bluuebunny/crossref_metadata_2025 huggingface dataset:
285Arrhythmias after transcatheter closure of persistent foramen ovale are related to the type and size of the implanted device
Authors: Komar M , Przewlocki T , Prochownik P , Gancarczyk U , Sobien B , Libiszewska N , Skoczek A , Olszowska M , Podolec P
Published: October 2019

Transient supraventricular arrhythmias may occur in patients following persistent foramen ovale (PFO) closure. Therefore, the aim of the study was to prospectively perform 24-hour ECG monitoring to assess the electrocardiographic effects of transcatheter closure of PFO depending on the type of implanted devices.

Material and methods

351 consecutive adult subjects (196 F, 155M; mean age: 40.9±15.3) were enrolled into the study to undergo PFO closure with an Amplatzer Septal Occluder - ASO (157 pts: 117 occluders – size 25; 40 pts – size 30), and Cardia device (194 pts: 163 occluders – size 25; 31 – size 30).

Holter monitoring was performed on all patients before, at 1 and 12 months after the procedure.

Results

The success rate of PFO closure was 97.8% (351 cases from 359 qualified in TEE), in 8 cases the PFO tunnels were too small to be forced by a catheter, in one case the PFO device caused an injury of the septum and an ASD Amplatzer device was implanted. During the procedure in 3 (0.85%) cases transient supraventricular arrhythmia and in 1 (0.28%) case bradycardia to 27 bpm occurred.

At 1 month: in 7 (2%) pts changes in AV conduction occurred: 1 pt (0.28%) had complete AV dissociation, 6 (1.7%) pts intermittent first degree AV block; paroxysmal atrial fibrillation (pAF) occurred in 6 (1.7%) pts, 2 of whom had pAF prior to closure.

A significant increase in the number of SVE premature beats/24h was noted at 1 month after the procedure: 1167.9±409 (27–9976) compared to baseline data 60.2±44 (0–601) (p<0.0001), at 12 months the SVE number decreased to 57.2±51 (7–752) and did not differ significantly from the baseline data.

There was no change in the mean number of ventricular arrhythmias/24h after the procedure.

There was a significant correlation between SVE premature beats/24h at 1 month after the procedure and device size (p<0.001 r=97211).

Pts with ASO device had a significantly higher number of SVE ectopy at 1 month after PFO closure (19123.9±70) compared to pts with Cardia device (811.9±324), p<0.0001.

Conclusions

1. Transcatheter closure of PFO is associated with a transient increase in supraventricular premature beats and a small risk of AV conduction abnormalities and paroxysmal atrial fibrillation in the early follow-up. There is regression of periprocedural arrhythmias after 12 months of PFO closure.

2. Transcatheter closure of PFO with Cardia device is related to a lower risk of supraventricular arrhythmias in the early follow-up.

3. The smaller device is implanted the lower risk of periprocedural arrhythmias is expected.
297Seeing is believing: the feasibility and acceptability of using wearable cameras to enhance self-management of heart failure
Authors: Cartledge S , Rogerson M , Singh T K R , Huynh Huu V , Phung D , Gurrin C , Neil C , Ball K , Maddison R
Published: October 2019

Introduction

For people with heart failure (HF), self-management (e.g., adhering to prescribed medication, management of fluid restrictions and daily weighing) and dietary management is critical for disease management. The rise of technologies (mobile phones, wearable cameras) for healthcare use offers potential support for people to better manage their disease. We aimed to test the feasibility and utility of wearable cameras for identifying self-management practices and to determine if these images can be used to enhance self-management in people with HF.

Methods

Participants wore the “narrative clip”, a small wearable camera for one month during waking hours; still images were taken every 30 seconds. Using state-of-the-art artificial intelligence techniques, we investigated automated image analysis of daily life activities to determine the potential of these systems to identify four categories of human activities: medication management, dietary intake, meal preparation and physical activity. Participants also completed a semi-structured questionnaire about acceptability and feasibility.

Results

30 participants (mean age 73.6 years, 60% male) with HF NYHA Class II-III were recruited. A total of 629,603 images were available for analysis. Higher order analyses were conducted to determine precision of identifying correct images for the pre-defined self-management categories. Precision of identifying the correct images was highest in dietary intake (average 49%, range 13–94%) followed by meal preparation (average 40%, range 1–99%) and physical activity (average 31%, range 0–95%). Medication management had the lowest precision (average 6%, range 6–22%). Manual review of images revealed substantial periods of sedentary time, typically paired with screen time (watching television, playing cards on a computer). All participants agreed the camera was easy to use and felt they had privacy when using the camera. The majority of participants felt comfortable wearing the camera (93%) and thought this technique will help people with HF in the future (93%).

Conclusions

Images from wearable cameras provided rich contextual data to better understand the lived experiences of people with HF and the device was acceptable to participants. Automated machine learning tools require more annotated data for training to enhance precision, which will be achieved via further annotation, fine-tuning and retraining the data analysis model. Despite these challenges, the data collected can be used as an adjunct to traditional data collection methods such as self-report. Once data analysis techniques are refined, objective data from wearable cameras may also prove useful for nurses to provide tailored education for self-management.

Acknowledgement/Funding

Heart Foundation Vanguard Grant, Australia (101348)
410Heart failure risk stratification and efficacy of dapagliflozin in patients with type 2 diabetes mellitus
Authors: Berg D , Wiviott S , Scirica B , Gurmu Y , Mosenzon O , Murphy S , Bhatt D , Leiter L , McGuire D , Wilding J , Johansson P , Langkilde A , Raz I , Braunwald E , Sabatine M
Published: October 2019

Background

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure (HF). Treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors reduces the risk of hospitalization for HF (HHF) in patients with T2DM.

Purpose

To develop and validate a practical, multivariable clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with an SGLT2 inhibitor.

Methods

We developed a clinical risk score for centrally-adjudicated HHF using independent clinical risk indicators of HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53. Candidate variables were assessed using multivariable Cox regression and independent clinical risk indicators achieving statistical significance of p<0.001 were included in the risk score and given weights proportional to the regression coefficients. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58. Discrimination was assessed using Harrell's c-index. The relative and absolute risk reductions in HHF with the SGLT2 inhibitor dapagliflozin were assessed by baseline HHF risk.

Results

The 5 independent clinical risk indicators were prior heart failure, atrial fibrillation, coronary artery disease, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio (UACR) (Figure, left). A simple integer-based scheme using these predictors identified a strong >16-fold gradient of HHF risk (p-trend <0.001) in both the derivation and validation cohorts, with c-indices of 0.81 and 0.78, respectively. Whereas relative risk reductions were similar across the risk score (25–34%), absolute risk reductions were greater in those at higher baseline risk (interaction p-value for absolute risk reduction <0.01), with high-risk (2 points) and very high-risk patients (≥3 points) having 1.5% and 2.7% absolute risk reductions in HHF at 4 years with dapagliflozin, translating into NNTs of only 65 and 36, respectively (Figure, right).

Conclusion(s)

Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater benefit from treatment with the SGLT2 inhibitor dapagliflozin.

Acknowledgement/Funding

SAVOR-TIMI 53 and DECLARE-TIMI 58 were sponsored by AstraZeneca.
483Blood pressure and white matter lesions in patients with atrial fibrillation
Authors: Aeschbacher S , Blum S , Meyer-Zurn C , Vischer A S , Meyre P , Rodondi N , Beer J H , Moschovitis G , Moutzouri E , Sticherling C M , Wurfel J , Bonati L H , Osswald S , Conen D , Kuhne M
Published: October 2019

Background

Hypertension (HTN) is one of the most common cardiovascular risk factors in patients with atrial fibrillation (AF). As a potential risk factor for cerebral white matter lesions (WML), HTN might explain the increased risk of cognitive dysfunction in AF patients.

Methods

In a multicenter cohort study of patients with documented AF in Switzerland, systolic and diastolic blood pressure (SBP, DBP) was measured up to three times in a supine position and the mean was calculated. HTN was defined as controlled, when SBP was <140 and DBP <90 mmHg with treatment, and uncontrolled when SBP was ≥140 or DBP ≥90 mmHg with treatment. All patients underwent brain magnetic resonance imaging. Volumes of WML were assessed and graded using the Fazekas scale. A Fazekas score of ≥2 was defined as moderate or severe WML. Multivariable adjusted regression models were used to assess the association between BP and WML.

Results

Overall, 1738 patients were enrolled in this cross-sectional analysis (mean age 73 years, 73% males). Mean BP was 135/79 mmHg, 69% had a history of HTN. Any WMLs were found in 99% of the patients and 54% had at least moderate WMLs. The prevalence of Fazekas ≥2 was 47%, 50% and 61% among AF patients with SBP <120, 120–140 and ≥140mmHg (p<0.001), respectively. Volumes of WMLs significantly increased across the same SBP categories (2943, 3512 and 4988 mm3, p<0.001). Among patients with normotension, controlled and uncontrolled HTN, moderate or severe WMLs were present in 173 (42.5%), 345 (55%) and 307 (61%), respectively. SBP was associated with Fazekas ≥2 and WML volume after multivariable adjustment (Table). Compared to normotension, both controlled and uncontrolled HTN were significantly associated with higher WML volume (Table).

Association between blood pressure and white matter lesions Blood pressure Fazekas ≥2 OR (95% CI) Volume WML β-coefficient (95% CI) <120 mmHg Ref Ref 120–140 mmHg 1.17 (0.88; 1.55) 0.14 (−0.01; 0.30) ≥140 mmHg 1.49 (1.11; 2.00) 0.28 (0.12; 0.43) Continuous, per SD 1.20 (1.09; 1.36), p<0.001 0.12 (0.06; 0.18), p<0.001 Normotension Ref Ref Treated hypertension 1.26 (0.94; 1.68), p=0.12 0.22 (0.07; 0.38), p=0.005 Treated, uncontrolled hypertension 1.52 (1.13; 2.05), p=0.005 0.38 (0.21; 0.54), p<0.001 Regression analyses were adjusted for age, sex, BMI, smoking status, stroke, diabetes, coronary heart disease, AF type, and antihypertensive treatment. One standard Deviation (SD) of SBP = 18 mmHg. Volume of WML was log-transformed.

Conclusion

Moderate or severe cerebral WMLs are highly prevalent in AF patients and strongly associated with SBP. Our data suggests that optimal treatment of HTN might play an essential role in preventing WMLs.

Acknowledgement/Funding

Swiss National Science Foundation
P301Preserved global longitudinal strain predicts left ventricular reverse remodeling one year after edge-to-edge mitral valve repair in functional mitral regurgitation
Authors: Papadopoulos K , Ikonomidis I , Chrissoheris M , Chalapas A , Kourkoveli P , Chrysohoou C , Avgeropoulou A , Parissis J , Vardas P , Spargias K
Published: October 2019

Background

Percutaneous edge-to-edge mitral valve repair (PMVR) has emerged as an effective treatment modality for high surgical risk patients with severe functional mitral regurgitation (FMR). Novel echocardiographic parameters, such as deformation imaging and their predictive significance have not been analyzed in this group of patients.

Purpose

The purpose of this study is to identify echocardiographic predictors of response in patients with FMR undergoing PMVR.

Methods

We retrospectively analyzed 44 consecutive patients with ischemic or dilated cardiomyopathy, reduced ejection fraction and severe functional MR (FMR), aged 71±9 years, 71% males, LVEF 30.9±8.7%, mitral valve effective regurgitant orifice area (EROA)>20mm2, regurgitant volume (RV) >30ml and logistic EuroSCORE 22±14.7%. At baseline and 1-year after PMVR we assessed echocardiographic parameters such as LV longitudinal strain (LVGLS) and peak left atrial longitudinal strain (PALS) using speckle tracking echocardiography, LV end-systolic and end-diastolic volumes (LVESV, LVEDV), LA volume, MR severity by Doppler echocardiography along with BNP levels, NYHA class and 6 minute walking distance.

Results

One year after edge-to-edge repair there was a significant reduction of MR (74.2% had mild to moderate MR, 22.6% moderate-to-severe MR and 3.2% severe MR) and BNP levels (933±943pg/ml to 669±824pg/ml), improvement of NYHA class (3.11±0.55 to 2.0±0.6, P<0.05) and increase of the 6 minute walking distance (251±141 to 296±148m, P<0.05). LA volume was reduced (132.5±62.1ml to 115.2±57.7ml) and PALS was improved (6.89±3.47 to 7.94±5.27) (P<0.05 for all comparisons). Baseline LVGLS did not change significantly post intervention (−8.8±4.1 vs. −8.8±3.9, P=0.7) but the baseline value predicted the percentage difference in LVEDV (r=−0.61, P<0.01), LVESV (r=−0.47, P=0.03), BNP (r=0.45, P=0.04) and NYHA class (r=0.63, P<0.01). The best reverse LV remodeling was found in patients with GLS better than −10% and the trend was that the better the GLS the greater the LVEDV and LVESV reduction post-intervention. Additionally, patients with GLS between −10% and −5% had the largest improvement in BNP (P<0.05) and NYHA class (P=0.005).

Conclusions

Edge-to-edge repair is effective in reducing MR in patients with severe functional MR and has a positive impact in patients' clinical status at one year follow up. A preserved LVGLS seems to be a good predictor of reverse modeling and clinical improvement post intervention.
P585Intra left ventricular hemodynamics assessed using 4D flow MRI in the patient with left ventricular thrombus
Authors: Sakakibara T , Suwa K , Kaneko Y , Akita K , Sato R , Mogi S , Naruse Y , Ohtani H , Saitoh T , Saotome M , Urushida T , Maekawa Y
Published: October 2019

Background

Early detection of left ventricular mural thrombus (LVT) in patients with reduced ejection fraction (EF) is crucial in prevention of arterial embolism. 3D-cine phase-contrast magnetic resonance imaging (4D flow MRI) can visualize the intra-LV vortex flow in diastole and quantify the maximum flow velocity (Vmax) at the apex. it remains, however, unknown whether 4D flow MRI is useful for detecting LVT.

Purpose

The purpose of our study is to examine the intra-LV vortex formation and flow velocity in patients with severe LV dysfunction using 4D Flow MRI, and to compare differences in intra-LV flow dynamics between patients with and without LVT. We also examined the diagnostic accuracy to detect LVT by 4D flow MRI.

Methods

Twenty-nine patients with impaired LV function (LVEF 25.8±7.4%, 62.5±12.3 years old, 24 males, 11 with ischemic cardiomyopathy, 9 with LVT) underwent 4D flow MRI from January 2012 to August 2018 in our institution. Intra-LV vortex size was evaluated as vortex/LV area ratio by streamline imaging (Figure 1). The diagnostic accuracy to predict LVT by vortex size and Vmax at the apex was determined by ROC analysis.

Results

The vortex was smaller (vortex/LV area ratio; 30.6±7.0% vs. 45.1±9.0%, p<0.05) and Vmax at the apex was lower (0.20±0.04 m/s vs. 0.28±0.09 m/s, p=0.013) in patients with LVT compared to those without LVT. The AUC was 0.789 for Vmax (cut-off value=0.226 m/s, sensitivity=0.889, specificity=0.650) and was 0.900 for vortex/LV area ratio (cut-off value=34.7%, sensitivity=0.889, specificity=0.850).

Figure 1

Conclusion

The smaller size of intra-LV vortex and the lower flow velocity at the LV apex may have association with LVT formation in patients with reduced EF. 4D flow MRI might be useful to predict LVT formation. Large scale longitudinal study is warranted to evaluate the incidence of LVT in the patients with lower flow velocity.

Acknowledgement/Funding

None
P624The prognostic value of myocardial deformation in patients with congenital aortic stenosis
Authors: Van Grootel R W J , Van Den Hoven A T , Bowen D , Ris T , Roos-Hesselink J W , Van Den Bosch A E
Published: October 2019

Background

Congenital aortic stenosis (AoS) is associated with significant mortality and morbidity but predictors for clinical outcome are scarce. Strain analysis provides a robust and reproducible method for early detection of left ventricular (LV) dysfunction, which might be of prognostic value. Therefore we aimed to assess the prognostic value of LV global longitudinal strain (GLS) and global longitudinal early diastolic strain rate (GLSre) with regard to cardiovascular events.

Methods

This prospective study, included clinically stable patients with congenital AoS between 2011–2013. LV GLS and GLSre was performed in the apical 4, 3 and 2-chamber views using Tomtec software. The endpoint was a composite of death, heart failure, hospitalization, arrhythmia, thrombo-embolic events and re-intervention.

Results

In total 138 patients were included (33 [26–43] years, 86 (62%) male), NYHA class I: 134 (97%). Mean LV GLS was −15.3±3.2%, GLSre 0.66±0.18 s–1. Both correlated with NT-proBNP, LV volumes and ejection fraction (strongest LV GLS with LV EF: r −0.539, p<0.001, strongest LV GLSre with age: r −0.376 p<0.001). During median follow-up of 5.9 [5.5–6.2] years, the endpoint occurred in 53 (38%) patients: 4 patients died, 9 developed heart failure, 22 arrhythmias, 8 thrombo-embolic events and 35 re-interventions. Both LV GLS (standardized HR (sHR 0.62 (95% CI 0.47–0.81) and GLSre (sHR 0.62 (95% CI 0.47–0.83) were associated with the endpoint. Additional multivariable analysis showed that both GLS and GLSre were associated independent of left atrial volume, NT-proBNP and prior re-interventions.

Figure 1

Conclusion

Left ventricular GLS and GLSre are reduced in adult patients with congenital AoS. Both markers are associated with adverse cardiac events and have clear clinical relevance

Acknowledgement/Funding

Erasmus Thorax Foundation
P633Comparative analysis of exercise programmes with aerobic moderate and high-intensity interval training in patients after coronary artery bypass grafting
Authors: Kakuchaya T , Pachuashvili N V , Dzhitava T G , Kuular A M , Filatova A G , Bockeria L A
Published: October 2019

Background

High-intensity interval training is emerging as a potential time efficient strategy in contemporary cardiac rehabilitation. According to current guidelines 150 minutes of moderate physical activity per week is reduced by half to 75 minutes if the week's activity is done at a vigorous intensity. Objective: The main goal of our study was to assess and compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) within cardiac rehabilitation after coronary artery bypass grafting.

Methods

Sixty three patients (48 male, 15 female, at the mean age of 57±12 years) after coronary artery bypass grafting were recruited into exercise training program on cycle ergometer. The training course started 2 weeks after surgery, lasted 4 weeks and then continued in an outpatient care after 3–6 months. MICT was considered as 50% to 75% of VO2 max (maximal oxygen consumption) or 50–75% of heart rate reserve, while HIIT was considered as ≥85% of VO2 max or ≥85% of heart rate reserve. Training protocols included constant load and ramp interval programs. Control group comprised 40 patients without exercise training program. The safety of HIIT/MICT was the primary end point in our study. Secondary end-points included body mass index, echo and hemodynamic parameters, NT-proBNP and HbA1c levels along with standard cardiorespiratory fitness indicators.

Results

Significant increase in anaerobic threshold (by 16.9%), VO2 max (by 18.6%) and tolerance of physical load in MET (by 6.4%) were mentioned in study groups compared to equivalent measurements in control group (9.7%, 7.9% and 5.4% correspondingly). Substantial changes were also observed in following variables compared to control group: body mass index reduced (p=0.0032), end diastolic diameter decreased (p=0.0315), LV ejection fraction improved (p=0.045), NT-proBNP reduced (p=0.0015) and HbA1c improved (p=0.023). While analyzing aerobic capacity alterations due to HIIT versus MICT by standardized mean difference (95% CI), HIIT was significantly superior to MICT. Aerobic capacity covered VO2 max (ml/kg/min), anaerobic threshold (%), work rate (Wt) and EQo2=VE/Vo2.

Conclusions

High-intensity interval training proved to be as safe as a moderate-intensity training in patients after coronary artery bypass grafting. It appeared to be significantly superior to moderate-intensity continuous training in improving cardiorespiratory fitness. Obtained results allow implementing aerobic interval training individually after open-heart surgery and shorten rehabilitation period.
P650Lipopolysaccharide-nuclear factor-kappa B pathway and lipoprotein apheresis effects in patients with familial hypercholesterolemia and coronary artery disease
Authors: Liu H , Zhu C G , Cui C J , Cao Y X , Sun D I , Wu N Q , Guo Y L , Gao Y , Dong Q T , Santos R D
Published: October 2019

Abstract

Background

Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status.

Purpose

This study aimed to examine the LPS-NF-κB axis status and the impact of lipoprotein apheresis (LA) on this pathway in patients with FH and coronary artery disease (CAD).

Methods

In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 (IL-6) production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent LA. Blood samples were taken immediately before and regularly after LA for measuring LPS and NF-κB.

Results

FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p values <0.01). LPS-induced IL-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p values <0.01). Moreover, plasma LPS levels (p<0.001) and NF-κB activity (p<0.01) were dramatically reduced after apheresis in FH patients.

Conclusion

Genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while LA significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.
P652Lower use of statins among patients with peripheral artery disease compared with those with coronary heart disease
Authors: Colantonio L D , Dai Y , Hubbard D , Rosenson R S , Brown T M , Jackson E A , Mues K E , Woodward M , Farkouh M E , Muntner P
Published: October 2019

Background

Adults with atherosclerotic cardiovascular disease are recommended to take a statin to reduce their risk for future cardiovascular events. Prior studies suggest that statins are being taken by most adults with coronary heart disease (CHD). However, there are few data on the use of statins among adults with peripheral artery disease (PAD).

Purpose

To compare the use of statins among US adults with a history of PAD versus those with a history of CHD.

Methods

We conducted a retrospective cohort study among US adults ≥19 years of age with commercial or government health insurance who had a history of CHD or PAD as of December 31, 2014 (n=1,006,451, mean age 63 years, 47% male). We used pharmacy claims between January 1 and December 31, 2014 to identify use of any statin and of a high-intensity statin (i.e., atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg). Patients with a history of CHD without PAD (CHD only), both CHD and PAD, and PAD without CHD (PAD only) were analysed. Prevalence ratios for use of any statin and a high-intensity statin among those taking a statin were calculated after multivariable adjustment for sociodemographics and cardiovascular risk factors.

Results

Overall, 69.1% of patients included in the current analysis had CHD only, 21.4% had both CHD and PAD, and 9.5% had PAD only. Overall, 66.0%, 68.2% and 47.5% of patients with CHD only, CHD and PAD, and PAD only were taking a statin. After multivariable adjustment and compared to patients with CHD only, the prevalence ratio for statin use was 1.02 (95% CI 1.01, 1.02) for those with both CHD and PAD and 0.82 (95% CI 0.82, 0.83) for those with PAD only. Among patients taking a statin, 29.4% of those with CHD only, 28.6% of those with both CHD and PAD, and 17.3% of those with PAD only were taking a high-intensity dosage. Compared to patients with CHD only, the multivariable adjusted prevalence ratio for taking a high-intensity dosage was 1.05 (95% CI 1.04, 1.06) for those with both CHD and PAD and 0.71 (95% CI 0.70, 0.73) for those with PAD only.

Conclusion

Adults with PAD receive less intensive statin therapy compared with their counterparts who have CHD. Interventions aimed to increase statin use among patients with PAD are warranted.

Acknowledgement/Funding

This study was supported through a research grant from Amgen, Inc. (Thousand Oaks, CA, USA).
P670Clincal and echocardiographic characteristics in patients with pathology proven cardiac papillary fibroelastomas
Authors: Kurmann R , El-Am E , Bois M , Scott C , Lee A , Sorour A , Maleszewski J , Klarich K
Published: October 2019

Background

Papillary fibroelastoma (PFE) is a rare benign cardiac tumor with embolic potential. It is most commonly found on cardiac valves but can also be present on non-valvular endocardial surfaces. We sought to better understand the average PFE growth and recurrence rates, and characteristics that might be associated with embolization.

Purpose

To examine growth and recurrence rates and factors associated with embolization in patients with pathology-proven PFE.

Methods

Pathology-proven PFEs from 279 patients were identified at a single center between January 1995 and December 2018,and those with at least two transesophageal echocardiograms (TEE) more than 30 days apart were analyzed (n=62). Medical records were retrospectively reviewed for clinical characteristics and outcomes. In addition, intra-operative TEEs were manually reviewed and compared to previous TEEs at our institution to estimate overall size, location, and average PFE growth rates.

Results

The TEEs from 62 patients with pathology-proven PFE (mean age 65±12 years, female 63%) were reviewed. PFE was discovered incidentally during cardiac surgery in 18% of patients. Most PFEs were located on the aortic valve (AV) (73%) followed by the mitral valve (MV) (16%). The majority of PFEs (71%) presented with a stalk versus a sessile configuration. Average maximal length for PFE (including stalk if present) on the AV was 8.5±3.3 mm, and on the MV 6.8±2.0 mm. The number of PFEs located in other locations was too small to be analyzed for growth. PFE growth varied depending on location and configuration. The PFE growth on the AV was an average increase of 0.47 mm/year, those on the MV was 0.115 mm/year.

Valvular PFE was associated with significant functional valve abnormality in 15% of patients, and the abnormality was attributed to the PFE in 9% of patients. There were 25 patients (40%) who had a documented stroke/transient ischemic attack prior to PFE removal (46% located on AV, 44% on MV, 10% other locations). In addition, some patients had other documented embolic complications, such as myocardial infarction, amaurosis fugax, and peripheral embolization to the spleen and kidney. PFE size and location (up-/ downstream of the valve) were not predictive of cardiovascular thromboembolic events. At a median follow up of 2 years, PFEs recurred in the same location in 7.5% of the patients.

Conclusion

PFE is highly associated with thromboembolic events and seem to grow slowly, with an average growth rate of 0.47mm/year on AV and 0.115mm/year on MV. Growth rates for PFE have not been previously described. PFE can be safely excised with preservation of the native valve and recurs in 7.5% of patients, suggesting that close follow-up maybe warranted.
P673Moderate anti-tumor effect of the nanoliposomal anti-PCSK9 vaccine in BALB/c mice bearing colorectal cancer
Authors: Momtazi-Borojeni A A , Nik M E , Jaafari M R , Banach M , Sahebkar A
Published: October 2019

Background

The higher levels of low-density lipoproteins (LDL) cholesterol (LDL-C) have been reported to correlate with higher prevalence and risk of colon cancer. Proprotein convertase subtilisin/kexin 9 (PCSK9) function, through reducing protein levels of liver LDL receptor, leads to elevated levels of plasma LDL-C.

Purpose

Here, we evaluated anti-tumor effect of nanoliposomal anti-PCSK9 vaccine in mice bearing colon carcinoma.

Methods

To formulate nanoliposomal anti-PCSK9 vaccine, liposome nanoparticles prepared by lipid-film hydration method were covalently attached to immunogenic PCSK9 peptide. The liposomal vaccine formulation was adsorbed to Alum adjuvant (L-IFPTA+) and injected subcutaneously four times with a bi-weekly interval in BALB/c mice. Two weeks after the last immunization, the vaccinated and unvaccinated mice were subcutaneously inoculated with CT26 colon cancer cells into the right flank. After tumor mass was palpable (approximately 10 mm3), the mice were randomly divided into three groups and involved to different treatments: (1) PBS (untreated control), (2) vaccine group, and (3) Doxil®(positive control) group which involved unvaccinated tumor-bearing mice who received Doxil®. To study therapeutic efficacy, mouse body weight, tumor size, and survival were monitored in a 3-day interval for 50 days.

Results

The nanoliposomal anti-PCSK9vaccine could efficiently induce specific antibodies against PCSK9 in BALB/c mice, and thereby reduce plasma level and function of PCSK9. Tumor size in the vaccinated mice was significantly lower than in Doxil and the control mice. Tumor size analysis revealed that time to reach endpoint (TTE) of the vaccine group was slightly but not significantly higher than that of Doxil and the control groups. The vaccinated mice survived slightly but not significantly longer than Doxil and the control mice. The vaccinated mice's life was prolonged by 24.4% as compared with the control mice, while it was increased by 9.8% in Doxil group (see Figure below).

Conclusions

Our findings declare that the nanoliposomal anti-PCSK9vaccine not only have no harmful effects, but also can mildly reduce tumor growth, and enhance live span and survival in mice bearing colon cancer.
P681Acute Myocardial Infarction in patients with Leukaemia: A national analysis of prevalence, predictors and outcomes in United States hospitalisations (2004 to 2014)
Authors: Mohamed M O , Lopez-Mattei J C , Iliescu C A , Purwani P , Bharadwaj A , Kim P Y , Palaskas N L , Rashid M , Potts J E , Kwok C S , Gulati M , Al Zubaidi A B , Mamas M
Published: October 2019

Background

Patients with leukaemia are at increased risk of cardiovascular events. There is limited outcomes data for patients with a history of leukaemia who present with an acute myocardial infarction (AMI).

Purpose

To examine the prevalence and clinical characteristics of patients with leukaemia presenting with AMI, and evaluate differences in clinical outcomes according to the subtype of leukaemia in comparison to patients without leukaemia.

Methods

We analysed the Nationwide Inpatient Sample (2004–2014) for patients with a primary discharge diagnosis of AMI and concomitant leukaemia, and further stratified according to the subtype of leukaemia into 4 groups; AML; ALL; CML; and CLL. Multiple logistic regression was conducted to identify the association between leukaemia and major acute cardiovascular and cerebrovascular events (MACCE; composite of mortality, stroke and cardiac complications) and bleeding.

Results

Out of 6,750,927 AMI admissions, a total of 21,694 patients had a leukaemia diagnosis. The leukaemia group experienced higher rates of MACCE (11.8% vs. 7.8%), mortality (10.3% vs. 5.8%) and bleeding (5.6% vs. 5.3%). Following adjustments, leukaemia was independently associated with increased odds of MACCE (OR 1.26 [1.20,1.31]) and mortality (OR 1.43 [1.37,1.50]) without an increased risk of bleeding (OR 0.86 [0.81,0.92]). Acute myeloid leukaemia (AML) was associated with approximately three-fold risk of MACCE (RR 2.81 [2.51, 3.13]) and a four-fold risk of mortality (RR 3.75 [3.34, 4.22]) (Figure 1). Patients with leukaemia were less likely to undergo coronary angiography (CA) (48.5% vs. 64.5%) and percutaneous coronary intervention (PCI) (28.2% vs. 42.9%) compared to those without leukaemia.

Figure 1.Relative risk of adverse events

Conclusion

Patients with leukaemia, especially those with AML, are associated with poor clinical outcomes after AMI, and are less likely to receive CA and PCI compared to those without leukaemia. A multi-disciplinary approach between cardiologists and haematology oncologists may improve the outcomes of patients with leukaemia after AMI.
P693Cardiac biomarkers for the detection of anthracycline cardiotoxicity in childhood cancer - a meta-analysis
Authors: Michel L , Mincu R I , Mrotzek S M , Neudorf U , Rassaf T , Totzeck M
Published: October 2019

Introduction

Heart failure is the most concerning cardiovascular side effect of anthracycline chemotherapy. Pediatric cancer patients and survivors of childhood cancer are particularly vulnerable to cancer therapy-related cardiotoxicity. Cardiac biomarkers may be beneficial for screening and diagnosis of anthracycline-related heart failure in pediatric cancer patients and survivors of childhood cancer but systematic data is not yet available.

Purpose

To evaluate (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) and cardiac troponin for screening and prediction of cancer therapy-related cardiotoxicity in pediatric cancer patients and survivors of childhood cancer.

Methods

Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in pediatric cancer patients receiving anthracycline therapy or survivors of childhood cancer. The primary endpoint was left ventricular (LV) dysfunction as defined by decreased ejection fraction (EF) or fractional shortening (FS). The study was registered at the International prospective register of systematic reviews (PROSPERO) (CRD42018106616).

Results

A total of 1643 subjects from 27 studies were included. BNP/NT-proBNP levels were higher in patients post-treatment compared to control subjects or pre-treatment values (standardized mean difference = 1.0; 95% CI: 0.6–1.4; n=239). The risk for left ventricular (LV) dysfunction was increased in patients with elevated BNP/NT-proBNP (OR=5.5; 95% CI: 2.0–15.2; n=357). This was demonstrated for acute cardiotoxicity (OR=22.3; 95% CI: 3.3–151.1; n=88) and in survivors of childhood cancer (OR=3.2; 95% CI: 1.0–10.0; n=269). Sensitivity for the prediction of acute or subacute LV dysfunction was 28.9% and specificity was at 91.7%. The frequency of troponin elevations was increased after anthracycline therapy (OR=3.6; 95% CI: 2.0–6.5; n=305) but troponin was not associated with LV dysfunction (OR=0.2; 95% CI: −0.2 to 0.5; n=273).

Conclusion

BNP/NT-proBNP is elevated in pediatric patients receiving anthracycline chemotherapy and serves as a marker for the prediction of cardiotoxicity and screening for late cardiotoxicity in survivors of childhood cancer. So far, there is no systematic evidence on a benefit of cardiac troponin for the detection of anthracycline cardiotoxicity in children. Standardized recommendations on the role of cardiac biomarkers are needed for the optimal detection of anthracycline cardiotoxicity in childhood cancer patients.

Acknowledgement/Funding

IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany
P729The functional relevance of bile acids in the improvement of HDL-mediated endothelial protection after bariatric surgery
Authors: Jomard A , Chavez-Talavera O , Tailleux A , Bueter M , Taheri A , Wolfrum C , Lutz T A , Von Eckardstein A , Ruschitzka F , Staels B , Osto E
Published: October 2019

Introduction

Roux-en-Y gastric bypass (RYGB) reduces cardiovascular mortality. We showed that high density lipoproteins (HDL)-mediated vasoprotection is improved early after RYGB. Circulating BAs increase upon RYGB and contribute to the weight-loss independent metabolic improvements after surgery. Bile acids (BA) are signaling molecules increasingly recognized as regulators of cardiometabolic homeostasis. BAs circulate in the blood either free or bound to albumin and HDL. The signaling role of HDL-bound BAs (HDL-BAs) is unknown. Indeed, HDL may facilitate BA delivery directly to endothelial cells where BA may synergize with HDL to promote vasoprotection.

Purpose

We studied whether RYGB changes the composition of HDL-BA and whether HDL functional properties may be modulated by specific BA bound to HDL.

Methods

HDL were isolated by ultracentrifugation from 29 morbidly obese patients before and 1 year after RYGB. The HDL-BA composition was determined by liquid chromatography-mass spectrometry (LC/MS-MS) and HDL vasoprotective properties were evaluated ex-vivo in human aortic endothelial cells (HAEC). The size and abundance of HDL particles were determined by NMR spectroscopy in plasma.

Results

The increase in total BA concentrations observed in plasma 1 year after RYGB also translated into higher concentrations (up to 25%) of BA bound to HDL. Moreover, obesity-induced HDL dysfunction was reversed after surgery, as shown by improved HDL-mediated endothelial NO production, anti-apoptotic effects and cholesterol efflux capacity. The size function analyses showed a post-operative shift towards larger HDL. After RYGB there was a remodeling of BA bound to HDL, which are either agonists of the endothelial nuclear farnesoid X receptor (FXR), e.g. chenodeoxy-CA (CDCA), cholic acid (CA) or for the membrane TGR5 receptor, e.g. deoxy-CA (DCA). The composition-function analysis revealed that among all BA subclasses, the specific enrichment in CA and in CDCA bound to HDL correlated with an improved endothelial anti-apoptotic capacity of HDL (R −0.52, p=0.006 for CA-HDL and R −0.35, p=0.07 for CDCA-HDL). Further, the exogenous loading of CA onto healthy native HDL isolated from human serum significantly enhanced their endothelial anti-apoptotic function. In the case of obese, dysfunctional, pro-apoptotic HDL, exogenous CA loading was able to restore HDL anti-apoptotic function.

Conclusion

Exogenous loading of CA restored HDL anti-apoptotic function of HDL from obese patients mimicking the beneficial remodeling of BA bound to HDL observed after RYGB. These results suggest a crucial interaction between endothelial cells and BA in the improvement of HDL's vasoprotective properties.

Acknowledgement/Funding

Swiss national Science Foundation Ambizione and PRIMA grant to EO
P765One-year mortality risk after intensification of outpatient diuretics
Authors: Madelaire C , Gustafsson F , Kristensen S L , Stevenson L W , Koeber L , Torp-Pedersen C , D'Souza M , Andersen J , Gislason G , Biering-Sorensen T , Andersson C , Schou M
Published: October 2019

Background

Mortality is increased following a hospitalization for heart failure (HF). It is not clear whether outpatient intensification of diuretic confers the same increased risk in the general population with heart failure

Purpose

This study sought to assess 1-year mortality risk after worsening HF, defined either as hospitalization due to HF or as intensified diuretic therapy in an outpatient setting, in a complete nationwide cohort of patients with HF on angiotensin converting enzyme inhibitors/ angiotensin receptor blocker and beta blockers.

Methods

From nationwide administrative registers, we identified all patients in Denmark diagnosed with HF in 2001–2016 and prescribed angiotensin converting enzyme inhibitor/ angiotensin receptor blocker and beta blocker within 120 days. During follow-up we defined worsening HF by the following events: Inpatient worsening (HF readmission) and outpatient worsening (intensified diuretic therapy, defined as the first event of new addition or doubled dosage of loop diuretic therapy or new onset addition of thiazide to loop diuretic therapy). Patients with a worsening event were risk set matched to two HF controls each at time of the event – based on age, sex and calendar year. One-year mortality risk was estimated with Kaplan-Meier and multivariable Cox regression models.

Results

We included 74,990 patients, median age 71 years (interquartile range: 62–79), 36% women. During five years of follow up, 8,727 patients had an inpatient worsening event, and 12,290 had an outpatient worsening event as first event. Absolute risk of 1-year mortality was 22.6% (95%-confidence interval (95%-CI): 21.7%-23.5%) after inpatient worsening, 18.0% (95%-CI: 17.3%-18.7%) after outpatient worsening compared to 9.8% (95%-CI: 9.5%-10.1%) for the matched controls. In a multivariable Cox model adjusted ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease and diabetes, the hazard ratio for mortality among patients experiencing inpatient worsening was 2.46 (95%-CI: 2.33–2.60) and for outpatient worsening was 1.87 (95%-CI: 1.77–1.97), compared with the matched HF controls as reference (figure 1). Among patients who had an outpatient worsening as first event, 1,245 (10.1%) had a subsequent HF readmission within one year.

Conclusion

In a nationwide cohort of patients with HF, outpatient worsening defined by a diuretic intensification was associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization is associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.

Acknowledgement/Funding

The Danish Heart Foundation, (grant number 17-R116-A7610-22048)
P771Metoprolol succinate efficacy in patients with chronic heart failure on the background of obesity: genetic aspects of individual sensitivity and tolerability
Authors: Gasanov I , Medentseva O , Rudyk I , Galchinskaya V
Published: October 2019

Background

The cornerstone of modern cardiology is the problem of comorbidity, the combination of chronic heart failure (CHF) with obesity as well. Efficacy of treatment with beta-blockers in different patients varies significantly, partly depending on genotypically determined features of its metabolization with enzymes.

Purpose

To improve the CHF treatment with metoprolol succinate efficacy in patients with obesity by detection of genetic aspects of individual sensitivity and tolerability.

Methods

A prospective randomized dynamic (1 year) study was conducted involving 127 patients with CHF II–III stages at the age of 32–87 years; they were distributed into main group with combination of CHF and obesity (73 patients) and control group with only CHF (54 patients). The examination included an assessment of CYP2D6 gene 1846G/A polymorphism, clinical symptoms, quality of life (by Minnesota questionnaire), 6-minute walk test data, doppler echocardiography, heart rate variability, serum insulin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Metoprolol succinate was administered according to a standard regimen with dose titration every 2 weeks from 12.5 to 100–200 mg. The critical p-level was 0.05.

Results

An association of “unfavorable” allele A with an increase in body weight was found (p=0.05). As a result of treatment, better indicators of the clinical status were found in control group (6 [5; 7] versus 7 [6; 8] points in obese patients, p=0.05) and quality of life in patients with genotype GG than the GA genotype (p<0,05).

The use of metoprolol succinate in patients with GG genotype is associated with more pronounced positive dynamics of treatment efficacy. In contrast to the carriers of the GA genotype, in patients with the GG genotype there were an increase in left ventricle ejection fraction (by 21.5% versus 9.3%, p<0.01) and the reduction of the left ventricle end-diastolic size (p=0.02). The GG genotype carriers significantly increased the amount of exercise tolerance (p<0.05), and showed a more pronounced improvement in quality of life (p<0.03) and the clinical state (p=0.05), as well as the normalization of the vegetative balance (LF/HF index). The level of serum NT-proBNP in the GG genotype was lower than in patients with GA genotype (p=0.05). At the same time, patients with a GA genotype showed a more pronounced decrease in heart rate compared to those with a GG genotype (p<0.05).

In carriers of the GA genotype, a tendency to a greater incidence of side effects compared with the GG genotype (bradycardia 42.0% vs. 28.0%, p<0,05; cold extremities 44.0% vs. 32.0%, p<0.05, fatigue 39.0% vs. 31.0%, p<0.05, headache 32.0% vs. 24.0%, p<0,10, drowsiness 38,0% vs. 27,0%, p<0,05).

Conclusions

It is useful to take into account the CYP2D6 gene 1846G/A polymorphism in order to improve the CHF treatment with metoprolol succinate in patients with obesity.