bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual fractional flow reserve derived from coronary angiography – artery and lesion specific correlations
Authors: Mano T , Ferreira V , Ramos R , Bras P , Reis J , Grazina A , Jacinto S , Teixeira R , Oliveira E , Santana A , Melo J , Cacela D , Cruz Ferreira R
Published: October 2021

Introduction

Virtual Fractional flow reserve (vFFR) from standard non-hyperaemic invasive coronary angiography (ICA) has emerged as a promising non-invasive test to assess hemodynamic severity of coronary artery disease (CAD).

Purpose

To investigate the difference in vFFR analysis between vessels and specific lesions.

Methods

Retrospective analysis of consecutive patients (pts) who underwent invasive functional assessment (iFA) in a tertiary center between 2019 and 2020. vFFR was calculated using dedicated software (CAAS Workstation 8.4) based on coronary angiograms of the acquired in ≥2 different projections, by operators blinded to iFA results. Diagnostic performance of vFFR was evaluated and correlated with iFA, according to coronary vessel, vessel diameter at stenosis, diameter stenosis and area stenosis at lesion. vFFR was considered positive when <0.80. FFR <0.8 and iFR/RFR <0.90 were classified as positive according to current clinical standards.

Results

106 coronary arteries of 95 pts (78% male, mean age 67.8±9.7 years) underwent vFFR evaluation. ICA indications were chronic coronary syndrome in 63% or acute coronary syndrome (non-culprit lesion) in the remaining pts. VFFR accuracy was good (AUC 0.839 (p<0.001) and Pearson's correlation coefficient 0.533 (p<0.001) when vFFR was measured in the distal vessel segment. The correlation improved when vFFR were assessed at lesion site (r=0.631, p<0.001) or up to 1cm below the stenosis (0.610, p<0.001). Binary concordance of 89% were observed in RCA and LAD (Sensibility -S 68%, Specificity-Sp 96%, False positive -FP 3.8%, False negative - FN 31%, predictive positive value-PPV 87%, predictive negative value- PNV 89%), while in the circumflex coronary artery binary concordance were of 77% (S 50%; Sp 82%; FP 18%; FN 50%; PPV 33% and PNV 90%). Correlation between vFFR and iFA was higher in vessels ≥2mm (r=0.730, p<0.001). and in lesions in the extremes of the severity spectrum (Table 1).

Conclusion

vFFR has a moderate to high linear correlation to iFA, depending on the artery and type of lesion studied. The higher correlation was found when vFFR were measured at lesion site, in non-circumflex artery stenosis, in vessels ≥2mm and in vessels with mild or severe stenosis.

Funding Acknowledgement

Type of funding sources: None.
Comparison of clinical effect of living alone between urban area and rural area in patient with acute coronary syndrome
Authors: Takeuchi M , Dohi T , Takahashi N , Endo H , Wada H , Doi S , Kato Y , Ogita M , Okai I , Iwata H , Okazaki S , Isoda K , Suwa S , Miyauchi K , Minamino T
Published: October 2021

Background and objective

Living alone is reported as an independent risk factor for worse clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Manifestations of psychological stress such as depression and anxiety in patients living alone is thought to be associated with subsequent cardiovascular events. The impact of living alone on the psychological factors of patients may be differ depending on their living environment. However, comparison of the effects of living alone in different living environment on the prognosis of patients with ACS has not been reported.

Purpose

The aim of the present study was to compare the clinical effect of living alone on clinical outcomes in patients with ACS between urban area and rural area.

Methods

Data from a multi-center, observational study of consecutive patients who underwent emergency PCI for ACS between January 2012 and December 2016 were analyzed. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE). MACCE was defined as composite of cardiovascular death, ACS, and stroke.

Results

In this study, 1349 patients were enrolled and divided into two population according to their living environment: urban area population (n=417), and rural area population (n=932). In urban area population, 87 patients (20.9%) were living alone, and 330 (79.1%) were living together. In rural area population, 169 (18.1%) were living alone, and 763 (81.9%) were living together. There are no significant differences in baseline characteristics between the living alone group and the living together group in both urban area population and rural area population. During a median follow-up period of 2.1 years, Kaplan-Meier curves showed the living alone group had higher risk of MACCE than the living together group in urban area population (log-rank, p=0.01). On the other hands, there are no significant differences in the incidences of MACCE between two groups in rural area population (p=0.86). After adjustment for other covariates, the living alone was significantly associated with MACCE (hazard ratio [HR], 2.83; 95% confidential interval [CI], 1.16–6.91; p=0.02) compared with the living together group in urban area population. However, in rural area population, the living alone group was not significantly associated with MACCE (HR, 1.02; 95% CI, 0.66–1.57; p=0.92) compared with the living together group.

Conclusion

Living alone was significantly associated with worse clinical outcomes after emergency PCI of ACS in urban area but not in rural area.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Symptoms reported in calls to emergency medical services 24 hours prior to out-of-hospital cardiac arrest
Authors: Gnesin F , Mills E H A , Moeller A L , Jensen B , Zylyftari N , Ringgren K B , Boeggild H , Christensen H C , Blomberg S N F , Lippert F , Folke F , Torp-Pedersen C
Published: October 2021

Background and purpose

It remains unknown whether patients with out-of-hospital cardiac arrest (OHCA) experience prodromal symptoms. We aimed to investigate symptoms reported by patients with OHCA contacting emergency medical services (EMS) within 24 hours prior to arrest.

Methods

We linked OHCAs occurring from 2016 through 2018 to corresponding emergency calls occurring within 24 hours prior to arrest (defined as “pre-arrest calls”). These calls were included and evenly split and evaluated by authors.

Results

Among 4071 patients with OHCA, 481 patients (11.8%) had pre-arrest calls (59.9% males, median age 74 years) with a total of 539 calls. Figure 1 shows the reported symptoms across calls. The most commonly reported symptoms were breathing problems (59.4%), confusion (23.0%), unconsciousness (20.2%), chest pain (19.5%) and paleness (19.1%). The most common co-occurring symptom pairs were breathing problems in combination with paleness (14.5%), confusion (14.1%), unconsciousness (13.5%), sweating (13.0%) and chest pain (11.9%), respectively. An urgent response was dispatched in 68.7% of calls containing breathing problems compared to 83.0% of calls containing chest pain.

Conclusion

Among patients with OHCA, 11.8% had a call to EMS within 24 hours prior to arrest and breathing problems was the most commonly reported symptom occurring in 59.4% of calls.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationResearch Grant from Nordsjællands Hospital Figure 1
Comorbidities associated with anatomical and functional myocardial impairments assessed by 13 N-ammonia positron emission tomography
Authors: Alexanderson-Rosas E , Espinola-Zavaleta N G , Antonio-Villa N E , Gurrola-Luna H
Published: October 2021

Background

There has been an increase in the number of comorbidities in that predispose to ischemic heart disease in developing countries. Nevertheless, the identification of associated risk factors could unveil impairments within myocardial function

Purpose

We aimed to assess the prevalence and factors associated with reduced modifications of LVEF (>5%), ischemia (SDS ≥6 pts), reduced coronary flow reserve (≤2.5 pts) and coronary artery obstruction (≥50%) using a positron emission tomography–computed tomography.

Methods

A cross-sectional study of patients with clinical suspicious of angina who attended the PET/CT unity in a faculty of medicine was designed. We designed a clinical questionnaire to capture information regarding clinical history of comorbidities, angina, medication use and lifestyle habits. A myocardial perfusion study (MPS) was performed to identify myocardial ischemia, infarction, dyssynchrony and reduced coronary flow reserve. Logistic regression analyses were performed to identify associated factors.

Results

1273 patients underwent a PET/CT study; 66.1% (n=841) were male with a median age of 62.4 (±12.7) years. In our population, 36.4% (n=464) reported 1 or 2 comorbidities, 31.6% (n=402) 3 to 4 and 4.7% (n=60) more than 5; arterial hypertension (46.9%), dyslipidemia (43.9%), and diabetes (20.8%) were highly prevalent. Angina (34.4%) and palpitations (13%) were the most frequent symptoms at evaluation (Table 1). We found that that the presence of age ≥65 years, history of myocardial infarction, male sex, precordial chest pain, agrarians in chest pain, familiar history of myocardial infarction and comorbidities such as diabetes, arterial hypertension and obesity were associated with impairments in LVEF, ischemia, reduced coronary flow reserve and coronary artery obstruction (Figure 1).

Conclusions

The presence of comorbidities in our population is high. The identification of a cardiovascular profile using associated factors would allow early identification of those patients with alterations in myocardial function parameters.

Funding Acknowledgement

Type of funding sources: None.
Is there association between epicardial obesity and the severity of coronary artery atherosclerosis?
Authors: Polyakova E A , Baranova E I , Shlyakhto E V
Published: October 2021

Background

To assess the diagnostic capabilities of the ultrasound method for estimation of the epicardial fat (EF) and evaluate the association of the thickness of EF and the severity of coronary atherosclerosis in coronary heart disease (CHD) patients.

Methods

461 people (age Me 58 years, Q1=52; Q3=64) were examined: 182 patients with CHD (age Me 61 years, Q1=56; Q3=66; 72% men), 279 control patients without CHD, undergoing heart valve surgery (age Me 55 years, Q1=51; Q3=59; 51% men). The severity of coronary artery lesions was assessed according to the current 2013 ESC Guidelines (>50% for the left main coronary artery and >70% for other coronary arteries). Coronary angiography, heart computer tomography (CT), echocardiography (ECHO) were estimated. Statistical data analysis (SPSS, version 17.0, USA).

Results

In CHD patients the volume of EF (heart CT) was significantly higher than in patients without CHD (167.0 cm3 (128,9; 167,1) and 89.1 cm3 (62,7; 102,7), z=−7.060, p<0.001). The thickness of EF in the area of atrioventricular sulcus (according to the ECHO) most closely corresponds to the volume of EF (according to heart CT), ρ=0.731, p<0.001. According to multiple linear regression analysis, it was found that in patients with CHD, an increase in age by 1 year is associated with an increase in the volume of EF by 1.4 cm3 (95% CI from 1.0 to 1.9). The volume of EF in CHD patients is meen 56.7±3.1 cm3 (95% CI from 46.6 to 66.8) more than in patients without CHD. The correlation between the number of coronary arteries affected by atherosclerosis and the values of the parameters characterizing the EF was not revealed.

Conclusion

The volume of epicardial fat measured by cardiac CT in patients with CHD is greater than epicardial fat volume measured in subjects without ischemic heart disease. The volume of epicardial adipose tissue measured by heart CT in patients with CHD increases with age. The number of coronary arteries affected by atherosclerosis in CHD patients does not depend on the thickness and volume of epicardial adipose tissue.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The study has been supported by the grant from the Ministry of Science and Higher Education of the Russian Federation
Management of bifurcation culprit lesion in the setting of anterior ST elevation myocardial infarction
Authors: Assal A , Almaghraby A , El Amrawy A
Published: October 2021

Introduction

Coronary bifurcation lesions are considered one of the challenging entities in the field of coronary intervention due to the risk of side branch loss and higher risk of stent thrombosis. However, there is limited data about the proper management of such lesions in the setting of myocardial infarction as most bifurcation lesion studies excluded patients with acute coronary syndrome (ACS).

Aim

To compare in-hospital and mid-term outcomes of single-stent and two-stents strategy in the management of bifurcation culprit lesions in patients presenting with anterior STEMI

Methods

This retrospective multi-center study included all consecutive patients presented with anterior STEMI who underwent primary PCI between January 2017 and December 2019, coronary angiography showed true bifurcation lesion with sizable side branch that can be managed by stenting. Patients with left main bifurcation lesion, patients indicated for urgent CABG, or patients in cardiogenic shock were excluded. Included patients were divided into two main groups according to the stenting strategy either single or two stents strategy. Six months of follow up data were collected by telephone calls and the examination of medical records

Results

Out of 1355 anterior STEMI patients presented between January 2017 and December 2019, 158 patients (11.6%) were identified to have bifurcation culprit lesions with a sizable diagonal branch. The baseline characteristics and angiographic findings were similar in both groups except for higher side branch involvement in the two stents group (83.31%± 11.20 and 71.88%±15.05, t=−5.39, p<0.001). Mean fluoroscopy time (23.96±8.90 vs 17.81±5.72 min) and contrast volume (259.23±59.45 vs 232.58±96.18 ml) were significantly higher in two stents group than single stent group (p=0.049). However the angiographic success rates (residual stenosis ≤30% and restoration of TIMI flow grade II or III) were comparable (96.8% vs 99%, MC p=0.151). There is no significant difference regarding the overall incidence rate of MACCE in both groups 6 months following the index procedure (13.9% vs 16.9%, FEp=0.698), with no difference between different bifurcation stenting techniques in patients managed with two stents

Conclusion

Although two stents strategy in the setting of STEMI is much complex with more fluoroscopy time and contrast volume, the procedural success rate and the incidence of complications between two groups were comparable on the medium-term follow up

Funding Acknowledgement

Type of funding sources: None.
Incremental predictive value of adding the CHA2DS2-VASc score to the GRACE score for in-hospital mortality in patients with ST-segment elevation myocardial infarction
Authors: Lyu S , Yu L , Zhu J , Yang Y
Published: October 2021

Objective

The Global Registry of Acute Coronary Events (GRACE) score is recommended for risk stratification for patients with ST-segment elevation myocardial infarction (STEMI) by clinical guidelines. Data about comorbidities were not incorporated in the GRACE score. This study aimed to evaluate the incremental predictive value of adding the CHA2DS2-VASc score to the GRACE score for in-hospital mortality in patients with STEMI.

Methods

7476 patients with STEMI were recruited and divided into five groups according to the CHA2DS2-VASc score (1, 2, 3, 4 and ≥5 points) at admission. The primary outcome was defined as in-hospital mortality, while the secondary outcomes were recurrent MI, stroke and major adverse cardiovascular events (MACE) during hospitalization. Univariate and multivariate logistic regression were performed to evaluate the association between the CHA2DS2-VASc score and outcomes. Incremental predictive performance of adding the CHA2DS2-VASc score to the GRACE score were evaluated through analysis of the receiver operating characteristic (ROC) curves, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results

With the increase of CHA2DS2-VASc score, patients with STEMI tended to have more comorbidities, receive less evidence-based treatments and carry worse in-hospital outcomes. Multivariate logistic regressions demonstrated that the CHA2DS2-VASc score was an independent predictor for in-hospital mortality [OR (95% CI): 1.320 (1.238–1.407), p<0.001], recurrent myocardial infarction [OR (95% CI): 1.233 (1.086–1.401), p=0.001], stroke [OR (95% CI): 1.433 (1.207–1.702), p<0.001] and MACE [OR (95% CI): 1.146 (1.088–1.207), p<0.001]. The c statistic value of combining the GRACE score with the CHA2DS2-VASc score was significantly higher than that of the GRACE score alone in predicting in-hospital mortality (0.784, 95% CI: 0.774–0.793 vs. 0.769, 95% CI: 0.760–0.779, z=4.180, p<0.001). The addition of the CHA2DS2-VASc score to the GRACE score resulted in significantly improved predictive performance for in-hospital mortality, with a NRI of 0.356 (95% CI: 0.280–0.432, p<0.001) and a IDI of 0.013 (95% CI: 0.009–0.018, p<0.001).

Conclusion

The CHA2DS2-VASc score was an independent predictor of in-hospital outcomes in patients with STEMI. Compared to the GRACE score alone, the addition of the CHA2DS2-VASc score to the GRACE score improved the predictive performance for in-hospital mortality in patients STEMI.

Funding Acknowledgement

Type of funding sources: None. Receiver operating characteristic curve
Local or general anesthesia for TAVI surgery? An updated systematic review and meta-analysis
Authors: Cheng D R
Published: October 2021

Background

The choice of anesthesia for transcatheter aortic valve implantation (TAVI) is still under controversial. This systematic review and meta-analysis was performed to evaluate the safety of local anesthesia (LA) with or without conscious sedation (CS) and general anesthesia (GA) for the TAVI-procedure.

Methods

This meta-analysis is registered with PROSPERO (CRD42021221777). We searched OVID, PUBMED, EMBASE, Web of Science databases to collect all the related studies published from January 1, 2002 to December 31, 2020. The primary outcome measures were hospital length of stay, operation time, 30-day mortality, use of cardiovascular drugs, permanent pacemaker (PPM) implantation rate, stroke rate, the incidence of myocardial infarction (MI), incidence of acute kidney injury (AKI), major bleeding (MB) rate, rate of procedural success.

Results

A total of 33 studies (3 RCT studies, 23 retrospective cohort studies, 4 prospective cohort studies, 3 case-control studies) including 23244 patients were analyzed. There were no significant statistically differences between LA and GA with respect to PPM [OR=0.99, 95% CI (0.88, 1.11), P=0.88], shock [OR=0.91, 95% CI (0.69, 1.21), P=0.52], MI [OR=0.89, 95% CI (0.52, 1.53), P=0.68], AKI [OR=1.26, 95% CI (0.99, 1.62), P=0.06], rate of procedural success [OR=0.66, 95% CI (0.43, 1.03), P=0.06]. However, compared to GA, LA for TAVI was associated with a significantly shorter hospital length of stay [WMD=−2.45, 95% CI (−2.77, −2.13), P<0.ehab724.16701], a reduction in procedure time [WMD=−12.32, 95% CI (−13.78, −10.87), P<0.ehab724.16701], a reduction in using of cardiovascular drugs [OR=0.52, 95% CI (0.35, 0.78), P=0.002] and in MB [OR=0.59, 95% CI (0.46, 0.75), P<0.0001], reduced 30-day mortality rate [OR=1.19, 95% CI (1.00, 1.42), P=0.05].

Conclusion

This Systematic review and meta-analysis showed that compared to GA, LA for TAVI can reduce hospital length of stay, procedure time, 30-day mortality rate, use of cardiovascular drugs, and MB rate, but no significant differences in PPM, shock, MI, AKI, and the rate of procedural success.

Funding Acknowledgement

Type of funding sources: None.
Aortic tortuosity is related to aortic phenotype in patients with bicuspid aortic valve: a CT scan study of 83 cases
Authors: Wallet T , Milleron O , Eliahou L , Paul J F , Arnoult F , Lansac E , Raffoul R , Pellenc Q , Ou P , Jondeau G
Published: October 2021

Background

Although the incidence of aortic dissection is higher in patients with bicuspid aortic valve (BAV) compared to tricuspid aortic valve (TAV), risk stratification remains unclear. Guidelines focus on ascending aorta diameters, regardless of the location, and do not take into account the morphology of the aorta. Aortic tortuosity (AT) is emerging as a novel biomarker associated with more severe aortopathy in patients with Marfan syndrome. AT has not been accuretely assessed in BAV.

Our aim is to describe the relationship between AT and ascending aortic phenotype in patients with BAV.

Methods

83 patients (43±16 years, 19 women) diagnosed with BAV and without significant aortic valve disease nor prior aortic intervention were included. CT scans were retrospectively analysed with measurements of aortic diameters and aortic tortuosity. For 61 patients with abdominal images available, descending and total aortic length and tortuosity were measured.

Results

In our cohort, 62 (75%) patients presented a typical BAV. Pathological aorta (Root and/or tubular Z-score >2) was found in 80 patients (96%) and 67 (81%) presented a tubular dilatation. The aortic phenotype, the maximal aortic diameters and aortic tortuosity index were similar in typical and atypical BAV.

Total aortic tortuosity index was correlated to Z-score tubular diameter (r=0.31; p=0,014) but not with Z-score Valsalva diameter (p=0,55). In patients with tubular dilatation (Z score >2), total aortic tortuosity index was higher than in patient without tubular dilatation (2.01 vs 1.85; p=0,015).

Conclusion

Total aortic tortuosity is associated with tubular dilatation but not with root dilatation in BAV patients suggesting that tubular phenotype may be at higher risk of complication in BAV. Further studies evaluating the association between aortic tortuosity and clinical outcomes in BAV are needed.

Funding Acknowledgement

Type of funding sources: None.
Normal values of aortic root diameters in sub saharan africans: the TAHES study
Authors: Vandroux D , Houehanou C , Saka D , Sonou A , Magne J , Houinato D , Preux P M , Aboyans V , Lacroix P
Published: October 2021

Introduction

Reference values of aortic root diameters (ARD) are proposed to define normal versus diseased aorta. However, reported ranges of normal values are mostly issued from Caucasian cohorts. Data on blacks African subjects are sparse and not issued from community-dwelling cohorts.

Purpose

Our study aimed to establish reference values for ARD in a Beninese general population cohort.

Methods

This study is a part of TAHES, a population-based prospective cohort study initiated in 2015 in the district of Tanvè, Republic of Benin. Demographic, blood pressure and blood glucose data were collected using a questionnaire adapted from WHO-STEPS tools. Transthoracic echocardiography examinations were performed by 4 cardiologists, and analyzed off-line by a single observer. ARD were measured using inner-edge to inner-edge diameters during diastole for sinuses of Vasalva (SV), sinotubular junction (STJ) and proximal ascending aorta (AA), and during systole for annulus. Normal limits were defined as the 95th percentiles. Variables are presented as mean ±SD (5th-95th percentiles).

Results

We included 513 normotensive, non-diabetic and cardiovascular disease-free individuals (206 men and 307 women, age 40±14 years [26–68]). The absolute values of ARD were significantly greater in men: the non-indexed ARD values for the annulus, SV, STJ and AA were respectively 21.3±2 (18.5–25), 28.5±3.4 (23–34), 24.1±3 (19–29) and 27±3 (22.5–32) mm for men and 19.3±1.8 (1.8 (15- 22), 25.8±2.8 (21.6–30), 22±2.7 (18–26) and 24.8±2.8 (21–30) mm for women, respectively (all p<0.0001). No significant differences between sexes were recorded for body surface area (BSA)-indexed ARD for Annulus, STJ and AA. BSA-indexed SV dimension was greater in men (17.3±2.6 mm; 13.5–22) than women (16.8±2.5 mm; 13–21). There was a correlation between SV, STJ, AA indexed-diameters and age in both sexes but not for annulus indexed-diameter (r=0.14, 0.19 and 0.36 for women and 0.34, 0.45 and 0.32 for men, all p<0.05). The upper limits for ARD are summarized in Table 1. In order to compare these values to those in Caucasians, the data of the NORRE study are also displayed.

Conclusion

Normal values from a general population in West Africa appear could to differ from those established in Caucasian populations. This ethnic-appropriate reference is proposed for appropriate diagnosis in patients in sub-Saharan Africa.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): APREL (CHU Limoges) Table 1
Prognostic nutrition index predicts outcomes in critically ill stroke patients: a database-based cohort study
Authors: Zhang B , Zhu Q , Lu Z
Published: October 2021

Background

Although there are many indicators to assess nutritional status, a more comprehensive and objective indicator is still needed in clinical practice. In this study, we evaluated the relationship between the prognostic nutritional index (PNI) and clinical outcomes in patients with critically ill stroke.

Methods

Subjects who were diagnosed as stroke in the Beth Israel Deaconess Medical Center between 2001 and 2012 were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). The multivariate logistic regression and the Cox regression analysis were performed to assess the impact of PNI on 3-month and 4-year mortality in stroke patients.

Results

A total of 624 subjects were included in this study. Compared with the high-PNI group, those in the Low PNI group had lower body mass index (BMI), hemoglobin, neutrophil count, lymphocyte count and albumin. On the contrary, Age, Blood urea nitrogen (BUN), Creatinine (Cre), simplified acute physiologic scoreII (SAPSII) score and sequential organ failure assessment (SOFA) score of the low PNI group were higher than the high PNI group. After adjusting for other confounders, PNI was independently associated with 3-month mortality (adjusted odds ratio = 1.910; 95% confidence interval, 1.244–2.933; P=0.003). By the Kaplan-Meier analysis, patients in the low PNI group presented significantly shorter survival time and higher death rate. The Cox regression model indicated low PNI as an independent risk factor of 4-year all-cause mortality of stroke patients (hazard ratio = 1.824; 95% CI, 1.340–2.483; P<0.001).

Conclusions

Low PNI is independently associated with short-term and long-term prognosis in patients with critically ill stroke.

Funding Acknowledgement

Type of funding sources: None.
Exploring biomarkers of age in routine diagnostics for the risk stratification of older patients in the emergency department
Authors: Bahrmann P , Kunz A L , Schoenstein A , Giannitsis E , Wahl H.-W , Katus H , Frey N , Bahrmann A
Published: October 2021

Objectives

To estimate the association of the routinely applied biological age-related biomarkers hs-TnT, CRP and Hemoglobin (Hb) with mortality for the purpose of older patient's risk stratification in the emergency department (ED).

Design

Exploratory, prospective cohort study with a follow-up at 2.5 years after recruitment start.

Setting and participants

A cardiological emergency department (ED), chest pain unit, of our University Hospital. N=256 cardiological ED patients with a minimum age of 70 years and with an expected life-expectancy above 24h.

Methods

Data from the hospital files were supplemented by a questionnaire. Patients were followed-up for mortality by requesting registry office information.

Results

Among N=256 patients 63 died over the follow-up period. Positive results in each of the three biomarkers alone as well as the combination were associated with increased all-cause mortality at follow-up. The number of positive age-related biomarkers appeared to be strongly indicative of the risk of mortality, even when controlled for major confounders (age, sex, BMI, creatinine clearance, and comorbidity).

Conclusion and implications

In older ED patients, biomarkers explicitly related to biological aging processes such as hs-TnT, CRP and Hb were independently of each other as well as combined associated with an increased risk of all-cause mortality. Thus, they may have the potential to be used to supplement the general risk stratification of older patients in the ED. Validation of the results in a large dataset is needed.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Robert Bosch Foundation, Stuttgart, Germany Kaplan-Meier curves with 95% CIKaplan-Meier curves for patients grouped
Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and NOAC therapy
Authors: Kim Y R , Shin D G , Kim S
Published: October 2021

Background

The combined use of antiplatelet agents (APT) and non-vitamin K antagonist oral anticoagulants (NOACs) in patient with atrial fibrillation (AF) is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) and monotherapy (NOAC only).

Methods and results

We analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major or any bleeding events and the secondary outcomes were stroke/systemic embolism (SE) and major adverse cardiac events (MACE). Of 1,068 participants, there were 264 (24.7%) patients in the combination group.

The prevalence of diabetes (p=0.017) and history of stroke and transient ischemic attacks (p<0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6±9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination group than in the monotherapy group (p<0.001). Major bleeding, stroke/SE, and MACE between the two groups were similar. The rate of under-dosage NOACs prescriptions was higher in the combination group than in the monotherapy group (p=0.024).

Conclusions

The combination therapy had higher incidences of any bleeding events compared to the monotherapy. However, there was no difference in stroke/SE and MACE.

The bleeding risk in patients taking the combination of NOACs and APT should be carefully evaluated.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Primary and secondary outcomes
Expressing a truncated SARS-COV-2 spike protein in mouse heart induces cardiac hypertrophy
Authors: Negron S , Kessinger C , Lin Z
Published: October 2021

Cardiac injury is common in hospitalized and non-hospitalized COVID-19 patients, for which systemic inflammation stress is one of the causes (Topol, 2020). Although rare, COVID-19 cases that SARS-CoV-2 infecting cardiomyocytes (CMs) have been reported. In vitro, SARS-CoV-2 infection of human induced-pluripotent-cells derived CMs triggered innate immune responses and induced apoptosis (Bojkova et al., 2020; Chen et al., 2020). Therefore, the current literature indicates that the heart is attacked by SARS-CoV-2 directly or indirectly; however, the underlying mechanism remains largely unknown. Involved in the pathogenesis of heart diseases, Toll-like receptors (TLR) are a family of pattern recognition receptors that sense the pathogenic stimuli and signal the cardiac residential cells to cope with harsh conditions (Yu and Feng, 2018). Among the best characterized TLR signaling pathways is TLR4/NF-kB axis (Lu et al., 2008), in which TLR4 convey the danger signals through its down stream kinases, such as TAK1 and TBK1, to activate NF-kB. SARS-CoV-2 Spike protein is well known for its role of mediating virus entry into host cells, but its immunogenic role has not been clearly defined. Recently, we have found that SARS-CoV-2 Spike protein directly interacts with TLR4 and activates NF-kB transcriptional activity. Pharmaceutically blocking either TBK1 or TAK1 attenuates Spike protein's immunogenic activity. To pinpoint Spike protein's role in the heart, we generated an AAV to specifically express a truncated Spike protein (S1-TM) in the CMs. Our data show that expressing S1-TM in CMs induces cardiac hypertrophy and decreases heart systolic function in mice. On the molecular level, Spike protein increases RelA (p65 subunit of the NF-kB complex) and activates the expression of pro-inflammatory cytokine genes. In summary, our study suggests that Spike protein directly interacts with TLR4 to trigger innate immune signaling, and that Spike protein induced CM innate immune responses might be one of the underlying mechanisms of cardiac injury in COVID-19.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Masonic Medical Research Institute
Altered atrial restitution dynamics and refractoriness in metabolic syndrome due to up-regulation of potassium repolarizing currents increases susceptibility to atrial fibrillation
Authors: Calvo C J , Rodriguez A , Almar E , Arias O , Lozano W , Alberola A , Zarzoso M
Published: October 2021

Background

Metabolic alterations, such as Metabolic Syndrome (MS), describe an association of factors including diabetes, hypertension, obesity and dyslipidemia, linked to higher risk and prevalence of overall cardiovascular disease, arrhythmogenesis and sudden cardiac death. Obese and diabetic patients have shown an increased risk for developing atrial fibrillation (AF). However, underlying mechanisms are not understood.

Purpose

To study the effects of MS and obesity remodeling in atrial restitution dynamics, frequency-dependent adaptation, refractoriness and its potential susceptibility to AF.

Methods

Electrophysiological experimental data from High-fat (HF-O, standard rabbit chow with an additional 15% fat) and Hig-fat High-Sucrose Metabolic Syndrome (HFHS-MS, 10% hydrogenated coconut oil and 5% lard, 15% high-sucrose dissolved in water) rabbit models were used to adjust computational models atrial electrophysiology remodeling under each condition. Additionally, isoproterenol and AF conditions were considered to challenge both in-silico models. Validation and sensitivity analysis were performed for each model parameters. Computational simulations in conditions of pacing at different pacing cycle lengths was assessed at 100, 125, 150, 200, 250, 350, 450, 500, 650, 750, 850, 1000 ms. Restitution dynamics were automatically determined and analyzed, as well as restitution slopes and presence of automaticity, early after-depolarizations, alternans and cardiac arrhythmia induction.

Results

Shortening of action potential duration and refractoriness in the left atrium was observed under HFHS-MS. Upstroke velocity, maximum excitability and sodium availability were altered both in HF-O and HFHS-MS. HF-O remodeling showed presence of alternans at high pacing frequencies. Repolarization restitution was shortened in conditions of ISO and MS-AF. Restitution slopes were >1 in HF-O and HFHS-MS, which was correlated to higher susceptibility to AF, and further increased in MS-AF. Under MS-AF, abbreviation in APD in both atria, resulted in increased reentrant frequencies in AF, which was exacerbated under IK1 up-regulation, increasing atrial vulnerability.

Conclusions

HFHS-MS underlies modifications in atrial electrophysiology including shorter refractoriness in HFHS-MS, as well as modifications in atrial excitability, which may be pro-arrhythmic mainly at high frequency rates. This could be explained in part by an up-regulation of outward potassium channels. These results could partially explain increased susceptibility for AF in MS.

Funding Acknowledgement

Type of funding sources: None.
Monounsaturated fatty acid antagonizes saturated fatty acid-induced cardiomyopathy via improving membrane fatty acid composition and endoplasmic reticulum stress
Authors: Yamamoto T Y , Endo J E , Shinmura K S , Sano M S , Fukuda K F
Published: October 2021

Background

Obesity-induced lipotoxicity causes cardiac dysfunction in our modern lifestyle. Previously, we have shown that an increase in cardiomyocyte membrane saturated fatty acid (SFA)/ monounsaturated FA (MUFA) ratio mediates endoplasmic reticulum (ER) stress, which was implicated in the pathogenesis of SFA-induced cardiomyopathy. Furthermore, SFA supressed Sirt1/ stearoyl-CoA desaturase-1 (SCD1, converting enzyme from SFA to MUFA) signaling, which further worsened the membrane SFA/MUFA ratio.

Purpose

To evaluate the effectiveness of targeting membrane fatty acid composition by MUFA.

Methods and results

In wild-type mice, 16-weeks SFA-rich high lard diet feeding (HLD) caused activation of PPARα signaling and the accumulation of toxic lipid intermediates (diacylglycerol and ceramide) in the heart to the same extent as a MUFA-rich high olive oil diet feeding (HOD). However, only the HLD impaired Sirt1 activity, SCD1 expression, diastolic function (increased left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure-volume relationship (EDPVR)), and cardiac remodeling (hypertrophy and fibrosis). Lipidome analysis showed that HLD-induced diastolic dysfunction coincided with an increase in membrane SFA/MUFA ratio and ER stress induction. 8-weeks HOD after 8-weeks HLD (HOD switch) showed the same degree of obesity and PPARα activation with 16-weeks HLD. By contrast, HOD switched heart were less severe Sirt1/SCD1 signaling dysregulation, increased in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy (hypertrophy, fibrosis, and diastolic dysfunction) compared to 16-weeks HLD. Moreover, in cardiomyocyte-specific Sirt1 knockout mice, HOD switched heart also showed less severe increase in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy compared to 16-weeks HLD although decreased SCD1 expression was not changed.

Conclusions

We demonstrated that MUFA-rich diet counteracted SFA-induced Sirt1/SCD1 signaling dysregulation and prevented SFA-induced increase in membrane SFA/MUFA ratio. Hence, MUFA-rich diet antagonized SFA-induced ER stress and cardiomyopathy even if Sirt1 deactivated heart (e.g., aged heart). Targeting the cardiomyocyte membrane SFA/MUFA ratio by MUFA might have a new therapeutic potential for SFA-induced cardiomyopathy.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): JSPS KAKENHI
Autonomic and cardiac evaluation upon sub-therapeutic doxorubicin administration
Authors: Amaro-Leal Â , Machado F , Afonso A I , Rocha I , Geraldes V
Published: October 2021

Doxorubicin (DOX) is a chemotherapeutic agent that improves the survival and quality of life of patients with solid tumours. However, these improvements are counterbalanced by various dose-dependent side effects including cardiac dysfunction, which may occur in a subset of patients leading to treatment discontinuation. In addition, despite overall insufficiently studied, available data clearly show that women are more susceptible to drugs toxicity due to sex differences in drug metabolism or sensitivity. Regarding doxorubicin, apart its acute toxicity, women are also more vulnerable to late cardiotoxicity. Currently, there are no robust clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline and, despite treatment personalization, subclinical signs of toxicity are not yet well identified.

Thus, in the present work, we sought to characterize the toxic effects of a sub-therapeutic dose of doxorubicin upon cardiovascular and autonomic function. For that, adult healthy female wistar rats (n=14), aged >3 months, were intraperitoneally treated with doxorubicin (2 mg/kg) at weekly intervals for up to 4 weeks. A control (Ctrl, n=7) group received saline solution 0,9% NaCl as a vehicle. Rats underwent an echocardiographic evaluation at 4 weeks. Blood pressure, heart rate and respiratory frequency were assessed in an acute experiment. Cardiovascular variability studies in the time-frequency domain (LF, HF and LF/HF calculation) and cardiorespiratory reflexes assessment were performed. T-Student test for paired observations was applied (level significance p<0.05)

DOX-treated animals showed a severe bradypnea and hypotension, significant decrease in ejection fraction and fractional shortening, sympatho-inhibition and reduced baroreceptor reflex gain and chemoreflex sensitivity. Our functional results might be due to cellular respiratory dysfunction and vascular adaptations induced by doxorubicin via TNF alpha actions at central nervous system (CNS) and peripheral level.

In fact, peripheral TNF alpha release elicits NO production, which through vasodilation will induce hypotension and baroreceptor reflex adjustments. Reinforcing these actions, and despite doxorubicin low ability to pass BBB, TNF alpha acting at CNS induces neuronal apoptosis and impairment of mitochondrial function which might also contribute to affect autonomic and respiratory function, expressed by a decreased chemoreflex sensitivity and sympathetic tone.

In conclusion, sub-therapeutic doses of doxorubicin are able to produce per se the impairment of autonomic and cardiac functions. Thus, a tight monitoring of these functions in patients treated with therapeutic doses of doxorubicin is highly recommended.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fundação para a Ciência e a Tecnologia
Circulating metabolome does not predict development of aortic stenosis
Authors: Koljonen E , Karkkainen O , Klavus A , Voutilainen A , Turpeinen A , Virtanen J , Lehtonen M , Auriola S , Kauhanen J , Hartikainen J , Rysa J
Published: October 2021

Background

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in Western world. CAVD is ranging from mild aortic valve sclerosis to severe obstructive aortic stenosis (AS). The development of AS has been associated with several risk factors including age, sex and hypertension. However, there is limited knowledge about factors that predict the development of aortic stenosis.

Purpose

We investigated if the circulating metabolite profile can predict the development of aortic stenosis in Finnish males.

Methods

We did a non-targeted LC-MS metabolomics analysis to baseline (1984–1989) serum samples from a prospective population-based Kuopio Ischemic Heart Disease risk factor study (KIHD) cohort of 2682 random Finnish males aged from 42 to 60 years. During the follow-up (until year 2020), 53 subjects developed either moderate (peak flow gradient 36–64mmHg or mean flow gradient 20–40mmHg) or severe aortic valvular stenosis (peak flow gradient over 64mmHg or mean gradient over 40mmHg). The AS patients were collected from the KIHD database using appropriate ICD-10 -codes for aortic valvular disease (from baseline to the end of the year 2017) and the diagnosis was checked manually using hospital medical records of the individuals.

Results

The AS patients seemed to have altered lipid metabolism and possibly altered composition of gut microbiota, since several acylcarnitines (e.g. octanoylcarnitine [Cohen's d=−0.40], decanoylcarnitine [d=−0.43], layroylcarnitine [d=−0.41], and oleoylcarnitine [d=−0.40]), and branched chain amino acids (BCAA, e.g. leucine [d=0.39], and isoleucine [d=0.49]) had p-values below 0.05. However, after correction for multiple testing, there were no significant differences between the cases and controls.

Conclusions

The present preliminary results, in need of verification with a larger set of samples, suggest that subjects, who will later develop AS might have reduced levels of acylcarnitines and increased levels of BCAA when compared to matched controls. However, these changes do not have large effects sizes and are likely not good candidates for biomarkers to predict future diagnosis of AS.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Finnish Cultural Foundation, The Finnish Foundation for Cardiovascular Research.
Novel perfusion ex-vivo culture system enables physiological and pathological studies on porcine arteries
Authors: Matos R , Maselli D , McVey J , Campagnolo P
Published: October 2021

Introduction

Routine cardiovascular interventions such as cardiac bypass, balloon angioplasty and stenting provoke vascular activation and remodelling often leading to rehospitalization and further interventions. Conventional in vitro models fail to account for the complex vascular environment essential for vascular tissue fitness.

Purpose

Our research aims to culture whole porcine arteries in using a novel cost efficient and versatile perfusion system (EasyFlow) and identify the contribution of adventitial progenitors to post-injury remodelling.

Methods

EasyFlow insert was 3D printed to convert a conventional 50 ml centrifuge tube into a mini bioreactor. Porcine arteries were excised and cultured under constant pulsatile flow for up to 7 days. Injury was performed by balloon catheter at day 0. Tissues were evaluated by doppler ultrasound, immunofluorescence and confocal imaging and PCR, at different timepoints.

Results

The EasyFlow adaptor takes advantage of 50 ml centrifuge tubes isolating reaction space from the environment and reducing the culture volume. The adaptability of the design facilitates the incubation of vessels of different size and origin while the self-contained perfusion allows parallel cultures and minimal media consumption. EasyFlow perfusion culture of porcine arteries preserves the endothelial coverage and the smooth muscle cell organisation, as compared to static culture.

Gene expression analysis and immunofluorescence indicated an increased expression of platelet-derived growth factor receptor beta (PDGFRb) and a decrease in smooth muscle actin (SMA) in the static culture, compared to the perfusion. Furthermore, static culture showed an increased cellular activation in adventitia (proliferating cell nuclear antigen expression), as compared to perfused tissues. Balloon injury followed by flow culture recapitulated the early hallmarks of vascular remodelling, including intimal denudation indicated by loss of platelet endothelial cell adhesion molecule signal, smooth muscle cell disarray shown by loss of actin stress fibre organisation and activation in the media, as supported by confocal microscope and gene expression analysis, accompanied by significant morphological changes based on ultrasound imaging.

Conclusion

This work lay the basis for future investigations into the pathological remodelling of blood vessels, by providing a robust and controlled culture system for the maintenance of porcine blood vessels in culture.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): University of Surrey En-Face Staining of Arterial Lumen