bluuebunny/crossref_metadata_2025 huggingface dataset:
P4780Effectiveness and safety of non-vitamin k antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease
Authors: Moon I K , Lee S R , Choi E K , Lee E J , Jung J H , Han K D , Cha M J , Oh S I , Lip G Y H
Published: October 2019

Background

Patients with atrial fibrillation (AF) often have concomitant valvular heart disease (VHD), especially in Asia. There are limited data on non-vitamin K antagonist oral anticoagulants (NOAC) impact on outcomes for stroke prevention and bleeding for these patients in real world clinical practice.

Purpose

To investigate the effectiveness and safety of NOACs compared with warfarin in patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHD.

Methods

We identified oral anticoagulants naive patients with AF and EHRA type 2 VHD from the Korean National Health Insurance Service database between 2014 and 2016 (n=2,671 taking warfarin; n=3,058 taking NOAC). Six clinical outcomes including ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GI), major bleeding, all-cause death, and their composite outcome and fatal clinical events (any events that led to death within 30-day of its occurrence) were evaluated. Inverse probability of treatment weighting (IPTW) method was used to balance covariates between the two groups.

Results

After weighted using 5% trimmed IPTW method (n=2371 taking warfarin; n=2792 taking NOAC), the mean age was 71.2 years, male was 57% and CHA2DS2-VASc score was 3.9. During a mean 1.4-year follow-up, weighted incidence rate of ischemic stroke, ICH, GI bleeding, and all-cause death were lower in the NOAC group than in the warfarin group. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.53–0.96), GI bleeding (HR 0.50, 95% CI 0.35–0.72) and major bleeding (HR 0.61, 95% CI 0.45–0.80). Although NOAC and warfarin groups showed similar incidence rate of ICH, NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group (HR 0.28, 95% CI 0.07–0.83). Overall, NOACs were associated with a lower risk of the composite outcome (HR 0.68, 95% CI 0.58–0.80). For an exploratory analysis, patients with EHRA type 1 VHD (n=366 taking warfarin; n=345 taking NOAC) was evaluated. In multivariable Cox regression analysis, NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death and composite outcome.

Clinical outcome in AF patients with VHD

Conclusion

In this nationwide Asian AF population with EHRA type 2 VHD, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin.
P4799Long-term thromboembolic risk in patients with postoperative atrial fibrillation after left-sided heart valve surgery
Authors: Butt J H , Olesen J B , Gundlund A , Olsen P S , Havers-Borgersen E , Aagaard D T , Gislason G H , Torp-Pedersen C , Kober L , Fosbol E L
Published: October 2019

Background

New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are sparse. In addition, data on stroke prophylaxis in this setting are lacking.

Objective

To assess the long-term risk of thromboembolism in patients developing new-onset POAF following isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF).

Methods

Using data from the Eastern Danish Heart Surgery Database and Danish nationwide registries, we identified patients who developed POAF following isolated left-sided heart valve surgery (i.e. biologic aortic/mitral valve replacement or aortic/mitral valve repair) from 2000 through 2015. These patients were matched with patients with nonsurgical NVAF in a 1:4 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Long-term risk of thromboembolism was examined by the Aalen-Johansen estimator and cause-specific Cox regression models adjusted for comorbidities, concomitant pharmacotherapy, and oral anticoagulation therapy as a time-dependent covariate.

Results

A total of 1,539 patients undergoing isolated left-sided heart valve surgery were identified. Of these, 716 (46.5%) patients developed POAF after surgery. A total of 630 patients with POAF were matched with 2,520 patients with NVAF. In the matched study population, the median age was 71 years (25th-75th percentile 66–77 years) and 59.5% were men. Oral anticoagulation therapy was initiated within 30 days post-discharge in 62.7% and 51.4% of these patients, respectively. Compared with NVAF, POAF was not associated with a significantly different 5-year absolute risk of thromboembolism (10.7% [95% confidence interval [CI], 8.0%-13.9%] versus 8.9% [95% CI, 7.6%-10.2%] in the POAF and NVAF group, respectively) (Figure). In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio [HR] 1.01 [95% CI, 0.71–1.44]). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (HR 0.45 [95% CI, 0.18–0.99]) as well as NVAF (HR 0.58 [95% CI, 0.42–0.80]) compared with no anticoagulation therapy.

Conclusions

New-onset POAF following isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism compared with NVAF. Future studies addressing the role of oral anticoagulation therapy in POAF after heart valve surgery are warranted to examine the efficacy and safety as well as the timing and duration of anticoagulation therapy.
5164New risk prediction score for life-threatening ventricular tachyarrhythmias in laminopathies
Authors: Wahbi K , Ben Yaou R , Gandjbakhch E , Anselme F , Gossios T , Lakdawala N , Stalens C , Sacher F , Babuty D , Charron P , Vigouroux C , Bonne G , Kumar S , Elliott P , Duboc D
Published: October 2019

Background

An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter defibrillator (ICD) implantation.

Methods

We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as a) sudden cardiac death or b) ICD-treated or hemodynamically unstable VTA. The prognostic model was derived using Fine-Gray's regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (standard deviation) or medians [interquartile range].

Results

We included 444 patients 40.6 (14.1) years of age in the derivation sample and 145 patients 38.2 (15.0) years in the validation sample, of whom 86 (19.3%) and 34 (23.4%) suffered LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, non-missense LMNA mutation, 1st degree and higher atrioventricular block, non-sustained ventricular tachycardia, and left ventricular ejection fraction. In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842). In the external validation sample, the C-index was 0.800 (0.642–0.959) and calibration slope 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA compared with the guidelines-based approach.

Conclusions

Compared to the current standard of care, this risk prediction model for LTVTA in laminopathies facilitated significantly the choice of ICD candidates.

Acknowledgement/Funding

AFM Téléthon
5878Renal insufficiency is associated with progressive increase in risk of cardiovascular death in patients without preexisting cardiovascular disease
Authors: Schytz P , Gislason G , Carlson N
Published: October 2019

Introduction and aims

Chronic kidney disease has previously been observed to be associated with increased cardiovascular risk. Observations are however predominantly limited to patients with either severe or end-stage renal disease. We investigate the associated risk of diminishing renal function with cardiovascular death across all levels of non-dialysis dependent renal insufficiency.

Methods

Based on cross-referencing of data from numerous nationwide health care registers, patients with a recorded plasma creatinine measurement were identified in Denmark between 1997 and 2017. Patients with preceding cardiovascular disease, end-stage renal disease, age <18 years, and patients with events within a 30 days quarantine period after their first-time plasma creatinine measurement were excluded. Estimated glomerular filtration rates (eGFRs) were calculated from the first recorded plasma creatinine. Hazard ratios for two-year risk of cardiovascular death were computed for strata of renal function in a multiple Cox regression model with adjustment for age and gender, and cumulative incidences were estimated using the Aalen-Johansen estimator.

Results

In total 2,000,626 patients were identified. Median follow-up was 3.6 years (IQR 1.7–9.0 years). A total of 22,657 (0.01%) cardiovascular deaths were recorded. Patients were predominantly female (54%), median age was 40 years (IQR 29–63 years), and median eGFR was 98 ml/min/1.73m2 (IQR 83–117 ml/min/1.73m2). Hazard ratios with confidence intervals of cardiovascular death were 0.85 [0.82–0.89], 1.24 [1.18–1.31], 2.02 [1.89–2.15], and 3.19 [2.91–3.49] for the eGFR strata 90–60 ml/min/1.73m2, 59–45 ml/min/1.73m2, 44–30 ml/min/1.73m2, <30 ml/min/1.73m2, respectively (eGFR >90 ml/min/1.73m2 as reference).

Cumulative incidence

Conclusion

In a nationwide cohort of non-dialysis treated patients without pre-existing cardiovascular disease, renal dysfunction was associated with progressive increase in risk of cardiovascular death in patients with eGFR <60 ml/min/1.73m2.
5938Mortality risk stratification in patients with severe tricuspid regurgitation - Insights from the Tricuspid Regurgitation REgistry (TRuE)
Authors: Alushi B , Beckhoff F , Leistner D M , Staehli B E , Jamaluddin M , Bigalke B , Latib A , Falk V , Grubitzch H , Landmesser U , Hahn R , Lauten A
Published: October 2019

Background/Introduction

Severe tricuspid regurgitation (TR) is associated with progressive right atrial (RA) and ventricular (RV) dilation, dysfunction and increased mortality. Risk factors impacting the long-term prognosis in patients with severe TR are largely undetermined.

Purpose

Herein, we aimed to identify risk factors associated with long-term mortality in patients with severe TR and implement a novel risk stratification strategy based on an individual five-year mortality prediction score.

Methods

From January 2013 to December 2017, 1238 patients with severe functional TR were enrolled in the TRuE-registry, of which 914 with a complete dataset were included in the present study. Echocardiographic quantification of RV-function and size included measurements of tricuspid annular plane systolic excursion (TAPSE), the end-diastolic basal (RVDbasal) and longitudinal diameters (RVDlong) and the RA-volume index (RAVI). The cohort was randomly divided into a development (n=610) and validation (n=304) sample. A risk stratification model was developed using a multivariable Cox regression.

Results

The variables statistically significant to predict five-year-mortality, included in the final model and used as score parameters were: age, COPD, dialysis, pulmonary artery systolic pressure, RAVI, TAPSE RVDbasal, RVDlong and systolic hepatic vein flow reversal (sHVFR). Progressive enlargement of RV and RA and concomitant sHVFR was associated with higher values of hazard ratios (HR, Figure A). Based on the HR values, a risk score with 3 categories was developed (Figure B): low (0–2), intermediate (3–5), high (6–16). Among the risk groups, Kaplan Meier estimates of all-cause mortality at 5 years were 18%, 52% and 84% respectively (p<0.001; https://thetruerisk.com). The score showed good discrimination, with a concordance index of 0.75. At internal validation, a good agreement between the derivation and validation datasets indicated a good calibration of the survival curves.

Implementation of a long term risk score

Conclusion

The present study demonstrates the prognostic impact of comorbidities and right heart remodeling on long-term mortality in patients with severe TR. The presented risk score provides an easy and accurate estimation of long-term mortality and may thus help to guide therapeutic decision-making in this difficult group of patients.
5940Right ventricular reverse remodeling occurs early after transcatheter tricuspid valve repair for isolated severe tricuspid regurgitation and is associated with better outcome
Authors: Orban M , Stolz L , Braun D , Stocker T , Stark K , Orban M , Steffen J , Weber C , Nabauer M , Massberg S , Hausleiter J
Published: October 2019

Background

Transcatheter edge-to-edge tricuspid valve repair (TTVR) is a novel treatment option in patients with severe tricuspid regurgitation (TR), right-sided heart failure and prohibitive surgical risk.

Purpose

We investigated whether RVRR can occur early after TTVR in patients with isolated TR and its potential association with clinical outcome.

Method

We measured right ventricular parameters by transthoracic echocardiography (TTE) at baseline (BL) in 44 consecutive patients undergoing TTVR for isolated severe TR. We obtained follow-up (FU) TTEs after 1 month.

Results

At BL, we observed dilated RVs with an RV end-diastolic area (RVEDA) of 28.0±8.3cm2, RV mid diameter of 40.7±7.3mm and tricuspid annulus of 47.5±8.1mm. The majority of patients (63%) showed RV systolic dysfunction with either a tricuspid annular plane excursion (TAPSE) <17mm or fractional area change (FAC) <35%. In 40 Patients (90%), a periprocedural TR reduction by at least 1 degree was achieved (p<0.01). During further clinical FU (272±183 days), 21 patients died (of whom 14 had prior hospitalizations for heart failure before death), 8 patients had hospitalizations for heart failure, 1 patient underwent heart transplantation and 1 patient was lost to clinical FU.

We acquired a short-term echocardiographic follow-up (Echo-FU) after 30 days in 36 patients (82%). TR reduction was stable after 1 month with a TR grade ≤2+ in 26 of 36 patients (72%, p<0.01 vs BL). We detected RVRR in the majority of patients with 1-month Echo-FU: RVEDA decreased from 28.8±8.2 to 26.3±7.4cm2 (p<0.01), RV mid diameter from 41.2±7.3 to 38.5±7.7mm (p<0.01) and tricuspid annulus from 48.3±8.3 to 42.8±6.6mm (Figure, p<0.01). We observed a non-significant trend towards reduction of TAPSE (17.5mm to 16.1 mm, p=0.12) and FAC (37.8% to 35.5%, p=0.17), which could represent a normalization of systolic function of a previously hyperactive RV.

Next, we evaluated whether RVRR is potentially associated with clinical outcome. We stratified patients into two groups with more or less than median change in RVEDA, RV mid diameter and TV annulus. Fewer combined clinical events (time to death or repeat intervention or first hospitalization for heart failure) were observed in patients with pronounced decrease of RV mid diameter (p=0.03) and TV annulus (Figure, p=0.02) at FU. A decrease of RVEDA showed a non-significant trend towards better outcome (p=0.06).

Figure 1

Conclusions

Our report demonstrates that RVRR occurs already 1 month after TTVR for isolated TR and is associated with less clinical endpoints.
5945Single nucleotide polymorphisms of PAR2 gene is associated with subclinical myocardial damage in the general population
Authors: Aono T , Watanabe T , Takahashi T , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Shishido T , Watanabe M
Published: October 2019

Introduction

The protease activated receptor (PAR) 2 is a G protein-coupled receptor and expressed in cardiomyocytes, vascular cells, and leukocytes. Experimental studies demonstrated that PAR2 signaling is associated with adverse cardiac remodeling, heart failure, vascular inflammation and atherosclerosis. Recently, we and others demonstrated that subclinical myocardial damage is associated with cardiovascular mortality in general population. However, the impact of single nucleotide polymorphisms (SNPs) of PAR2 gene on subclinical myocardial damage in general population is unclear.

Purpose

The aim of this study was to investigate whether SNPs of PAR2 gene is associated with subclinical myocardial damage in general population.

Methods

The present study included 2,926 apparently healthy subjects (aged ≥40) who participated in a community-based health checkup. We investigated 639 SNPs and measured serum heart-type fatty acid binding protein (H-FABP) as markers of subclinical myocardial damage.

Results

We found the association of SNPs rs616235 within a PAR2 gene with subclinical myocardial damage. The homozygous A-allele (AA), heterozygous (AG), and homozygous G-allele (GG) carriers of rs616235 were identified in 2084 (71%), 791 (27%), and 51 (2%) subjects, respectively. The prevalence rates of subclinical myocardial damage were 29% in AA carriers, 23% in AG carriers, and 18% in GG carriers. Multivariate logistic analysis showed that the homozygous (AA) of rs616235 was independently associated with subclinical myocardial damage (odds ratio: 1.330, 95% confidence interval: 1.077–1.641, P=0.0080) after adjustment for conventional cardiovascular risk factors.

Conclusions

Genetic variant of PAR2 gene was independently associated with subclinical myocardial damage in the general population.
5950Lymphocyte-to-monocyte ratio could predict adverse clinical outcomes in patients with heart failure with preserved ejection fraction
Authors: Aono T , Watanabe T , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Shishido T , Watanabe M
Published: October 2019

Background

Heart failure with preserved ejection fraction (HFpEF) is increasing with aging of the population, whereas the mechanisms of HFpEF remain poorly understood. It was reported that systemic inflammation is associated with pathophysiology of HFpEF. Lymphocyte-to-monocyte ratio (LMR) is a marker of systemic inflammation, which predicts clinical outcomes in various cancers. However, the prognostic value of LMR has not yet been elucidated in patients with HFpEF.

Purpose

The aim of this study was to investigate the impact of LMR on clinical outcomes in patients with HFpEF.

Methods and results

We prospectively analyzed 414 consecutive patients with HFpEF. Preserved EF was defined as an EF ≥50%. During a median follow-up period of 740 days, there were 111 major adverse cardiovascular events (MACE). When patients were divided into tertiles according to LMR, Kaplan-Meier analysis demonstrated that the low LMR was associated with the greatest risk for MACE. Multivariate Cox proportional hazard regression analysis showed that the low LMR was significantly associated with MACE after adjustment for confounding factors.

Conclusions

Low LMR could predict poor clinical outcomes in patients with HFpEF. LMR is a feasible marker for predicting MACE in patients with HFpEF.
6098The role of diastolic function in risk stratification of patients with moderate aortic stenosis
Authors: Ito S , Miranda W , Nkomo V , Boler A , Pislaru S , Pellikka P , Crusan D , Lewis B , Oh J
Published: October 2019

Background

Currently data on the risk stratification of patients with moderate aortic stenosis (AS) are very limited.

Method

Patients diagnosed with moderate AS in 2012 (aortic valve area [AVA]: >1 and ≤1.5cm2) were identified. Patients were stratifying by LV diastolic function (normal vs high filling pressure), left ventricular ejection fraction (LVEF ≥50 vs <50%) and stroke volume index (SVI ≥35 vs <35 ml/m2). High filling pressure was defined as average E/e' ≥14 or septal E/e' ≥11 when atrial fibrillation was present. The prognosis was compared to age- and sex-matched general population.

Results

898 patients were included (age 74 years, 58% male, AVA 1.25 cm2). During a median follow-up of 2.9 years, there were 346 deaths. In patients with moderate AS, mortality was higher than expected (P<0.001, Fig 1A). LV high filling pressure, LVEF<50% and SVI<35ml/m2 were present in 416 (55%), 140 (17%) and 81 (9%) patients, respectively. Those with normal filling pressure had similar prognosis when compared to controls (Fig 1C, P=0.35); whereas mortality rates remained higher than reference even when LVEF≥50% or SVI≥35ml/m2 (Fig 1E, 1G, P<0.001). Amongst all groups, mortality rates were the highest in patients with LVEF <50% or SVI <35 ml/m2 (Fig 1D, 1F, P<0.001); mortality ratios were 3.78 (95% CI 3.01–4.67) and 6.91 (95% CI 5.13–9.11), respectively. Noteworthy, high filling pressure allowed further risk stratification when LVEF or SVI was preserved (Fig 2, P<0.001).

Figures 1 & 2

Conclusions

Patients with moderate AS showed poor survival. A clinical trial examining role of aortic valve replacement would be beneficial not only in patients with reduced LVEF or SVI but also in those with high LV filling pressures.
P4994Severe hypoglycemia: a marker for worse cardiovascular outcomes? A meta-analysis of randomised controlled trials
Authors: Malik A H , Yandrapalli S , Aronow W S , Jain D , Panza J A , Cooper H A
Published: October 2019

Background

Observational data have suggested that severe hypoglycemic events increase the risk of subsequent cardiovascular morbidity and mortality but the evidence from randomised studies has been inconsistent.

Purpose

This meta-analysis evaluates the relationship between severe hypoglycemic events (SHEs) and the subsequent risk of mortality and major adverse cardiovascular events (MACE).

Methods

PubMed, Embase, and Cochrane Central databases were searched for randomised controlled trials (RCTs) that reported cardiovascular outcomes in patients with diabetes with a history of SHE. Treatment effects and relative standard errors were calculated from the available data. These values were imputed in software R to perform meta-analysis via generic inverse variance method.

Results

Data from 9 RCTs and 3,462 randomised patients were available. Patients, who suffered a SHE, were found to have a significantly increased risk of subsequent all-cause mortality (HR 2.24; 95% CI 1.70, 2.95; p-value <0.01), cardiovascular mortality (HR 2.32; 95% CI 1.67, 3.22; p-value <0.01), and MACE (HR 1.66; 95% CI 1.35, 2.06; p-value <0.01) compared to the patients without a SHE. An increased risk of subsequent stroke and arrhythmic death (p-value<0.05) were also found. There was no significant association between SHE and the risk of subsequent myocardial infarction and hospitalisation for unstable angina or heart failure.

Predictors of severe hypoglycemia Older age, Lower weight, Insulin-treated, CKD, Neuropathy, previous CVD Older age, Females, Lower weight, Insulin-treated, Longer duration of diabetes, CKD, Previous CVD Older age, Females, Lower weight, Insulin-treated, Longer duration of diabetes, CKD, Previous CVD Older age, Females, Insulin-treated, Longer duration of diabetes, CKD Older age, Females, Lower weight, Insulin-treated, CKD Older age, Lower weight, Longer duration of diabetes, CKD, Poor cognition, Previous CVD CKD = Chronic kidney disease; CVD = Cardiovascular disease.

Conclusion

In patients with diabetes, the occurrence of a SHE was associated with a significantly increased risk of subsequent cardiovascular morbidity and mortality. Further studies are required to explore and circumvent the predictors of SHEs in these patients.

Acknowledgement/Funding

None
P5253Does regional myocardial strain by cardiac magnetic resonance feature tracking reflect scar in ischemic heart disease?
Authors: Stathogiannis K , Mor-Avi V , Lang R , Patel A R
Published: October 2019

Background

Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) is the gold standard for detection of myocardial scar. We hypothesized that CMR Feature Tracking (FT)-derived regional myocardial strain may reflect the presence of scar and could thus potentially be used instead of LGE imaging.

Purpose

The aim of this study was to determine the relationship between FT-derived regional myocardial strain and LGE in patients with coronary artery disease (CAD).

Methods

Seventy-five patients with CAD and typical ischemic LGE patterns on CMR (1.5T) were included (mean age 60±12 years, 70% males). Myocardial strain analysis and LGE identification were performed using dedicated commercial software. Scar was defined by presence of LGE in the same area of the myocardium in both short- and long-axis views. Peak systolic regional longitudinal and circumferential strain (RLS, RCS) values were calculated in the region of interest corresponding to the LGE area and also in a non-LGE myocardial region as a reference in each patient. These comparisons were repeated for a subgroup of 36 patients with left ventricular (LV) ejection fraction (EF) <40% to determine whether the relationship between strain and LGE holds in the presence of reduced LV function, when strain measurements may be altered as a reflection of reduced LVEF itself.

Results

Both global longitudinal and circumferential strain values were abnormal (−12.8±5.1% and −11.4±4.1%, respectively), reflecting LV dysfunction in this CAD cohort (EF = 40±16%). The magnitude of both RLS and RCS was significantly reduced in areas of LGE, compared to those without LGE: RLS −10.0±5.8% versus −20.4±7.5% (p<0.001); RCS −10.1±5.3±% versus −18.9±7.5%, respectively (p<0.001). Same pattern was noted in the reduced EF subgroup: RLS −8.0±4.7% versus −16.9±6.6% (p<0.001), RCS −7.7±4.3±% versus −16.0±7.9%, respectively (p<0.001). The figure depicts 2 representative cases in long and short axis views, LGE detection and concomitant regional strain analysis.

LGE and regional strain analysis.

Conclusion

Reduced magnitude of regional longitudinal and circumferential strain by CMR-FT correlates with presence of LGE. Pending further validation, this finding may constitute the basis for detection of scar without contrast enhanced imaging, and would result in reduced cost, scan time and risk associated with gadolinium.

Acknowledgement/Funding

ARP: Research support (software) from Neosoft and Philips
P5263Genotype and cardiac findings in non transfusion dependent thalassemia patients
Authors: Meloni A , Pistoia L , Giunta N , Renne S , Missere M , Grassedonio E , Peritore G , Pulini S , Pasin M , Sanna P M G , Positano V , Pepe A
Published: October 2019

Background

In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice.

Purpose

Our aim was to detect if the presence of a β°/β° homozygous genotype was associated to different rate of cardiac findings by Cardiovascular Magnetic Resonance (CMR) and cardiac complications.

Methods

We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project. CMR was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All cardiac complications were classified according to international guidelines.

Results

Two groups of patients were identified: non homozygous β°/β° genotype (N=61) and homozygous β°/β° genotype (N=20.) No significant differences for sex and age were found between the groups.

Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060).

No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table).

Frequencies of heart failure and arrhythmias were comparable between the groups.

Non-β0/β0 homozygous genotype β0/β0 homozygous genotype P Left Atrial Area (cm2/m2) 13.87±2.59 16.63±2.59 0.001 LV EDVI (ml/m2) 94.88±15.59 112.94±21.52 0.003 LV ESVI (ml/m2) 35.22±9.55 41.88±9.70 0.018 LV SVI (ml/m2) 61.98±12.57 69.81±11.20 0.029 LV mass index (g/m2) 61.26±10.15 68.63±15.89 0.030 RV EDVI (ml/m2) 91.27±23.50 107.53±23.87 0.019 RV ESVI (ml/m2) 33.93±17.55 40.81±15.20 0.043

Conclusions

Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. These data can support the knowledge of different phenotypic groups in the management of NTDT patients.
P5265Magnetic resonance multilayer assessment of strain in patients with heart failure
Authors: Tanacli R , Hashemi D , Lapinskas T , Duengen H.-D , Edelmann F , Gebker R , Pieske B , Kelle S
Published: October 2019

Introduction

Muscular architecture of the heart is three dimensionally complex and contractility parameters vary widely. Cardiac magnetic resonance (CMR) feature tracking is a largely available and facile method to assess myocardial strain at different layers of the myocardium.

Purpose

Assessing and compare the myocardial longitudinal (GLS) and circumferential strain (GCS) at three distinct layers of the myocardium in patients with heart failure (HF).

Methods

59 patients with a clinical diagnosis of HF who were post-hoc subdivided according to the measured EF and echo assessment of diastolic impairment into 3 groups, following ESC guidelines, were included: (1) patients with HF with preserved ejection fraction (HFpEF) where EF >50% and diastolic dysfunction (E/e' ratio) is present and plasma levels of natriuretic peptides are elevated, (2) patients with HF with mid-range ejection fraction (HFmrEF), where EF = 40–49% and similar additional criterias are present, (3) patients with HF with reduced ejection fraction (HFrEF) where EF <40%. Exclusion criteria: valvulopathy, arrhythmias, insufficient acquisition and artefacts.

Results

Strain values are the highest in the Endo− and progressively lower in the Myo− and Epi− layers with a gradient present in all groups but decreasing in HFmEF and further in HFrEF. GLS decrease with the severity of the disease in all 3 layers Normal > HFpEF > HFmrEF > HFrEF (Endo−: −23.0±3.5 vs −20.0±3.3 vs −16.4±2.2 vs −11.0±3.2, p<0.001, Myo−: −20.7±2.4 vs −17.5.0±2.6 vs −14.5±2.1 vs −9.6±2.7, p<0.001, Epi−: −15.7±1.9 vs −12.2±2.1 vs −10.6±2.3 vs −7.7±2.3, p<0.001) (Figure A), GCS is not different between the Normal and HFpEF (Endo−: −34.5±6.2 vs −33.9±5.7, p=0.51; Myo−: −21.9±3.8 vs −21.3±2.2, p=0.39; Epi−: −11.4±2.0 vs −10.9±2.3, p=0.54) but markedly lower in systolic HF groups Normal > HFmrEF > HFrEF (Endo−: −34.5±6.2 vs −20.0±4.2 vs −12.3±4.2, p<0.001; Myo−: −21.9±3.8 vs −13.0±3.4 vs −8.0±2.7, p<0.001; Epi−: −11.4±2.0 vs −7.9±2.3 vs −4.5±1.9) (Figure B). ROC analysis renders Endo− GCS (AUC=0.89) and respectively Endo− GLS (AUC=0.74) as optimal to detect contractile impairment in HF with Youden's thresholds of −20.2 for Endo− GLS and, respectively, −28.1 for Endo− GCS. Endo− GCS is not different between control and HFpEF and GLS impairment is present only inconstantly in HFpEF.

Conclusions

Feature tracking CMR successfully assess layer-specific myocardial strain and emerges as a powerful tool in functional stratification of patients with HF. Strain amplitude varies consistently throughout the myocardium and its quantification warrants careful standardization. Sub-endocardial strain values of strain are comparatively the highest and show most predictive power to detect contractile impairment. Underlying systolic impairment is present only in a subgroup of patients with HFpEF and only GLS and not the GCS is for this purpose a useful diagnostic tool.
P5317Prevalence of cardiovascular diseases in the Middle-East: systemic review and meta-analysis
Authors: Shehab A , Bhagavathula A S
Published: October 2019

Background

Cardiovascular diseases are the leading cause of mortality in the world and CVDs are responsible for 34% of all deaths in the middle east population. To better understanding of the current CVD prevalence in the middle east population we conducted this systematic review and meta-analysis.

Aim

To assess the prevalence and risk factors of CVD among middle east adult population from the published literature.

Methods

Electronic data basis such as PubMed, Sciencedirect, Embase and Google scholar were searched, from the year 2011 to December 2018. All the original articles published in English and have investigated the prevalence of CVD and risk factors. Study characteristics, participants demographics and risk factors of CVD were recorded. To pull the CVD prevalence, we used random effect meta-analysis. we assess heterogeneity using both the formal tests and subgroup analysis. We also assessed the quality of the studies and examined the publication bias.

Results

We retrieved 2931 potentially relevant papers through searches of electronic and gray literatures, of which 44 articles met inclusion criteria after the screening and were included in systematic review and meta-analysis (N=191,979). The weighted pooled prevalence of CVD was 13.7% (95% CI: 11.1%-16.3%) in the Middle-East. The prevalence of cardiovascular disease risk factors such as dyslipidemia accounts 43.1% (95% CI: 17%-69.3%), diabetes mellitus 32.3%, 95% CI: 23.8%-40.8%), hypertension 30.7% (95% CI: 25.2%-36.3%). Other traditional CVD risk factors, smoking 16.3% (95% CI: 12.9%-19.7%), and family history of CVDs 18.7% (95% CI: 15.2%-22.2%).

Conclusion

A high CVD prevalence of 13.7% was identified and dyslipidemia remain to be a significant independent risk factor for CVD in the Middle-East. Interventional strategies are urgently required for primary prevention of CVD and its associated risk factors in Middle East population.
P5354Echocardiographic findings in pregnant indigenous Australians: under utilised?
Authors: Marangou J , Ferguson D , Ilton M , Remenyi B
Published: October 2019

Background

The Indigenous population of Australia has one of the highest prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) globally. RHD is more common in females and the incidence peaks in the 3rd to 4th decade of life, corresponding with child-bearing age. It is the number one cause of cardiac complications in pregnancy globally. Signs and symptoms of normal pregnancy may overlap with those of cardiac pathology. Significant valvular disease can complicate pregnancy and delivery. Current practice sees pregnant women referred for echocardiography if there are signs or symptoms of possible cardiac pathology or a history of RHD.

Aim

To assess the current practice of echocardiography in pregnant women in a region with a high prevalence of rheumatic heart disease.

Method

A retrospective study of all echocardiograms requested for an indication relating to pregnancy over a three-year period were reviewed in the Northern Territory of Australia. Data collected included patient demographics, echocardiography indication, history of RHD, ARF or other cardiac disease, echocardiographic parameters, location of delivery, peri-partum morbidity and mortality.

Results

The total number of patients reviewed were 257. The 158 Indigenous Australian women had a mean age of 25 years and the 99 non-indigenous women had a mean age of 30 years. The Indigenous women had a higher rate of abnormal echocardiograms, 36.1% compared with 9.1% for non-indigenous women. Table 1 outlines echocardiography indications and outcomes. Indigenous women had extremely high rates of ARF or RHD representing 37% of echocardiography referrals, with 17.1% (27/158) having moderate or severe valve lesions. 5 cases (3.2%) had a history of prior valve surgery. 10 (6.3%) Indigenous patients required transfer to a tertiary centre with valve intervention services available for delivery. There was one maternal death, one post-partum stroke and one foetal death in utero.

Echocardiogram indications and outcomes Incidental murmur Cardiac symptoms Other cardiac disease History of RHD and/or ARF Normal study Rheumatic heart disease Congenital heart disease Other heart disease Indigenous (n=158) 60 (38%) 15 (9.4%) 24 (15%) 59 (37.3%) 101 (63.9%) 47 (29.7%) 7 (4.4%) 3 (1.9%) Non-indigenous (n=99) 44 (44.4%) 24 (24.2%) 31 (31.3%) 0 90 (91%) 2 (2%) 3 (3%) 4 (4%)

Conclusion

In the Top End of Australia, Indigenous patients have a very high rate of abnormal echocardiograms during pregnancy compared with their non-indigenous counterparts, mainly as a result of RHD. Data suggests that pregnant Indigenous women are being under serviced by the current medical model and referral practices. Guidelines are urgently needed in relation to echocardiography and pregnancy in populations that are burdened by RHD.
P5360Cardiovascular adaptation characteristics in women with preeclampsia
Authors: Buzdugan E C , Goidescu C , Nemeti G , Goidescu I , Procopciuc L M , Crisan S , Radulescu D , Muresan D , Caracostea G
Published: October 2019

Introduction

Even in normal pregnancies, physiologic functional and structural cardiovascular adjustments are required for progression of a successful pregnancy. In preeclamptic patients, these pregnancy-induced adaptive processes are intensified. It has been suggested that preeclampsia should be regarded as a failed stress test, a marker for increased later life cardiovascular risk.

Purpose

To differentiate between cardiovascular remodelling patterns in preeclamptic vs. normal pregnancies, using echocardiography and digital photoplethysmography.

Material

We conducted a single-center case–control study, performing cardiovascular assessment during last trimester of pregnancy in 56 pregnant women with preeclamsia (PE) and 62 healthy pregnant women, without CV risk factors.

Echocardiography was performed to characterize left ventricular (LV) remodelling patterns and to assess LV systolic and dyastolic function. Also, digital photoplethysmography was used to determine stiffness index (SI) and vascular age (VA). Data between groups were compared.

Results

The two groups were matched by age (30.42±6.37 vs 29.96±5.18 y/o, p=0.74), body mass index (29.84±5.31 vs. 28.53±5.33g, p=0.30), and parity (primiparous 33 vs. 25, p=0.47, multiparous 23 vs. 27, p=0.78). The prevalence of LV hypertrophy, expressed as LV mass (185.75±39.61 vs. 144.85±28.81 g, p=0.0023) and LV relative wall thickness (0.49±0.08 vs. 0.42±0.069), was higher in preeclamptic women, corresponding to higher blood pressure values (systolic blood pressure 164.27±20.09 vs 114±18.04 mmHg, p=0.0014, dyastolic blood pressure 103.22±14.13 vs. 72.83±11.34 mmHg, p=0.0015). The most common remodeling type in preeclamptic group was concentric hypertrophy (28/56, 50%), while in normal pregnancy group, normal geometry (21/62, 34%) and concentric remodeling (21/62, 34%), were more frequently encountered. No significant differences between groups were found in terms of LV ejection fraction, while dyastolic LV function, depicted through transmitral flow parameters, varied only when E/A ratio was measured (1.38±0.34 vs. 1.62±0.46, p=0.03). In preeclamptic women, SI was increased (9.27±1.86 vs. 7.13±1.86 m/s, p=0.0091), with a significantly higher VA also (47.44±21.61 vs. 28.75±7.51y/o, p=0.0001), for a similar maternal age of the study groups.

Conclusions

We documented a higher prevalence of LV hypertrophy, with the concentric remodelling pattern predominance, as well as a significantly advanced vascular age due to an increased arterial stiffness, among preeclamptic group. Follow-up of these patients may reveal features, or cut-off values, useful to early identify a population that may benefit from early interventions to prevent cardiovascular disease.
P5364Safety profile of bempedoic acid: pooled analysis of 4 phase 3 clinical trials
Authors: Ballantyne C M , Banach M , Catapano A L , Duell P B , Laufs U , Leiter L A , Mancini G B J , Ray K K , Bloedon L T , Sasiela W J , Ye Z , Bays H E
Published: October 2019

Background/Introduction

Bempedoic acid (BA), an oral, first-in-class, ATP-citrate lyase inhibitor, lowers low-density lipoprotein cholesterol (LDL-C) in patients who do not achieve sufficient lipid lowering with guideline-recommended first-line therapies.

Purpose

We evaluated the safety profile of BA in phase 3 trials.

Methods

Data were pooled from 4 randomised, double-blind, placebo-controlled studies that enrolled patients with hyperlipidaemia who were receiving stable lipid-lowering therapy (LLT; maximally tolerated statins +/− nonstatin therapies) and required additional LDL-C lowering. Patients were randomised (2:1) to BA 180 mg or placebo daily for 12 to 52 weeks.

Results

Median exposure for 3621 patients (2424 BA, 1197 placebo) was 363 days. Background LLT included a statin +/− other LLT (83.8%), nonstatin LLT alone (9.4%), or none (6.8%). Adverse event (AE) and serious AE rates were similar between groups (Table). The most common AEs in the BA and placebo groups were nasopharyngitis (7.4% vs 8.9%), myalgia (4.9% vs 5.3%), and urinary tract infection (4.5% vs 5.5%). Rates of new-onset/worsening diabetes were 4.0% for BA and 5.6% for placebo. No AEs leading to discontinuation differed by ≥0.5% between treatments. All fatal AEs were judged by the investigator as unrelated to treatment. A trend was observed for a lower 3-component major adverse cardiac event rate with BA vs placebo (hazard ratio, 0.85; 95% confidence interval: 0.53 to 1.37). Changes in uric acid, creatinine, and haemoglobin were apparent at week 4, stable over time, and reversible after stopping BA. Gout occurred in 1.4% and 0.4% of patients in the BA and placebo groups, respectively. The safety profile of BA was consistent across background therapies, demographics, and disease characteristics.

Table 1. Safety summary Placebo (n=1197) BA (n=2424) Any AE / SAE, % (n) 72.5 (868) / 13.3 (159) 73.1 (1171) / 14.1 (341) Drug discontinuation due to an AE, % (n) 7.8 (93) 11.3 (273) AE with a fatal outcome, % (n) 0.3 (4) 0.8 (19) Aminotransferase elevation >3 x ULN, % (n) 0.3 (3) 0.7 (18) Aminotransferase elevation >5 x ULN, % (n) 0.2 (2) 0.2 (6) Creatine kinase elevation >5 x ULN, % (n) 0.2 (2) 0.3 (8) Creatinine, mean change at week 12, mg/dL −0.002±0.11 0.046±0.12 Uric acid, mean change at week 12, mg/dL −0.02±0.82 0.82±0.97 Haemoglobin, mean change at week 12, g/dL 0.06±0.69 −0.31±0.71

Conclusion(s)

BA added to LLT was well tolerated, with a safety profile comparable to placebo.
P5390Adipolin/C1q/Tnf-related protein 12 attenuates adverse cardiac remodeling in a mouse model of myocardial infarction
Authors: Takikawa T , Ohashi K , Fang L , Kawanishi H , Otaka N , Ogawa H , Murohara T , Ouchi N
Published: October 2019

Background

Ischemic heart disease is one of leading causes of death worldwide. Obesity is closely linked to the development of cardiovascular diseases including ischemic heart disease. Adipose tissue produces various secretory bioactive proteins called as adipokines, and dysregulation of adipokine production contributes to the pathogenesis of obesity-related complications. Previously we identified adipolin, also referred to as C1q/Tnf-related protein12, as an insulin-sensitizing adipokine that is down-regulated in obesity. Here, we investigated the effects of adipolin on cardiac remodeling in a mouse model of myocardial infarction (MI).

Method

Male adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI. Echocardiographic and histological analyses were performed to evaluate cardiac function and myocardial remodeling at 4 weeks after MI. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Cardiomyocyte cross sectional area was evaluated by Wheat Germ Agglutinin staining. Perivascular fibrosis was assessed by Masson's trichrome staining. Neonatal rat ventricular myocytes were used as cultured cardiac myocytes for in vitro study.

Results

APL-KO mice exhibited increased ratios of the heart weight/body weight and lung weight/body weight after MI compared with WT mice. APL-KO mice showed increased left ventricular diastolic diameter and decreased fractional shortening after MI compared with WT mice. APL-KO mice had increases in myocardial apoptosis, cardiomyocyte hypertrophy and perivascular fibrosis at the remote zone of infarct hearts as compared with WT mice. Treatment of cultured cardiomyocytes with adipolin protein reduced apoptosis in response to 24 hours of hypoxia. Treatment with adipolin protein also increased the phosphorylation of Akt in cardiomyocytes. Inhibition of PI3 kinase/Akt signaling by LY294002 reversed the anti-apoptotic effects of adipolin in cultured cardiomyocytes.

Conclusion

Our data indicate that adipolin prevents pathological myocardial remodeling after chronic ischemia, at least in part, by suppressing myocardial apoptosis through an Akt-dependent mechanism.
P5444Plasma Indoleamine 2,3-dioxygenase is highly predictive of cardiac remodeling after myocardial infarction
Authors: Vodovar N , Saadi M , Paven E , Sadoune M , Mercadier J J , Launay J M , Logeart D
Published: October 2019

Background

Acute myocardial infarction (MI) is associated with a strong inflammatory response resulting from the cardiac insult. On the other hand, such an inflammation may lead and/or worsen adverse left ventricular (LV) remodeling after MI. Among the markers of inflammation is Indoleamine 2,3-dioxygenase (IDO), which production is induced upon inflammation. IDO catalyzes the transformation of tryptophane into kynurenine.

Purpose

We tested plasma IDO activity as a predictor of LV remodeling post-MI.

Methods

The PREGICA cohort recruited prospectively patients who were admitted because of first acute myocardial infarction. Blood samples were collected on admission, at day 4 and at day 6. Echocardiography and cardiac MRI were obtained at day 4 and at 6 months. To be included, the number of akinetic LV wall segments had to be ≥3 on 17 at day 4. IDO activity was the ratio between kynurenine and tryptophane measured by high pressure liquid chromatography coupled with fluorimetric detection. Remodelers were identified as patients with a variation of end-diastolic left ventricular volume (EDLVV) between day 4 and 6 months post-MI >20%.

Results

Among the 292 patients studied (mean age 57y, mean necrosis size 26% on MRI), the median increase in EDLVV was 16.7% and 137 (47%) were classified as remodelers. On admission as well as at day 4, IDO activity was significantly higher in remodelers (8.2±4.2% vs 5.3±2.5% and 8.7±5.7% vs 5.6±4.4%, p<0.001) and remained higher at 6 months post-MI. IDO activity at day 4 was highly predictive of LV remodeling (Figure): AUC = 87% [95% CI 83–91%]; IDO threshold of 5.8% resulted in specificity = 81%, sensitivity = 89%, negative predictive value = 89%, positive predictive value = 80%. In contrast, blood levels of NTproBNP, ST2, Galectin 3 or CRP at day 4 were poorly predictive. In multivariate analysis including other predictive variables at day4 (primary angioplasty, EDLVV, LVEF, necrosis size), increase in IDO activity was significantly associated with LV remodeling (OR 1.21 [95% CI 1.11–1.33].

Conclusions

IDO activity appears as a promising biomarker for the prediction of LV remodeling after MI. Its specific role in postMI remodeling pathways requires further investigation.

Acknowledgement/Funding

PHRC national