bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal and maternal outcomes in patients with tetralogy of Fallot
Authors: Mano T , Ferreira V , Moreira R I , Teixeira B , Agapito A , Rito T , Pinto F , Cruz Ferreira R , De Sousa L 
Published: October 2021

Abstract

Introduction
Women with tetralogy of Fallot (TOF) have an increased risk of adverse cardiac and neonatal events during pregnancy. The aim was to assess fetal and maternal outcomes in patients (pts) with uncorrected and corrected TOF.

Methods
Retrospective analysis of cardiological and obstetric data in women with TOF followed at our institution. Pregnancy and neonatal outcomes were compared in patients (pts) submitted to corrective surgery vs pts with no previous intervention and in pts with or without cyanosis.

Results
51 women (median age 27 years; median number of previous interventions of 2), 22% with cyanosis, who experienced 126 pregnancies resulting in 73 live births A previous corrective surgery was found in 78% (40 pts), while 4% (2 pts) had previous palliative surgery and 18% (9 pts) no previous procedure. We found that women that were not submitted to previous intervention had a significant higher incidence of preterm birth (56% vs 17.5%, p=0.029), spontaneous abortion (56% vs 10%, p=0.006) and stillbirth (22% vs 0%). No difference was found for obstetric complications between groups. Cyanotic pts also demonstrated higher incidence of low birth weight (LBW) (36% vs 7.5%, p=0.031), preterm birth (54% vs 17.5%, p=0.021), spontaneous abortion (55% vs 10%, p=0.004) and stillbirth (18% vs 0%). There were no cardiac complications during pregnancy nor evident deterioration on cardiac status. Congenital heart disease was reported in 2 infants (3% of live births).

Conclusions
Pregnancy is well tolerated in pts with TOF. In our population, even in uncorrected TOF and in pts with cyanosis, there were no cardiac complications during pregnancy, although those pts had worse fetal outcomes. An explanation for the low incidence of cardiac events may be less severe forms of the disease, allowing survival into adulthood without intervention.

Funding Acknowledgement
Type of funding sources: None.
Dose-dependent dynamics of glomerular filtration rate in patients with reduced renal function in the postinfarction period
Authors: Salyamova L , Kvasova O , Tomashevskaya Y , Borisova N 
Published: October 2021

Abstract

Objective
To evaluate the effect of 48-week therapy with atorvastatin at various doses on the glomerular filtration rate (GFR) in patients after acute ST-segment elevation myocardial infarction (STEMI).

Methods
103 STEMI patients aged 52 (45.5; 59) years (92 men and 11 women) were examined. The patients were randomized into three groups: group 1 – 39 patients taking atorvastatin 80 mg; group 2 – 26 patients who received atorvastatin 40 mg; group 3 – 38 people who took atorvastatin 20 mg. The compared subjects were matched by age, sex, height, BMI, and office BP. All patients were receiving STEMI treatment prior to study entry. Initially and after 24, 48 weeks of follow-up, the creatinine level was determined on an Olympus AU400 analyzer (Olympus Corporation, Japan), followed by the calculation of GFR using the CKD-EPI formula.

Results
In group 1, GFR was 86.3 at baseline [95% CI 80.3; 92.3], after 24 weeks – 85.1 [95% CI 80.4; 89.7], after 48 weeks – 85.9 [95% CI 80.4; 91.4] ml/min. In group 2, the following GFR values were found: on days 7–9 – 78.4 [95% CI 73; 83.8], after 24 weeks – 82.2 [95% CI 75.5; 89], and 48 weeks – 78.9 [95% CI 74.1; 83.6] ml/min. In group 3, GFR was 88.2 at baseline [95% CI 80.9; 95.5], at the 24th week – 84.9 [95% CI 80.4; 89.4], after 48 weeks of therapy – 81.1 [95% CI 75.5; 86.7] ml/min. Individuals with a baseline decreased GFR &lt;90 ml/min were identified in each group in accordance with the clinical practice guidelines of KDIGO (2012). At the same time, against the background of therapy with atorvastatin 80 mg, a significant increase in GFR from 71.8 [95% CI 67.9; 75.7] to 79.9 [95% CI 74.2; 85.6] after 24 weeks (p=0.02) and the subsequent increase in GFR to 81.0 [95% CI 74.9; 87.2] ml/min after 48 weeks (p=0.02). Against the background lower doses of atorvastatin, GFR dynamics were not observed: in group 2 – 74.0 [95% CI 69.1; 78.9], 79.3 [95% CI 71.5; 87.1], 77.2 [95% CI 71.7; 82.7] ml/min; in group 3 – 70.9 [95% CI 67.6; 74.1], 79.2 [95% CI 73.1; 85.4], 74.9 [95% CI 65.9; 83.9] ml/min.

Conclusions
In STEMI patients with an initially reduced GFR level, only atorvastatin therapy at a dose of 80 mg for 48 weeks of treatment was accompanied by a significant improvement in renal function.

Funding Acknowledgement
Type of funding sources: None.
Prognostic value of myocardial injury and chronic kidney disease in an emergency unit
Authors: Lal-Trehan Estrada N , Carrasquer A , Del Moral V , Sanchez R , Bonet G , Peiro O , Fort I , Bardaji A 
Published: October 2021

Abstract

Background
Cardiac troponin is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Their joint effect is yet to be clarified.

Purpose
This study aims to evaluate the prognostic implication of myocardial injury and CKD in patients attended in an emergency room.

Methods
Retrospective study carried out between January 2012 and December 2013 with consecutive patients attended in an emergency room with troponin determination, who were distributed into four cohorts according to positive troponin and/or glomerular filtration rate (GFR) &lt;45ml/min/ 1.7. We analysed their baseline characteristics and the four-year prognosis.

Results
3622 patients were included (median age 68.5 years [IQR 55.5–79.5]; 43% were women). Compared to subjects with normal GFR, the 565 subjects with CKD were significantly older (80.5 vs 66.5 years), with worse cardiovascular profile (arterial hypertension: 87% vs 56%; diabetes mellitus: 46% vs 22%) and greater comorbidity (history of myocardial infarction: 29% vs 18%; heart failure: 17% vs 5%; peripheral vascular disease: 16% vs 5%; cerebrovascular disease: 13% vs 7%%). Myocardial injury was also related to elderly and worse cardiovascular profile and comorbidity, especially in normal GFR subjects. 23.5% (718 subjects) of normal GFR subjects presented with myocardial injury. This percentage was much higher in the presence of renal impairment (331 subjects, 58.6%). Troponin was associated with a higher risk of death (both in-hospital and during follow-up) and of readmission due to infarction or heart failure, regardless of GFR. The reference cohort in the multivariate competing risk mode was that with subjects without myocardial injury or kidney disease. This analysis showed the worst MACE (all-cause death, non-fatal myocardial infarction and heart failure admission) in four-year follow-up in patients with renal impairment and positive troponin (HR 3.94, 95% CI 3.317–4.682), second worst MACE in those with myocardial injury and with normal GFR (HR 2.408, 95% CI 2.064–2.811), and then abnormal GFR patients with negative troponin (HR 1.532, 95% CI 1.220–1.923). Patients with both myocardial injury and renal impairment had the highest mortality (HR 4.633, 95% CI 3.829–5.604) and more readmissions for heart failure (HR 2.163, 95% CI 1.647–2.841). The myocardial-injury-and-normal-GFR cohort showed significantly higher mortality than the renal-impairment-with-negative-troponin cohort (HR 2.669 vs HR 1.794), more heart failure (HR 1.951 vs 1.067) and more myocardial infarctions (HR 2.439 vs 1.235) in the follow-up.

Conclusion
The results suggest that myocardial injury has better predictive power than chronic kidney disease for MACE events and also for individually mortality, readmission for heart failure or myocardial infarction.

Funding Acknowledgement
Type of funding sources: None.
Uncontrolled diabetes predicts anxiety and depression in CAD patients
Authors: Nura L , Hysein K , Beqiri L , Henein M Y , Bytyci I 
Published: October 2021

Abstract

Background and aim
Coronary artery disease (CAD) is a major public health problem worldwide because of high incidence of comorbidity and mortality. Diabetes mellitus (DM) is associated with clustered risk factor for CAD. The aim of this study was to assess the impact of diabetes in CAD and its relationship with depression.

Methods
The study included 77 patients (mean age 64±11 years, 63% female) with CAD. Based on comorbidity patients were classified into CAD with DM (n=49) and CAD without DM (n=28). In this prospective study demographic, clinic, echocardiographic and angiographic indices were collected as well as scale of anxiety and depression.

Results
Patients with CAD and DM were older (p=0.001), had reduced left ventricular ejection fraction-EF (p=0.02), more obese (p=0.03), had higher NYHA class (p=0.04), more prevalent arterial hypertension (p=0.04), and higher anxiety and/or depression scales (p&lt;0.001) compared with patients without DM. Whereas gender was not significantly difference (p=0.11). Diabetes most closely correlated with the scale of depression (r=0.61, p&lt;0. 001).
In multivariate analysis, only diabetes OR=1.099 (95% CI 1.028 to 1.231, p&lt;0.001), predicted depression in patients with CAD. Glycemic &gt;8.9 mmol/L, predicted the scale of depression in patients with CAD (sensitivity 75%, specificity 70%, AUC=0.72, p&lt;0.001).

Conclusions
Diabetes is the most important risk factor for CAD and the uncontrolled levels are related to patient's disturbed mental health. These results constitute important knowledge for nurses serving CAD patients.

Funding Acknowledgement
Type of funding sources: None.
Prevalence of dyspnea and/or chest pain persistence at mid-term after COVID-19 infection: a systematic review and meta-analysis
Authors: Mustafic H , Cekovic D , Yordanov Y , Dinh A , Helft G , Jourdain P 
Published: October 2021

Abstract

Introduction
COVID-19 is a recent infection that affects the whole world. Symptoms such as dyspnea and/or chest pain may persist in some people after the acute infection phase. However, the extent of this phenomenon is not yet well known.

Purpose
To determine the prevalence of dyspnea and/or chest pain at least at one month after COVID-19 infection diagnosis.

Methods
EMBASE, Ovid MEDLINE in-process and other nonindexed citations, and Ovid MEDLINE (between 1948 and January 15, 2021), and EBM Reviews-Cochrane Central Register of Controlled Trials and EBM Reviews-Cochrane Database of Systematic Reviews (between 2005 and January 15, 2021) were searched for a combination of keywords related to the type of exposure (COVID-19 infection) and to the type of outcomes (dyspnea persistence and/or chest pain persistence at least one month after COVID-19 infection diagnosis). Two independent reviewers selected studies of any design and in any language, using original data. Descriptive and quantitative information was extracted from each selected study and study quality was also assessed. We estimated prevalence in percentage and 95% Cis for each outcome, using a random-effects model. Statistical heterogeneity across the studies was calculated by the I2 statistic to quantify inconsistencies between studies. To assess the potential for publication bias, we visually inspected funnel plots and added the Egger's regression test p-value for funnel symmetry.

Results
After an exhaustive screening of 1287 citations in title and abstract, 31 studies were reviewed from entire article and 10 studies with 2004 patients were finally selected for meta-analysis. Interrater agreements were very high (0.91 and 1 respectively for the two selection steps). The pooled dyspnea persistence prevalence from 10 studies was of 39%; 95% Ci [29%-49%], p&lt;0.01, I2=91%, Egger's regression test p=0.19. The pooled chest pain persistence prevalence from 6 studies was of 18%; 95% Ci [11%-24%], p&lt;0.01, I2=89%, Egger's regression test p=0.12).

Conclusion
Dyspnea and/or chest pain persistence prevalences after COVID-19 infection diagnosis are unexpectedly high, at least at one month. We have to take into account high heterogeneity due to subjects characteristics, various COVID-19 infection severities and study methodologies but there were no statistical argument for a publication bias. Nevertheless, this phenomenon requires more research to determine the long-term prevalence of these symptoms persistence and the mechanisms involved.

Funding Acknowledgement
Type of funding sources: None.
Inhibition of RAS components attenuates progression of heart failure and its adverse consequences on myocardial remodeling in both normotensive and hypertensive rats
Authors: Sykora M , Kratky V , Tribulova N , Kopkan L , Szeiffova Bacova B 
Published: October 2021

Abstract

Rationale and purpose
Prevention or attenuation of heart failure (HF) is persistent task in clinic as well as challenge for progress in research. Both, intercellular connexin-43 (Cx43) channels and extracellular matrix (ECM) exert high impact on heart function. Thus, we aimed to explore whether HF due to volume overload (VO) induces alterations in myocardial Cx43, ECM proteins MMP2, SMAD2/3, TGFβ1 and PKC signaling as well as changes that may be revealed by enzyme histochemistry. Moreover, we tested the impact of treatment suppressing RAS on examined targeted proteins.

Methods
VO-HF was induced in male normotensive Hannover Sprague- Dawley (HSD) and mRen-2 transgenic hypertensive (TGR) rats by creating an aorto-caval fistula (ACF) and heart response was examined 20-weeks later. Sham-rats were compared with non-treated rats with ACF and those treated for 15-weeks with ACEI (trandolapril, 6mg/l, p.o.) or ARB (losartan (200mg/l, p.o.). Left ventricular heart (LV) tissue was analyzed using western blot, zymography and enzyme histochemistry.

Key results
Echocardiography confirmed an increase in cardiac output and a decrease in ejection fraction in both strains of rats. BW was higher in TGR vs HSD and it was not affected by VO. HW and LVW were higher in TGR vs HSD and VO increased both parameters regardless the strain while ACEI&gt;ARB attenuated it. In parallel, myocardial pro-hypertrophic PKCd expression was higher in TGR vs HSD and increased in both strains due to VO while both drugs prevent it. Glycogen phosphorylase and capillary associated 5-nucleotidase, alkaline phospatase and dipeptidyl peptidase IV activities were reduced due to VO in HSD and TGR and it was attenuated by treatment. Cx43 expression and its functional phosphorylation status were lower in TGR vs HSD and suppressed in both strains due to VO but ACEI&gt;ARB prevented it. Similar trend of changes was observed in PKCe expression, which phosphorylates Cx43. Profibrotic TGFβ1-Smad2/3 pathway was suppressed along with reduced MMP2 activity in TGR comparing to HSD. VO reduced SMAD2/3 in HSD and TGFβ1 in TGR as well as MMP2 expression in both strains, whereby treatment abolished these changes. VO decreased MMP2 (63kDa) activity only in TGR and ARB prevented it. VO did not affect collagen deposition in either strain vs sham rats.

Conclusions
Hypertrophic and hypofibrotic phenotypes are induced by volume overload in both rat strains. Together with deterioration of Cx43 mediated intercellular coupling it may contribute to heart dysfunction. Inhibition of RAS components attenuates progression of VO and its adverse consequences.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20
Telomerase and myocardin co-expressing mesenchymal cells increase survival and induce cardiac and vascular markers in cardiac stromal cells undergoing simulated ischemia/reperfusion
Authors: Madonna R , Guarnieri S , Csenger Kovacshazi C , Gorbe A , Giricz Z , Geng Y J , Mariggio M A , Ferdinandy P , De Caterina R 
Published: October 2021

Abstract

Background
Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favoring their paracrine activities.

Aim
To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs).

Methods and results
Murine CSCs were isolated with the cardiosphere (CSps) isolation technique.
T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28±4 vs 10±3%, p=0.02). Pretreatment with CM (15±2, p=0.02) or with the EV-enriched fraction (10±1%, p=0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more prononunced with CM (7±1%, p=0.01) or the EV-enriched fraction (2±1%, p=0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin.

Conclusions
The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.

Funding Acknowledgement
Type of funding sources: None.
Genetic predisposition in pediatric acute myocarditis: a pilot study
Authors: Gourzi P , Pantou M P , Vagenakis G , Tsoutsinos A , Vatsellas G , Makrythanasis P , Rammos S , Degiannis D 
Published: October 2021

Abstract

Background
Myocarditis is an inflammatory disease of the heart muscle with a wide range of clinical presentations, from asymptomatic to cardiogenic shock and death. Although acute myocarditis is rare in pediatric population, it is caused by common viral infections, like parvovirus B19 or enteroviruses. Limited scientific evidence supports the existence of a genetic background that could underlay the susceptibility to virus-induced myocarditis.

Purpose
The aim of the present study was to identify mutations in genes associated with cardiomyopathies, that could possibly underly acute myocarditis in pediatric patients with biopsy-proven parvovirus B19 infection, verified by real time PCR.

Methods
Nine pediatric patients presented in our center with acute myocarditis were genotyped with next generation sequencing using Clinical Exome Solution kit (Sophia Genetics) covering 4493 disease-related genes. Variant pathogenicity was accessed according to guidelines by American College of Medical Genetics (2015).

Results
Genetic analysis revealed that three of the nine patients were found positive for pathogenic/likely pathogenic mutations in TTR, ABCC6 and SLC22A5 genes. The patient that carried the SLC22A5 variant initially received telbivudine and her ejection fraction was improved from 20% to 45%. Genetic test results suggested that the patient may suffer from mild L-carnitine deficiency. Oral supplementation with high dose of L-carnitine during one month period improved dramatically her EF to normal (65%). The patient that carried the ABCC6 mutation, also carried a variant of unknown significance in MYH7 gene. Four patients carried variants of unknown significance. The variants of unknown significance detected in MYBPC3, SCN5A, and MYH7 genes are of particular interest since they accumulate evidence of pathogenicity. Two patients did not harbor any mutations.

Conclusion
A significant proportion of rare variants in genes associated with cardiomyopathies has been identified in a small cohort of pediatric patients with parvovirus-induced acute myocarditis. The findings of our study, although limited, support the existence of a genetic background that could function as a predisposing factor influencing the clinical course of the disease.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Onassis Foundation
Interleukin 6 –174 G/C polymorphism: its relation to coronary artery disease and circulating IL-6 levels – a systematic review and meta-analysis
Authors: Rai H , Colleran R , Cassese S , Joner M , Kastrati A , Byrne R A 
Published: October 2021

Abstract

Introduction
Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 –174 G/C, rs1800795) have been found to be independently associated with coronary artery disease (CAD). However, the association status of this polymorphism with CAD remains unclear.

Purpose
We conducted a systematic review and updated meta-analysis to comprehensively ascertain the association status of IL6 –174 G/C with CAD and its effect on the levels of circulating IL-6 in humans.

Methods
Comprehensive online search was undertaken to find relevant case-control/cohort studies investigating the association of IL6 –174 G/C with CAD. The association status of –174 G/C with CAD amongst pooled sample as well as separately amongst different ancestral populations was assessed. Association of –174 G/C with circulating IL-6 levels was also assessed amongst pooled sample as well as separately for CAD cases and CAD-free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled by Mantel-Haenszel fixed-effects models.

Results
Quantitative synthesis for assessing the role of this polymorphic variant in CAD was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases / 32,053 controls). The pooled association of –174 G/C with CAD was found to be statistically significant through dominant (OR= 1.15, 95% CI= 1.05–1.25, p=0.002) as well as allelic genetic model comparisons (OR= 1.13, 95% CI= 1.06–1.21, p=0.0003). Asian and Asian-Indian ancestral subgroups showed significant association with CAD in both genetic model comparisons (OR range= 1.29 to 1.53, p value range ≤0.02). Other ancestral subgroups did not show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the “C” allele carriers in the pooled sample (Standard mean difference, SMD= 0.31, 95% CI= 0.01–0.22 pg/ml, p=0.009) as well as the CAD-free control subgroup (SMD= 0.10, 95% CI= 0.02–0.17 pg/ml, p=0.009). CAD case subgroup did not show any significant association (p=0.12).

Conclusions
The present systematic review and meta-analysis confirms an association between IL6 –174 G/C polymorphism residing in the IL6 gene and CAD, especially amongst Asian and Asian-Indian ancestral groups. Upregulation of plasma IL-6 levels in the “C” allele carriers seem to be at least partly responsible for the observed association. Further investigations with large structured case-control studies amongst these ancestral groups are warranted.

Funding Acknowledgement
Type of funding sources: None.