bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort
Authors: Blaum C , Brunner F.J , Kroeger F , Braetz J , Bay B , Graef A , Gossling A , Lorenz T , Zeller T , Karakas M , Schnabel R.B , Westermann D , Blankenberg S , Seiffert M , Waldeyer C
Published: November 2020

Introduction

The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors.

Purpose

We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients

Methods

We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C >140 mg/dl or >100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017).

Results

We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively).

Conclusion

The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently.

Funding Acknowledgement

Type of funding source: None
Reduction of epicardial adipose tissue thickness with PCSK9 inhibitors
Authors: Rivas Galvez R.E , Morales Portano J.D , Trujillo Cortes R , Gomez Alvarez E.B , Sanchez Cubias S.M , Zelaya S.M
Published: November 2020

Introduction

Epicardial adipose tissue (EAT) is clinically related to atherosclerosis and increased cardiovascular risk. The proprotein convertase subtilisin/kexin type 9 inhibitors (IPCSK9) are a novel group of effective drugs for lowering LDL cholesterol and cardiovascular events, however their effect on EAT has not yet been determined.

Objective

To assess the effect of treatment with PCSK9 inhibitors on epicardial adipose tissue.

Methods

The study enrolled 41 patients under treatment with PCSK9 inhibitors. At the end of the study only 24 patients were included, who were measured thickness of epicardial adipose tissue (TEAT) by transthoracic echocargiogram (just an echocardiographer using Siemens Acuson SC 2000 Prime with two-dimensional 4V1c transducer in two projections: long parasternal axis in the pericardial space of the outer edge of the myocardium above the right ventricle and in a short parasternal axis at the height of papillary muscles on the right ventricle, in telesystole and averaging three measurements; It was measured in millimeters.) using in 2 times before and after 6 months of initiation of treatment.

Results

Of 24 patients, 16 patients recieved evolocumab and 8 alirocumab patients; the mean TEAT pre-treatment and post-treatment was 6.84 mm (1.97) and 5.41 mm (1.86), respectively (p=0.0001); The mean percentage of change of the TEAT after 6 months of treatment was −20.39 (17.20). The mean serum LDL cholesterol levels pre-treatment and post-treatment were 188.04 mg/dL (144.0) and 94.96 mg/dL (106.04), respectively (p=0.0001); The mean change in LDL cholesterol was −51.89 (22.81). Just one patient had myocardial infarction. There was no difference between the means of reducing the percentage of change in epicardial adipose thickness between evolocumab and alirocumab. There was no correlation between lipid decrease and TEAT.

Conclusion

There is a significant reduction after 6 months of treatment with PSCK9 inhibitors in thickness of epicardial adipose tissue.

Effect of IPCSK9 in TEAT and Lipids

Funding Acknowledgement

Type of funding source: None
Impact of body mass index on outcomes in European patients with atrial fibrillation: the ESC EHRA EORP Atrial Fibrillation General Long-Term registry (AFGen LT)
Authors: Boriani G , Proietti M , Laroche C , Fauchier L , Marin F , Nabauer M , Potpara T , Dan G.A , Kalarus Z , Tavazzi L , Maggioni A.P , Lip G.Y.H
Published: November 2020

Introduction

The impact of body mass index (BMI) on outcomes in patients with atrial fibrillation (AF) has been largely debated.

Aims

To describe the relationship between BMI categories and clinical outcomes in a large cohort of European AF patients.

Methods

We included all AF patients with available baseline BMI and creatinine clearance and 1-year follow-up data enrolled in the EORP-AF General Long-Term Registry. Outcomes considered were: i) a composite of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death; ii) CV death; iii) all-cause death.

Results

A total of 7,759 patients were included in this analysis. Of these, 55 (0.7%) were underweight, 2,074 (26.7%) were normal weight, 3,170 (40.9%) were overweight, 1,703 (21.9%) were obese and 757 (9.8%) were severe obese. Mean age was progressively lower across the categories (p<0.0001), with proportion of patients aged≥75 years also progressively lower (52.7% in underweight to 19.4% in severe obese patients; p<0.001). Both underweight (41.8%) and severe obese (25.0%) patients were more likely symptomatic (p<0.001). Mean CHA2DS2-VASc score was higher in underweight patients (p=0.0325). Use of any oral anticoagulant therapy was progressively higher across the BMI categories (p<0.001). At 1-year follow-up the rate of all outcomes considered were highest for underweight patients and lowest in severe obese [Figure 1]. On univariate Cox regression analysis, being underweight was consistently associated to a higher risk for all outcomes, while increasing of weight categories was associated with progressively lower risk for adverse outcomes. After full adjustment with clinical and pharmacological characteristics, no effect of higher BMI classes was found for any outcome, but an independent association with an increased risk of CV death and all-cause death was seen for underweight patients (Table 1).

Conclusions

In a large cohort of European AF patients a progressively lower rate of outcomes was found across increasing BMI classes. After full adjustments, no significant association was found between the higher BMI classes and outcomes. Underweight was associated with an increased risk for CV death and all-cause death.

Figure 1. Outcomes at 1-year Follow-up

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants
Pulmonary hemodaynamic in obesity
Authors: Zhou N , Klass M , Corentin S , Kevin F , Motoji Y , Beatrice P , Loi P , Closset J , Naeije R , Faoro V
Published: November 2020

Background

Higher prevalence of pulmonary hypertension exist in obesity subjects. Little known about pulmonary hemodynamics during exercise in obesity population.

Purpose

To assess and compare the response of pulmonary vascular resistance during exercise in obese subjects vs healthy controls.

Methods

Seventeen obesity subjects (gender: 25%men, age: 44±11 years, height: 1.7±0.1 m, weight: 111±17 kilogram, BMI: 38±4 kg/m2) were compared to twenty gender-, age-, height- and race-matched healthy control subjects (age: 46±12 years, height: 1.7±0.1 m, weight: 64±11 kilogram, BMI: 22±2 kg/m2). All subjects underwent an incremental exercise stress echocardiography with measurements of pulmonary artery pressure (PAP), cardiac output (CO), cardiac index (CI) and tricuspid annular plane systolic excursion (TAPSE) at rest and at increasing exercise intensities. Total pulmonary vascular resistance index (PVRi) was calculated as mean PAP/CI and right ventricular-arterial coupling as TAPSE/systolic PAP.

Results

The results are described in the table 1. Pulmonary hemodynamic was not different at rest between two groups, but lower at maximal exercise in obesity subjects. In obesity subjects, identical exercise level was associated with a higher mean PAP and PVRi, and a lower TAPSE/systolic PAP ratio.

Conclusion

While pulmonary hemodynamic seems preserved at rest in obesity patients, pulmonary vascular resistance is increased and right ventricular coupling is decreased, particularly at exercise.

Funding Acknowledgement

Type of funding source: None
Association between the phenotype of metabolically healthy obesity and the risk of myocardial infarction
Authors: Malyutina S , Mustafina S , Vinter D , Rymar O , Shcherbakova L , Verevkin E.U , Gafarov V , Bobak M
Published: November 2020

Aim

This study aimed to investigate the associations between the metabolically healthy obesity (MHO) and the risk of myocardial infarction (MI) in a Russian population sample.

Materials and methods

A random population sample of men and women aged 45–69 years old at baseline was examined in 2003–2005 in a Russian city; after that the cohort was followed-up for 12 years on the average (2003–2016). A sub-cohort of subjects with body mass index (BMI) ≥30 kg/m2 at baseline was selected for present study (3157 individuals, 73.2% women); of those, 3008 subjects free from baseline history of MI/acute CHD was included for analysis. The data on incident myocardial infarction (MI) were ascertained from register of MI, two repeated examinations and repeated postal interviews during 12-year follow-up of the cohort. We used two definitions of MHO: by NCEP ATPIII, 2001 (the presence of 2 or less components of the metabolic syndrome) and by IDF 2005 (waist circumference (WC) ≥94 cm in men and ≥80 cm in women regardless of risk factors). Multivariable Cox regression was conducted using the SPSS package (V. 13.0).

Results

The prevalence of MHO at baseline ranged from 20% (by IDF) to 45% (by NCEPATPIII) in obese sub-cohort. Among subjects with MHO at baseline, about one half of subjects developed metabolically unhealthy obesity phenotype (MUO) during 12-years. Women were more likely to retain MHO (32%) and more frequent transited from MUO to MHO (14%) compared to men (22% and 6% by IDF criteria, correspondently) during 12 years.

The relative risk of incident MI in subjects with MUO at baseline was 1.9 times higher than in those with MHO (HR 1.9, 95% CI 1.2–2.9) by NCEPATP III. Among men, the relative risk of MI in those with MUO (by NCEP ATP III) was 2 times higher than in a group with MHO (HR 2.1, 95% CI 1.1–4.0). Among women, the relative risk of MI in those with MUO (by NCEP ATP III) was 2.2 (95% CI 1.2- 4.2) compared to MHO group. Using the IDF criteria, the relative risk of MI in MUO vs. MHO was 2.2 (95% CI 0.9–5.7) in men and 2.2 (95% CI: 0.9–5.7) in women.

Conclusions

In this study population, men aged 45–69 have more frequent progression from metabolically healthy to metabolically unhealthy obesity during 12 years compared to women. The 12-year risk of incident MI in subjects with MUO was approximately twice higher compared to MHO and the excess risk was similar in men and women.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): Wellcom Trust
Alcohol consumption behavior and new-onset atrial fibrillation in patients with newly-diagnosed type 2 diabetes mellitus: a nationwide population-based study
Authors: Choi Y.J , Choi C.E.K
Published: November 2020

Background

Type 2 Diabetes mellitus (T2DM) has a high risk of being associated with cardiovascular diseases including atrial fibrillation (AF). Although excessive alcohol consumption is an established modifiable risk factor for AF, alcohol behavior modification for preventing the risk of AF is not widely studied.

Objective

We explored the clinical effects of alcohol consumption behavior on the prevention from new-onset AF in patients with T2DM.

Methods

A total of 180,964 patients newly diagnosed with T2DM were identified between 2009 and 2014 from the Korean National Health Insurance Service database after excluding a previous history of AF. We followed up them until 2017, and compared the risk of AF according to alcohol consumption behavior.

Results

During follow-up of mean 4.3 years, new-onset AF occurred in 2,386 patients. Compared to non-drinkers, heavy drinker (≥30 g/day) at the baseline had a higher risk of AF (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.112–1.492), whereas mild-drinker had no statically significant difference. According to alcohol consumption behavior, subject who stopped drinking from the time of T2DM diagnosis had the lower risk of AF; abstinence group (HR 1.33, 95% CI 1.135–1.569), restart group (HR 1.38, 95% CI 1.131–1.688) and continuous group (HR 1.48, 95% CI 1.238–1.776). In subgroup analysis, the impact of alcohol consumption behavior was more pronounced in male, but not in female; abstinence group (HR 1.30, 95% CI 1.101–1.536), restart group (HR 1.40, 95% CI 1.141–1.711), and continuous group (HR 1.49, 95% CI 1.244–1.789).

Conclusions

Abstention from alcohol reduced the risk of AF development in patient newly diagnosed with T2DM. Especially, in men, alcohol consumption behaviour modification is an important strategy for preventing cardiovascular event in patient newly diagnosed with T2DM.

Funding Acknowledgement

Type of funding source: None
Association between maternal diabetes and cardiac left ventricular structure and function in the neonate: a study from the Copenhagen Baby Heart Study
Authors: Ghouse J , Voegg O , Sillesen A.S , Pihl C , Axelsson A.R , Vejlstrup N , Oyen N , Jensen M.T , Wohlfart J , Damm P , Olesen M.S , Mathiesen E.R , Iversen K , Bundgaard H , Boyd H
Published: November 2020

Background

Prenatal exposure to maternal diabetes has been associated with increased risk of congenital heart defects.

Purpose

To evaluate whether maternal diabetes is associated with more subtle morphological and functional cardiac changes in neonates without congenital heart defects.

Methods

We included 17,869 newborns sampled from the Copenhagen Baby Heart Study, all of whom underwent transthoracic echocardiography within 30 days of delivery. We investigated the association between exposure to maternal diabetes (pre-existing diabetes [type 1 or type 2 diabetes] or gestational diabetes [GDM]) and the neonates' echocardiographic indices of left ventricular structure (left posterior wall thickness in end-diastole [LVPWd], interventricular septum thickness in end-diastole [IVSd], left ventricular internal diameter in end-systole [LVIDs] and end-diastole [LVIDd]), systolic function (fractional shortening [FS], stroke volume [SV]) and diastolic function (mitral valve peak early and atrial filling velocities, deceleration time of early filling, and E/A-ratio), using linear and logistic regression. Models were adjusted for maternal age, infant sex, infant birth weight for gestational age and gestational age in days. In additional analyses, we evaluated the relationship between HbA1C levels in first and third trimester and left ventricular structure and function.

Results

We found that infants exposed to pre-existing maternal diabetes (n=x) had, on average, a thicker LVPWd (mean difference 0.12 mm [95% CI: 0.06–0.19]), a smaller LVIDs (−0.27 mm [95% CI: −0.46, −0.07]) and LVIDd (−0.43 mm [95% CI: −0.66, −0.19]), and decreased SV (−0.50 ml [95% CI: −0.77, −0.23]). We found no significant differences in IVSd, FS, and measures of diastolic function for infants exposed to pre-existing maternal diabetes compared with infants not exposed to diabetes. Infants exposed to GDM (n=) also had thicker LVPWd (0.06 mm [95% CI: −0.28, −0.01]) and smaller LVIDs (−0.15 mm [95% CI: −0.28, −0.01]); however, on average, IVSd, LVIDd, and measures of systolic and diastolic function did not differ for infants born to mothers with and without GDM. We observed no consistent association between HbA1C levels measured early and late in pregnancy in mothers with diabetes and indices of left ventricular structure and function.

Conclusion

In conclusion, we found that exposure to maternal pre-existing diabetes, and to a lesser degree GDM, was associated with changes in neonatal left ventricular structure and function, including a thicker left ventricular posterior wall, smaller left ventricular internal diameters, and lower stroke volumes.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Rigsbospitalet Research Foundation
Effects of tirzepatide, a novel dual GIP and GLP-1 receptor agonist, on lipid profiling in patients with type 2 diabetes
Authors: Ruotolo G , Roth K.D , Milligan P.L , Lin Y , Wilson J.M , Pirro V , Duffin K.L , Haupt A
Published: November 2020

Background/Introduction

In a Phase 2 trial, tirzepatide (TZP) dose-dependently reduced HbA1c, body weight and serum triglycerides in moderately obese type 2 diabetes (T2D) patients.

Purpose

To understand changes in fasting serum lipids with TZP, lipidomics profiling of multiple lipid classes was conducted.

Methods

Patients (n=314) were randomized to receive weekly subcutaneous TZP, dulaglutide, or placebo for 26 weeks. Shotgun lipidomic analysis was performed in positive electrospray using a Sciex Triple TOF 5600 mass spectrometer operating in MS/MSALL mode and sphingomyelin (SPM) data were acquired in positive electrospray TOF mode. Data were assessed using MMRM.

Results

At 26 weeks, total cholesterol esters (CE), phosphatidylcholines (PC) and phosphatidylinositols (PI) increased with placebo; dulaglutide treatment did not affect any lipid class (Table). With TZP 10 and 15 mg, total triacylglycerides (TAG), diacylglycerides (DAG), phosphatidylethanolamines (PE), PC and PI dose-dependently decreased at 4, 12 and 26 weeks, whereas total CE and phosphatidylserines (PS) levels did not change at any timepoint. At 26 weeks, individual, but not total, SPM and ceramide (Cer) changes were observed with TZP 15 mg. Most saturated, long chain SPM (14:0, 20:0, 21:0, 22:0, 23:0, 24:0) and Cer (22:0, 23:0, 24:0) were reduced by 8–16% and 14–20%, respectively. Conversely, unsaturated SPM (24:1,24:2) increased by 6.5% and 11.4%, and unsaturated glycosylated Cer 16:0 lactosyl and 24:1 hexosyl increased by 22.4% and 19.3%, respectively. TZP 10 and 15 mg decreased total SPM by 4–6% at 4 weeks, and total Cer between 8% and 13% at 4 and 12 weeks.

Conclusions

Tirzepatide dose-dependently reduced levels of total TAG, DAG, PE, PC, and PI at all timepoints, whereas levels of saturated long chain SPM and Cer were reduced and those of some unsaturated SPM and glycosylated Cer increased at 26 weeks. Net improvements in lipidomics profiling with tirzepatide warrant further evaluation of potential benefits on cardiovascular events and NASH.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Eli Lilly and Company
Living alone combined with physical frailty or cognitive frailty is independent risk factor of outcomes in the patients with acute heart failure after discharge
Authors: Takabayashi K , Kitaguchi S , Nohara R
Published: November 2020

Background

Living status is an important factor to manage the conditions of acute heart failure (AHF) patients after discharge. In patients with heart failure (HF), a frailty is a common and serious complication. However, the association between living alone and the outcome in HF patients have not been well described.

Purpose

The purpose of this study is to identify the association between living alone and following outcomes. Furthermore, we reveal the impact of living alone combined with physical or cognitive frailty in AHF patient after discharge.

Methods

We have enrolled 1117 discharged patients with AHF in the Kitakawachi Clinical Background and Outcome of Heart Failure Registry (KICKOFF Registry; 13 hospitals in a city in Japan) from April 2015 to January 2017. The KICKOFF Registry is a prospective multicenter community-based cohort of AHF patients. We defined physical frailty as impossible outdoor walking and cognitive frailty as dementia. We divided into three groups, living without alone (non-alone, n=898), living alone without frailty (alone without frailty, n=148) and living alone with physical or cognitive frailty (alone with frailty, n=71). We compared the clinical characteristics and outcomes between three groups. We defined a primary outcome as a composite endpoint that included all-cause mortality and hospitalization for HF.

Results

During the follow-up period whose median was 573 days, a total of 548 patients (49.1%) had the composite endpoint, and the highest proportion of the composite endpoint was in alone with frailty, 63.4%. This was followed by 49.2% in non-alone, and 41.2% in alone without frailty. In the Kaplan-Meier analyses, the composite endpoint was a significantly higher in alone with frailty than the other groups (Figure A), but there was no significant difference between all patients with living alone and those without living alone (Figure B). After adjustment by gender, age, and the other co-morbidities (HF, coronary artery disease, valvular disease, hypertension, diabetes, atrial fibrillation and chronic kidney disease) in the Cox proportional hazard model, the composite endpoint hazard ratio (HR) increased significantly in the factor of alone with frailty when compared with the others (adjusted HR, 1.38; 95% confidence interval, 1.00–1.86; p=0.048).

Conclusion

In this study, the patients with only living alone have not independently prognostic impact, but those with living alone combined physical frailty or cognitive frailty have independently prognostic impact after discharged AHF.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This research was supported by research funding from Nakajima Steel Pipe Company Limited.
Effects of late aerobic exercise on cardiac remodeling of rats with small myocardial infarction
Authors: Souza L.M , Okoshi M.P , Gomes M.J , Rodrigues E.A , Pontes T.H.D , Damatto F.C , Oliveira L.R.S , Lima A.R.R , Gatto M , Borim P.A , Zornoff L.A.M , Okoshi K , Pagan L.U
Published: November 2020

Background

Physical exercise has been highlighted as an important non-pharmacological therapy for prevention and treatment of several cardiovascular diseases. However, its effects on hearts with minor cardiac remodeling are not clear.

Purpose

To evaluate the influence of aerobic physical exercise on functional capacity, cardiac structure, left ventricular (LV) function, and gene expression of NADPH oxidase subunits in rats with small-sized myocardial infarction (MI).

Methods

Three months after MI induction, Wistar rats were divided into three groups: Sham; sedentary MI (MI-SED); and aerobic exercised MI (MI-EA). Rats exercised three times a week for 12 weeks on a treadmill. Echocardiogram was performed before and after experimental period. Infarction size and cardiomyocyte diameters were evaluated by histology. Gene expression was assessed by RT-PCR.

Results

Only rats with MI size lower than 30% of LV total area were included in the study. Functional capacity was higher in MI-AE than the other groups. Infarction size did not differ between groups. Infarcted rats had increased LV diastolic and systolic diameter, left atrial diameter, and LV mass, with systolic dysfunction. LV diastolic posterior wall thickness was higher in MI-AE than Sham, and relative wall thickness was lower in MI-SED than MI-AE and Sham groups. Cardiomyocyte diameter was smaller in infarcted groups than Sham. Myocardial gene expression of the NADPH oxidase subunits NOX2, NOX4, p22phox, and p47phox did not differ between groups.

Conclusion

Small-sized myocardial infarction changes cardiac structures and left ventricular systolic function. Late aerobic physical exercise improves functional capacity and cardiac remodeling by preserving left ventricular geometry. NADPH oxidase subunits gene expression is not involved in cardiac remodeling or modulated by aerobic exercise in rats with small myocardial infarction.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): CNPq; CAPES
Trimetazidine combined with exercise improves anti-stress capacity through enhancing autophagy and apoptosis of myocardium in mice
Authors: Jiang L
Published: November 2020

Aims

To observe the effects of trimetazidine, aerobic exercise alone or combined on the anti-stress capacity of mice, and further explore its potential mechanism.

Methods

Forty-four C57/BL male mice aged 8 weeks were randomly divided into four groups: control group (group C, n=11), exercise group (group E, n=11), trimetazidine (TMZ)group (group T, n=11),exercise combined with TMZ group (group TE, n=11). Saline intragastric administration, medium intensity swimming training, TMZ (10mg/kg) intragastric administration, medium intensity swimming training combined with TMZ intragastric administration were given respectively. Swimming for 6 days a week, 1 hour a day lasting for 4 weeks. After the intervention, each group was randomly subdivided into the rest and the exhaustive exercise (EE) subgroups. The mice in the EE-subgroup (n=6) underwent exhaustive exercise. The myocardial ultrastructure was observed under electron microscope to measure the anti-stress ability of mice. The expression of key autophagy proteins LC3-II, P62 and BNIP3 were detected and the number of myocardial autophagosomes were observed under electron microscope. The protein of apoptosis related, Bcl-2 and the expression of heat shock protein 70 (HSP70) were also being detected.

Results

Exhaustive exercise induced the cardiac muscle damage successfully. TMZ and exercise alone or combined alleviated the cardiac damage significantly with improved autophagy (P<0.05) at the basal state and after exhaustive exercise. The level of apoptosis (P<0.05) and the expression of HSP70 was upregulated after the exhaustive exercise.

Conclusions

TMZ and exercise alone improved the anti-stress capacity of mice effectively and the combination has a synergistic effect. The mechanism may be related to the promotion of autophagy, apoptosis and HSP70 expression of myocardium.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): China natual science founding
Adherence to cardiac rehabilitation after acute coronary syndrome and its impact on patient outcome
Authors: Sulzgruber P , Sinkovec H , Kazem N , Hofer F , Hammer A , Koller L , Todorovic M , Katsch F , Gall W , Duftschmid G , Heinze G , Niessner A
Published: November 2020

Background

Secondary prevention after acute coronary syndrome (ACS) mirrors a key position in the reduction of morbidity and mortality in this highly vulnerable patient population. Especially cardiac rehabilitation proved to be one of the most beneficial therapeutic approaches for the reduction of re-events and overall modification of cardiovascular risk factors. However, profound epidemiological measures on adherence to a recommended cardiac rehabilitation after ACS remain scare, but seem of major importance in terms of preventing fatal cardiac adverse events. Therefore, we aimed to investigate adherence to cardiac rehabilitation after ACS and its impact on patient outcome from an Austrian nationwide perspective.

Methods

Within this population-based national observation all patients presenting with ACS between 04/2011 and 8/2015 in Austria were enrolled. Patient characteristics and co-morbidities were assessed via the Austrian national health insurance system and elucidated according to ICD10 definitions. Adherence to recommended cardiac rehabilitation was investigated according to health insurance documentation. Patients were followed prospectively until the primary study endpoint (= mortality) was reached. Cox Regression hazard analysis was used to investigate the impact of non-adherence to cardiac rehabilitation on patient outcome and was adjusted for a comprehensive subset of confounders within the multivariate model.

Results

During the observation period a total of 16.518 patients (median age: 64 years [54–74]; male: 68.4% [n=11.306]) met the inclusion criteria. Of alarming importance 86.6% (n=14.305) of all patients presenting with ACS did not perform any cardiac rehabilitation as recommended by current guidelines. During patient follow-up until 01/2018 a total of 1774 (10.7%) individuals died. Adherence to recommended cardiac rehabilitation had a strong an independent inverse association with mortality with an adjusted hazard ratio of 0.73 (95% CI: 0.54–0.98; p=0.036) (see Figure 1).

Conclusion

The present nationwide investigation highlighted an overall low adherence to recommended cardiac rehabilitation after ACS. Since cardiac rehabilitation after ACS was associated with a 27% risk reduction for fatal cardiovascular events during the observation period, awareness in terms of cardiac rehabilitation and associated intensified risk factor modification should be promoted, in order to prevent fatal atherothrombotic events.

Figure 1. Cumulative mortality

Funding Acknowledgement

Type of funding source: None
Relationship between papillary muscles abnormalities and apparently unexplained infero-lateral T-wave inversion in athletes
Authors: Bettella N , De Lazzari M , Zorzi A , Vessella T , Cipriani A , Motta R , Perazzolo Marra M , Corrado D
Published: November 2020

Aims

To evaluate by cardiac magnetic resonance (CMR) if left ventricle papillary muscle abnormalities, such as hypertrophy and abnormal location, may be the anatomo-functional substrates responsible for TWI inversion in lateral or infero-lateral leads in otherwise healthy athletes.

Methods

We included competitive athletes with TWI in lateral or infero-lateral leads in the absence of cardiac diseases detected by CMR. The control population included healthy athletes with normal ECG, matched for age and gender. We compared thickness, volume (both absolute and relative to the cardiac mass) and position of the papillary muscles between cases and controls.

Results

We included 53 athletes with apparently unexplained TWI in the lateral or infero-lateral leads (median age 20 years (17–42), 86.8% males) and 53 athletes with no TWI matched for age and gender. 4 patients (7.6%) had family history for cardiomyopathy or sudden cardiac death. Athletes with TWI showed more hypertrophic papillary muscles compared to controls, with statistically significant difference in diameter, area and volume (p<0.01). The median ratio between the papillary muscles and the left ventricular mass was 4.4% among athletes with TWI versus 3% among those without TWI (p<0.001). Papillary muscles showed apical displacement in 47% of cases, compared to 17% in the control group (p=0.001).

Conclusions

Idiopathic TWI in lateral or infero-lateral leads is associated with left ventricle papillary muscle hypertrophy and their apical displacement detected by CMR. The comprehension of clinical and prognostic significance of papillary muscle abnormalities responsible for these ventricular repolarization alterations requires further studies.

Example

Funding Acknowledgement

Type of funding source: None
The platelets behaviour in non-alcoholic fatty liver disease. A potential role for antiplatelets drugs?
Authors: Baratta F , Del Ben M , Pastori D , Bartimoccia S , Cammisotto V , Cocomello N , Colantoni A , Pani A , Nocella C , Carnevale R , Angelico F , Violi F
Published: November 2020

Background and purpose

Previous studies showed a favorable effect of aspirin, which irreversibly acetylates cyclooxygenase-1 (COX1) so preventing Thromboxane (Tx) A2 biosynthesis, in non-alcoholic steatohepatitis (NASH) and its sequelae. However, the behavior of COX1 in NASH patients is still unknown.

Methods

We conducted a cross-sectional study on 44 outpatients with NASH, 50 subjects with simple steatosis (NAFL) and 50 subjects without hepatic steatosis balanced for age, gender and BMI. Serum TxB2, a stable metabolite of TxA2, and urinary 11-dehydro-TxB2, as markers of COX1 activation, plasma soluble P-selectin (sP-selectin), a maker of in vivo platelet activation, serum bacterial lipopolysaccharide (LPS) and serum zonulin, a marker of gut permeability, were measured.

Results

Urinary 11-dehydro-TxB2 (p<0.001) and serum TxB2 (p<0.001) levels as well as sP-selectin (p<0.001) were significantly higher in patients with NASH/NAFL compared to the controls (figure 1); the markers of COX1 activation significantly correlated with sP-selectin (p<0.001). Serum LPS was higher in patients with NASH compared with NAFL and controls (p<0.001) and serum zonulin was significantly higher in patients with NASH as compared to controls (p=0.031). A positive correlation (rS=0.37; p<0.001) was observed between serum LPS and serum zonulin. Moreover, serum LPS correlated with serum and urinary 11-dehydro-TxB2 (rS=0.30; p<0.001 and rS=0.61; p<0.001, respectively) and with sP-Selectin (rS=0.32; p<0.001) (figure). At multivariate analysis, LPS above median (OR=3.15, p=0.015) and liver diagnosis (NAFL vs. Controls: OR=6.54; p<0.001 and NASH vs Controls: OR=4.54; p=0.007) were independently associated with sP-selectin above median (table).

Conclusions

Patients with NAFLD display enhanced platelet activation, which is associated to COX1 up-regulation. LPS increased by impaired gut permeability may favor platelet activation.

Figure 1

Funding Acknowledgement

Type of funding source: None
Incidence and predictors of arrhythmias in patients with systemic sclerosis and no overt cardiac disease
Authors: Stronati G , Manfredi L , Dichiara C , Dello Russo A , Gabrielli A , Guerra F
Published: November 2020

Background

Cardiac involvement in SSc is frequent, mostly subclinical and represents a negative prognostic factor. Speckle tracking derived measurement global longitudinal strain (GLS) has been able to identify primary heart involvement in patients with SSc and no overt cardiac disease. SSc-related cardiomyopathy, defined as a condition affecting the heart primarily and globally, has been proven to progress over time and seems to be correlated to cardiac arrhythmias. Nonetheless, cardiac arrhythmias represent 6% of the overall causes of death in SSc patients.

Purpose

The aim of our study was to assess the incidence of cardiac arrhythmias in SSc patients with no overt cardiac disease and to identify potential predictors.

Methods

Prospective longitudinal study enrolling all consecutive patients with a diagnosis of SSc and no overt cardiac disease or pulmonary hypertension. Echocardiographic parameters and GLS were obtained at baseline and at each follow up. Presence of atrial fibrillation (AF), atrial tachycardia (AT), ventricular ectopic beats >1000/24 h (VEB), supraventricular ectopic beats (SVEB), bundle branch block (BBB) and atrioventricular block (AVB) was assessed through clinical history, ECG and 24-Holter monitoring over time.

Results

Among 67 consecutive patients with SSc, 11 (16.7%) had at least one episode of AF or AT. Moreover, respectively 12 (17.9%) and 16 (23.9%) had a significant amount of SVEB and VEB at Holter monitoring. Conduction defects were common, with 4 (4.6%) of all patients with grade I AVB, 1 (1.5%) with grade II AVB and 1 (1.5%) with complete heart block. Complete right BBB was seen in 6 (6.9%) of patients. Four patients (4.6%) experienced a sudden cardiac death during follow-up (median 20 months, 1st-3rd quartile 12–24 months).

Years from SSc diagnosis (RR 1.10; 95% CI 1.02–1.23; p=0.047) and indexed right atrial volume (iRAV; RR 1.22; 95% CI 1.07–1.39; p=0.004), but not indexed left atrial volume were independently correlated with the diagnosis of AF/AT. The same two variables were independently correlated with any degree of AV block (years from SSc diagnosis: RR 1.11; 95% CI 1.01–1.23; p=0.004; iRAV: RR 1.14; 95% CI 1.02–1.27; p=0.019). Due to the low sample size, we were unable to detect any clinical predictors of sudden cardiac death in our population, however those who died experienced a larger worsening in left ventricle GLS values (4.0±1.6 vs. 0.9±0.4, p=0.056).

Conclusions

Supraventricular arrhythmias and conduction defects are common in patients with SSc. Time from diagnosis and right atrial volumes are able to predict the incidence of such conditions, supporting the hypothesis that a long-lasting disease and the anatomical remodelling of the right atrium could contribute to the developing of tachy- and bradyarrhythmias in this population.

Funding Acknowledgement

Type of funding source: None
Primary signs of vasular inflammation in children with familial hypercholesterolemia
Authors: Slastnikova E , Sadykova D.I , Galimova L.F , Usova N.E
Published: November 2020

Familial hypercholesterolemia is one of the most common genetic diseases that leads to premature atherosclerosis. We investigated endothelial function in children with heterozygous familial hypercholesterolemia in order to detect the first signs of endothelial inflammation in non-invasive ways.

In 57 children with heterozygous familial hypercholesterolemia (Group 1), endothelial function was studied by measuring levels of nitric oxide (NO), endothelin and hypersensitive C-reactive protein (hsCRP). All secondary causes that could lead to a change in these indicators were excluded. Children from Group 1 had no Clinical or ultrasound signs of atherosclerosis. No children from Group 1 were ever treated by statins or other lipid-lowering therapy. Results were compared with a group of children comparable in age and sex (Group 2). Average age of Group 1 was 9 years old ±2 months, Group 2 is 9 years old ±3 months. Average lipid values in Group 1: total cholesterol (TH) – 7.2±0.9 mmol/L, low density lipoproteins (LDL) – 4.7±0.7 mmol/L, triglycerides and high density lipoproteins (HDL) corresponded to normal. Group 2 average lipids: TH – 4.2±0.7 mmol/L, LDL – 2.3±0.4 mmol/L, the level of triglycerides and (HDL) corresponded to normal.

Results

The results in Group 1 were: NO 66.15±1.19 μmol/L, endothelin 0.418±0.121 pmol/L, hsCRP 0.25±0.1 mg/dl. They showed in Group 2: NO 39.15±0.15 μmol/L, endothelin 0.231±0.05 pmol/L, hsCRP 0.11±0.2 mg/dl. The results in group 1 were significantly higher (endothelin and hypersensitive reactive protein) and lower (NO) in terms of indicators.

Conclusions

There is significant difference in the levels of vasodilators, vasoconstrictors and hsCRP between Group 1 and Group 2, that means there are the signs of inflammation in the Children with no clinics of peripheral or coronary atherosclerosis. It can be used as biomarkers of premature atherosclerosis and can help to avoid it.

Funding Acknowledgement

Type of funding source: None
Long-term follow-up of paediatric patients with a subcutaneous implantable cardioverter-defibrillator
Authors: Van Der Stuijt W , De Wilde K.C , Baalman S.W.E , Quast A.B.E , Blom N.A , Wilde A.A.M , Knops R.E
Published: November 2020

Background

Inherited channelopathies, cardiomyopathies and structural heart diseases are known to increase the risk of sudden cardiac death in children and are occasionally treated with an implantable cardioverter-defibrillator (ICD). Due to their physical growth and higher level of activity, children experience more adverse events than adults, such as lead fractures, vascular problems and infections. The subcutaneous ICD (S-ICD) was introduced to avoid these lead-related complications and is expected to be especially beneficial for children who require ICD therapy. However, long-term follow-up data of this population are lacking.

Purpose

To evaluate long-term clinical outcomes of the S-ICD in the paediatric population.

Methods

Follow-up data were prospectively collected of all paediatric patients (age <18 years) who received their S-ICD in our tertiary centre between November 2009 and June 2019. Clinical outcomes that were assessed were appropriate or inappropriate shocks and complications that required surgical intervention.

Results

A total of 21 paediatric patients received an S-ICD, with a median age of 15 years (ranged 8–17) and a median body mass index of 18.8 kg/m2 (ranged 15.5–28.8, lowest weight 30kg). The indication for ICD implantation was mostly idiopathic ventricular fibrillation (38.1%) or genetic arrhythmic disease (28.6%). The subcutaneous lead was implanted in an S-shape to accommodate for growth in small patients, and straightening of the lead could be observed on successive chest X-rays (see figure). There was no need for lead or device revisions in this cohort. After a median follow-up of 4.3 years (IQR 2.7–6.5), five patients (23.8%) received an appropriate shock for ventricular arrhythmias and six patients (28.6%) received an inappropriate shock for supraventricular tachycardia (n=4) or double-counting (n=2). Complications that required device extraction occurred in three patients after 0.8±1.1 years and was the result of inappropriate shocks (n=1) and pocket infection (n=2). In two patients the S-ICD was extracted due to progression of their cardiac disease, of whom one needed biventricular pacing and one underwent heart transplantation.

Conclusions

The S-ICD appears efficacious in this heterogeneous paediatric population. Although higher than reported in adults, the long-term complication rate in paediatric S-ICD recipients is similar to the paediatric transvenous ICD population.

Funding Acknowledgement

Type of funding source: None
Alterations in mechanical properties of carotid artery in overweight and obese children
Authors: Kim S.A , Park P.K.H
Published: November 2020

Background

Atherosclerosis begins at a young age in a process that is clinically silent before events occur. Obesity in childhood has been associated with the alterations of vascular properties.

Purpose

The aim of this study was to investigate the subtle changes of mechanical properties of carotid artery (CA) in overweight and obese children.

Methods

We prospectively recruited a cohort of overweight (n=25) and obese (n=176) children aged 7–17 years and non-obese children with same age and gender (controls, n=31). Overweight is defined as a body mass index (BMI) at or above the 85th percentile and below the 95th percentile and obesity as a BMI at or above the 95th percentile for children of the same age and gender. The mechanical properties of carotid artery were directly measured in a cross-sectional image of common carotid artery using a velocity-vector imaging (VVI) analysis including instantaneous vessel area and deformation parameters as fractional area change (FAC), circumferential strain, and strain rate (SR).

Results

Compared to controls, obese children had higher blood pressures and serum glucose and worse lipid profiles than controls, whereas overweight children showed no any difference in blood pressure and laboratory findings. Among vascular properties, there were no differences in carotid intima-media thickness (cIMT) between the three groups. However, obese children showed larger vessel area and higher arterial stiffness presented as lower FAC, circumferential strain and SR than controls, whereas overweight children showed no difference in vascular properties with obese children and with controls except for circumferential SR. Circumferential SR in overweight children was significantly reduced than controls (0.47±0.19 cm/s, 0.75±0.22 cm/s, respectively, p<0.001) and was the only vascular parameter distinguishing overweight children from controls. In multiple linear regression analysis, independent determining factors of the circumferential SR of carotid artery were age (β=−0.13, p=0.03), serum triglycerides (β=−0.14, p=0.01) and BMI (β=−0.37, p<0.001) in this population.

Conclusions

In overweight and obese children, a decrease in circumferential SR of carotid artery precedes the changes of vessel wall thickness and vessel area. We demonstrated the subtle changes of mechanical properties of carotid artery precede the changes of structural properties in overweight and obese children.

Funding Acknowledgement

Type of funding source: None
Increasing age as a major determinant of major adverse outcomes in patients with atrial fibrillation: the EURObservational research programme in atrial fibrillation general long-term registry
Authors: Boriani G , Proietti M , Laroche C , Piot O , Lane D.A , Potpara T , Maggioni A.P , Lip G.Y.H
Published: November 2020

Introduction

Increasing age is a well-known determinant for incident atrial fibrillation (AF) as well as for adverse outcomes. With a progressively ageing population in Europe (and elsewhere), contemporary data are needed to investigate the impact of age in relation to major adverse events in AF patients.

Purpose

To evaluate the impact of increasing age on major adverse outcomes in a contemporary European AF cohort.

Methods

Patients enrolled in the EORP-AF Long Term General Registry were categorized by age: <65, 65–74, 75–84, and ≥85 years. Any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death, CV death, all-cause mortality were considered as outcomes.

Results

Among the 9762 patients included in this analysis, 2946 (30.2%) were <65 years, 3288 (33.7%) were 65–74 years, 2954 (30.3%) were 75–84 years and 574 (5.9%) were ≥85 years. With increasing age categories, there was a progressively higher prevalence of most risk factors and comorbidities. Accordingly, both mean CHA2DS2-VASc and HAS-BLED scores were progressively higher across the age categories (both p<0.0001). At discharge, use of any oral anticoagulant (OAC) drug was lower in patients ≥85 years compared to those aged 65–74 or 75–84 years (83.6% vs. 89.4% and 88.8%, respectively) but significantly higher than in those <65 years (80.2%) [p<0.001]. Rate of all major adverse events progressively increased across the age categories, being higher in those aged ≥85 (all p<0.001). Kaplan-Meier curves showed an increasing cumulative risk across the age groups for all the outcomes (p<0.0001) (Figure 1). A fully adjusted Cox regression analysis demonstrated a progressively increasing association between age categories and the risk of all major adverse outcomes (Table 1).

Conclusions

In a large contemporary cohort of European AF patients, increasing age was a major determinant of major adverse outcomes.

Figure 1. Kaplan-Meier Curves for All-Cause Death

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies supported its activities with unrestricted grants.