bluuebunny/crossref_metadata_2025 huggingface dataset:
The loss of left atrial contractile function predicts worse outcome in HFrEF: a speckle tracking study
Authors: Mandoli GE , Pastore MC , Benfari G , Setti M , Maritan L , D"ascenzi F , Focardi M , Carrucola C , Vigna M , Valente S , Mondillo S , Cameli M
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

in chronic heart failure (HF), high cardiac pressure induces a progressive remodeling of small pulmonary arteries up to pulmonary hypertension development. At the end of left atrial (LA) conduit function, pulmonary and left heart end-systolic pressures equalize. This might affect LA systole.

Purpose

we investigated whether peak atrial contraction strain (PACS), measured by speckle tracking echocardiography (STE), was independently associated with outcome in HF with reduced ejection fraction(HFrEF).

Methods

168 outpatients with HFrEF and sinus-rhythm referred to our echo-labs were prospectively enrolled. After clinical and echocardiographic evaluation, off-line STE analysis was performed. The endpoints were cardiovascular (CV) death and HF hospitalization respectively. Spline knotted survival model identified the optimal cut-off value for PACS.

Results

The 152 included patients were stratified based on PACS < 8%(n = 76) or PACS≥8%(n = 76). Mean age was 61 ± 12, mean EF was 30 ± 9%. Characteristics of the two groups are presented in Table 1. Over a mean follow-up of 3.41 ± 1.9 years, 117 events (51 CV death, 66 HF hospitalizations) were collected. By univariate and multivariate Cox analysis, global PACS emerged as a strong and independent predictor of CV death and HF hospitalization, even after adjusting for age, sex, LV strain, E/e’, LA volume index (HR 0.6 per 5 unit decrease in PACS). Kaplan Meier curves showed a sustained divergence in event-free survival rates for the two groups (Fig.1).

Conclusions

The reduction of PACS significantly and independently affects CV outcome in HFrEF. Although limited to patients with sinus rhythm, it could offer additive prognostic information for HFrEF patients.

Table 1 Variable PACS < 8 PACS ≥ 8 P value Age 61.5± 11.4 61.8 ± 12.7 0.4 NYHA class >2 26% (n = 39) 11% (n = 17) <0.0001 NT pro BNP 2293.7 ± 1636 1335 ± 242 0.04 E/E’ ratio 16.1 ± 9.09 12.1 ± 7.09 0.0015 LV GLS -7.28 ± 3.4 -10.17 ± 3.2 <0.001 sPAP 40.5 ± 13.7 30.3 ± 9.3 <0.0001 LAVI 64.4 ± 20.4 45.5 ± 15.8 <0.0001 PALS 9.8 ± 4.9 20.2 ± 7 <0.0001 E, peak early diastolic “E” wave; E’, medium velocity of early mitral annulus descent; GLS, global longitudinal strain; LAVI, left atrial volume index; LV, left ventricular; PACS, peak atrial contraction strain; PALS, peak atrial longitudinal strain; sPAP, systolic pulmonary artery pressure. Abstract Figure. Fig.1
Computed tomography derived left ventricular global longitudinal strain associate with clinical outcomes in patients undergoing transcatheter aortic valve replacement
Authors: Fukui M , Hashimoto G , Lopes B , Du Y , Stanberry L , Garcia S , Goessl M , Enriquez-Sarano M , Bapat V , Sorajja P , Lesser J , Cavalcante J
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Computed tomography angiography (CTA) is key imaging modality for procedure planning for transcatheter aortic valve replacement (TAVR). Functional assessment by CTA with LV global longitudinal strain (LVGLS) has recently shown to be feasible. However, there is limited data on its prognostic value in patients with severe aortic stenosis (AS) who treated with TAVR.

Purpose

To evaluate the association of baseline CTA-LVGLS with post-TAVR outcome.

Methods

 Patients who underwent contrast multiphasic gated CTA for TAVR planning were studied. LVGLS was measured using dedicated feature-tracking software (Medis®). Cox regression analysis evaluated the association of baseline LVGLS with a composite outcome of all-cause death and heart failure hospitalization after TAVR.

Results

A total of 431 patients were included (median [IQR] age, 83 [77,87]years; 44% female); the society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score, 3.3 [2.3,5.1]%; CTA-LVGLS, -18.0 [-21.6,-14.2]%; LV ejection fraction was preserved at 60 [55,65]%. After a median follow-up of 19 [13,27] months, 99 composite outcomes occurred after TAVR. On multivariable Cox regression analysis, LVGLS was associated with the risk of composite outcome even after adjustment for baseline characteristics (Figure A). Patients with reduced LVGLS (above the median >-18.0%) had higher risk of the composite outcome than those with preserved GLS (p = 0.003; Figure B).

Conclusion

Baseline CTA-LVGLS was associated with the risk of death or heart failure hospitalization over the clinical and echocardiographic characteristics in severe AS patients undergoing TAVR.

Abstract Figure.
How clinical question influences radiation dose in paediatric cardiac CT scan?
Authors: Adla T , Koci M , Suchanek V , Salagovicova Z , Polovincak M , Miksik L , Rocek M
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Number of Cardiac CT examinations in paediatric population is rising. Clinical questions might vary from cardiac anatomy, coronary arteries, cardiac function assessment to chest examination including evaluation of large vessels, eventually combinations of these tasks. Dose reduction in children is especially important. CT scanning mode selection, reduction of kVp and limited extent of scanning in z-axis are the most important parameters for dose reduction. However, dose reduction optimization should not limit the readability of the CCT, and consequently the ability to reply the clinical question.

Purpose

This study analyses the influence of different clinical questions to radiation dose of paediatric cardiac CT.

Methods

In total 123 patients (42 females, 81 males) were examined using third generation dual-source CT scanner (SOMATOM Force, Siemens Healthineers, Forchheim, Germany), age mean 10.5 ± SD 5.9 years (min 50 days – max 18.9 years), height 138 ± 39 cm (54 – 200), weight 49 ± 25 kg (3.7 – 103). Three main categories of clinical questions (Q) were set: Q1) Extent of scanning in z-axis: heart only (from carina to diaphragm) or whole chest, Q2) Coronary arteries evaluation: yes/no, Q3) Cardiac function assessment (yes/no). Radiation dose is represented as a dose length product (DLP) in mGy*cm. Effective dose (ED) in mSv and calculated from DLP using converting factor 0.026 mSv/mGy*cm. Multiple regression was used to evaluate influence of clinical question to radiation dose.

Results

Total DLP was 202 ± 282 mGy*cm (6 – 1751), ED was 5.25 ± 7.33 mSv (0.16 – 45.53). Multiple regression of Total DLP versus Q1-Q3, height, weight and average heart rate showed statistically significant influence of cardiac function assessment (413 ± 263 vs 132 ± 253 mGy*cm, p 0.0001) and weight (p 0.0443). Multiple regression after adjusting to weight showed statistically significant influence of cardiac function assessment only (p <0.0001).

Conclusions

Only clinical question about cardiac function assessment caused statistically significant higher radiation dose acquired from cardiac CT in paediatric patients. There was no statistically significant influence of coronary artery evaluation and extent of scanning.

Abstract Figure.
Right ventricular function and outcome in patients undergoing transcatheter aortic valve implantation
Authors: Koschutnik M , Dannenberg V , Nitsche C , Dona C , Siller-Matula J , Winter MP , Andreas M , Bartko P , Loewe C , Aschauer S , Anvari-Pirsch A , Goliasch G , Hengstenberg C , Kammerlander A , Mascherbauer J
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed.

Objectives. To compare RV function parameters on echocardiography and CMR for prognostication in TAVI patients.

Methods. Consecutive patients scheduled for TAVI underwent echocardiography and CMR.  RV fractional area change (FAC), TAPSE, RV free-lateral-wall tissue Doppler (S’) and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with 1) NT-proBNP levels, 2) prolonged in-hospital stay (>14 days), and 3) a composite of heart failure hospitalization and death.

Results. 204 patients (80.9 ± 6.6y/o; 51% female; EuroSCORE-II: 6.5 ± 5.5%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay (adj. OR 1.98 [95%CI: 1.15-3.41], p = 0.013 and 2.29 [95%CI: 1.43-3.67], p = 0.001, respectively). A total of 56 events occurred during follow-up (mean 13.7 ± 9.5months). After adjustment for the EuroSCORE-II and NT-proBNP levels, only RVEF was significantly associated with the composite endpoint (adj. HR 1.69 [95%CI: 1.24-2.30], p < 0.001, Figure 1).

Conclusions. RVD as defined by echocardiography is associated with an advanced disease state, but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVI patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death.

Abstract Figure 1. Outcome analysis
Global longitudinal strain in patients with severe aortic stenosis: a comparison between cardiac magnetic resonance imaging feature tracking and speckle tracking echocardiography
Authors: Kylmala MM , Syvaranta S , Halva R , Orn R , Rajala H , Holmstrom M , Kivisto S , Lommi J , Suihko S , Uusitalo V
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Global longitudinal strain (GLS) by echocardiography is a sensitive method for measuring left ventricular (LV) function, and of better prognostic value in valvular heart disease than ejection fraction (EF). Cardiac magnetic resonance imaging (CMR) is the most accurate method for measuring LV volume and EF, but GLS has not been possible to measure by CMR until recently.

Purpose

This study compares GLS obtained by CMR and echocardiography in patients with severe aortic valve stenosis. Normal values for GLS by CMR are reported as well.

Methods

GLS was measured in 32 patients with severe aortic valve stenosis with speckle tracking echocardiography, using GE Vivid E95 (n = 15) and Philips EPIQ (n = 17) ultrasound machines, as well as with CMR (Avanto 1.5T FIT, Siemens Medical Solutions). For normal values, GLS was measured by CMR in 9 healthy controls. Endo- and epicardial borders of two, three and four chamber cine images were traced for CMR GLS using dedicated software (Qstrain 2.0, Medis, NL). Both CMR and Vivid E95 measured midmyocardial strain, whereas the EPIQ AutoStrain method measures endomyocardial strain. Absolute values of GLS are reported. Pearson correlation coefficient was calculated and paired Student’s t-test was used for comparisons.

Results

A significant correlation (r = 0.45, p = 0.01) was found between echocardiographic and CMR GLS (Figure). GLS by Vivid E95 had a very good correlation with CMR GLS (r = 0.84, p = 0.0001), whereas GLS by Philips EPIQ did not correlate significantly (r = 0.14, p = 0.01). In patients with aortic stenosis and healthy controls, the average GLS by CMR was 18.3 ± 3% and 20.9 ± 2% respectively. The average GLS by CMR was comparable to that obtained by GE Vivid E95 (17.3 ± 4% vs. 17.2 ± 3%, p = 0.92), and higher than by Philips EPIQ (19.2 ± 2% vs. 15.4 ± 2%, p < 0.0001).

Conclusion

This study shows that GLS by CMR is feasible and correlates with GLS obtained by echocardiography, especially when quantifying midmyocardial strain. Echocardiographic GLS values based on endomyocardial strain were lower.

Patient characteristics Age 75 ± 14 y NYHA 1 1 (3 %) NYHA 2 20 (67 %) NYHA 3 8 (27 %) NYHA 4 1 (3 %) CMR EF 66 ± 8 % AVA 0.7 ± 0.2 cm² NYHA = NYHA class of symptoms, EF = ejection fraction by CMR, AVA = aortic valve area by echocardiography Abstract Figure. GLS by CMR vs. Echocardiography
Longitudinal change in left ventricular 4D flow kinetic energy after myocardial infarction
Authors: Ben-Arzi H , Das A , Kelly C , Van Der Geest RJ , Chowdhary A , Craven T , Jex N , Thirunavukarasu S , Levelt E , Bissell M , Swoboda PP , Greenwood JP , Plein S , Dall"armellina E
Published: February 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation HRUK

Background. Four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) imaging provides quantification of intra-cavity left ventricular (LV) flow kinetic energy (KE) parameters in three dimensions. Myocardial infarction (MI) is known to cause acute alterations in intra-cardiac blood flow but assessments of longitudinal changes are lacking.

Purpose. Assess longitudinal changes in LV flow post ST-elevation myocardial infarction (STEMI).

Method. Twenty acutely reperfused STEMI patients (13 men, 7 women, mean age 54 ± 9 years) underwent 3T CMR acutely (within 5-7 days) and 3 months post-MI.  CMR protocol included functional imaging, late gadolinium enhancement and 4D flow. Using Q-MASS, LV KE parameters were derived and indexed to LV end-diastolic volume (LVKEiEDV). Based on acute ejection fraction (EF), patients were grouped as follows: preserved (pEF) EF >50%, reduced (rEF) EF <50% including mild (rEF= 40-49%), moderate to severe (EF <40%) impairment. 

Results. Out of 20 patients, 13 had rEF acutely (7 mild rEF, 6 moderate to severe rEF). Acute LVKEiEDV parameters varied significantly between pEF and rEF (Table). At 3 months, pEF and mild rEF patients showed a significant (P < 0.05) reduction in average, systolic and peak-A wave LVKEiEDV. Mild rEF patients also had significant (P < 0.05) reduction in minimal and peak-E wave LVKEiEDV. However in patients with moderate to severe rEF in the acute scan, there were no significant change by 3 months (Figure).

Conclusion. Following MI, 4D flow LVKE derived biomarkers significantly decreased over time in pEF and mild rEF groups but not in moderate to severe rEF group. 4D flow assessment might provide incremental prognostic value beyond EF assessment alone.

Table pEF (n = 7) rEF (n = 13) V1 V2 P-value V1 V2 P-value EF(%) 56 ± 5 55 ± 4 0.40 41 ± 7 47 ± 9 0.01 Infarct Size(%) 31 ± 20 15 ± 9 0.04 18 ± 13† 16 ± 11 0.41 LV KEiEDV parameters Average(µJ/ml) 9 ± 2 7 ± 2 0.02 10 ± 3† 8 ± 3 0.01 Minimal(µJ/ml) 1 ± 0.6 1 ± 0.5 0.46 1.3 ± 0.5 1 ± 0.6 0.03 Systolic(µJ/ml) 10 ± 4 7 ± 2 <0.01 12 ± 4† 7 ± 3 <0.01 Diastolic(µJ/ml) 8 ± 3 7 ± 2 0.13 9 ± 3 8 ± 3 0.09 Peak-E wave(µJ/ml) 22 ± 9 23 ± 8 0.44 20 ± 7 18 ± 10 0.23 Peak-A wave(µJ/ml) 18 ± 10 11 ± 4 0.04 17 ± 9 14 ± 7 0.02 †P < 0.05 V1 comparison between pEF and rEF Abstract Figure
Prognostic role of cardiac MRI in the evaluation of patients with pericarditis: a long-term follow-up study
Authors: Conte E , Lauri G , Agalbato C , Dalla Cia A , Mushtaq S , Mapelli M , Teruzzi G , Biondi ML , Pontone G , Pepi M , Andreini D
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Recurrent pericarditis complicates 30% of acute pericarditis cases. Aim of the present study is to evaluate the role of cardiac MRI in the identification of patients subgroup at higher risk of recurrent pericarditis.

Material and methods

From a registry of consecutive patients who underwent cardiac MRI from January 2014 to January 2019 we retrospectively selected a subgroup of patients with clinical diagnosis of pericarditis according ESC guidelines on pericardial disease, for which a recent (less the 2 months before cardiac MRI) transthoracic echocardiography was available. CMR protocol included bSSFP images, T2w images and LGE in all patients. Transthoracic echocardiography was considered to be positive for pericardial disease if pericardial effusion and/or sign of pericardial constriction were present; cardiac MRI was considered to be positive for pericardial disease if pericardial effusion and pericardial hyperintensity signal were detected on T2w or LGE images. Clinical follow-up was recorded for a composite end-point including new episodes of recurrent pericarditis and subsequent diagnosis of chronic constrictive pericarditis

Results

A total of 25 patients were included in this preliminary analysis of the study. Pericarditis etiology was unknow (idiopathic) in 17 (68%), related to systemic autoimmune disease in 5 patients (20%) and related to cancer in 3 patients (12%). In 6 patients (24%) a myopericarditis was diagnosed. According to predefined criteria 10 patients had echocardiography positive for pericardial disease (40%), while in 9 patients cardiac MRI was positive for pericardial inflammation (36%). Both echocardiography and cardiac MRI were positive in 5 patients (20%). At a mean follow-up of 35.4 ± 12.2 months a total of 9 recurrent pericarditis events were recorded. At multivariate analysis MRI positive for pericardial inflammation [HR (95%CI) 15.9 (2.7-95.5)] but not echocardiography positive for pericardial disease [HR (95%CI) 0.33 (0.1-1.5)] resulted to be associated to recurrent pericarditis at follow-up.

Conclusion

Cardiac MRI positive for pericardial inflammation could identify patients that may merit more aggressive anti-inflammatory therapy to prevent recurrent pericarditis.
Prognostic benefit of nonemergent revascularization on ischaemic dilated cardiomyopathy depending on patient symptoms
Authors: Herrador Galindo L , Rodenas Alesina E , Jordan Marchite P , Pizzi N , Espinet-Coll C , Romero Farina G , Aguade-Bruix S , Ferreira Gonzalez I
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

INTRODUCTION

Both angina and dyspnea symptoms are the most common clinical manifestations of cardiac ischaemia. Nevertheless, cardiac ischaemia may be detected on control functional tests of patients with ischaemic dilated cardiomyopathy despite being asymptomatic. The aim of this study was to assess the effect of elective myocardial revascularization on patient’s prognosis  depending on baseline clinical symptoms.

METHODS

All consecutive patients with ischaemic left ventricular dysfunction (LVEF <40% determined by gated-SPECT) who underwent stress-rest SPECT in our hospital between January 2010 and February 2018 were included. Baseline patients’ clinical presentation (angor pectoris, dyspnea or asymptomatic) and major adverse events (myocardial infarction, heart failure hospitalization and cardiovascular death) were retrospective recorded. 

RESULTS

A total of 748 patients with multiple comorbid conditions (smoking habit 69%, hypertension 78,7%, diabetes mellitus 49,5%, atrial fibrillation 22,1%, previous myocardial infarction 69% and previous heart failure hospitalization 24,9%) were included. Nonemergent coronary intervention during the first year (17,9% of patients) was associated with a reduction in the composite event (HR 0.69 [0.5-0.95]) but the multivariate analysis showed a prognostic benefit of revascularization in symptomatic patients (HR = 0.59 [0.37 - 0.94]) that was not observed among asymptomatic patients. The relative risk of the composite endpoint was RR = 0.63 (p <0.001) for asymptomatic vs. symptomatic non-revascularized patients and RR = 1.09 (p = 0.60) for asymptomatic vs. symptomatic revascularized patients. Finally, asymptomatic patients presented more necrosis (17.3 vs. 20.2%, p <0.01) and less ischemia (9.7 vs. 5.7%, p <0.001) than symptomatic patients. 

CONCLUSION

Patients with ischaemic dilated cardiomyopathy without symptoms of dyspnea or angina present less ischaemia and more necrosis in stress-rest SPECT than symptomatic patients. Moreover, unlike symptomatic patients, asymptomatic patients do not benefit from elective revascularization. Therefore, the clinical presentation should be considered when deciding revascularization of patients with ischaemic dilated cardiomyopathy and a positive SPECT test.

Abstract Figure. Kaplan-Meyer curves
The first-phase ejection fraction - association with outcome in aortic valve stenosis
Authors: Carter-Storch R , Mortensen NSB , Christensen NL , Ali M , Laursen K , Pellikka PA , Moeller JE , Dahl JS
Published: February 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Danish Heart Association.

Background

First-phase ejection fraction (EF1), the ejection fraction (EF) until the time of peak systolic flow may be a sensitive marker of subclinical left ventricular (LV) dysfunction. This study investigated the prognostic value of EF1 in asymptomatic and symptomatic severe aortic stenosis (AS).

Methods

This study included 94 asymptomatic and 108 symptomatic patients with severe AS. The prognostic value of EF1 was compared with other echocardiographic markers and magnetic resonance imaging (MRI) measured end-systolic wall stress and late gadolinium enhancement fibrosis (LGE). Asymptomatic patients were followed up for 3.0 years (primary outcome death or aortic valve replacement). Symptomatic patients were followed up for 4.3 years (primary outcome death).

Results

In multivariate regression analysis wall stress (p < 0.001) and LGE (p = 0.03) were associated with EF1. In the asymptomatic cohort EF1 was significantly associated with the end-point, especially among the subgroup of patients with a mean gradient < 40 mmHg (HR 0.91, p = 0.005), while global longitudinal strain was not. In the surgical cohort, EF1 was borderline associated with death (p = 0.08) which was significant after correction for LGE (HR 0.90, p = 0.02).

Conclusion

EF1 is a predictor of death or AVR in asymptomatic AS, especially among discordantly graded patients with low area and low gradient.

Univariate β (95% CI) p-value Multivariate β (95% CI) p-value Age (years) .03 (-.09 to .16) 0.58 .03 (-.12 to .18) 0.69 Sex (male) -.12 (-2.26 to 2.03) 0.91 .24 (-2.31 to 2.80) 0.85 Hypertension -.08 (-2.22 to 2.07) 0.95 Aortic valve area (0.01 cm2) .09 (.04 to .14) 0.001 Aortic mean gradient (mmHg) -.02 (-.08 to .04) 0.56 LV end-diastolic volume (ml) -.07 (-.11 to -.03) <0.001 LV end-systolic volume (ml) -.17 (-.22 to -.12) <0.001 -.07 (-.15 to .02) 0.11 LV ejection fraction (%) .28 (.19 to .38) <0.001 LV peak ejection time (ms) -.07 (-.16 to .02) 0.13 LGE fibrosis -3.04 (-5.67 to -.42) 0.02 -2.64 (-4.99 to -.30) 0.03 Wall stress (kdynes/m3) -.10 (-.13 to -.08) <0.001 -.08 (-.12 to -.04) <0.001 Multivariate linear regression analysis for associations with first phase ejection fraction. LV is left ventricular, LGE late gadolinium enhancement Abstract Figure. AVR-free survival according to EF1
Prediction of atrial fibrillation in men with coronary artery disease by artificial neural network
Authors: Yaroslavskaya E , Dyachkov S , Gorbatenko E
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Atrial fibrillation (AF) is quite common in patients with coronary artery disease (CАD). However, there is no data whether AF is associated with coronary lesion of specific localization.

Purpose

To select the most sensitive parameters for creating artificial neural networks (ANN) model to predict AF in men with CАD using ANN.

Methods

We selected the data of men of comparable age with angiographically proven CAD from the Register of coronary angiography: the main group - 180 men with AF, the comparison group - 713 men without AF. To assess the risk of AF the ANN mathematical model was applied - a multilayer perceptron with one hidden layer. The initial number of patients was divided into 3 samples: training, test and control.

Results

Patients with AF were significantly less frequently employed in budget organizations (55.0% vs 63.7%, p = 0.040), more often demonstrated higher (III-IV) heart failure NYHA classes (49.2% vs 21.1% , p < 0.001), had higher body mass index (BMI) (30.2 [27.4; 33.2] kg/m² vs 29.0 [26.1; 32.3] kg/m², p = 0.002), echocardiographic indices of increased left ventricular (LV) myocardial mass (163.7 [144.5; 192.4] g/m² vs 143.9 [126.1; 169.0] g/m², p < 0.001), LV (25.8 [24.1; 29.1] mm/m² vs 25.6 [23.9; 27.5] mm/m², p = 0.020) and right ventricular dimensions, enlarged left atrium (23.6 [21.7; 25.7] mm/m² vs 21.1 [19.7; 22.7] mm/m², p < 0.001). Rate of hemodynamically significant mitral regurgitation in AF patients was higher (48.2% vs 14.1%, p < 0.001), index of aortic root dimensions (7.7 [16.4; 19.0] mm/m² vs 18.3 [17.8; 20.0] mm/m², р=0.002) and LV ejection fraction (EF) in this group was lower (49 [42; 56]% vs 56 [47; 60]%, p < 0.001), coronary calcification (23.2% vs 15.7%, p = 0.024 ) and proximal lesions of the right coronary artery (RCA) (28.3% vs 22.7%, p = 0.025) were detected more often. Sensitivity of the final model which included 10 parameters was 85%, specificity 86%.

Conclusion

In CAD men AF can be predicted by ANN model that takes into account the presence of significant mitral regurgitation, non-budgetary employment, severity of heart failure, coronary calcification and proximal lesion of RCA, BMI, echocardiographic indices of the left heart and aortic root dimensions, LVEF.
Identification and prognostication of the substrate of ventricular arrhythmia with cardiac magnetic resonance (CMR) imaging in patients with normal echocardiography
Authors: Younus S , Maqsood H , Gulraiz A , Khan MD , Awais R
Published: February 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): Self

Introduction

Malignant ventricular arrhythmia contributes to approximately half of the sudden cardiac deaths. In common practice, echocardiography is used to identify structural heart diseases that are the most frequent substrate of VA. Identification and prognostication of structural heart diseases are very important as they are the main determinant of poor prognosis of ventricular arrhythmia.

Purpose :

The objective of this study is to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had no pathology observed on echocardiography.

Methods :

A total of 864 consecutive patients were enrolled in this single-center prospective study with significant ventricular arrhythmia. VA was characterized as >1000 ventricular ectopic beats per 24 hours, non-sustained ventricular arrhythmia, sustained ventricular arrhythmia, and no pathological lesion on echocardiography. The primary endpoint was the detection of SHD with CMR. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis.

Results :

CMR studies were used to diagnose SHD in 212 patients (24.5%) and abnormal findings not specific for a definite SHD diagnosis in 153 patients (17.7%). Myocarditis (n = 84) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 51), ischemic heart disease (n = 32), dilated cardiomyopathy (n = 17), hypertrophic cardiomyopathy (n = 12), congenital cardiac disease (n = 08), left ventricle noncompaction (n = 5), and pericarditis (n = 3). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.5 and 2.33, respectively) and sustained ventricular tachycardia (ORs: 2.62 and 2.21, respectively).

Conclusion : Our study concludes that SHD was able to be identified on CMR imaging in a significant number of patients with malignant VA and completely normal echocardiography. Chest pain and sustained ventricular tachycardia were the two strongest predictors of positive CMR imaging results.

Abstract Figure. Distribution of different SHD
Linking diastolic function to cardiac exercise performance in heart failure with preserved ejection fraction: a virtual patient study
Authors: Van Loon T , Knackstedt C , Cornelussen R , Reesink KD , Brunner-La-Rocca HP , Delhaas T , Van Empel VPM , Lumens J
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO-ZonMw

Background

The relative impact of left ventricular (LV) diastolic dysfunction (LVDD) and impaired left atrial (LA) function on cardiac exercise performance (CEP) in heart failure with preserved ejection fraction (HFpEF) remains largely unknown

Purpose

To elucidate the relative effects of LVDD and impaired LA function on hemodynamics at rest and on cardiac performance during exercise by performing virtual HFpEF patient simulations.

Methods

Using a well-validated cardiovascular system model (CircAdapt), impaired LV relaxation was simulated by increasing the rate of myocardial relaxation (tau) from 35 to 65 ms. To study the effect of moderate and sever LV myocardial stiffness increase, LV end-diastolic elastance was increased from 0.15 mmHg/ml to 0.60 mmHg/ml and 2.00 mmHg/ml, respectively. In each simulation, LV diastolic function at rest (cardiac output (CO) and heart rate (HR) of 5.1 l/min and 70 bpm, respectively) was assessed using LV ejection fraction (LVEF), mitral E/A ratio, maximum LA volume (LAV), and mean left atrial (LA) pressure (mLAP). To investigate the relative effect of these cardiac abnormalities on exercise capacity, CO and HR were gradually increased using a fixed CO-HR relationship until mLAP exceeded a threshold pressure of 35 mmHg, which was assumed to be a physiological limit of exercise intensity.

Results

Simulations showed that regardless of the modelled LV and LA function, LVEF was preserved (>50%). Impaired LV relaxation function was associated with decreased E/A-ratio and a small increase in mLAP at rest, regardless of LA function. Increased LV passive stiffness resulted in increased E/A-ratio, LA dilation and markedly elevated mLAP at rest, regardless of LA function (Figure: top-left). Impaired LA function resulted in reduced A-peak velocity, and increased E/A–ratio, LAV and mLAP at rest regardless of LV function (Figure: top-right) Exercise simulations showed that increased LV passive stiffness exerts a stronger exercise-limiting effect than impaired LV relaxation function, in particular when LA function is impaired (Figure: bottom).

Conclusions

Through simple and well-controlled variations in LV and LA function, we were able to simulate virtual HFpEF patients with a wide range of LVDD severities at rest, preserved LVEF, and reduced cardiac exercise performance. In general, our simulations suggest that increased LV passive stiffness, rather than impaired LV relaxation function, reduces exercise tolerance, especially in the presence of LA dysfunction.

Abstract Figure. Simulating rest & exercise hemodynamics
Visual acuity and risk of overall, injury-related, and cardiovascular mortality: the Kangbuk Samsung Health Study
Authors: Han So Young , Chang Yoosoo , Shin Hocheol , Choi Chul Young , Ryu Seungho
Published: February 2021

Aims 

The associations of visual impairment (VI) with cardio-metabolic risk factors have been reported but its association with cardiovascular mortality remains uncertain. Therefore, we evaluated the association of visual acuity (VA) with overall, injury-related, and cardiovascular mortality.

Methods and results

A cohort study was performed in 580 746 Korean adults (average age, 39.7 years) who were followed for a median of 8.1 years (maximum, 16 years). Presenting VA was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity in the better vision eye was categorized as normal vision (≥0.8), lowered vision (0.5–0.8), mild visual impairment (VI) (0.3–0.5), or moderate to severe VI (<0.3). Vital status and cause of death were ascertained through linkage to national death records. During 4 632 892.2 person-years of follow-up, 6585 overall deaths, 974 cardiovascular deaths, and 1163 injury-related deaths were identified. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall mortality among participants with lowered vision, minimal VI, and moderate to severe VI were 1.21 (1.13–1.29), 1.26 (1.15–1.37), and 1.54 (1.40–1.68), respectively, compared with those with normal vision. The corresponding HRs (95% CIs) for injury-related mortality were 1.12 (0.96–1.32), 0.98 (0.76–1.26), and 1.36 (1.04–1.79), respectively, and the corresponding HRs (95% CIs) for cardiovascular mortality were 1.32 (1.12–1.57), 1.43 (1.15–1.77), and 2.41 (1.94–2.99).

Conclusion 

In this large cohort of young and middle-aged individuals, VI was associated with increased risk of mortality especially due to cardiovascular disease.
High-Normal Thyroid Function Predicts Incident Nonalcoholic Fatty Liver Disease Among Middle-Aged and Older Euthyroid Subjects
Authors: Gu Yeqing , Wu Xiaohui , Zhang Qing , Liu Li , Meng Ge , Wu Hongmei , Zhang Shunming , Wang Yawen , Zhang Tingjing , Wang Xuena , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Niu Kaijun
Published: February 2021

Background

Thyroid hormones (THs) influence hepatic lipid homeostasis through multiple pathways, suggesting that THs may predict the risk of nonalcoholic fatty liver disease (NAFLD). However, prospective studies on the association between THs levels and incident NAFLD in euthyroid subjects are limited. This prospective cohort study aimed to explore whether THs were associated with the development of NAFLD in middle-aged and older euthyroid subjects.

Method

A total of 6462 subjects without baseline NAFLD were included in the cohort study (~6-year follow-up period, median: 4.2 years). Chemiluminescence immunoassay was used to measure serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and NAFLD was diagnosed by abdominal ultrasonography. Multivariable Cox proportional hazards regression models were used to assess the association between baseline THs, TSH, and the risk of NAFLD.

Results

During the follow-up period, 1675 subjects developed NAFLD. The incidence rate of NAFLD was 85.0 per 1000 person-years. Compared with the lowest FT3, FT4, and TSH quartiles, the multivariable-adjusted hazard ratios (95% confidence interval) of incident NAFLD for highest quartiles were 1.30 (1.12, 1.51), 1.07 (0.93, 1.23), and 0.82 (0.71, 0.95) (p < .001, p = .56, p = .01, respectively).

Conclusions

In middle-aged and older euthyroid subjects, high-normal FT3 and low-normal TSH are independently associated with a higher incidence of NAFLD.
The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application
Authors: Yamada Issaku , Campbell Matthew P , Edwards Nathan , Castro Leyla Jael , Lisacek Frederique , Mariethoz Julien , Ono Tamiko , Ranzinger Rene , Shinmachi Daisuke , Aoki-Kinoshita Kiyoko F
Published: February 2021

Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites. However, only very few of these reports find their way into databases or data repositories. One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans. Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site. To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data. GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats. The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
The scale-up and integration of contraceptive service delivery into nursing school training in the Democratic Republic of the Congo
Authors: Ntabona Alexis , Binanga Arsene , Bapitani Mr Désiré Josué , Bobo Beatrice , Mukengeshayi Bitshi , Akilimali Pierre , Kalong Gloria , Mujani Zenon , Hernandez Julie , Bertrand Jane T
Published: February 2021

In Kinshasa, Democratic Republic of the Congo (DRC), modern contraceptive prevalence is low by international standards: 29.6% as of 2020. A 2015 pilot study demonstrated the feasibility and acceptability of using medical and nursing students to administer DMPA-SC (the subcutaneous injection) among other methods at the community level. The more far-reaching discovery was the potential of clinically trained students to increase access to low-cost contraception in the short-run, while improving the quality of service delivery for future generations of healthcare providers. Scale-up involved integrating the family planning curriculum into the training of nursing students, including classroom instruction in contraceptive technology and service delivery, coupled with a year-long field practicum in which students offered a range of contraceptive methods during intermittent outreach events, door-to-door distribution or sales from their homes. Starting in 2015, a multi-agency team consisting of an international non-governmental organizations (NGO), several Ministry of Health directorates and a local NGO used the ExpandNet/WHO framework to guide this scale-up. This article details the nine steps in the scale-up process. It presents results on increases in contraceptive uptake, feedback from participating nursing school personnel and the employment experience of the graduates from this programme. Between 2015 and 2019, the family planning curriculum was incorporated into 30.8% of the 477 nursing schools in 7 of the 26 provinces in the DRC. Students delivered 461 769 couple-years of protection (the key output indicator for family planning programmes). Nursing school personnel were strongly favourable to the approach, although they needed continued support to adequately implement a set of additional interventions related to the service delivery components of the new training approach. Post-graduation, only 40.1% of graduates had paid employment (reflecting the staggering unemployment in the DRC); among those, over 90% used their family planning training in their work. We describe the multiple challenges faced during the scale-up process and in planning for expansion to additional schools.
Genome-wide association studies identify two novel loci conferring susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes
Authors: Imamura Minako , Takahashi Atsushi , Matsunami Masatoshi , Horikoshi Momoko , Iwata Minoru , Araki Shin-ichi , Toyoda Masao , Susarla Gayatri , Ahn Jeeyun , Park Kyu Hyung , Kong Jinhwa , Moon Sanghoon , Sobrin Lucia ,   International Diabetic Retinopathy and Genetics CONsortium (iDRAGON), Yamauchi Toshimasa , Tobe Kazuyuki , Maegawa Hiroshi , Kadowaki Takashi , Maeda Shiro
Published: February 2021

Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stages 1 and 2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, P = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, P = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci was not replicated in Korean, European or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (P = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.
Breastfeeding in Refugee Camps: A Child and Maternal Right?
Authors: Ebrahimi Aleisha
Published: February 2021

In recognition of the health benefits breastfeeding offers for both mother and child, breastfeeding has been acknowledged in various International Human Rights Law instruments. Furthermore, against the backdrop of aggressive formula milk marketing campaigns, significant soft law provisions contained within the International Code of Marketing of Breast-milk Substitutes 1981 regulate and control the promotion of breastmilk substitutes. Refugee camps, however, remain aligned with pre-code practice, as formula milk is often one of the first donations to arrive in camps. Mothers, who are still affected by historical formula marketing campaigns, receive formula milk and perceive its availability and distribution as an endorsement over breastfeeding. In this article, International Human Rights Law is analysed, within the framework of the principle of the best interests of the child, to determine if the choice to breastfeed should be protected as a human right and how the indiscriminate supply of formula milk interacts with this choice in refugee camps.
Is Dodd-Frank the Biggest Law Ever?
Authors: McLaughlin Patrick A , Sherouse Oliver , Febrizio Mark , King M Scott
Published: February 2021

The passage of the Dodd-Frank Wall Street Reform and Consumer Protection Act in 2010 continued a trend toward lengthier and more complex acts of Congress. In this article, we use novel metrics of the size, scope, and complexity of acts of Congress to assess Dodd-Frank’s place in this trend. Our analysis is consistent with the hypothesis that, in terms of its regulatory effects, Dodd-Frank is the biggest act of Congress in recent history and may become the biggest ever. We argue that this trend toward longer and more complex laws can cause deterioration in the quality of the regulations the laws authorize for two procedural reasons. First, a large act can create a regulatory surge that overwhelms the quality control process. Second, because a large act can precipitate the creation of many regulations by different agencies that target the same industry, the agencies create rules in relative ignorance of their potential interactions.
The clustering of critical points in the evolving cosmic web
Authors: Shim J , Codis S , Pichon C , Pogosyan D , Cadiou C
Published: February 2021

Focusing on both small separations and baryonic acoustic oscillation scales, the cosmic evolution of the clustering properties of peak, void, wall, and filament-type critical points is measured using two-point correlation functions in ΛCDM dark matter simulations as a function of their relative rarity. A qualitative comparison to the corresponding theory for Gaussian random fields allows us to understand the following observed features: (i) the appearance of an exclusion zone at small separation, whose size depends both on rarity and signature (i.e. the number of negative eigenvalues) of the critical points involved; (ii) the amplification of the baryonic acoustic oscillation bump with rarity and its reversal for cross-correlations involving negatively biased critical points; (iii) the orientation-dependent small-separation divergence of the cross-correlations of peaks and filaments (respectively voids and walls) that reflects the relative loci of such points in the filament’s (respectively wall’s) eigenframe. The (cross-) correlations involving the most non-linear critical points (peaks, voids) display significant variation with redshift, while those involving less non-linear critical points seem mostly insensitive to redshift evolution, which should prove advantageous to model. The ratios of distances to the maxima of the peak-to-wall and peak-to-void over that of the peak-to-filament cross-correlation are ${\sim} \sqrt{2}$ and ${\sim} \sqrt{3}$, respectively, which could be interpreted as the cosmic crystal being on average close to a cubic lattice. The insensitivity to redshift evolution suggests that the absolute and relative clustering of critical points could become a topologically robust alternative to standard clustering techniques when analysing upcoming surveys such as Euclid or Large Synoptic Survey Telescope (LSST).
Conserved dual-mode gene regulation programs in higher eukaryotes
Authors: Lee Jun-Yeong , Song Jawon , LeBlanc Lucy , Davis Ian , Kim Jonghwan , Beck Samuel
Published: February 2021

Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Here, through comparative epigenomic analyses, we demonstrate that the dual-mode gene regulation program is common in various eukaryotes, even in the species lacking CGIs. In cases of vertebrates or plants, we find that genes associated with high methylation level promoters are inactivated by forming heterochromatin and expressed in a context-dependent manner. In contrast, the genes with low methylation level promoters are broadly expressed and remain as euchromatin even when repressed by Polycomb proteins. Furthermore, we show that invertebrate animals lacking DNA methylation, such as fruit flies and nematodes, also have divergence in gene types: some genes are regulated by Polycomb proteins, while others are regulated by heterochromatin formation. Altogether, our study establishes gene type divergence and the resulting dual-mode gene regulation as fundamental features shared in a broad range of higher eukaryotic species.
Spatial coupling between DNA replication and mismatch repair in Caulobacter crescentus
Authors: Chai Tiancong , Terrettaz Céline , Collier Justine
Published: February 2021

The DNA mismatch repair (MMR) process detects and corrects replication errors in organisms ranging from bacteria to humans. In most bacteria, it is initiated by MutS detecting mismatches and MutL nicking the mismatch-containing DNA strand. Here, we show that MMR reduces the appearance of rifampicin resistances more than a 100-fold in the Caulobacter crescentus Alphaproteobacterium. Using fluorescently-tagged and functional MutS and MutL proteins, live cell microscopy experiments showed that MutS is usually associated with the replisome during the whole S-phase of the C. crescentus cell cycle, while MutL molecules may display a more dynamic association with the replisome. Thus, MMR components appear to use a 1D-scanning mode to search for rare mismatches, although the spatial association between MutS and the replisome is dispensible under standard growth conditions. Conversely, the spatial association of MutL with the replisome appears as critical for MMR in C. crescentus, suggesting a model where the β-sliding clamp licences the endonuclease activity of MutL right behind the replication fork where mismatches are generated. The spatial association between MMR and replisome components may also play a role in speeding up MMR and/or in recognizing which strand needs to be repaired in a variety of Alphaproteobacteria.