemoglobin level.
P3386Angioscopic comparison between polymer-free biolimus A9-coated stent and durable polymer drug-eluting stent 10 months after the implantation
Authors: Tsujimura T , Ishihara T , Iida O , Asai M , Masuda M , Okamoto S , Nanto K , Kanda T , Okuno S , Matsuda Y , Mano T
Published: October 2019

Background

Polymer-free biolimus A9-coated stent (DCS) has currently emerged as expected better arterial healing compared to durable polymer drug-eluting stent (DP-DES). However, superiority of DCS on arterial healing over DP-DES has not been well elucidated using intracoronary images.

Methods

This study examined 288 stents in 224 patients with de novo coronary artery lesions. We angioscopically compared 55 DCS from 35 patients with 233 DP-DES from 189 patients 10±2 months after the implantation. We assessed thrombus adhesion, which is a marker of incomplete re-endothelialization. Dominant neointimal coverage (NIC) grade, heterogeneity of NIC and maximum yellow color of plaque underneath the stent were also evaluated. Neointimal coverage was graded as follows: grade 0, stent struts exposed; grade 1, struts bulged into the lumen, although covered; grade 2, struts embedded by the neointima, but translucent; grade 3, struts fully embedded and invisible. NIC was judged as heterogeneous when differences in the NIC grade became apparent. Yellow plaque was graded as follows: grade 0, white; grade 1, light yellow; grade 2, yellow; grade 3, intensive yellow.

Results

Thrombus adhesion was similar between DCS and DP-DES (29% versus 23%, P=0.32). Dominant NIC was greater in DCS than in BP-DES (P<0.001), while NIC was more heterogeneous in DCS than in BP-DES (P=0.001, Figure). Maximum yellow color of stented segment was similar between DCS and DP-DES (P=0.09).

Conclusion

DCS provided similar thrombus adhesion to DP-DES, which suggested similar re-endothelialization 10 months after implantation. However, DCS showed thick and heterogeneous NIC compared to DP-DES. The specific feature of polymer-free and Biolimus A9 would cause the difference, and further investigation is necessary to evaluate the longer-term safety and efficacy.

Acknowledgement/Funding

None
P3398Cystatin C based eGFR estimation compared to crea-based estimation equation for assessing risk of cardiovascular and total mortality in population-based studies and patients with manifest CVD
Authors: Rothenbacher D , Rehm M , Iacoviello L , Tunstall-Pedoe H , Soederberg S , Salomaa V , Linneberg A , Sans S , Thorand B , Kee F , Kuulasmaa K , Waldeyer C , Zeller T , Blankenberg S , Koenig W
Published: October 2019

Introduction

Chronic kidney disease (CKD) represents a global public health problem and affects a large proportion of the adult population worldwide. Early detection, adequate risk stratification and specific treatment can prevent or delay the adverse effects of CKD.

Purpose

To assess cardiovascular risk and total mortality of subjects with CKD using cystatin C based and Crea-based estimated glomerular filtration rate (eGFR) equations (CKDEpi) in the general population, in diseased cohorts, and in specific subgroups.

Methods

The present study has been conducted within the BiomarCaRE project, with harmonized data from 21 population-based cohorts from 6 European countries and 3 cardiovascular disease (CVD) cohorts from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for age, sex, cohort, smoking status, body mass index, history of diabetes, history of hypertension, and total cholesterol.

Results

21 population-based cohorts (n=76,954, median age 51 years, 52.2% men, 4.4% diabetic) and 3 diseased cohorts (n=4,982, median age 63 years, 75.6% men, 18.7% diabetic) with an average follow-up between 2.8 and 23.5 years and between 0.5 and 9.4 years, respectively, were included in the analysis. Prevalence of CKD-stage 3–5 by CKD-EPIcrea and CKD-EPIcys eGFR respectively, was 3.4% and 7.3% in the population-based cohorts and 13.9% and 14.4% in the diseased cohorts. In the population-based cohorts the incidence (per 1000 person years) of a non-fatal or fatal CVD event and total mortality respectively, was 10.0 and 11.8, whereas it was 21.2 and 17.8 in the diseased cohorts. In the population-based cohorts the HR for a CVD-event was 1.32 (95% CI 1.21–1.44) for the population with CKD-EPIcrea stage 3–5 and it was 1.47 (95% CI 1.35–1.60) based on CKD-EPIcys after adjustment for covariates. The HR for total mortality for those with CKD-EPIcrea stage 3–5 was 1.31 (1.21–1.41) and for CKD-EPIcys it was 1.86 (95% CI 1.73–2.00). Discrepancies between CKD-EPIcrea and CKD-EPIcys were even more striking across subgroups with and without diabetes or across specific age groups.

Conclusion

CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of CKD-EPIcrea and CKD-EPIcys eGFR differ considerably between specific risk groups. Therefore, the clinical utility of both equations in different risk groups has to be considered and should be evaluated further.

Acknowledgement/Funding

7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011-278913
P3402Validation of the SCORE O.P. for prediction of cardiovascular disease mortality in a large population of elderly individuals
Authors: Andexlinger S , Fritz J , Edlinger M , Concin H , Nagel G , Brozek W , Ruttmann E , Foeger B , Ulmer H
Published: October 2019

Background

Estimation of absolute cardiovascular risk in apparently healthy individuals, using SCORE (Systematic COronary Risk Evaluation) is recommended by the ESC guidelines on cardiovascular disease (CVD) prevention in clinical practice. Recently, the SCORE system has been extended by the SCORE O.P. aiming to improve estimates of cardiovascular risk specifically in older persons (65 years and older).

Purpose

The aim of this study was to validate the SCORE O.P. in an Austrian population of 34,909 healthy individuals aged between 65 and 80 years which were prospectively followed for a minimum of 10 years.

Methods

Predicted fatal CVD and coronary heart disease (CHD) event rates within 10 years were calculated using the “SCORE O.P. risk function for low risk regions” and compared to the actually observed rates, thereby assessing calibration. In addition, predicted probabilities were plotted against observed mortality by deciles of predicted risk. Regarding discrimination, receiver operating characteristics (ROC) analysis and corresponding c-statistics were used.

Results

In 14,586 males, 1,509 deaths from CVD (10.4%) and 847 deaths from CHD (5.8%) occurred within 10 years of follow-up. SCORE O.P. predicted 1,699 fatal CVD (11.7%) and 872 CHD (6.0%) events. In male high risk individuals (10th decile), SCORE O.P. overestimated mortality from CVD and CHD. C-statistics were 0.68 (95% CI 0.67–0.70) for CVD and 0.67 (0.65–0.69) for CHD.

In 20,323 females, 1,340 deaths from CVD (6.6%) and 672 deaths from CHD (3.3%) were observed. SCORE O.P. predicted 1,232 fatal CVD (6.1%) and 539 CHD events (2.7%). In female high risk individuals (8–10th deciles), SCORE O.P. underestimated mortality from CVD and CHD. C-statistics were 0.77 (0.75–0.78) for CVD and 0.77 (0.75–0.79) for CHD.

Conclusion

With regard to overall accuracy, the SCORE O.P. performed considerably well in this elderly Austrian population. However, in high-risk individuals, cardiovascular risk was overestimated for males and underestimated for females. SCORE O.P. was able to discriminate high-risk from low-risk individuals, better in women than in men.
P3409Comparison of the European Society of Hypertension stratification and European Society of Cardiology HeartScore for prediction of coronary artery disease and stroke in essential hypertension
Authors: Vogiatzakis N , Tsioufis C , Dimitriadis K , Iliakis P , Kasiakogias A , Liatakis I , Koutra E , Leontsinis I , Konstantinidis D , Laina A , Kouremeti M , Thomopoulos K , Tousoulis D
Published: October 2019

Background/Introduction

For estimation of overall cardiovascular risk the European Society of Hypertension (ESH) proposes stratification according to blood pressure (BP), prevalence of risk factors, asymptomatic target organ damage, diabetes, kidney and symptomatic cardiovascular disease, while the European Society of Cardiology (ESC) HeartScore constitutes another potent predictive tool of adverse outcome.

Purpose

The aim of the present study was to compare the predictive role of ESH stratification and ESC HeartScore for the incidence of the composite end-point of coronary artery disease (CAD) and stroke in a cohort of essential hypertensive patients.

Methods

We followed up 2150 essential hypertensives (mean age 55.7 years, 1085 males, office BP=145/91 mmHg) for a mean period of 8 years. All subjects had at least one annual visit. Patients were divided based on the ESH risk categories as well as according to the ESC HeartScore. CAD was defined as the history of myocardial infarction or significant coronary artery stenosis revealed by angiography or coronary revascularization procedure. Stroke was defined as rapid onset of a new neurological deficit persisting at least 24 hours unless death supervened confirmed by imaging findings.

Results

The incidence of CAD, stroke and their composite over the follow-up period were 2.8% (n=60), 1.11% (n=24) and 3.9% (n=84), respectively. By using the ESH stratification, regarding the total population 15.3% (n=329) was of low and moderate risk, 54.4% (n=1170) was of moderate to high and high risk and 30.3% (n=651) was high to very high and very high risk. According to the ESC HeartScore 89.2% (n=1918) was of low to moderate risk, 10% (n=215) of high risk and 0.8% (n=17) of very high risk. Cox-regression analyses revealed that high to very high and very high ESH risk category was related to increased risk for the composite end-point of CAD and stroke (hazard ratio=4.5, p<0.0001), while focusing on the ESC Heart Score the composite end-point was predicted by the high risk category (hazard ratio=3.43, p<0.0001). Using the Akaike's information criterion the ESH risk model had better fit than the ESC HeartScore due to the lowest Akaike's values (1442.66 vs 1498.31, respectively).

Conclusions

In essential hypertensive patients categorization of patients by means of the ESH stratification and the ESC HeartScore are both predictive of future cardiovascular events. Based on our results, the ESH risk stratification constitutes a better prediction model for CAD and stroke than the ESC HeartScore in essential hypertension and its estimation is essential in order to improve overall risk assessment in this setting.
P3412Risk factors, biomarkers and framingham risk estimate fail to identify presence of subclinical atherosclerosis in young individual with family history of premature coronary artery disease
Authors: Ghadiri S , Leipsic J , Elahi N , Anastasius M , Huang A , Mugharbil A , Brunham L , Pimstone S , Golmohammadzadeh M , Thompson C , Argulian E , Narula J , Ahmadi A
Published: October 2019

Introduction

Patients with family history of premature coronary artery disease (CAD) are at increased risk of CAD events at a younger age. Risk factor based approaches and clinical evaluation are most commonly used to assess these individuals. However, it has been recently shown that up to 50% of individual presenting with their first myocardial infarction (MI) were considered to be “low risk” prior to that event. MI is often a result of plaque rupture preceded by progression of subclinical atherosclerosis. Detection of subclinical atherosclerosis may therefore help target prevention of plaque progression. We assessed the value of clinical risk factor, biomarkers and Framingham Risk Score (FRS) in predicting subclinical atherosclerosis in individuals with a family history of premature CAD.

Methods

From 310 referrals, 222 individuals between the ages of 35 and 55 with a family history of premature CAD (CAD events in first-degree family members (male <55, female <65)) were enrolled for evaluation of risk of CAD. Those with familial hypercholesteremia (possible, probable or definite) were excluded. Patients underwent clinical and risk factor evaluations as well as Cardiac CT or Calcium Score (CS) to assess presence of subclinical / clinical atherosclerosis at the discretion of the treating physician.

Results

In this pilot, 141 individuals (59% male, mean age 45.9±6.0 years) completed evaluation, and 65 (46%) had evidence of subclinical atherosclerosis on CT coronary angiography or CT calcium score with a mean segment involvement score (SIS) of 2.8 and mean CS of 152, putting them above the 80th percentile for their age and sex. Aside from male sex, age, and smoking history, other traditional risk factors and biomarkers including diabetes mellitus, hypertension, total cholesterol, LDL-C, HDL-C and Cholesterol/HDL-C were not significantly different between those with or without subclinical atherosclerosis (Table 1).

Table 1

Conclusion

In young individuals with a family history of premature CAD, risk factors, biomarkers, and FRS failed to identify individuals with premature, subclinical atherosclerosis in this pilot study. Detection of subclinical atherosclerosis and early implementation of treatment with the aim of stabilizing plaques and stopping progression might prove vital in reducing events in these individuals. Further studies are warranted.
P3424Gender differences in the implementation of CVD prevention In patients with coronary disease: Results from the EUROASPIRE V Survey
Authors: Kotseva K , De Backer G , De Bacquer D , Grobbee D , Hoes A , Jennings C , Maggioni A , Marques-Vidal P , Ryden L , Wood D
Published: October 2019

Introduction

EUROASPIRE V was a cross-sectional survey carried out by the European Society of Cardiology, EURObservational Research Programme in 2016–2017 in 27 European countries

Purpose

To describe gender differences in lifestyle and risk factor management, and the use of cardioprotective drug therapies in patients with coronary heart disease in Europe.

Methods

Patients <80 years with coronary disease (CABG, PCI or an acute coronary syndrome) were identified from the hospital medical records and interviewed and examined by trained staff ≥6 months and ≤2 years later using standardized methods including central laboratory measurements.

Results

A total of 8,261 (25.8% females), mean age 63.6 (SD 9.6) were interviewed, with a median time between the index event and interview 1.12 years (IR 0.82–1.56). Women were older (mean age 65.4 years [SD 9.2] vs 63.0 [9.7] and had a lower level of education than men.Comparing women with men, the prevalence of the risk factors were as follows: current smoking 12.8% vs 20.7%,obesity (BMI ≥30 kg/m2) 45.7% vs 34.9%, central obesity (waist circumference ≥102 cm in men or ≥88 cm in women) 78.0% vs 51.8%, raised blood pressure (BP ≥140/90 mmHg, ≥140/80 mmHg in patients with diabetes) 47.1% vs 46.0%, elevated LDL-cholesterol (≥1.8 mmol/l) 77.9% vs 68.5% and self reported diabetes 33.1% vs 28.0%. Reported use of prophylactic drug therapies for the same comparison was: antiplatelets 91.8% vs. 92.8%; beta-blockers 81.8% vs. 80.8%; ACE inhibitors/ARBs 75.0% vs. 75.3%; and statins 76.8% vs. 82.2%. The therapeutic control of blood pressure, LDL-cholesterol and diabetes (HbA1c <7 mmol/L) was: 48.2% vs 49.9%; 25.7% vs 34.1% and 48.5% vs 56.7%, respectively.

Conclusions

The results show that women with coronary disease have higher prevalence of obesity, central obesity, elevated LDL-cholesterol and self-reported diabetes than men. There were no differences in terms of blood pressure management. All coronary patients require professional support to make lifestyle changes and manage risk factors more effectivelyin order to reduce their risk of recurrent cardiovascular events.

Acknowledgement/Funding

ESC-EORP supported by Amgen, Eli Lilly, Pfizer, Sanofi, Ferrer and Novo Nordisk
P3432Coronary artery calcium score is of limited sensitivity in detecting subclinical atherosclerosis in young individuals with family history of coronary artery disease
Authors: Huang A , Mugharbil A , Anastasius M , Ghadiri S , Leipsic J , Elahi N , Brunham L , Pimstone S , Golmohammadzadeh M , Thompson C R , Argulian E , Narula J , Ahmadi A
Published: October 2019

Introduction

Family history of premature coronary artery disease (CAD) is known to predispose individuals to adverse CAD events, often at a younger age. Current risk stratification strategy is suboptimal, as up to 50% of individuals were considered “low-risk” prior to their first presentation of myocardial infarction. Coronary artery calcium score (CACS) is a marker of atherosclerosis and provides incremental value in risk stratification. However, the utility of CACS may be limited in younger patients as they often have non-calcified atherosclerotic plaques. In this study, we evaluate the sensitivity of CACS in detecting subclinical atherosclerosis in different age groups.

Method

From 310 referrals to a specialized unit in the management of early atherosclerosis, 222 individuals with a family history of premature CAD (defined as CAD events in first-degree family members, male<55 and female<65) and aged between 35 and 55 were enrolled for assessment of their CAD risks. Individuals with possible, probably or definite familial hypercholesterolemia were excluded. In addition to clinical and risk factor evaluation, cardiac CT and CACS were performed in select individuals, at the discretion of the treating physician.

Results

Of the 141 (59% male, mean age 45.9±6.0 year) individuals that completed clinical evaluation, 65 (73% male, mean age 47.4±6.9 years) have subclinical atherosclerosis (defined by the presence of atherosclerotic plaques in any of the coronary artery segments in cardiac CT). Of them, 52 have CACS>0, giving an overall sensitivity of 80%. The breakdown by age group is shown in table 1. The sensitivity of CACS in detecting subclinical atherosclerosis is quite modest in younger individuals (60% in individuals <45 year-old) but improves with patient age (>85% in >45 years).

Table 1. Sensitivity of CACS in different age groups Age group True Positive Fast Negative Sensitivity N (CAC+ CTCA+) (CAC+ CTCA−) (%) <40 6 4 60 10 41–45 7 4 55 11 46–50 19 3 86 22 51–55 20 1 95 21

Conclusion

In younger individuals (<45 years) with family history of premature CAD, CACS is of limited sensitivity in detecting subclinical atherosclerosis, and should not be used to rule out CAD. Further studies are warranted.
P3445Subclinical myocardial dysfunction in pediatric kidney transplant recipients: a two-dimensional speckle-tracking echocardiography study
Authors: Lakatos B K , Barczi A , Cseprakal O , Szilagyi M , Kis E , Tokodi M , Szabo A , Reusz G Y , Kovacs A , Merkely B
Published: October 2019

Chronic kidney disease is associated with increased risk of cardiovascular mortality and morbidity in pediatric patients as well. Renal transplantation results in improved survival, however, several factors contribute to markedly elevated cardiovascular complication rate compared to the healthy population. While major cardiac events occur rarely in pediatric population, detection of subclinical changes in cardiac morphology and function may be of high interest to effectively identify high-risk patients.

Accordingly, our aim was to investigate left (LV)- and right ventricular (RV) morphology and function using conventional and two-dimensional (2D) speckle-tracking echocardiography (STE) in pediatric renal transplant recipients.

Our study group consisted of 41 kidney transplanted children (RTX; mean age: 14±3 years, m/f: 25/16) and 39 age- and gender matched healthy controls. Using 2D echocardiography, LV and RV focused apical loops were obtained and LV end-diastolic volume index (EDVi), ejection fraction (EF), mass index (Mi), RV end-diastolic area index (EDAi) and fractional area change (FAC) were measured. Using STE, we have determined LV global longitudinal (GLS) and circumferential strain (GCS), RV GLS, and LV and RV early diastolic longitudinal strain rate (LSrE).

LV EDVi did not differ between RTX and controls (51±13 vs. 52±10 mL/m2, p=NS), while LVMi was markedly higher in RTX patients (36±8 vs. 28±6 g/m2, p<0.0001). LVEF was comparable between the two groups (62±5 vs. 62±3%; p=NS), while LV GLS was significantly lower in RTX (−20.6±2.1 vs. −21.8±2.1%, p=0.01) along with a tendential increase in LV GCS (−31.6±4.3 vs. −29.7±4.6%, p=0.06). LV LSrE was significantly lower in RTX patients (1.29±0.29 vs. 1.45±0.27 1/s, p<0.05). RV EDAi did not differ between the two groups (11.2±2.3 vs. 11.6±2.0 cm2/m2, p=NS). Interestingly however, RTX patients had significantly higher RV FAC and RV GLS (FAC: 46±7 vs. 42±4%, GLS: −24.6±3.7 vs. −22.4±2.6%, both p<0.01) along with lower RV LSrE (1.32±0.57 vs. 1.60±0.43, p<0.05).

Cardiac morphology and function shows distinct changes after RTX. Along with comparable ventricular dimensions, LV hypertrophy and subclinical systolic and diastolic dysfunction is present. RV systolic function is relatively increased accompanied by subclinical diastolic dysfunction of the chamber, which may refer to previous RV overload. STE may be a useful tool to reveal early myocardial dysfunction in pediatric kidney transplant recipients.
P3451Female gender is an independent predictor of one-year mortality following primary angioplasty for ST-segment elevation myocardial infarction, regardless of age, clinical severity and frailty
Authors: Viana-Llamas M C , Silva-Obregon A , Arroyo Espliguero R , Estrella-Alonso A , Saboya-Sanchez S , Uribe-Heredia G , Garcia-Magallon B , Toran-Martinez C , Castillo-Sandoval A , Eguileor-Marin Z , Arriero-Fernandez N , Marian-Crespo C
Published: October 2019

Background

Gender-based differences in mortality of patients with ST-segment elevation myocardial infarction (STEMI) have been reported. However, controversy exists about the impact of female gender on mortality after correcting for baseline risk differences.

Purpose

Assess gender-based mortality in a cohort of STEMI patients following primary angioplasty.

Methods

Retrospective cohort of 427 consecutive STEMI patients (64 years [55–75]; 78% men) admitted to a general ICU between November-2013 and February-2017. We used Kaplan-Meier and Cox regression models for survival analysis. The Clinical Frailty Scale (CFS) was used to assess frailty.

Results

Women were older and had a higher GRACE 2.0 and frailty (CFS≥4). Women had lower creatine-phosphokinase and albumin levels and higher B-natriuretic peptide levels, despite the lack of gender-based differences in left ventricular ejection fraction (LVEF) and MI size and location. One-year mortality rate was higher in women, most often from cardiogenic shock during admission and at 30-day follow-up (Table). After Cox regression analysis, women had a 2.23-fold higher risk of one-year mortality compared with men (Figure), independently of age, frailty, GRACE 2.0, LVEF and inotropic agents requirements.

Baseline characteristics Women (n=93) Men (n=334) P value One-year mortality, n (%) 15 (16.1) 15 (4.5) <0.001 Cardiogenic shock, n (%) 10 (62.5) 6 (37.5) <0.001 Age (years) 70.8 [51.2–80.3] 61.9 [54.2–71.8] <0.001 Hypertension, n (%) 54 (58.1) 149 (44.6) 0.022 GRACE 2.0 129 [104.5–156] 112 [94–139] 0.001 Clinical Frailty Scale≥4, n (%) 28 (30.1) 32 (9.6) <0.001 MI location (anterior), n (%) 42 (45.2) 152 (45.5) 0.953 Creatin-phosphokinase (UI/L) 1040 [300.5–2134] 1517 [620.5–2852.8] 0.004 High-sensitivity troponin I (pg/mL) 4003 [62.1–48526.6] 9070 [65.8–65893] 0.473 Left ventricular ejection fraction (%) 52 [40–60] 55 [45–60] 0.465 B-natriuretic peptide (pg/mL) 241.1 [99.9–896.9] 103.6 [28.3–259.2] <0.001 Albumin (g/L) 36.1 [34.3–38.5] 38.4 [35.6–40.5] <0.001 Inotropic agents, n (%) 14 (15.1) 26 (7.8) 0.033

Kaplan-Meier and Cox survival curves.

Conclusions

Female gender is an independent predictor of one-year mortality in STEMI patients, regardless of age, clinical severity and frailty. A potential myocardial disfunction probably mediated by an increased frailty, may play a role in the high mortality rate among women after STEMI.
P3465Inducible left ventricular outflow tract obstruction is associated with a higher incidence of perioperative cardiac arrest in liver transplantation
Authors: Cailes B , Koshy A N , Han H , Sajeev J K , Ko J , Weinberg L , Gow P , Testro A , Srivastava P , Lim H , Teh A , Farouque O
Published: October 2019

Background

Inducible left ventricular outflow tract obstruction (LVOTO) is not infrequently encountered in liver transplant (LT) candidates undergoing cardiac workup. While the impact of LVOTO on adverse cardiovascular haemodynamics is well reported, it is unclear whether it predisposes to perioperative cardiovascular complications following LT.

Purpose

To investigate the effect of inducible left ventricular outflow tract obstruction on perioperative cardiovascular complications in a modern cohort of liver transplant patients.

Methods

Consecutive patients undergoing dobutamine stress echocardiography (DSE) were evaluated from a quaternary LT centre between 2010 and 2017. Inducible LVOTO was defined as LVOT gradient ≥36mmHg. Perioperative major adverse cardiovascular events (MACE) at 30 days and all-cause death were recorded from a prospectively maintained transplantation database and augmented by electronic medical record review.

Results

We evaluated 560 patients who underwent DSE as part of a workup for LT. Of these, 319 progressed to transplant. Inducible LVOTO was observed in 68 patients (21.3%). A higher baseline cardiac output (7.7 L/min vs 7.0 L/min, p=0.002) predicted for development of inducible LVOTO. Seventy-seven patients (4.1%) experienced a MACE including five deaths, 19 cases of heart failure, 11 cardiac arrests, 10 acute coronary syndromes and 46 cases of arrhythmias (VT/AF). Overall MACE occurred in 17/68 patients (25.0%) with LVOTO and 60/251 patients (23.9%) without LVOTO (p=0.85). However, there was a significantly increased risk of resuscitated perioperative cardiac arrest in patients with LVOTO (7.4% vs 2.4%, p=0.04). Patients with LVOTO also required significantly greater volumes of fluid intra-operatively (8.37L vs. 6.71L, p=0.043).

Cardiac Arrest in LT Patients with LVOTO

Conclusions

Inducible LVOTO is a frequent finding occurring in 21.3% of LT candidates. Despite higher intraoperative fluid resuscitation, LVOTO increased the risk of a perioperative cardiac arrest. Further studies are required to confirm these findings and to assess whether patients with LVOTO undergoing liver transplantation may benefit from heightened perioperative surveillance.
P3470Comparative effectiveness and safety of non-vitamin K oral anticoagulants and warfarin in non-valvular atrial fibrillation - a cohort study in 3 Nordic countries
Authors: Johnsen S , Madsen M , Linder M , Sulo G , Ghanima W , Gislason G , Halvorsen S , Hohnloser S H , Jenkins A , Al-Khalili F , Tell G S , Ehrenstein V
Published: October 2019

Background

Non-vitamin K oral anticoagulants (NOACs) are an alternative to warfarin in the prevention of stroke in non-valvular atrial fibrillation (NVAF). Nordic countries have high quality of warfarin treatment, making them an especially suitable setting for assessing effectiveness and safety of NOACs against warfarin.

Purpose

The BEYOND Pooled (BEnefit of NOACs studY of nOn-valvular AF patieNts in NorDic countries) study compared risks of ischaemic or haemorrhagic stroke/systemic embolism (S/SE), and risk of bleeding with acute hospitalisation with an overnight stay (bleeding) in NVAF patients treated with apixaban, dabigatran or rivaroxaban, each compared with warfarin treatment.

Methods

A cohort study of treatment-naïve adult NVAF patients dispensed apixaban, dabigatran, rivaroxaban or warfarin was identified from 01 Jan 2013 to 31 Dec 2016. The population and study variables were identified from national registries in Denmark, Norway and Sweden. After 1:1 propensity score (PS) matching for each NOAC-warfarin comparison, individual-level data were pooled across the countries. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (aHRs) of the endpoints.

Results

PS matched NOAC cohort sizes were: apixaban (55,696) dabigatran (28,526) and rivaroxaban (30,701), and the total follow-up in the PS-matched population was 291,171 years (mean 1.3 years). During the follow-up, 35,450 oral anticoagulation (OAC) patients had a S/SE and 38,620 OAC patients had bleeding. Adjusted HRs for the two endpoints are presented in the table. PH assumption has not been formally tested but cum incidence curves did not indicate substantial differences in the effects over time.

Table 1. Adjusted hazard ratios (aHR) of stroke/systemic embolism and bleeding for non-vitamin K oral anticoagulants versus warfarin Endpoint Apixaban vs Warfarin: aHR (95% CI) Dabigatran vs Warfarin: aHR (95% CI) Rivaroxaban vs Warfarin: aHR (95% CI) Stroke/SE 0.93 (0.85–1.03) 0.89 (0.80–1.00) 0.97 (0.88–1.08) Bleeding 0.72 (0.67–0.77) 0.87 (0.80–0.95) 1.12 (1.04–1.20)

Conclusions

Relative to warfarin, apixaban and dabigatran were associated with lower rates of bleeding whereas rivaroxaban was associated with a higher rate. The three NOACs had comparable rates of stroke and systemic embolism relative to warfarin.

Acknowledgement/Funding

This study was funded by the Pfizer/Bristol-Myers Squibb Alliance.
P3483Diet governs metabolic and electrical properties of the atrial myocardium in mice
Authors: Baptista E , Doisne N , Piquereau J , Ichou F , Lhomme M , Pichard C , Galand V , Mougeneot N , Suffee-Mosbah N , Le Goff W , Meriskay M , Hatem S N
Published: October 2019

Background

Obesity is associated with an increased risk of atrial fibrillation. This epidemiologic observation may not only be due to shared co-morbidities but also from direct impacts of metabolic disorders on myocardium Here, we examined the impact of high fat diet (HFD) induced obesity on atrial properties in mice.

Methods

Eight weeks old C57Bl/6J mice were subjected to 2 or 4 months of HFD (60% fat) or normal diet (ND, 4% fat). Rapid burst atrial pacing were delivered using a trans-esophageal probe to induced AF in anesthetized animals. Action potential (AP) were recorded in left atrial trabeculae using glass microelectrode technique. Potassium currents were recorded in isolated atrial myocytes using the whole cell or perforated patch clamp configurations. Metabolomic and lipidomic analysis were performed on whole left atria. Mitochondrial respiration was studied in situ in saponin-permeabilized atrial muscle fibres using a Clarke electrode and oxygen consumption was measured after successive addition of ADP (2 mM), malate (4 mM), palmitoyl-CoA and carnitine (pCoA-Ca) (100 μM and 2 mM), pyruvate (1 mM), glutamate (10 mM), succinate (15 mM), amytal (1 mM) and tetramethyl-paraphenylenediamine (TMPD)/ascorbate (0.5/0.5 mM).

Results

HFD mice showed a higher atrial vulnerability to AF as indicated by longer AF episodes compared to ND mice. APs were shorter in HFD versus ND mice (AP duration measured at 90% of repolarization: 47.9±2.4 msec in HFD vs 58.2±1.4 msec in ND, P<0.001 after 2 months of HFD) and more sensitive to the K ATP channel blocker, glibenclamide. In perforated but not whole cell, patch clamped atrial myocytes, the K-ATP component of the potassium current was enhanced in HFD mice (at +70 mV: 0.41±0.12 pA/pF in HFD vs 0.13±0.08 pA/pF in ND, P<0.05). Metabolomic analysis indicated an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long chain fatty acid. Although the mitochondrial respiration measurements showed a trend towards a lower complex IV-driven respiration in HFD mice, no significant difference between ND and HFD was noted regarding complex I and complex II-driven respiration. However, the ability of fatty acids (pCoA-Car) to support mitochondrial respiration was higher in HFD

Conclusions

High fat diet induces a shift from carbon hydrate to a beta oxidation of the atrial myocardium metabolism together with an enhanced use of fatty acids by mitochondria. These metabolic changes could result in an enhanced activity of K-ATP channels and AP shortening that might contribute to AF vulnerability in this clinical setting.

Acknowledgement/Funding

ANR-10-IAHU-05
P3485Autophagy insufficiency participates in hyperhomocysteinemia-induced cardiac aging
Authors: Wang W , Zhou Y , Xu J , Zhang S , Meng Y
Published: October 2019

Background

The elevated plasma homocysteine (Hcy) level can lead to severe cardiovascular injuries, which participates in the progression of atherosclerosis, heart failure and so on. Except cardiovascular diseases, accumulated researches further revealed that hyperhomocystenemia (HHcy) can also induce aging-related diseases, including Alzheimer's disease, Parkinson's disease, diabetic cardiomyopathy, etc. Though some researches had revealed that Hcy stimulation would lead to endothelial cells senescence, whether cardiac aging could be induced by HHcy still remain unknown.

Purpose

This study aimed to reveal whether HHcy can induce cardiac aging and the underlying mechanisms.

Methods

SD rats were utilized to establish HHcy rat model and natural aging rat model. The cardiac function were determined by Echocardiography. Transmission electron microscope were used to detect mitochondria injuries of myocardium. 18F-FDG PET/CT was used to detect the state of glucose metabolism in myocardial cells. Agilent mRNA Array was used to detect possible altered pathways in myocardium of HHcy rats. The autophagy level was determined by detection of both autophagy-related proteins expressions with Western Blot and autophagic flux with mRFP-GFP-LC3.

Results

HHcy rats showed overall aging phenotypes, which were consistent with natural aging rats. The impaired cardiac function and severely injured myocardium morphology were observed in HHcy rats. Aging-related markers were increased significantly in HHcy rats and Hcy-treated cells, presented as increased p16, p21 and p53 expressions and increased senescence-associated beta-galactosidase (SA-β-gal) activity. Mitochondria dysfunction and morphology injuries were also detected in HHcy rats. Moreover, decreased serum Beclin-1 level was tested in CHD patients with HHcy. The decreased autophagy level was further verified in HHcy rats and Hcy-treated cells. Furthermore, the over-expression of Atg5 could attenuate Hcy induced cellular senescence.

Conclusion

HHcy can reduce autophagy level, which leading to severe mitochondria injuries, and resulted in cardiac aging eventually.

Acknowledgement/Funding

Natural Science Foundation of China (81671382,91839107)
P3487Pre-ischemic succinate dehydrogenase inhibition is protective against ischemia-reperfusion injury in rat and human myocardium with and without diabetes mellitus
Authors: Jespersen N R , Hjortbak M V , Lassen T R , Stoettrup N B , Johnsen J , Tonnesen P T , Larsen S , Kimose H H , Boetker H E
Published: October 2019

Background

Ischemia-reperfusion (IR) injury can be attenuated through modulation of mitochondrial metabolism with succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). However, it is unknown whether SDH inhibition yields protection in aged, diabetic individuals and whether protection translate into human cardiac tissue.

Purpose

We wished to evaluate if SDH inhibition can be protective in aged, diabetic rat hearts and could be translated to the human myocardium.

Methods

We studied infarct size in aged non-diabetic and diabetic rat hearts subjected to isolated, retrograde perfusion and global ischemia and reperfusion. The hearts were randomized to: Sham hearts, IR injured hearts and IR injured hearts co-perfused with 0.1 mM or 0.6 mM DiMAL. Infarct size and mitochondrial respiratory capacity were evaluated post-ischemic. To translate our findings into human cardiac tissue, we tested the efficacy of DiMAL treatment in human atrial trabeculae from patients with and without diabetes mellitus undergoing cardiac surgery. We randomized atrial trabeculae to: IR injury, IR injury treated with ischemic preconditioning (IPC) and IR injury treated with 5 mM DiMAL. Contractile force recovery and mitochondrial respiratory capacity were evaluated post-ischemic.

Results

In non-diabetic rat hearts, DiMAL 0.1 mM reduced infarct size/area-at-risk (IS/AAR) compared to IR hearts (53±7% vs. 69±6% of IS/AAR; p<0.05). In diabetic hearts, an increased concentration of 0.6 mM DiMAL was required to confer protection (62±13% vs. 80±8% of IS/AAR; p<0.05). Mitochondrial complex I linked respiratory capacity was higher in both Sham and DiMAL 0.1 mM groups than with DiMAL 0.6 mM in non-diabetic hearts (157.4±26.5 and 140.0±35.3 vs. 81.8±42.4 pmol O2/(s*mg); p<0.01 and p<0.05). In trabeculae from humans without diabetes mellitus, IPC and DiMAL improved contractile force recovery compared to IR (43±12% and 43±13% vs. 23±13%, p<0.05). In trabeculae from patients with diabetes, IPC but not DiMAL administration improved contractile force recovery compared to IR (48±16% and 19±7% vs. 25±13%, p<0.01 and p>0.99). Mitochondrial complex I linked respiration capacity did not improve by IPC or DiMAL compared to IR in non-diabetic trabeculae (p>0.99).

Conclusion

Inhibition of the SDH by DiMAL protects the aged non-diabetic and diabetic heart from IR injury but the threshold for cardioprotection is increased in diabetic rat hearts. DiMAL provides cardioprotection similar to IPC in non-diabetic trabeculae but does not protect the human diabetic myocardium when given in identical concentrations. SDH inhibition can provide protection in both animal and human tissue and may provide a new target for pharmacologic conditioning in patients.
P3489Endothelial adenosine-to-inosine RNA editing is indispensable for vascular integrity
Authors: Tual-Chalot S , Bonini F , Vlachogiannis N I , Doddaballapur A , Shook K , Gatsiou A , Stellos K
Published: October 2019

Background

Adenosine (A)-to-inosine (I) RNA editing is a powerful upstream regulator of double-stranded RNA (dsRNA) metabolism, its role however in tissue homeostasis remains poorly understood. We have recently reported that RNA editing is dysregulated in human atherosclerotic heart disease, although its role in the maintenance of endothelial cell (EC) function is unknown.

Purpose

The goal of the present study is to evaluate the role of EC-specific ADAR1 in vascular homeostasis in vivo.

Methods

Constitutional or inducible EC restricted ADAR1 ablation was achieved by crossing mice carrying a conditional (floxed) ADAR1 allele with either a Tie2-Cre or with a tamoxifen-inducible Cdh5-CreERT2 mouse line. EC function was assessed by the postnatal retinal angiogenesis model and barrier function assays and immunohistochemistry of lung and liver tissues. Cell culture assays, gene-silencing techniques, RT-qPCR, western blot and confocal microscopy were utilized to assess the ADAR1 effects in intracellular endothelial signalling.

Results

Constitutive endothelial ADAR1 ablation caused prenatal lethality at embryonic stage E13.5, demonstrating an essential role for endothelial ADAR1 in development. Postnatal ADAR1 ablation resulted in reduced vascular outgrowth, reduced vessel branching in the central vascular plexus and decreased filopodial protrusions from ECs at the angiogenic front of the vascular plexus compared with littermate control mice at P5. Furthermore, endothelial ADAR1 ablation in adult mice resulted in sudden death within 6–8 days after activation of Cre recombinase due to development of severe pleural effusions caused by widespread vascular leakage, indicating a disturbance of EC barrier function in lung microvasculature. Mechanistically, ADAR1-mediated RNA editing is essential for the metabolism of endogenous long-to-short dsRNAs, while silencing of endothelial ADAR1 resulted in accumulation of cytoplasmic long dsRNAs. Long dsRNAs are recognised as a danger-associated molecular pattern by the cytosolic innate immune sensing and signalling sensors. Consequently, the cytoplasmic accumulation of endogenous long dsRNAs resulted in activation of innate immune system in ECs, as assessed by the induction of interferon-β. Concomitantly, activation of the cytoplasmic dsRNA sensors resulted in dissociation of beta-catenin from VE-cadherin in EC junctions and endocytosis of VE-cadherin.

Conclusion

ADAR1-mediated RNA editing of long dsRNAs is essential for the long-to-short dsRNA metabolism and thus suppression of endogenous innate immune sensing and signalling. EC-restricted ADAR1 ablation results in embryonic lethality, impaired retinal angiogenesis at P5 and sudden death in adult mice due to pleural effusions, which all indicate that ADAR1-mediated RNA editing is indispensable for maintenance of vascular barrier integrity.
P3494Dapagliflozin reduced lactate release by epicardial adipose tissue from CAD patients: switch from fatty acids to glucose aerobic oxidation
Authors: Couselo-Seijas M , Agra-Bermejo R M , Fernandez A L , Martinez-Cereijo J M , Soto-Rodriguez M , Rozados-Luis A , Gonzalez-Juanatey J R , Eiras S
Published: October 2019

Background

Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, improves the glucose uptake by epicardial adipose tissue (EAT). However, its metabolic pathways are still unknown. Our aim was to clarify the EAT glucose-lipid metabolism from patients with and without coronary artery disease (CAD).

Methods

Paired subcutaneous (SAT) and EAT biopsies from 49 patients undergoing heart surgery were cultured and treated with or without dapa at 10 or 100 μM for 6 hours. Glucose, lactate and oxygen were analyzed on supernatants by colorimetric or fluorescence assays. Glycolytic, lipolytic, glyceroneogenic and lipogenic genes or protein expression levels were determined on fat tissues by RT-qPCR or western blot, respectively.

Results

Glyceroneogenic and lipid metabolism-involved genes were higher expressed in SAT than in EAT. Dapa reduced their expression in SAT but not in EAT. Lipid-droplet protein levels, perilipin (PLN A) and hormone-sensitive lipase (HSL), were reduced in EAT. Mitochondrial biogenesis-related gene PGC1α was upregulated (p<0.05). Despite this drug improved glucose utilization, it reduced lactate release and oxygen consumption in both fat pads. After classifying patients according presence/absence of CAD, we observed a greater release of lactate by EAT in patients with CAD (3.22±2.40 mM) that was remarkably reduced after dapagliflozin treatment at 10 μM (2.17±1.53 mM, p<0.01) and 100 μM (2.45±2.11 mM, p<0.001).

Clinical characteristics regarding CAD presence (n=49) Non CAD patients (n=26) CAD patients (n=23) p value Gender (male) (n/%) 14/54 20/87 0.010* Age (years) 73±9 67±12 0.026* BMI (kg/m2) 29.±4 30±4 0.377 HTA (n/%) 21/80.8 17/73.9 0.578 T2DM (n/%) 12/46 9/39 0.629 HF (n/%) 2/8 6/26 0.096 L-Lactate (mM) 2±1.1 3.2±2.4 0.029* Glucose (mg/dL) 65±15 62±22 0.539 Oxygen (RFU) 47±9 46±14 0.899 CAD: Coronary artery disease, BMI: Body mass index, HTA: arterial hypertension, T2DM: Diabetes mellitus type 2, HF: Heart failure, RFU: relative fluorescence units.

Lactate in CAD

Conclusions

Dapagliflozin reduced the anaerobic glycolytic pathway, lowering the released lactate by EAT, overall in patients with CAD. This effect suggests a protective metabolic role since high lactate was found to be a marker of poor outcomes in HF patients.

Acknowledgement/Funding

Astrazeneca