bluuebunny/crossref_metadata_2025 huggingface dataset:
P4749Renal function worsening in factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - insights from the RELOADED study
Authors: Bonnemeier H , Kreutz R , Enders D , Schmedt N , Haeckl D , Vaitsiakhovich T , Kloss S
Published: October 2019

Background

Data on the effectiveness and safety of Factor-Xa non-vitamin-K oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF) and renal disease is scarce. Among others, our study aimed to investigate the risk of renal function worsening in new users of NOACs vs. phenprocoumon with renal disease.

Methods

We conducted a new user cohort study (one year washout period) in patients with NVAF overall and additionally with renal disease defined by either an extended list of ICD-10 codes (definition 1) or chronic kidney disease (CKD) stages 3 or 4 (definition 2). German claims data between January 1st, 2013 and June 30th, 2017 were utilized and a multiple Cox-regression was performed to calculate confounder-adjusted hazard ratios (HRs) for the risk of end stage renal disease (ESRD)/dialysis and acute kidney injury in new users of NOACs (rivaroxaban, apixaban and edoxaban) vs. new users of phenprocoumon.

Results

In the overall population 22,339 patients initiating rivaroxaban, 16,201 patients initiating apixaban, 2,828 patients initiating edoxaban and 23,552 patients initiating phenprocoumon were included. NOAC patients with renal disease (definition 1) initiating reduced doses comprised 2,121 initiators of rivaroxaban, 2,507 of apixaban and 292 of edoxaban. 7,289 patients of phenprocoumon were identified. Patients with CKD (definition 2) initiating reduced doses of Factor-Xa inhibitors comprised 1,216 initiators of rivaroxaban, 1,522 of apixaban, 166 of edoxaban and 3,513 of phenprocoumon. In the confounder-adjusted analysis, a beneficial effect for both, rivaroxaban and apixaban over phenprocoumon was seen for the risk of ESRD/dialysis for all populations (overall, renal definition 1 and renal definition 2). In addition, in the CKD population we found a statistically significant risk reduction related to acute kidney injury only for rivaroxaban initiators (44%). There was not sufficient data to conduct the analyses for edoxaban.

Figure 1

Conclusion

This is the first observational retrospective database study evaluating the effect of renal function worsening in Germany. Results indicate a beneficial effect for both, reduced doses of rivaroxaban and apixaban related to renal function worsening over time when compared to phenprocoumon. This effect was more pronounced for the risk reduction with rivaroxaban related to ESRD /dialysis and specifically also related to a significant risk reduction for AKI.

Acknowledgement/Funding

The study was funded by Bayer AG
P4752Apixaban 2.5 mg twice daily is effective and safe for patients with atrial fibrillation and combinations of advanced age, low body weight, and elevated creatinine: insights from ARISTOTLE
Authors: Zeitouni M , Giczewska A , Lopes R D , Wojdyla D , Christersson C , De Caterina R , Steg P G , Granger C B , Wallentin L , Alexander J H
Published: October 2019

Background

In ARISTOTLE, patients with atrial fibrillation and ≥2 dose-reduction criteria [age ≥80 years, weight ≤60 kg, and creatinine ≥1.5 mg/dL (133 μmol/L)] were randomized to apixaban 2.5 mg twice daily (b.i.d) or warfarin.

Purpose

To determine whether the apixaban dose adjustment in ARISTOTLE resulted in similar efficacy and safety compared to warfarin.

Methods

The effects of apixaban 2.5 mg b.i.d versus warfarin on stroke or systemic embolism, major bleeding and death in ARISTOTLE patients with ≥2 dose-reduction criteria were compared with the effects of apixaban 5 mg b.i.d in patients with 0 or 1 dose-reduction criterion.

Results

Of 751 (4.1%) patients with ≥2 dose-reduction criteria, 386 were assigned to apixaban 2.5 mg b.i.d and 365 to warfarin. Compared to patients with 0 or 1 dose reduction criteria (n=17,322), these patients had a higher risks of stroke/systemic embolism (HR =1.78; 95% CI [1.24–2.57]), major bleeding (HR =1.73; 95% CI [1.28–2.32]) and death (HR=3.21; 95% CI [2.69–3.83]), irrespective of whether they were assigned to apixaban or warfarin. The benefits of apixaban 2.5 mg b.i.d compared with warfarin on stroke or systemic embolism, major bleeding, and death in patients with ≥2 dose-reduction criteria were consistent with that of apixaban 5 mg b.i.d in patients with either 0 or 1 dose-reduction criteria (Figure).

Conclusions

While they are at higher overall risk, patients with appropriate dose reduction criteria have consistent benefits with apixaban 2.5 mg b.i.d. over warfarin. Additional analyses investigating the relationship between apixaban dose and both apixaban plasma concentrations and levels of thrombosis biomarkers are underway.

Acknowledgement/Funding

Bristol-Myers Squibb and Pfizer, Inc.
P4762What do atrial fibrillation ablation procedural volume differences across European centers reflect? An ESC EORP registry: atrial fibrillation long-term
Authors: Pagourelias E , Vassilikos V , Blomstrom-Lundqvist C , Kautzner J , Maggioni A P , Pokushalov E , Tavazzi L , Dagres N , Brugada J , Arbelo E
Published: October 2019

Background

Data from the European Atrial Fibrillation (AF) Ablation Long-Term Registry suggest that there are significant differences in the volume of AF ablation procedures performed across different centers even in the same country. If these differences in AF ablation volume between centers reflect regional, socioeconomic, infrastructural/technical or other disparities has not been addressed till now.

Purpose

The aim of this study was to investigate patient and non-patient related differences among European AF ablation centers according to the volume of AF ablations performed.

Methods

Data for this analysis originate from the European AF Ablation Long-Term Study, a prospective registry designed to describe the clinical epidemiology of patients undergoing AF ablation. Based on 25th and 75th percentiles of AF ablation numbers performed, the participating centers were classified into high volume (HV) (≥250 procedures/year), medium volume (MV) (<250 and ≥58/year) and low volume (LV) (<58/year). Patient (demographics, comorbidities) and non-patient (center infrastructure, procedural characteristics) related differences were assessed.

Results

A total of 91 centers in 26 European countries enrolled 3368 patients. There were no significant differences concerning regional distribution, hospital/cardiology facilities or services provided among centers with the exception of electrophysiology procedures and labs which were more abundant in HV centers (p=0.02 and <0.001 respectively). HV and MV centers ablate twice more cases of long-standing persistent and persistent AF compared to LV centers, in which paroxysmal AF reaches 78.9% of all cases (Figure A). Accordingly, first AF ablation procedure was far more frequent in LV centers compared to MV and HV (85.8% vs 76.0% vs 76.1% respectively, p<0.001). Even though HV centers ablate significantly more high risk patients (CHA2DS2-VASc score ≥2 51.4% in HV vs 46.5% in MV vs 37.2% in LV, p<0.001) (Figure B) with accompanying comorbidities, applying more elaborate ablation techniques, fluoroscopy time and radiation dose were higher among patients undergoing AF ablation in LV centers (p<0.001 for all). Despite the above-mentioned dissimilarities, Kaplan-Meier survival analysis, based on adjusted data, demonstrated non-significant differences in complication rate (p=0.402) or AF recurrence rate (p=0.363) among HV, MV and LV centers.

Conclusions

Volume of AF ablations in a center is not correlated with regional or infrastructural characteristics. The higher volume in HV centers consists mainly by more long-term persistent AF and higher risk patients, suggesting that differences in volume reflect differences in experience and personnel's commitment towards AF ablation.
P4790Haematuria is not elevated in AF patients treated with NOACs versus VKAs: GARFIELD-AF study
Authors: Verstraete S , Virdone S , Bassand J P , Cools F , Pieper K , Kayani G , Kakkar A K
Published: October 2019

Background

Haematuria in atrial fibrillation (AF) patients taking oral anticoagulants (OACs) is usually viewed as less serious than intracranial and gastrointestinal bleeding. It is speculated that haematuria may result from renal excretion of active new oral anticoagulants (NOACs) causing a direct anticoagulating effect in the urinary tract. Vitamin K antagonists (VKAs) such as warfarin, on the other hand, undergo hepatic metabolism and may pose lower risk of haematuria. This large registry study investigated whether NOACs more likely cause haematuria compared with VKAs.

Purpose

To assess whether there is any difference in the incidence rate of haematuria in AF patients taking NOACs versus VKAs using data from the GARFIELD-AF registry.

Methods

GARFIELD-AF is an international prospective registry of nonvalvular AF patients with at least one additional risk factor for stroke, followed for at least 2 years. Macroscopic haematuria was identified by local investigators. Event rates were estimated by Poisson model. Adjusted hazard ratio (HR) for haematuria between treatment groups was calculated using overlap-weighted Cox model including a range of patient demographics and clinical parameters as variables. Only the first haematuria occurrence was considered. Patients who were not treated with either VKAs or NOACs were excluded.

Results

Among a registry population of 34,926 patients 24,079 were anticoagulated and 24,061 had available follow-up data. Baseline characteristics were evenly balanced between the VKAs and NOACs subgroups, except a somewhat higher proportion of VKA patients than NOAC patients received concomitant antiplatelet therapy. Rate of haematuria was similar between the two groups: VKAs, 115/12,307 cases (0.9% over study period; 0.55 [95% CI, 0.46–0.65] per 100 patient-years); NOACs, 119/11,754 cases (1.0% over study period; 0.49 [95% CI, 0.41–0.59] per 100 patient-years). Over 2 years cumulatively, adjusted HR for haematuria in NOAC group versus VKA was 0.85 (95% CI, 0.63–1.15; p=0.29). Most haematuria cases (approximately 94%) were minor or clinically relevant non-major bleeds, occurring at a similar rate in both subgroups. Major bleeds were very rare. No intervention was necessary in two thirds haematuria cases (65.2%); surgical procedures were performed in only 8.3%. No haematuria-related deaths were observed.

Incidence of haematuria

Conclusions

The incidence and severity of haematuria were not increased in AF patients taking NOACs versus VKAs. Haematuria may occur in approximately one in 100 AF patients on long-term OACs therapy and is usually non-serious.

Acknowledgement/Funding

The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.
P4796Risk prediction of atrial fibrillation in the community combining biomarkers and genetics
Authors: Boerschel C , Ohlrogge A , Geelhoed B , Niiranen T , Havulinna A S , Palosaari T , Blankenberg S , Zeller T , Salomaa V , Schnabel R B
Published: October 2019

Background

Classical cardiovascular risk factors (CVRF), biomarkers and genetic variation have been suggested for risk assessment of atrial fibrillation (AF).

Purpose

To evaluate their clinical potential, we analysed their individual and combined effectiveness in AF prediction.

Methods

In N=6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP) and 145 recently identified single nucleotide polymorphisms (SNPs) for incident AF.

Results

Over a median follow-up of 17.8 years, N=551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP (hazard ratio (HR) per standard deviation (SD) 1.90, 95% confidence interval (CI): 1.71–2.11, P<0.001) and the polygenic risk score (PRS) (HR per SD 1.66, 95% CI: 1.51–1.84, P<0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared to a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of all CVRF, NT-proBNP and the PRS reached 0.82 compared to 0.77 for CVRF only (P<0.001). Comparing the highest versus lowest quartile, age remained the strongest risk factor with a 15-fold increased risk of AF. The highest quartiles of NT-proBNP and the PRS both showed an approximately 3-fold increased AF risk compared to the lowest quartiles.

C-Index for AF prediction

Conclusions

The PRS and the established biomarker NT-proBNP predicted incident AF comparably. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs.

Acknowledgement/Funding

European Research Council, German Ministry of Research and Education, DZHK, European Union Seventh Framework Programme, CHANCES, THL
4937Global longitudinal strain by feature tracking predicts adverse remodeling in ST-elevation myocardial infarction incremental to
Authors: Reinstadler S , Reindl M , Tiller C , Holzknecht M , Mayr A , Klug G , Metzler B
Published: October 2019

Objectives

To evaluate the independent and incremental value of left ventricular (LV) strain assessed by cardiac magnetic resonance feature tracking (CMR-FT) for prediction of adverse LV remodeling following ST-elevation myocardial infarction (STEMI).

Background

The role of LV myocardial strain by CMR-FT for prediction of adverse remodeling after STEMI in comparison to LV ejection fraction and infarct severity is unclear.

Methods

STEMI patients treated with primary percutaneous coronary intervention within 24 hours after symptom onset were enrolled. CMR core laboratory analysis was performed to assess LV ejection fraction, infarct pathology and LV myocardial strain. The primary endpoint was adverse remodeling defined as ≥20% increase in LV end-diastolic volume from baseline to 4 months.

Results

From the 232 patients included, 38 (16.4%) reached the primary endpoint. Global longitudinal strain (GLS), global radial strain, and global circumferential strain were all predictive of adverse remodeling (p<0.01 for all), but among strain values only GLS was an independent predictor of adverse remodeling (hazard ratio: 1.36 [1.03–1.78]; p=0.028) after adjustment for strain parameters, ejection fraction and CMR markers of infarct severity. A GLS >-14% was associated with a 4-fold increase in risk for LV remodeling (hazard ratio: 4.16 [1.56–11.13]; p=0.005). Addition of GLS to a baseline model comprising ejection fraction, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.26 ([0.13–0.38]; p<0.001) and integrated discrimination improvement of 0.02 ([0.01–0.03]; p=0.006).

Conclusions

In STEMI survivors, determination of GLS using CMR-FT provides important prognostic information for the development of adverse remodeling that is incremental to LV ejection fraction and CMR markers of infarct severity.
4939Clinical significance of global strain estimated by 3D speckle tracking acutely after onset of ST-elevation myocardial infarction on prediction of long term prognosis
Authors: Iwahashi N , Kirigaya J K , Horii M H , Akiyama E A , Okada K O , Matsuzawa Y M , Konishi M K , Maejima N M , Hibi K H , Kosuge M K , Ebina T E , Tamura K T , Kimura K K
Published: October 2019

Background

Three-dimensional (3D) speckle tracking echocardiography (STE) is a novel method for assessing cardiac function because of free form out-of-plane motion effects.

Aim

To explore the role of 3D-STE for prediction of the long term prognosis in patients with a first-time ST elevation acute myocardial infarction (STEMI).

Methods

A total of 238 patients (mean age 64.6 years) with a first-time STEMI treated with reperfusion therapy were enrolled in our study. Twenty four hours after admission, standard 2D echocardiography and 3D full volume imaging were obtained and strain parameters (GLS: global longitudinal strain, GCS: global circumferential strain) were calculated using 4D LV analysis. Infarct size was measured with single-photon emission computed tomography imaging 7 to 14 days after onset. We followed them for median 94 months (inter quartile range: 69–109 months). The primary end point was the major adverse cardiac and cerebrovascular events (MACE: cardiac death, non-fatal MI, heart failure requiring intravenous diuretics administration and stroke). The patients with persistent chronic atrial fibrillation, poor image quality, emergency bypass surgery were excluded.

Results

During follow up periods, 78 patients experienced MACE (26 cardiac death, 48 heart failure, 29 non-fatal MI, 5 stroke) and 48 patients died (22 non-cardiac death). In multivariate analysis, 3D-GLS was the strongest predictor for MACE. Kaplan-Meier Curve demonstrated that 3D-GLS >−11.4 was the independent predictor for MACE (Log-rank χ2=73.818, p<0.0001). When combined with 3D-GCS >−19.2, the patients with higher value both of 3D-GLS and 3D-GCS were extremely high risk.

The figure shows the Kaplan-Meier curve according to the 4 groups based on the cut-off values determinded by ROC curves.

Conclusions

Global strain estimated by 3D-STE immediately onset of STEMI was useful tool for the prediction of long term prognosis.

Acknowledgement/Funding

None
4940Early reverse remodelling assessed by myocardial work after sacubitril-valsartan therapy
Authors: Valentim Goncalves A , Galrinho A , Pereira-Da-Silva T , Ilhao Moreira R , Soares R , Moura Branco L , Rio P , Feliciano J , Abreu J , Timoteo A T , Mendonca T , Reis J , Mano T , Cruz Coutinho M , Cruz Ferreira R
Published: October 2019

Introduction

Sacubitril/Valsartan (LCZ696) had prognosis benefit demonstrated in PARADIGM-HF trial, however less is known about his effects in cardiac dimensions and function.

Myocardial work (MW) is a new transthoracic echocardiographic (TTE) parameter. None is known about the effects of LCZ696 therapy in MW parameters.

Purpose

The aim of this study was to prospectively compare several TTE parameters, including MW, before and after LCZ696 therapy.

Methods

Prospective evaluation of chronic HF patients with optimized standard of care therapy and LVEF≤40%, in which LCZ696 therapy was started.

TTE study was performed before and 6 months after LCZ696 therapy. A semiautomated analysis of GLS was performed and MW were estimated using custom software of GE Vivid E95 ultrasound system.

Results

Of the 42 patients, 35 (83.3%) completed the 6 months follow-up, since 2 patients (4.8%) died and 5 patients (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years with 82.9% of male patients.

LV dimensions and atrial volumes were significantly lower at 6 months of treatment. LVEF had a mean absolute raise of 8.9% and GLS a relative decrease of 27.8%. MW had a significant increase in constructive work (720.2mmHg VS 900.6mmHg, p=0.016) and work efficiency (78.6% VS 86.6%, p=0.027), with a non-significant decrease in the wasted work (150.2mmHg VS 136.8mmHg, p=0.441).

TTE data before and after 6 months of LCZ696 treatment Time 0 6 months p LV end-diastolic diameter (mm) 71.3±8.4 66.9±7.6 0.001 LV end-systolic diameter (mm) 57.8±9.4 53.1±9.3 0.002 Interventricular septum (mm) 9.6±1.7 9.9±1.9 0.280 LVEF (%) 29.3±6.4 38.2±8.9 <0.001 GLS (%) −7.0±2.9 −8.9±2.8 0.001 MW – Constructive (mmHg) 720.2±230.5 900.6±343.2 0.016 MW – Wasted (mmHg) 150.2±83.3 136.8±54.2 0.441 MW – Efficiency (%) 78.6±10.8 86.6±12.0 0.027 E/e' 13.7±4.5 12.8±4.9 0.449 Pulmonary artery systolic pressure (mmHg) 38.3±12.2 30.9±10.6 <0.001 Left atrium volume (ml/m2) 51.5±22.6 43.7±15.8 0.004 Right atrium volume (ml/m2) 33.1±4.4 28.5±13.5 0.036 TAPSE (mm) 19.2±4.4 20.0±4.9 0.404

Conclusion

LCZ696 therapy is associated with signs of reverse remodelling in TTE, including an increase in constructive work and work efficiency.
4943Remnant cholesterol increases the risk for recurrent vascular events independent of LDL-cholesterol in patients with clinical manifest vascular disease
Authors: Heidemann B E , Koopal C , Bots M L , Asselbergs F W , Westerink J , Visseren F L J
Published: October 2019

Background

For many years, low density lipoprotein cholesterol (LDL-C) is recognized as an important risk factor for the development of atherosclerosis and cardiovascular disease. However, even with normal LDL-C levels there is a residual risk for cardiovascular disease and mortality. Previous research in patients with ischemic heart disease, diabetes mellitus type 2 (T2DM) and in the general population has shown that this residual risk could be explained by elevated plasma levels of very low density lipoprotein- (VLDL) and chylomicron-remnant cholesterol.

Purpose

We evaluated the relation between plasma levels of VLDL- and chylomicron-remnant cholesterol and recurrent vascular disease and all-cause mortality in a cohort of patients with clinical manifest arterial disease.

Methods

Prospective cohort study in 8057 patients with manifest arterial disease from the UCC-SMART study. Patients with triglyceride levels >9 mmol/L or known homozygote Apo E2 genotype were excluded. Cox proportional hazard models were used to evaluate the effect of fasting VLDL- and chylomicron-remnant cholesterol (calculated by total cholesterol - high density lipoprotein cholesterol (HDL-C) - LDL-C) on occurence of myocardial infarction (MI), stroke, vascular death, a composite endpoint (i.e. MI, stroke, vascular death) and all-cause mortality. Models were adjusted for LDL-C, current smoking, waist circumference, creatinine and systolic blood pressure. Effect modification of HDL-C and T2DM on the relation between remnant cholesterol and vascular endpoints was evaluated.

Results

Patients mean age was 60.0±10.3 years, 74% were male, 4894 (61%) had a prior history of coronary artery disease (CAD), 2445 (30%) of stroke and 1990 (25%) patients had peripheral arterial disease (PAD) or aneurysm abdominal aorta (AAA). There were 1544 vascular events and 1792 deaths during a median follow up of 8.2 (interquartile range (IQR) 4.5–12.2) years and a total follow up of 68699 person-years. For every 1 mmol/L increase in remnant cholesterol, risk for recurrent vascular events was increased in patients with manifest vascular disease (HR 1.17; 95% CI 1.05–1.31 for the composite endpoint (figure 1)). There was no effect for all-cause mortality in this population. Furthermore, there was no significant effect modification of HDL-C and the presence of T2DM on the relation between remnant cholesterol and vascular endpoints.

Figure 1

Conclusion

In patients with clinically manifest arterial disease plasma remnant cholesterol confers an increased risk for recurrent vascular events, independent of traditional risk factors such as LDL-C levels.
4947Association between secondhand smoke exposure and diabetes mellitus in 131,724 Korean never smokers using self-reported questionnaire and cotinine: gender differences
Authors: Kim B J , Kim J H , Seo D C , Kim B S , Kang J H
Published: October 2019

Background

No study has reported the relationship between secondhand smoke (SHS) exposure and diabetes mellitus in self-reported never-smokers verified by nicotine metabolite.

Purpose

The aim of this study is to determine the relationship between SHS exposure and diabetes mellitus in self-reported and cotinine-verified never-smokers.

Methods

A total of 131,724 self-reported and cotinine-verified never-smokers (42,681 men; age 35.0±7.1 years) enrolled in Kangbuk Samsung Health Study (KSHS) and Kangbuk Samsung Cohort study (KSCS) between 2011 and 2016 were included. Cotinine-verified never-smoker was defined as individuals having urinary cotinine <50 ng/mL. SHS exposure was defined as having experienced passive smoking indoors at home or the workplace. Diabetes mellitus was defined as having a fasting blood glucose level of ≥7.0mmol/L, hemoglobin A1C ≥6.5% or taking anti-diabetic medication(s).

Results

The frequency of diabetes mellitus in the overall population was 1.6%; the frequency in males was higher than that in females (2.2% versus 1.3%, p<0.001). The overall frequency of SHS exposure was 22.9%, with rates of 27.6% for males and 20.7% for females (p<0.001). The frequency of diabetes mellitus in group with SHS exposure was higher than that in group without SHS exposure only in females (1.8% versus 1.2%, p<0.001 for females; 2.2% versus 2.2%, p=0.956 for males). There was significant gender interaction for the relationships between SHS exposure and diabetes mellitus (p for interaction <0.001). A multivariate regression model was adjusted for the baseline variables including age, waist circumference, body mass index, frequency of alcohol drinking and vigorous exercise, systolic blood pressure, blood urea nitrogen, creatinine, uric acid, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, and hsCRP. Only in females, SHS exposure was significantly associated with diabetes mellitus (odds ratio [95% confidence interval], 1.40 [1.20, 1.65] for females; 1.00 [0.85, 1.19] for males). Higher frequency and longer duration of SHS exposure were also significantly associated with diabetes mellitus (p<0.001) for all trends). In particular, females with SHS exposure of ≥1 hours/day, ≥3 times/week, and ≥10 years increased the risk of diabetes mellitus 51–64% above that for those without SHS exposure (1.64 [1.25, 2.13], 1.51 [1.21, 1.87], and 1.59 [1.30, 1.95], respectively.

Conclusions

This study showed that the SHS exposure in females was significantly associated with diabetes mellitus in self-reported never-smokers verified by urinary cotinine and this association was proportional to the frequency and duration of SHS exposure. These findings suggest the importance of banning smoking in the home and public to reduce the risk of diabetes mellitus.

Acknowledgement/Funding

None
4950Adiposity gain from 17 to 25 years has a substantial effect on cardiac structure, independent of haemodynamics
Authors: Park C M , Taylor H , Jones S , Rapala A , Williams S , Howe L , Fraser A , Chaturvedi N , Hughes A D
Published: October 2019

Introduction

Body mass index (BMI) is independently associated with increased left ventricle mass (LVM) and remodeling in children. However associations from adolescence to emerging adulthood are unknown.

Purpose

To investigate associations between the change (Δ) in BMI to Δ in cardiac structure from 17 to 25 yrs using a large population-based sample of echocardiography in youth, and to explore the role of possible haemodynamic mediators.

Methods

901 participants (61% female) underwent echocardiography, anthropometry and sitting blood pressure (BP) measurements aged 17 yrs and had repeated measures aged 25 yrs. BMI, LVM, concentricity0.67 (LVM/end-diastolic volume0.67), total arterial compliance (TACI), peripheral resistance (TPR) and effective arterial elastance (Ea) were calculated. Regression analysis was used to investigate associations between ΔBMI and ΔLVM indexed to height2.7 (ΔLVMI) and Δconcentricity0.67.

Results

From 17 to 25 yrs BMI increased by 2.05±2.1 g/m2 in males and 1.80±3.1 kg/m2 in females, LVMI increased by 3.10±6.2g/m2.7 and 2.01±6.0g/m2.7 and concentricity0.67 increased by 0.91±1.2g/ml0.67 and 0.03±1.1g/ml0.67. ΔBMI was associated with ΔLVMI and Δconcentricity0.67 independently of age, socioeconomic status (SES) and smoking status. Haemodynamic measures did not substantially mediate these associations.

Table 1 ΔLVMI (g/m2.7) ΔConcentricity0.67 (g/m0.67) Males Females Males Females Model 1: Age, SES and smoking @25 0.78±0.15** 0.53±0.08** 0.12±0.03** 0.083±0.02** + ΔSystolic BP (mmHg) 0.68±0.16** 0.46±0.09** 0.10±0.03* 0.069±0.016** + ΔDiastolic BP (mmHg) 0.83±0.16** 0.47±0.08** 0.12±0.03** 0.074±0.015** + ΔMean Arterial Pressure (mmHg) 0.77±0.17** 0.46±0.08** 0.11±0.03** 0.069±0.015** + ΔPulse Pressure (mmHg) 0.72±0.15** 0.54±0.08** 0.11±0.03** 0.083±0.015** + ΔTACI (ml/m2/mmHg) 0.68±0.16** 0.53±0.08 0.12±0.03** 0.091±0.015** + ΔTPR (mmHg/min/L) 0.76±0.17** 0.65±0.08** 0.10±0.03* 0.072±0.016** + ΔEa (mmHg/ml) 0.73±0.17** 0.54±0.08** 0.11±0.03** 0.083±0.015** Data are β±SE. *p<0.01, **p<0.0001.

Discussion

BMI gain from adolescence to emerging adulthood has a substantial effect on cardiac structure, independent of haemodynamics. These findings highlight the importance of weight control in early adulthood for good cardiovascular health.

Acknowledgement/Funding

BHF
4971Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension: a new elephant in the cathlab
Authors: Kempny A , Dimopoulos K , Fraisse A E , Diller G P , Price L C , Rafiq I , McCabe C , Wort S J , Gatzoulis M A
Published: October 2019

Background

Pulmonary vascular resistance (PVR) is an essential parameter assessed during cardiac catheterization. It is used to confirm pulmonary vascular disease, to assess response to targeted pulmonary hypertension (PH) therapy and to determine the possibility of surgery, such as closure of intra-cardiac shunt or transplantation. While PVR is believed to mainly reflect the properties of the pulmonary vasculature, it is also related to blood viscosity (BV).

Objectives

We aimed to assess the relationship between measured (mPVR) and viscosity-corrected PVR (cPVR) and its impact on clinical decision-making.

Methods

We assessed consecutive PH patients undergoing cardiac catheterization. BV was assessed using the Hutton method.

Results

We included 465 patients (56.6% female, median age 63y). The difference between mPVR and cPVR was highest in patients with abnormal Hb levels (anemic patients: 5.6 [3.4–8.0] vs 7.8Wood Units (WU) [5.1–11.9], P<0.001; patients with raised Hb: 10.8 [6.9–15.4] vs. 7.6WU [4.6–10.8], P<0.001, respectively). Overall, 33.3% patients had a clinically significant (>2.0WU) difference between mPVR and cPVR, and this was more pronounced in those with anemia (52.9%) or raised Hb (77.6%). In patients in the upper quartile for this difference, mPVR and cPVR differed by 4.0WU [3.4–5.2].

Adjustment of PVR required

Conclusions

We report, herewith, a clinically significant difference between mPVR and cPVR in a third of contemporary patients assessed for PH. This difference is most pronounced in patients with anemia, in whom mPVR significantly underestimates PVR, whereas in most patients with raised Hb, mPVR overestimates it. Our data suggest that routine adjustment for BV is necessary.
4974Waitlist outcomes for Eisenmengers patients listed for bilateral sequential lung transplant or heart-lung transplant
Authors: Kearney K , Bart N , Khush K , Hayes D , Keogh A
Published: October 2019

Background

Eisenmenger's syndrome (ES) is the end-stage of a longstanding intracardiac shunt, commonly an atrial septal defect (ASD) or ventricular septal defect (VSD). Transplantation is the final option to address the pulmonary hypertension and right heart failure that results. Both combined heart-lung (HLTx) and bilateral sequential lung transplantation (BSLT) have been performed for ES. Overall, BSLT are performed more commonly than HLTx because of donor organ availability. We postulated that ES patients would have higher waitlist mortality and longer time to transplant compared to patients listed for other indications, and BSLT patients would have reduced waitlist mortality and reduced time to transplant compared to HLTx based on availability.

Aim

This study compared waitlist outcomes between ES ASD, ES VSD and all patients listed for BSLT or HLTx.

Methods

We analysed the Organ Procurement and Transplant Network (OPTN) database for all patients listed for BSLT or HLTx between October 1, 1987 and March 31, 2018. Mood's median test was used for all tests of significance.

Results

Table 1 summarises the results of the analysis. A total of 56,698 patients were on the waitlist for BSLT for all aetiologies, which included 176 ES ASD patients and 156 ES VSD patients. A total of 3231 patients were on the waitlist for HLTx for all aetiologies, which included 89 ES ASD and 176 ES VSD patients. Median time to transplant was significantly longer for all ES patients on the waitlist for BSLT or HLTx compare to patients listed for other indications. Comparing time to transplant for BSLT to HLTx for either ES ASD or VSD did not reach statistical significance. Waitlist mortality was substantially higher for all ES patients regardless whether they were listed for BSLT or HLTx compared to patients listed for other indications.

Table 1 ES ASD ES VSD All patients BSLT HLTx BSLT HLTx BSLT HLTx Total number of patients listed 176 89 156 176 56698 3231 Transplanted 58 (33.0%) 38 (42.7%) 41 (25.8%) 78 (44.3%) 36441 (64.3%) 1229 (38.0%) Median time to transplant in days 330 (24 to 2723)* 431 (11 to 4527)$ 517 (10 to 2345)# 292 (16 to 2399)& 99 (0 to 6592) 174 (0 to 3606) p=0.54 p=0.08 *p≤0.001, #p=≤0.0001 $p=0.000, &p=0.003 Wait list mortality 27 (15.3%) 25 (28.1%) 23 (14.5%) 46 (26.1%) 2366 (4.2%) 371 (11.5%)

Conclusion

Our analysis identified longer waitlist time and higher mortality for all ES patients listed for BSLT or HLTx in the United States. These findings indicate current listing methods and prognostication place the ES population at disadvantage for thoracic transplantation.
4975Efficacy of pulmonary hypertension-targeted drugs for severe chronic thromboembolic pulmonary hypertension
Authors: Inami T , Kataoka M , Itoh J , Takeuchi K , Kikuchi H , Goda A , Soejima K , Satoh T
Published: October 2019

Background

High pulmonary vascular resistance (PVR) is a risk factor for reperfusion pulmonary edema by balloon pulmonary angioplasty (BPA). It has not been clarified whether improvement of hemodynamics by pulmonary hypertension (PH)-targeted drugs before BPA session is effective clinically. Severe chronic Thromboembolic pulmonary hypertension (CTEPH) patients have small vessel disease like pathological findings of idiopathic pulmonary arterial hypertension.

Objectives

The purpose of this study was to investigate the efficacy of PH-targeted drugs for patients with CTEPH before BPA.

Methods

This study included consecutive 147 CTEPH patients treated with PH-targeted drugs before BPA. All patients were divided into 2 groups such as severe group (PVR >12.5 wood units) and non-severe group (PVR <12.5 wood units).

PVR were compared between baseline and after treated with PH-targeted drugs. All data were expressed by median [25thpercentile-75thpercentile].

Results

The median age and male were 66 [53–74] years old and 42. Numbers of patients treated with phosphodiesterase V inhibitors, endothelin receptor antagonists and riociguat were 84 (57%), 92 (63%), and 43 (29%), respectively. PVR significantly decreased after treated with PH-targeted drugs in two groups (severe group: 16.3 [13.7–20.0] to 10.0 [7.2–13.3] wu, P<0.0001; non-severe group: 6.8 [4.9–8.9] to 5.7 [3.5] to 7.8, P<0.001). Changes of PVR in severe group were significantly larger than in non-severe group (−6.9 [−8.5 to −3.2] vs. −0.7 [−2.4 to 0.7], P<0.0001).

There was no significant difference in efficacy of BPA and numbers of dilated vessel between two groups (severe vs. non-severe group after BPA; PVR: 2.7 [1.9–3.5] vs. 2.1 [1.7–3.1] wu, P>0.05; numbers of dilated vessel: 18 [14–21] vs. 16 [10–21], P>0.05)

Conclusions

PH-targeted drugs may improve hemodynamics for severe CTEPH more effectively.
5033Effect of intraoperative hybrid surgery on incidence of CPB-AKI in children Congenital heart disease patients: a propensity score matched study
Authors: Guo S , Liu J , Duan X
Published: October 2019

Objective

Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a frequent complication after cardiac surgery in children patients. Intraoperative hybrid cardiac surgery (IPH) is a new technique which needed contrast administration. Contrast was also reported to induce AKI. Therefore, we hypothesized that the IPH would increase the occurrence of CPB-AKI in children Congenital heart disease patients.

Methods

A total of 1509 consecutive patients (age≤3 year) undergoing on-pump cardiac surgery were enrolled in this study from November, 2017 to May, 2018. Multivariate logistic regression was performed in this retrospective study. Propensity score matched analysis was applied for confounding factors. Perioperative and interoperative characteristics and outcomes in IHP group with or without AKI are compared. CPB-AKI was determined by serum Creatinine (SCr) increased twice as much as preoperative or need dialysis within 7 days postoperatively.

Result

IPH was found to be an independent risks factor in the development of CPB-AKI development (OR 2.798, 95% CI 1.823–4.296, p<0.001). Other independent risk factors for CSA-AKI were: CPB time >100 min (OR 2.068, 95% CI 1.521–2.811, P<0.001), weight≤5 kg (OR 3.409, 95% CI 2.192–5.302, P<0.001). Cohort analysis revealed that AKI occurred more frequently in the IPH group before and after matching (30.4% vs. 12.97%, P<0.001; 32.2% vs. 18.3% %, P=0.015, respectively). IPH group also had higher prolonged length of postoperative stay in the hospital (11 vs 7.5, P<0.001; 10.9 vs 7.7, p=0.01), and higher length of mechanical ventilation support (27 vs 10, P<0.001; 26 vs 16, <0.001) before and after matching. Perioperative and interoperative characteristics and outcomes of patients with or without AKI are compared. Only CPB duration was an independent factor for AKI in IPH group.

Comparison of outcomes Variablesa Without PSM PSM IPH group (n=128) No IPH group (n=1381) P IPH group (n=117) No IHP group (n=117) P Median LOSPHOS (days) 11 (8.0, 13.0) 7.4 (6.5, 10.6) <0.001d 11.0 (8.0, 13.0) 7.5 (6.5, 14.7) <0.001d Median LOSMV (hours) 27 (19.0, 71.0) 10 (5, 24) <0.001d 27.0 (18.0, 71.0) 17 (3.0, 49.0) <0.001d Overall mortality n (%) 0 (0%) 14 (1.0%) 0.252c 0 (0%) 2 (1.7%) 0.156c Dialysis, n (%) 3 (2.4%) 23 (1.6%) 0.573c 3 (2.6%) 6 (2.6%) 1.000c AKI, n (%) 39 (30.4%) 176 (12.7%) <0.001b 37 (31.6%) 21 (17.9%) 0.015b aLOSPOHOS: length of postoperative stay in hospital; LOSMV: length of mechanical ventilation; CPB: cardiopulmonary bypass. bχ2 test. cFisher's exact test. dRank sum test.

Study flow

Conclusion

IPH was associated with a higher incidence of CPB-AKI.
5105A deep neural network predicts atrial fibrillation from normal ECGs recorded on a smartphone-enabled device
Authors: Galloway C , Treiman D , Shreibati J , Schram M , Karbaschi Z , Valys A , Albert D , Stavrakis S
Published: October 2019

Background

Electrocardiographic predictors of atrial fibrillation (AF) from a non-AF ECG–such as p wave abnormalities and supraventricular ectopy–have been extensively documented. However, risk prediction tools for AF utilize little if any of the wealth of information available from the ECG. Better AF prediction from the ECG may improve efficiency of screening and performance of AF risk tools. Deep learning methods have the potential to extract an unlimited number of features from the ECG to improve prediction of AF.

Purpose

We hypothesize that a deep learning model can identify patterns predictive of AF during normal sinus rhythm. To test the hypothesis, we trained and tested a neural network to predict AF from normal sinus rhythm ambulatory ECG data.

Methods

We trained a deep convolutional neural network to detect features of AF that are present in single-lead ECGs with normal sinus rhythm, recorded using a Food and Drug Administration (FDA)-cleared, smartphone-enabled device. A cohort of 27,526 patients with at least 50 ECGs recorded between January 7, 2013, and September, 19, 2018, and the FDA-cleared automated findings of Normal and Atrial Fibrillation associated with those ECGs, were used for model development. Specifically, we trained the deep learning model on 1,984,581 Normal ECGs from 19,267 patients with 1) only Normal ECG recordings, or 2) at least 30% ECGs with AF. Of the 27,526 patients, an internal set of 8,259 patients with 841,776 Normal ECGs was saved for testing (validation).

Results

Among 8,259 patients in the test set, 3,467 patients had at least 30% of their ECGs with an automated finding of AF. When the deep learning model was run on 841,776 Normal ECGs, it was able to predict whether the ECG was from a patient with no AF or with 30% or more AF, with an area under the curve (AUC) of 0.80. Using an operating point with equal sensitivity and specificity, the model's sensitivity and specificity were 73.1%. Using an operating point with high specificity (90.0%), the model's sensitivity was 48.0%. When the model was applied to a randomly-selected, broader cohort of 15,000 patients (at least 50 ECGs recorded, any amount of AF), a positive, non-linear relationship between neural network output and AF burden per patient was observed (Figure).

Model Output vs AF Burden Per Patient

Conclusions

A deep learning model was able to predict AF from ECGs in normal sinus rhythm that were recorded on a smartphone-enabled device. The use of deep learning, if prospectively validated, may facilitate AF screening in patients with paroxysmal disease or warn patients who are at high risk for developing AF.

Acknowledgement/Funding

AliveCor
5193Percutaneous coronary intervention provided better result than optimal medical therapy in patients with chronic total occlusion: a metanalysis
Authors: Khanra D , Duggal B , Basu Ray I , Kumar B , Walia R
Published: October 2019

Background

Studies comparing the outcome of percutaneous coronary intervention (PCI) along with optimal medical therapy (OMT) versus OMT alone in treatment of chronic total occlusion (CTO) are limited by observational design, variable follow up period, diverse clinical outcome, high drop-out and cross-over rate. Prematurely terminated DECISION CTO trail and the promising result of the most recent EUROCTO trial still left the quest unanswered. Previous metanalysis on the present context were restricted to studies with propensity-matched analysis only and did not incorporate the recent randomized trials.

Purpose

This study aims to conduct a meta-analysis of published data of observational as well as randomized studies comparing long term outcomes of PCI+OMT versus OMT alone.

Methods

The present protocol is registered in PROSPERO. PubMed, Embase and Cochrane databases were systematically reviewed. Fourteen studies meeting criteria were included in the meta-analysis. The Cochrane Risk of Bias scale was used to appraise the overall quality of the studies. Revman 5.3 software was used to analyse the data and random-effects model with inverse variance method was undertaken. R packages were used for assessment of bias and metaregression.

Results

Baseline parameters of both the groups were comparable. Major adverse cardiovascular events (MACE) which comprises of cardiac death, myocardial infarction, stroke, and unplanned revascularization [Figure 1] were significantly lower in the PCI+OMT group. (RR: 0.77; 95% CI: 0.61 to 0.97; P≤0.ehz746.00521; I2=85%). High heterogeneity was partially (14%) explained by age factor. However study design, follow up duration, LVEF, presence of TVD did not attribute significantly to heterogeneity, in isolation or any combination in metregression model. All cause mortality and cardiac death [Figure 2, 3 respectively] were significantly lower in the PCI+OMT group (P=0.29, p=0.63, respectively). Myocardial infarction (P=0.25) and stroke rates (P=0.15) were lower in the PCI+OMT group, however they did not reach statistical significance. Unplanned revascularization (of any vessel) showed a higher trend in the PCI+OMT group, without reaching statistical significance (P=0.46, I2=88%).

Conclusion

PCI of CTO is rewarded with better long term outcome, in terms of MACE and all-cause mortality but limited to greater unplanned revascularization.

Acknowledgement/Funding

None
5209Stereotactic radioablation of ventricular tachycardia guided by direct integration of 3D electroanatomic mapping: development and validation of a new method
Authors: Sramko M , Cvek J , Peichl P , Knybel L , Kautzner J
Published: October 2019

Background

Stereotactic body radiotherapy (SBRT) has emerged as a promising bailout therapy for recurrent ventricular tachycardia (VT) in patients with failed radiofrequency catheter ablation. However, SBRT can function only if the ablation target is precisely identified.

Purpose

We sought to develop a novel method for direct integration of electroanatomic mapping (EAM) data to an SBRT work station for radioablation of VT.

Methods

Candidates for SBRT were patients with recurrent, drug-resistant VT who underwent ≥2 previous radiofrequency catheter ablations (CARTO 3, Biosense-Webster, Diamond Barr, CA) and continued to have inducible clinical VT or clinical recurrences of VT. At the end of the last catheter ablation, the operators performed additional EAM to obtain landmarks for image registration: aorta with the ostium of the left main coronary artery or left atrium with ostia of pulmonary veins. Correct position of the catheter at the landmark was verified by intra-cardiac echocardiography. VT substrate–defined by a combination of voltage mapping, pace mapping, and detection of local abnormal ventricular activity and/or late potentials was marked by custom tags as a target for SBRT. The CARTO maps were exported and converted to 3D shells with encoded EAM properties (VTK format). On the following day, the patients underwent contrast-enhanced computer tomography (CT) of the heart. Using 3D Slicer software 4.10 (slicer.org), the EAM-derived anatomical structures with the marked ablation target were projected onto CT images by landmark registration with manual correction. The CT study with the projected contours of the EAM-detected ablation target was imported as a DICOM-RT format into a stereotactic radiotherapy planning work station (Multiplan 3.5, Accuray, Sunnyvale, CA). SBRT was performed using a contemporary radiosurgery system with real-time motion tracking of the ablation target (CyberKnife 8.5, Accuray). The prescribed (X-ray) dose was 25 Gy during a single session.

Results

The proposed work-flow was verified in four patients with structural heart disease and drug-resistant VT who had 2–3 unsuccessful radiofrequency catheter ablations (all males; age: 68–78 years; left ventricular ejection fraction: 20–25%; ischemic/non-ischemic cardiomyopathy: 2/2). Integration of EAM data with CT was achieved in all patients. None of them experienced acute radiotoxicity after SBRT. At a follow-up checkup at one month, three of the patients remained arrhythmia-free. One patient experienced VT recurrence one day after SBRT, but no VTs recurred during the following month of follow-up.

Figure 1

Conclusions

This is the first report demonstrating the feasibility of SBRT of VT guided by direct integration of EAM. The proposed method is best suited as a bailout procedure for patients with previously failed catheter ablation.

Acknowledgement/Funding

M.S. was supported by ESC Research Fellowship 2018