bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled safety and efficacy of inclisiran in patients with statin intolerance (ORION-10 and ORION-11)
Authors: Wright R.S , Kallend D , Raal F.J , Stoekenbroek R , Koenig W , Leiter L.A , Landmesser U , Schwartz G , Wijngaard P.L.J , Kastelein J.J.P , Ray K.K 
Published: November 2020

Abstract

Introduction
Statin-associated side effects prevent a substantial proportion of patients from being adequately treated with statin therapy and achieving adequate LDL-C reductions. Phase 3 trials showed that inclisiran, a new siRNA, durably lowers LDL-C by ≥50% on top of maximally tolerated statin therapy.

Purpose
To evaluate inclisiran's tolerability and LDL-C lowering effects among individuals who were not receiving statin therapy mainly because of statin intolerance.

Methods
The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) with LDL-C &gt;70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. The primary efficacy endpoints were % change in LDL-C from baseline to Day 510 and time adjusted % change in LDL-C from baseline after Day 90 and up to Day 540. Absolute LDL-C reductions were secondary endpoints. This analysis included individuals who were not on statin therapy at baseline.

Results
The trials included 252 (7.9% of the pooled trial populations; mean age 68; male 62%; lipid-lowering therapy 28%). AE rates and LDL-C reductions are shown in the Table. Overall, 12 (4.7%) patients had myalgia (4.8% in the inclisiran groups, 4.7% in the placebo groups). There were 8 discontinuations in the inclisiran groups (6.5%) and 3 in the placebo groups (2.3%). The placebo-adjusted mean reduction in LDL-C at Day 510 was 45.8%, an absolute reduction of 68.0 mg/dL (p&lt;0.0001).

Conclusion
Among statin intolerant individuals in ORION-10 and 11, inclisiran potently and durably lowered LDL-C with an adverse event profile comparable to placebo. Inclisiran may represent a new and potent therapeutic option for patients with elevated LDL-C unable to tolerate statins.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): The Medicines Company
Epicardial obesity as a significant preclinical predictor of atherosclerosis of brachiocephalic arteries
Authors: Ott A , Chumakova G.A 
Published: November 2020

Abstract

Obesity is one of the significant factors of cardiovascular risk. Nowadays it is understood that it is visceral obesity (VO), which has metabolic activity due to the synthesis of adipokines, that determines cardiometabolic risk. The effect of epicardial obesity (EO), as a variant of VO on the formation of cardiometabolic risk (in particular coronary atherosclerosis) is being actively studied. The role of EO in the development of atherosclerosis of other localizations has been little studied.

Objective
To study the predictor value of EO as well as traditional criteria for obesity: body mass index (BMI) and waist circumference (WC) for the formation of atherosclerosis of brachiocephalic arteries (BCA).

Materials and methods
The study included 140 men 45.2±4.3 years old with arterial hypertension (AH) of the 1–3 degree and the absence of clinical manifestations and anamnesis of atherosclerosis of any localizations with a BMI of 20–35 kg /m2 and abdominal obesity according to WC ≥94 cm. Patients were divided into two groups depending on the thickness of the epicardial adipose tissue (EAT) measured behind the free wall of the right ventricle by echocardiography. Group 1 consisted of 60 patients with epicardial obesity (EAT ≥7 mm), group 2 included patients without epicardial obesity (EAT &lt;7 mm). Subclinical atherosclerosis of BCA was evaluated in all subjects using duplex brachiocephalic arteries (BCA).

Results
When assessing the thickness of the intima-media of the carotid arteries (TIM), a subclinical marker of BCA atherosclerosis, higher average TIM values in group 1 (EAT ≥7 mm) were revealed (1.09±0.34 mm versus 0.74±0, 05 mm in group 2 (EAT &lt;7 mm) (p=0.0001). Prevalence of subclinical BCA atherosclerosis from (20–45%) in group 1 patients was found in 57%, in group 2 only 4% (p=0.01). In the first group, hemodynamically significant asymptomatic BCA stenosis (50–65%) was found in 8% of patients. No hemodynamically significant BCA stenosis was detected in the second group. Using ROC analysis, the threshold value of EAT (9.25 mm) was obtained as a risk factor for hemodynamically significant stenoses of BCA (50% or more) with high prognostic significance (the area under the curve was 0.92). Using multivariate analysis of variance, the effect of various criteria of obesity on the formation of BCA atherosclerosis was studied. As a result of the analysis it was revealed that only EAT (p=0.02) influenced the development of BCA atherosclerosis (TIM more than 1.3 mm). WC and BMI did not affect the development of BCA subclinical atherosclerosis (p=0.21; p=0.24, respectively).

Conclusions
EO (EAT ≥7 mm) is an early marker of BCA subclinical atherosclerosis in contrast to the traditional criteria for obesity (BMI, WC). Patients with EAT of 9.25 mm or more need additional examinations and the appointment of pharmacotherapy aimed at the prevention of secondary complications.

Funding Acknowledgement
Type of funding source: None
Is cardiac troponin elevation following strenuous exercise clinically relevant in healthy subjects?
Authors: Orn S , Melberg T.H , Omland T , Skadberg O , Bjorkavoll-Bergseth M.F , Erevik C.B , Hansen M.W , Auestad B , Bergseth R , Aakre K.M , Kleiven O 
Published: November 2020

Abstract

Background
Exercise causes an increase in cardiac troponin (cTn) levels. Exercise-induced myocardial injury (cTn &gt; the 99th percentile) has been associated with adverse cardiovascular (CV) outcomes in older subjects with CV risk factors. The long-term clinical implications of exercise-induced cardiac troponin elevations in healthy individuals has not been determined.

Purpose
To assess the association between exercise-induced cardiac troponin increase above the 99th percentile and all-cause death, myocardial infarction, revascularization, sudden cardiac arrest, heart failure admission and stroke during 5-years follow-up in a large cohort of healthy recreational athletes.

Methods
1002 healthy subjects that completed a 91-km bike race in 2014 were eligible. Follow-up data was available for 991 subjects (99%). High-sensitivity cardiac troponin I (cTnI) and T (cTnT) were obtained 24h prior to the race, and at 3h and 24h after the race in 2014.

Results
Median age was 46 (25th-75th percentile: 40–53) years at inclusion, and 776 (78%) were male. Race duration was 3.8 (3.4–4.3) hours. At 3-hours following the race 821 (82.8%) of subjects exceeded the sex-specific 99th percentile of the cTnI assay and 910 (91.8%) of the cTnT assay. At 24-hours following the race 168 (17%) of subjects exceeded the sex-specific 99th percentile of the cTnI assay and 263 (27%) of the cTnT assay. During 5 years of follow-up 12 subjects (1.2%) suffered a CV event. Exercise-induced cardiac troponin increase above the 99th percentile was not associated with increased risk of adverse CV events, neither at 3-hours nor at 24-hours following the race (Figure 1). This finding was further supported by no significant relationship between adverse CV events and cTnI or cTnT at any time-point, assessed as continuous variables.

Conclusion
Myocardial injury, defined as a cardiac troponin level above the 99th percentile, occurs frequently following strenuous exercise. In the present study, however, healthy subjects with cardiac troponin increase above the 99th percentile following strenuous exercise were not found to have an increased five-year risk of cardiovascular events. frequent occurrence following strenuous exercise.
Figure 1

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Stavanger University Hospital, Abbott Diagnostics
First-degree atrioventricular block in children and adolescent athletes
Authors: Velasquez Rodriguez J , Gonzalez-Saldivar H , Li X , Bruna-Fernandez V , Valero-Masa M.J , De Hevia M , Diaz-Gonzalez L 
Published: November 2020

Abstract

Introduction
Intense regular training produces cardiac adaptations that manifests in various changes in the electrocardiogram (ECG), with sinus bradycardia being the most common finding. In adults the PR interval may be elongated and according to different series it can occur in 10–33% of cases, in the contrary in children and adolescent athletes the prevalence categorized by age has not been studied.

Purpose
Determine the incidence of first-degree atrioventricular (AV) block in a population of children and adolescent athletes in our environment, categorized by age.

Methods
We performed a cross-sectional study involving children and adolescent athletes between 5 and 16 years old who received a sport medical examination between August 2018 and May 2019. The ECG were obtained and analyzed following international standards, adequate electrode placement was ensured and was interpreted by cardiologists. The PR interval was obtained, considering prolonged if PR&gt;180 milliseconds (ms) in children under 10 years old, PR&gt;190 ms between 10 and 14 and PR&gt;200 ms in those over 14. We categorized our athletes by age into the following four groups corresponding to approximated quartiles: G1 5–8 years, G2 9–11 years, G3 12–13 years, and G4 14–16 years

Results
A total of 6401 subjects were included, mean age was 11.2±2.9 years, 93.7% were male, soccer players (97.2%) and Caucasian (99.2%). They trained a mean of 5.4±2.3 hours a week. 11.4% of the patients had mild (50–59 bpm) or moderate (40–49 bpm) bradycardia, but none had severe bradycardia (&lt;40 bpm). Sixty-one patients (0.96%) had 1st degree AV block and 19 (0.30%) had a PR interval at higher limit of normality. When stratified by age groups, the prevalence of 1st degree AV block was higher in the second quartile (Table 1). We did not find cases of Wenckebach or high-grade AV block (Mobitz II or 3rd degree AV block).

Conclusions
In children and adolescent athletes, the incidence of first-degree AV blockade is low (around 1%) and significantly lower than what is reported in adults. This may be due to a lower vagal tone in this population. If detected it may prompt clinicians to pursue further investigation given the low proportion of 1st degree AV block in children and adolescent athletes.
Figure 1. Sixteen year old patient ECG

Funding Acknowledgement
Type of funding source: None
The impact of sex, gender and healthcare system on quality of care among young adults with acute myocardial infarction
Authors: Raparelli V , Pilote L , Behlouli H , Dziura J , Bueno H , D'Onofrio G , Krumholz H.M , Dreyer R.P 
Published: November 2020

Abstract

Background
The quality of care among young adults with acute myocardial infarction (AMI) may be related to biological sex, psycho-socio-cultural (gender) determinants or healthcare system-level factors.

Purpose
To examine whether sex, gender, and the type of healthcare system influence the quality of AMI care among young adults.

Methods
A total of 4,564 AMI young adults (&lt;55 years) (59% women, 47 years, 66% US) were analyzed from the VIRGO and GENESIS-PRAXY studies consisting of single-payer (Canada, Spain) versus multipayer (US) systems. For each patient treated in each system we calculated a quality of care score (QCS) for pre-AMI (1-year pre admission), in-hospital, and post-AMI (1-year post discharge) phases of care (number of quality indicators received divided by the total number [range=0–100%], with higher scores indicating better quality). Ordinal logistic or linear regression models, and 2-way interactions between sex, gender and healthcare system were tested.

Results
Women in the multipayer system had the highest risk factor burden. Across the phases of care for AMI, 20% of quality indicators were missed in both sexes. High stress, earner status, and social support were associated with a higher QCS in the pre-AMI phase, whereas only employment and earner status were associated with QCS in all other phases. In the pre-AMI phase, women had higher QCS than men, mainly in the single-payer system (adjusted-OR=1.85, 95% CI 1.46,2.35 vs. 1.07, 95% CI 0.84,1.36, P-interaction= 0.002). Regardless of sex, only employment status had a greater effect in the multipayer system (adjusted-OR=0.59, 95% CI 0.44,0.78 vs 1.13, 95% CI 0.89,1.44, P-interaction &lt;0.001). In the in-hospital phase, women had a lower QCS than men, especially in the multipayer system (adjusted-mean-difference: −2.48, 95% CI-3.87, −1.08). Employment was associated with a higher QCS (2.0, 95% CI 0.9–3.17, P-interaction &gt;0.05). Finally, in the post-AMI phase, men and women had a lower QCS, predominantly in the multipayer system. However, primary earners had higher QCS regardless of system.

Conclusion
Sex, gender, and healthcare system affected the quality of care after AMI. Women had a poorer in-hospital than men and both women and men had suboptimal post-discharge care. Being unemployed lowered the quality of care, more so in the multipayer system.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health and Research (CIHR)
Cardiac function in pregnant women with a Fontan circulation following live birth
Authors: Lodge F , Castleman J , Fox C , Morris R.K , Ram C , Clift P , Hudsmith L 
Published: November 2020

Abstract

Background
Fontan circuits are used to palliate congenital heart disease where patients have a single functioning ventricle. The venous return to the heart is redirected to the pulmonary arteries through the use of a conduit, bypassing the heart. Many females with Fontan circuits are now reaching child-bearing age and some desire pregnancy. However, pregnancy in women with Fontan circuits is associated with high complication rates.

Purpose
We compared postnatal cardiac function in women with a Fontan circulation with pre-pregnancy cardiovascular investigations.

Methods
Data were collected from case notes of all women with a Fontan circulation giving birth after 24 weeks of gestation at Birmingham Women's Hospital between 1997 and 2019.

Results
18 women with a median age of 29±6 years were followed up for 8.0±9 years. There were 21 live births at a median gestation of 32±5 weeks, of which 81% were caesarean sections. Three infants (14%) were born before 30 weeks' gestation and only two (10%) at term. Significant dyspnoea complicated 19% of pregnancies and postpartum haemorrhage occurred in 24%.
Pre-pregnancy cardiac magnetic resonance (CMR) data were available for 11 women and post-pregnancy for 14. Post-pregnancy scans were performed a median of 1.5±4.8 years after birth. Ejection fraction was 63.6±5% at baseline and tended to reduce following pregnancy (median −5.0±8%, n=7). Pre-pregnancy peak oxygen consumption (VO2max) was 73±14% of predicted on cardiopulmonary exercise testing. Median change in VO2max was −8±22% post-pregnancy (n=4). There was no change New York Heart Association (NYHA) class or resting saturations after pregnancy.

Conclusions
Preterm delivery and maternal bleeding were prevalent in this cohort. Exercise capacity was moderately impaired and saturations were typically low. Pregnancy does not seem to have longer term impact on oxygen saturations or NYHA class. Larger series are needed to confirm whether pregnancy is detrimental to postpartum systolic function. CMR can give comprehensive assessment of cardiac function before and after pregnancy and provide data to inform the crucial pre-pregnancy counselling for Fontan patients of child-bearing age.

Funding Acknowledgement
Type of funding source: None
Right ventricular function and right heart catheterization as predictors of ECMO requirement in lung transplantation
Authors: Garcia Gomez S , Monivas V , Goicolea J , Oteo J.F , Campo-Canaveral De La Cruz J.L , Crowley Carrasco S , Garcia Gallo C , Romero Roman A , Fernandez-Diaz J.A , Garcia-Touchard A , Cavero Gibanel M.A , Mingo Santos S 
Published: November 2020

Abstract

Introduction
Lung transplantation (LT) often requires extracorporeal life support with extracorporeal membrane oxygenation (ECMO) because of several complications (included acute heart failure) during the intervention. Data on predictors of intraoperative ECMO use in these patients are scarce but it is an interesting topic because ECMO support has been linked to worse outcomes after LT.

Purpose
The main aim of our study is to assess which pre-surgical characteristics of right ventricular (RV) function and data from right heart catheterization (RHC) could help us to anticipate the need of ECMO in LT.

Methods
We conducted a retrospective observational study of all patients who underwent LT at our institution along 2018. We analysed data from echocardiogram (ECO) and RHC. All subjects underwent transthoracic echocardiography (TTE) according to the latest ASE/EACVI guidelines. Strain analysis was carried out by speckle-tracking echocardiography (QLAB 10.7, Philips).

Results
We included all 47 patients who underwent LT from January to December of 2018. They were middle age patients (52±11.8 years old) 51.1% men, 61.7% smokers (other cardiovascular risks: diabetes mellitus (8.5%), hypertension (23.4%) or dyslipidaemia (27.7%)). 24 (51%) of them needed intraoperative ECMO. 21 patients (45%) were evaluated by RHC before LT and ECO quality was good enough to evaluate different data in 41 patients (87%).
Variables related to ECMO requirement vs non-ECMO use were: mean pulmonary artery pressure (23.1±7.3 vs 16.67±4.9 mmHg, p=0.027), mean transpulonary gradient (16.9±6.6 vs 8.9±3.6 mmHg, p=0.027) and diastolic transpulmonary gradient (9.8±8.1 vs 2.3±4.7 mmHg, p=0.002) from RHC and RV mid cavity diameter (3.4±0.8 vs 2.8±0.6 mm, p=0.001) from ECO. Besides this, free-wall RV longitudinal strain (FWRVLS) showed a tendency to be lower in patients who required ECMO (17.3±4.5% in vs 21.4±4.5%, p=0.072).

Conclusion
According to our results, RV mid cavity diameter measured by ECO and mean pulmonary artery pressure, mean and diastolic pulmonary gradients measured by RHC are useful tools to predict which patients could require ECMO during LT. FWRVLS showed an interesting tendency of lower values of it in LT using ECMO. This exploratory finding opens an important investigation line about a parameter which could help us to identify patients with subclinical right ventricle dysfunction.
ROC curve

Funding Acknowledgement
Type of funding source: None
Defining the metabolomic profile associated with early cardiotoxicity in patients with breast cancer treated with anthracyclines
Authors: Cocco D , Ferro E.G , Ricci S , Deidda M , Noto A , Madeddu C , Atzori F , Scartozzi M , Mercuro G , Cadeddu Dessalvi C 
Published: November 2020

Abstract

Background
Anthracycline (ANT) therapy has dramatically improved clinical outcomes for patients with breast cancer, but it causes cardiotoxicity (CTX) in a dose-dependent manner. Current cardiac biomarkers (troponin, brain natriuretic peptide) and 2D echocardiography only detect CTX in advanced and often irreversible stages. Metabolomic analysis may allow early diagnosis of CTX, and prompt initiation of cardio protective therapies.

Purpose
To diagnose early CTX via speckle tracking echocardiography (STE), and to characterize the metabolomic fingerprint of patients affected by ANT-mediated CTX.

Methods
In 2019, patients with breast cancer and normal baseline ejection fraction (EF) were enrolled and longitudinally monitored through clinical assessment, blood sample collection and echocardiography, before initiation of ANT therapy and at 180, 270 and 360 mg/m2 of ANT. CTX, defined as &gt;15% reduction in Global Longitudinal Strain (GLS), was monitored at each ANT dose increment. Unsupervised Principal Component Analysis, supervised Partial Least Square and Partial Least-Square Discriminant Analyses were used to compare the metabolomic profiles of patients who did and did not develop CTX during the study period.

Results
In the study sample (n=33), no patient developed clinical heart failure, but 8 patients (25%) developed CTX by GLS criteria. Patients with CTX had a significant decrease in GLS compared to patients without CTX at 270 mg/m2 (GLS 20.5 vs 17.9, p=0.01) and 360 mg/m2 ANT (GLS 21.6 vs 17.7, p&lt;0.001), but no significant differences in EF or other 2D echocardiographic parameters. The PLS-DA model at 360 mg/m2 ANT (R2=0.92, Q2=0.53, p=0.03) identified a significantly higher prevalence of Krebs cycle intermediates (like fumarate and succinate), and fatty acids (like linoleic acid) in patients with CTX. On the contrary, patients without CTX at 360 mg/m2 ANT had significantly higher levels of cardioprotective metabolites, like tryptophan.

Conclusions
For the first time in a human population of breast cancer patients, we show that early ANT-induced CTX (diagnosed via asymptomatic GLS reduction) is associated with a unique metabolomic profile, which affects molecular pathways of energy production. Notably, CTX damage upregulates similar metabolites to those previously identified in clinical heart failure and in mouse CTX models. Our results suggest that a metabolomic fingerprint can be leveraged to create prediction models to identify patients at higher risk of developing cardiovascular complications from ANT therapy. This, in turn, will allow to personalize both chemotherapy and cardioprotective treatments.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): University of Cagliari
Hypertensive disorders of pregnancy and impact on in-hospital cardio-obstetric outcomes
Authors: Wu P , Chew-Graham C , Maas A , Chappell L , Potts J , Gulati M , Jordan K , Mamas M 
Published: November 2020

Abstract

Introduction
Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity. However, short-term outcomes of HDP subgroups remain unknown.

Methods
Using the United States National Inpatient Sample database, all delivery hospitalizations between 2004 and 2014 with or without HDP (preeclampsia/eclampsia, chronic hypertension, superimposed preeclampsia on chronic hypertension and gestational hypertension) were analysed to examine the association between HDP and adverse in-hospital outcomes.

Results
We identified &gt;44 million delivery hospitalizations, within which the prevalence of HDP increased from 8% to 11% over a decade with increasing comorbidity burden. Women with chronic hypertension have higher risks of myocardial infarction, peripartum cardiomyopathy, arrhythmia and stillbirth compared to women with preeclampsia. Out of all HDP subgroups, the superimposed preeclampsia population had the highest risk of stroke (OR 7.83, 95% CI 6.25, 9.80), myocardial infarction (OR 5.20, 95% CI 3.11, 8.69), peripartum cardiomyopathy (OR 4.37, 95% CI 3.64, 5.26), preterm birth (OR 4.65, 95% CI 4.48, 4.83), placental abruption (OR 2.22, 95% CI 2.09, 2.36), and stillbirth (OR 1.78, 95% CI 1.66, 1.92) compared to women without HDP. In conclusion, we are the first to evaluate chronic SH without superimposed preeclampsia as a distinct subgroup in HDP and show that women with chronic SH are at even higher risk of some adverse outcomes compared to women with preeclampsia.

Conclusion
The chronic hypertension population, with and without superimposed preeclampsia, is a particularly high risk group and may benefit from increased antenatal surveillance and the use of a prognostic risk assessment model incorporating HDP to stratify intrapartum care.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIHR