bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of obesity on myocardial microvasculature assessed using fully-automated inline myocardial perfusion mapping CMR
Authors: Joy G , Crane JD , Lau C , Augusto J , Brown LAE , Chowdhary A , Kotecha T , Plein S , Fontana M , Moon JC , Kellman P , Xue H , Cruickshank JK , Mcgowan BM , Manisty C
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospitals Biomedical Research Centre

Background

Obesity and cardiovascular disease are associated, but the relationship is poorly understood. Myocardial perfusion, metabolic derangement and lipotoxicity appear adversely associated in many scenarios (myocardial injury, diastolic dysfunction, diabetes). Altered perfusion (by PET) predicts outcome, and it is hypothesised that perfusion derangement is part of causality for cardiac disease and adverse outcomes.

Purpose

To assess the presence and pattern of myocardial microvascular dysfunction in patients with obesity (scheduled for bariatric surgery) using stress quantitative perfusion mapping.

Methods

38 subjects with obesity planned to undergo bariatric surgery and 38 age and sex matched healthy volunteers (no diabetes, no hypertension) underwent anthropometry, biochemistry and CMR at 1.5T (Siemens) with cine imaging, stress (adenosine 140-210 mcg/kg/min) and rest fully-automated quantitative perfusion mapping. 

Results

Bariatric patients had a higher BMI (44 ± 6.4 vs 26.5 ± 4kg/m2 p = 0.001); 58%(22) were diabetic and 58%(22) had hypertension. Bariatric patients had higher absolute but lower indexed end-diastolic volumes, and overall higher ejection fractions (+5%) (see Table). Rest myocardial blood flow (MBF) in bariatric patients was the same (1.00 ± 0.3 vs 0.88 ± 0.24 p = 0.052), but stress perfusion results were significantly lower both for stress MBF (2.35 ± 0.69 vs 2.93 ± 0.76ml/g/min p = 0.001) and myocardial perfusion reserve (MPR 2.48 ± 0.82 vs 3.4 ± 0.81ml/g/min p = 0.0001).  Although this was transmural, the endocardial stress MBF was particularly negatively affected in the bariatric cohort compared to controls (endocardial MBF 2.16 ± 0.65 vs 2.82 ± 0.73ml/g/min, p = 0.0001 vs epicardial MBF: 2.52 ± 0.76 vs 3.06 ± 0.79 p = 0.003), meaning there was an increased endo-epicardial stress MBF gradient in bariatric patients (0.87 ± 0.12 vs 0.92 ± 0.07 p = 0.03).

Conclusion

Compared to healthy controls, patients with obesity have abnormal myocardial stress perfusion with reduced global perfusion, perfusion reserve and an increased transmyocardial perfusion gradient.

Table - myocardial perfusion parameters Category Bariatric patients n = 38 Controls n = 38 p value Age (years) 48 ± 11 45 ± 13 0.25 n male (%) 12 (32%) 10 (36%) 0.32 LVEDV (ml) 168 ± 37 149 ± 31 0.017 LVEDVi (ml/m2) 70.4 ± 12.3 78.8 ± 12.1 0.004 LV Mass (g) 116 ± 31 99 ± 28 0.019 EF (%) 70 ± 8 65 ± 5 0.002 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction
Detrimental immediate and long-term clinical effects of right ventricular pacing in patients with myocardial fibrosis
Authors: Saunderson C , Paton MF , Brown LAE , Gierula J , Chew PG , Das A , Sengupta A , Craven TP , Chowdhary A , Levelt E , Dall"armellina E , Witte KK , Greenwood JP , Plein S , Swoboda PP
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients.

Objectives

We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing.

Methods

We recruited 110 patients (84 in final analysis) into two observational CMR studies. Patients (n = 34) with a dual chamber device and preserved atrioventricular (AV) conduction underwent CMR in two asynchronous pacing modes (AOO & DOO) to compare intrinsic conduction with RV pacing. Patients (n = 50) with high-grade AV block underwent CMR before and 6 months after pacemaker implantation to investigate the long-term effects of RV pacing.

Results: The three key findings were

1) Initiation of RV pacing in patients with fibrosis, compared to those without, was associated with greater immediate changes in both LV end-systolic volume index (LVESVi) (5.3 ± 3.5 vs 2.1 ± 2.4 mL/m2; p < 0.01) and LV ejection fraction (LVEF) (-5.7 ± 3.4% vs -3.2 ± 2.6%; p = 0.02); 2) Long-term RV pacing in patients with fibrosis, compared to those without, was associated with greater changes in LVESVi (8.0 ± 10.4 vs -0.6 ± 7.3 mL/m2; p = 0.008) and LVEF (-12.3 ± 7.9 vs -6.7 ± 6.2%; p = 0.012); 3) Patients with fibrosis did not experience an improvement in quality of life, biomarkers or functional class after pacemaker implantation.

Conclusions

Fibrosis detected on CMR is associated with immediate and long-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure prior to pacemaker implantation.

Characteristics before and after pacing Study 1 No fibrosis (n = 16) Fibrosis (n = 18) AOO DOO p-value AOO DOO p-value LVEDVi - mL/m² 66 ± 13 66 ± 12 0.67 78 ± 14 79 ± 13 0.34 LVESVi - mL/m² 30 ± 10 32 ± 9 0.003 38 ± 11 43 ± 12 <0.001 LVEF - % 56 ± 6 53 ± 5 <0.001 52 ± 8 47 ± 9 <0.001 Mechanical Dyssynchrony index - ms 61 ± 17 71 ± 25 0.07 81 ± 18 89 ± 21 0.04 Study 2 No fibrosis (n = 19) Fibrosis (n = 31) Pre-PPM Post-PPM p-value Pre-PPM Post-PPM p-value LVEDVi -mL/m² 88 ± 21 73 ± 14 <0.001 90 ± 18 83 ± 21 0.007 LVESVi -mL/m² 35 ± 9 34 ± 9 0.71 41 ± 14 49 ± 21 0.001 LVEF - % 60 ± 5 54 ± 7 <0.001 56 ± 8 43 ± 12 <0.001 Mechanical Dyssynchrony index - ms 70 ± 29 81 ± 22 0.15 84 ± 30 98 ± 31 0.03 Abstract Figure. Mechanism for heart failure after pacing
Myocardial changes detected with modern cardiac magnetic resonance techniques in patients with early rheumatoid arthritis
Authors: Jarvio J , Syvaranta S , Tuohinen S , Holmstrom M , Peltomaa R , Koivuniemi R , Leirisalo-Repo M , Kivisto S , Vaara S
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): HUS diagnostic imaging center

Aims

Subclinical myocardial disease is common in patients with rheumatoid arthritis (RA). Impaired cardiac function, myocardial fibrosis and inflammation have previously correlated with RA disease activity. Our aim was to study whether myocardial changes are detectable by cardiac magnetic resonance (CMR) at the time of RA diagnosis.

Material and methods: We recruited 21 untreated early RA patients without history of heart disease in Helsinki University Hospital and Lohja Hospital (Finland) between 10/2018 and 2/2020, and nine healthy volunteers. The patients underwent a clinical examination, laboratory tests, and CMR including mapping of extracellular volume fraction (ECV), and T1 and T2 relaxation times. The healthy controls underwent non-contrast CMR.

Results

 The RA patients were older than the controls (median 58.1 years vs. 41.6 years, respectively, table 1.). T1 was slightly higher in RA patients compared with healthy controls in anteroseptal segments (1015 ms vs. 982 ms, P = 0.017) (table 2).  No difference in T2 was detected and the ECV values were considered normal. Segmental T1, T2 or ECV showed no significant correlations with age, duration of the symptoms or with RA disease activity (DAS28-CRP score).

Conclusions

 The minor, but statistically significant, elevation of T1 relaxation time in the anteroseptal segments suggests that myocardial changes may occur already in the early phase of RA, the anteroseptal segments being most vulnerable. The elevation of T1 relaxation time can be caused by mild myocardial inflammation or fibrosis. Although no significant correlation with DAS28-CRP was observed, subclinical systemic inflammation may have contributed to the myocardial abnormalities.

Table 1. Pre-contrast T1 relaxation time (ms) T2 relaxation time (ms) ECV (%) Mean RA patients Controls P-value RA patients Controls P-value RA patients Global myocardial mean 996 (978-1011) 982 (964-1000) 0.304 48.0 (44.6-49.7) 46.3 (44.1-48.7) 0.295 26.6 (25.7-28.5) Anterior segments 954 (919-1000) 951 (921-998) 0.929 47.7 (46.4-49.8) 47.9 (43.5-50.1) 0.871 26.7 (25.3-28.8) Anteroseptal segments 1015 (987-1041) 982 (947-996) 0.017 48.3 (45.5-49.9) 45.7 (43.8-48.4) 0.150 28.3 (26.8-29.2) Inferoseptal segments 1012 (992-1023) 998 (967-1003) 0.077 48.0 (43.5-49.4) 44.9 (43.5-46.2) 0.533 26.7 (26.0-27.9) Inferior segments 1016 (987-1064) 1003 (992-1025) 0.625 47.5 (45.1-50.3) 46.1 (44.2-48.4) 0.304 27.3 (25.6-29.0) Inferolateral segments 997 (974-1043) 992 (980-1016) >0.999 46.6 (42.6-49.1) 45.1 (42.4-49.1) 0.689 25.8 (25.3-28.2) Anterolateral segments 973 (945-973) 981 (954-1010) 0.563 47.0 (45.1-48.5) 46.6 (43.5-49.6) 0.625 26.4 (24.7-28.0) T1 and T2 relaxation time mapping and ECV results. Abstract Figure. ECV mapping
Validation of a simple ECG score for infarct size estimation in patients with first-time ST-elevation myocardial infarction
Authors: Tiller C , Reindl M , Holzknecht M , Lechner I , Kalles V , Rangger A , Mayr A , Klug G , Brenner C , Bauer A , Reinstadler S , Metzler B
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund

Background

The magnitude of myocardial damage after acute ST-elevation myocardial infarction (STEMI) is a crucial prognostic determinant. Cardiac magnetic resonance (CMR) imaging offers a precise infarct severity assessment after STEMI; however, limited to restricted availability in daily clinical routine. Recently, a simple ECG score (DETERMINE score) was developed for infarct size (IS) estimation in STEMI patients with prior infarction. We sought to validate this score in patients with first-time STEMI for the assessment of myocardial injury visualized by CMR.

Methods

In this validation study, 423 revascularized first-time STEMI patients (median age 56, 17% women) were included. ECG was conducted at discharge for evaluation of the DETERMINE and Selvester score. CMR imaging was performed at a median of 3 days for the assessment of infarct characteristics (IS and microvascular obstruction [MVO]).

Results

Median DETERMINE score of the overall cohort was 8 points (interquartile range: 5-11). Patients presenting with a score > 8 points had more often anterior infarct localization (64% vs. 29%, p < 0.001) and higher peak hs-TnT levels (6957 ng/l vs. 3117 ng/l, p < 0.001). In linear and binary multivariable logistic regression analysis, the DETERMINE score remained as independent associate of IS (odds ratio [OR]: 1.09, 95% confidence interval [CI] 1.00 to 1.18, p = 0.047) and MVO (OR: 1.09, 95% CI 1.02 to 1.16, p = 0.016), after adjustment for Selvester score and peak hs-cTnT.

Conclusions

In survivors of first-time STEMI, the DETERMINE score provides an easy and inexpensive tool for suitable IS estimation. Moreover, the DETERMINE score showed significant and independent association with MVO. Thus, this simple ECG score might help identify patients at high risk of large infarct burden who might benefit from more aggressive treatment strategies.
Right ventricular non-compaction: myth or reality?
Authors: Kiss A , Gregor ZS , Horvath M , Furak A , Szabo LE , Toth A , Dohy ZS , Czimbalmos CS , Vago H , Merkely B , Szucs A
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Noncompaction cardiomyopathy (NCMP) is characterized by excessive left ventricular (LV) trabeculation. The involvement of the right ventricle (RV) is still questionable, furthermore, the normal range for RV trabeculation is undefined. 

Our aim was to describe the RV functional and strain values of patients with NCMP with preserved LV ejection fraction (EF) using cardiac MRI and to compare these parameters with healthy control subjects, furthermore, we aimed to define the normal range for RV trabeculation. 

We included 81 NCMP patients with good LV-EF (mean age: 37.0 ± 14 years; EF: 69.4 ± 13.2%) and without comorbidities. Their parameters were compared to an age and sex matched control group (mean age: 37.2 ± 13.7 years; EF: 77.2 ± 15.0%).

MR examinations were performed with 1,5T Philips Achieva and Siemens Aera devices. The Medis Suite software was used for post-processing analysis, the MedCalc software for statistics, p < 0.05 was considered statistically significant. 

The RV trabecular mass index (RV-TRABi) was significantly greater and the RV-EF significantly smaller in the NCMP group compared with the controls (NCMP vs. control; TRABi: 20.6 ± 7.0 vs. 16.9 ± 4.2 g/m2; RV-EF: 62.8 ± 5.5 vs. 64.5 ± 4.5%; p < 0.05).

As for the RV global longitudinal strain (GLS) the results were close to significant (NCMP vs. control: -25.1 ± 4.0 vs. -26.4 ± 4.3%; p = 0.05). We defined the normal range of RV-TRABi with a lower limit of 8.2 g/m2 (90% confidence interval (CI): 6.8-9.5) and the upper limit of 22.1 g/m2 (90% CI: 23.6-26.5). 27.2% of the NCMP patients exceeded the upper limit of RV-TRABi. 

The described differences in the RV-EF, RV-TRABi and RV-GLS draws attention to the possibility of the involvement of RV in patients with NCMP. Further follow-up studies would be necessary to evaluate the clinical importance of these alterations.
Feasibility and accuracy of the automated software for dynamic quantification of left ventricular and atrial volumes and function in a large unselected population
Authors: Italiano G , Tamborini G , Mantegazza V , Volpato V , Fusini L , Muratori M , Lang R , Pepi M
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Objective. Preliminary studies showed the accuracy of machine learning based automated dynamic quantification of left ventricular (LV) and left atrial (LA) volumes. We aimed to evaluate the feasibility and accuracy of machine learning based automated dynamic quantification of LV and LA volumes in an unselected population.

Methods. We enrolled 600 unselected patients (12% in atrial fibrillation) clinically referred for transthoracic echocardiography (2DTTE), who also underwent 3D echocardiography (3DE) imaging. LV ejection fraction (EF), LV and LA volumes were obtained from 2D images; 3D images were analysed using Dynamic Heart Model (DHM) software (Philips) resulting in LV and LA volume-time curves. A subgroup of 140 patients underwent also cardiac magnetic resonance (CMR) imaging. Average time of analysis, feasibility, and image quality were recorded and results were compared between 2DTTE, DHM and CMR.

Results. The use of DHM was feasible in 522/600 cases (87%). When feasible, the boundary position was considered accurate in 335/522 patients (64%), while major (n = 38) or minor (n = 149) borders corrections were needed. The overall time required for DHM datasets was approximately 40 seconds, resulting in physiologically appearing LV and LA volume–time curves in all cases. As expected, DHM LV volumes were larger than 2D ones (end-diastolic volume: 173 ± 64 vs 142 ± 58 mL, respectively), while no differences were found for LV EF and LA volumes (EF: 55%±12 vs 56%±14; LA volume 89 ± 36 vs 89 ± 38 mL, respectively). The comparison between DHM and CMR values showed a high correlation for LV volumes (r = 0.70 and r = 0.82, p < 0.001 for end-diastolic and end-systolic volume, respectively) and an excellent correlation for EF (r= 0.82, p < 0.001) and LA volumes.

Conclusions. The DHM software is feasible, accurate and quick in a large series of unselected patients, including those with suboptimal 2D images or in atrial fibrillation.

Table 1 DHM quality Adjustment Feasibility Good Suboptimal Minor Major Total of patients (n, %) 522/600 (87%) 327/522 (62%) 195/522 (28%) 149/522 (29%) 38/522 (6%) Normal subjects (n, %) 39/40 (97%) 23/39 (57%) 16/39 (40%) 9/39 (21%) 1/39 (3%) Atrial Fibrillation (n, %) 59/73 (81%)* 28/59 (47%) 31/59 (53%) 15/59 (25%) 6/59 (10%) Valvular disease (n, %) 271/312 (87%) 120/271 (%) 151/271 (%) 65/271 (24%) 16/271 (6%) Coronary artery disease (n, %) 47/58 (81%)* 26/47 (46%) 21/47 (37%) 16/47 (34%) 5/47 (11%) Miscellaneous (n, %) 24/25 (96%) 18/24 (75%) 6/24 (25%) 5/24 (21%) 3/24 (12%) Feasibility of DHM, image quality and need to adjustments in global population and in each subgroup. Abstract Figure 1
18F-Sodium fluoride PET/CT detects transcatheter aortic valve degeneration
Authors: Tzolos E , Kwiecinski J , Cartlidge TRG , Fletcher A , Doris MK , Tarkin JM , Slomka PJ , Newby DE , Rudd JHF , Berman DS , Dweck MR
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the British Heart Foundation, London, United Kingdom

Background

Early detection of transcatheter aortic valve implantation (TAVI) degeneration is challenging and only feasible when advanced haemodynamic valve dysfunction is apparent. 

Purpose

We tested whether 18F-sodium fluoride (18F-NaF) positron emission tomography and computed tomography (PET/CT) could detect structural TAVI degeneration and haemodynamic valve dysfunction. 

Methods

After TAVI implantation, patients underwent baseline echocardiography, CT angiography and 18F-NaF PET/CT (Figure). We assessed for morphological changes, stenosis or regurgitation on Doppler echocardiography, CT (hypoattenuated leaflet thickening [HALT] or spotty calcification) and PET (18F-NaF uptake; maximum target-to-background ratio, TBRmax). We categorised structural valve degeneration (SVD) according to the standardised definition for surgical and transcatheter bioprosthetic valves, as proposed in a recent consensus statement. 

Results

We recruited 47 patients (81 ± 6 years old, 79% male) 1 month (n = 9), 2 years (n = 22) or 5 years (n = 16) after TAVI: 25 (53%) had received a balloon expanded bioprosthesis and 22 (47%) a self-expanding valve. There was moderate valve dysfunction on Doppler echocardiography in 3 (6%) patients, HALT on CT in 6 (13%) patients, spotty calcification in one patient and 18F-NaF uptake in 7 patients (15%) (TBRmax range: 1.59-5.88); all enrolled 5 years post-TAVI.

All patients with increased 18F-NaF uptake (TBRmax ≥1.59) demonstrated either SVD without haemodynamic valve dysfunction (stage 1, n = 4) or structural valve dysfunction with moderate valve dysfunction and mean transprosthetic pressure gradients >20 mmHg (stage 2, n = 3). In patients without increased 18F-NaF uptake there was no evidence of structural valve degeneration (n = 40).

Within the increased 18F-NaF uptake (n = 7) group, patients with stage 2 SVD (n = 3) demonstrated higher uptake compared to patients with stage 1 SVD (TBRmax 4.3 [3.02-5.88] versus 1.8 [1.59-2.28]). Patients with stage 2 SVD (n = 3) had over 3 times higher TBRmax than those without SVD (n = 40) (4.30 [3.02, 5.88] versus 1.31 [1.21, 1.46]; p < 0.001); Figure).

Conclusion

18F-NaF PET/CT detects patients with SVD and potentially identifies those at risk of valve failure.

Abstract Figure.
Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy
Authors: Rootwelt-Norberg C , Lie ØH , Chivulescu M , Castrini AI , Almaas V , Lyseggen E , Haugaa KH , Edvardsen T
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovascular Diseases (ERA-CVD)

Background

Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease characterized by high risk of life-threatening ventricular arrhythmia. Male sex has been reported as a risk factor of high disease penetrance and arrhythmia, but data on sex-specific phenotype in AC are sparse.

Purpose

To assess sex-specific disease progression in AC patients and structural cardiac changes at time of arrhythmic event.

Methods

We included consecutive AC patients in a longitudinal cohort study. We performed echocardiography at baseline according to Task Force Criteria of 2010 with additional parameters including strain. Patients were followed with repeated echocardiographic examinations. Ventricular arrhythmia was defined as aborted cardiac arrest, sustained ventricular tachycardia or appropriate therapy by an implantable cardioverter-defibrillator. In patients with documented first time ventricular arrhythmias, echocardiographic findings obtained ±30 days around the event was noted separately.

Results

We included 191 AC patients (46% female, 51% probands, age 41 ± 17 years) of which 88% had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow up. Females and males had similar progression rate of right ventricular dimensions and left ventricular function, but right ventricular function decreased more in females (Figure). Arrhythmic events occurred in 85 (45%) patients and 39 patients had an echocardiographic examination at the time of their first event. There was no difference in right ventricular diameters or right or left ventricular function between females and males at the time of first arrhythmic event (right ventricular outflow tract diameter: 35 ± 7 mm vs. 39 ± 7 mm, p = 0.16, right ventricular fractional area change: 34 ± 9 % vs. 29 ± 11 %, p = 0.26, left ventricular global longitudinal strain: -18.8 ± 3.0 % vs. 17.2 ± 2.2 %, p = 0.12, respectively).

Conclusion

Disease progression was similar in male and female AC patients indicating no accelerated disease progression in males. First arrhythmic event occurred at similar cardiac dysfunction and diameters in both sexes indicating no lower risk in females.

Abstract Figure.
Assessment of myocardial deformation in patients with a singule left ventricle using CMR feature tracking and speckle tracking echcardiography
Authors: Strodka F , Logoteta J , Gabbert D , Uebing A , Voges I
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Patients with a single ventricle are at risk for ventricular dysfunction in the long-term follow-up during and after completion of the total cavopulmonary connection (TCPC). Hence a detailed assessment of ventricular function is of high clinical relevance in those patients. Echocardiography and cardiovascular magnetic resonance (CMR) are routinely used to examine ventricular function with newer techniques, such as tissue tracking, enabling to determine regional and global myocardial deformation. Studies focusing on patients with a single left ventricle (SLV) are sparse. We assessed LV function in a larger cohort of SLV patients by using CMR feature tracking (FT) and speckle tracking echocardiography (STE).

Methods

56 SLV patients (mean age 12.0.5 ± 8.1 years) who underwent CMR as part of a routine clinical examination were included. The study population consisted of 20 patients with double inlet left ventricle (DILV), 25 patients with tricuspid atresia (TA) and 11 patients with various diagnoses. 36 patients had an echocardiographic examination within 3 months of the CMR study. Left ventricular longitudinal, circumferential and radial strain and strain rate were measured from short axis stacks at basal, midventricular and apical levels as well as from 4-chamber-views using FT. LV end-diastolic and end-systolic volumes (LVEDV, LVESV), ejection fraction (LVEF) and myocardial mass were determined from short axis images. 2D-STE was used to measure global peak systolic longitudinal strain and strain rate. In a subgroup analysis we compared patients with a DILV with patients who had TA.

Results

Apart from two patients, all patients were in NYHA class I. LVEF was preserved in the total group of patients (LVEF 56.1 ± 8.4%) and correlated well with global and regional circumferential strain (r= -0.38 to -0.74, p < 0.01), global radial strain (r= 0.33, p < 0.05) and global longitudinal strain values (r= -0.31, p < 0.05). There was a mild association between LVEF and age at Fontan completion (r= -0.28, p = 0.04). There was no significant difference between the results for global longitudinal strain from FT and STE in the entire patient group. In the subgroup analysis there was no difference in LVEF, LV volumes and global strain and strain rate values from FT and STE between patients with DILV and TA.

Conclusion

SLV patients in this study had a preserved ejection fraction along with an overall good health. The correlation of global and regional strain values derived from CMR FT with LVEF demonstrates that FT might be valuable to assess ventricular function in SLV patients during long-term follow-up.
Ventricular and atrial function in transposition of the great arteries after arterial switch operation - a comprehensive cardiovascular magnetic resonance study
Authors: Schuwerk R , Freitag-Wolf S , Krupickova S , Gabbert D , Uebing A , Langguth P , Voges I
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Although good long-term results after arterial switch operation (ASO) in patients with transposition of the great arteries (TGA) have been described, a few studies suggest that patients can develop ventricular dysfunction. We established a comprehensive cardiovascular magnetic resonance (CMR) analysis protocol to evaluate biventricular and atrial function markers in a large cohort of paediatric and adult TGA patients after ASO.

Methods

103 TGA patients (median age 16.7 years, range 4.3-39.6 years) who underwent ASO were retrospectively included. 66 patients had simple transposition and 37 patients had associated anomalies (ventricular septal defect (VSD) n= 30, aortic coarctation n= 11). 77 healthy subjects were enrolled as controls (median age 15.4 years, range 6.3-43.2 years). 

Biventricular volumes, wall thickness as well as ventricular and atrial functional and deformation parameters were assessed using standard CMR analyses techniques as well as CMR feature tracking (FT). For statistical analysis each clinical variable was evaluated by standard nonparametrical tests and jointly assessed with machine learning methods (random forest, Boruta). The significant variables were used to build a logistic regression model for predicting the case-control status

Results

Results from Mann-Whitney-U test revealed that both, left and right ventricular function markers (left ventricular ejection fraction (LVEF); right ventricular ejection fraction (RVEF); MAPSE; TAPSE; LV long-axis strain) were reduced in patients compared to controls. In addition, left ventricular global longitudinal (-21.18 ± 4.49 / -23.93 ± 3.41; p < 0.001) and circumferential strain values (-29.28 ± 4.30 / -31.32 ± 3.63; p = 0.001) as well as longitudinal strain values for both atria (LA: 24.18 ± 8.04 / 37.81 ± 10.30; p < 0001; RA: 23.89 ± 11.12 / 34.47 ± 10.87; p < 0.001) were lower in patients compared to controls. Segmental FT analysis revealed that the interventricular septum appeared most affected. The logistic regression model demonstrated significant differences for MAPSE, TAPSE (Figure), left atrial global longitudinal strain and basal inferoseptal radial strain. Strong correlations were found between MAPSE and TAPSE (Figure) as well as between left atrial global longitudinal strain and MAPSE (r= 0.54, p < 0.001).

Conclusions

TGA patients after ASO are at risk for ventricular and atrial dysfunction. Using a comprehensive CMR analysis protocol along with statistical machine learning methods and a regression approach, we could demonstrate that especially biventricular longitudinal function, left atrial function and basal septal deformation is impaired.

Abstract Figure
Automated evaluation of the right-sided heart function and geometry using deep learning
Authors: Karuzas A , Sablauskas K , Zvirblyte R , Skrodenis L , Teleisyte E , Verikas D , Balciunas J , Matuliauskas D , Kiziela A , Rumbinaite E , Vaskelyte JJ , Ereminiene E , Jurkevicius R , Plisiene J
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

INTRODUCTION 

Deep learning (DL) has been successfully applied in the automated assessment of some transthoracic echocardiography (TTE) parameters such as left-ventricular ejection fraction. Nevertheless, automation of the right-sided heart assessment has not been widely studied, partially due to the relative difficulty involved in some of the right-sided heart measurement evaluation and time constraints in routine practice. Here we have explored the feasibility of a DL-based system capable of performing different tasks involved in the right-sided heart functional and geometric evaluation.

PURPOSE 

To develop a DL-based system assessing right atrium (RA) and right ventricle (RV) functional and geometric parameters and compare its accuracy to board-certified cardiologists.

METHODS

A total of 2,014 frames from 349 patients (with various indications for TTE) were used to train and validate four convolutional neural networks (CNNs) to perform either segmentation or landmark detection across four different TTE views: apical four-chamber (A4Ch), parasternal long-axis (PLAX), M-mode of tricuspid annulus and tissue Doppler imaging (TDI) of the right ventricular lateral wall. The CNNs were optimised to perform different right-sided heart measurements, namely, right atrial area in end-systole (RAA) and fractional area change (FAC) of RV in A4Ch view, proximal right ventricular outflow tract diameter (pRVOT) in PLAX view, tricuspid annular plane systolic excursion (TAPSE) in M-mode and S’ in TDI. Model performance was compared with two board-certified cardiologists using their average measurements on 20 test set patients. 

RESULTS

CNN predicted pRVOT diameter with a mean absolute error (MAE) of 1.02 mm and root mean squared error (RMSE) of 3.08 mm. The intersection over union (IoU) for the segmentation of RV and RA was 0.89 and 0.87, respectively. We then used  RV and RA segmentation predictions to calculate additional parameters which resulted in RMSE of 8.34% for FAC and 4.93cm2 for RAA. In the M-mode and TDI, the model achieved RMSE of 4.48 mm and 0.84 cm/s for the detection of TAPSE and S’, respectively.

CONCLUSIONS

We have demonstrated the feasibility of a DL-based system performing different measurements involved in right-sided heart evaluation. In a routine practice, where limited time resources might be available, such could assist in the thorough assessment of the right-sided heart geometry and function. Additional studies using cardiac magnetic resonance imaging to establish more precise accuracy of such systems is needed.
Site-specific automated contouring model generalisibiliy enhancement
Authors: Porumb M , Mumith A , Gao S , Parker A , Beqiri A , Sarwar R , Upton R , Leeson P , Woodward G
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Segmentation of cardiac structures in echocardiography is a pre-requisite for accurately assessing cardiac morphology and function. Manual or semi-automated segmentation are both routinely used in clinical practice, although these can be time-consuming, and can introduce high inter- and intra- operator variability resulting in decreased reproducibility. Effective contouring with no manual input has proven to be challenging due to variations in image quality, image noise, motion during the acquisition and the lack of a well-defined geometry.

Methods

This work proposes a coordinate regression method for automated left ventricle (LV) segmentation, presented in Figure 1 (a). The proposed method is based on a modified U-net architecture that outputs the likelihood of coordinates of landmark points. The obtained likelihood heatmaps are converted to 2D coordinates using a differentiable spatial to numerical transform. The model was trained and validated on UK multisite data (1383 subjects) comprising apical 2 and 4 chamber views for both contrast and non-contrast echocardiographic images.

The Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) echocardiographic image segmentation database was used to assess the performance of the proposed method acting as data from a new clinical site. The CAMUS dataset comprises apical 2 and 4 chamber views acquired from 500 patients with manually annotated cardiac structures for end-diastole and end-systole frames. The original CAMUS dataset was split into training (450 patients) and testing (50 patients), with manual contours being available only for the training dataset. Therefore, we used the CAMUS training dataset to both test and improve our model, by using a random sample of 100 studies as an independent testing dataset and the remaining 350 studies were used for retraining the initial model to improve performance for this dataset.

Results

The results obtained on the testing images are presented in Figure 1 (b). When the model was trained using no CAMUS data for the LV segmentation, a mean Dice coefficient of 0.890 and a median of 0.911 was obtained. Including 350 studies with the original 1383 UK dataset and retraining the same model improved the average Dice coefficient to 0.930 and the median to 0.939. The CAMUS dataset authors reported the best average Dice coefficient of 0.924 on the 50 CAMUS testing images, therefore the proposed points regression method introduces a promising alternative to mask-based segmentation models.

Conclusions

In conclusion, the auto-contouring framework has proven to be effective in terms of its performance and ability to generalise to new data. Furthermore, this work highlights the importance of both evaluating model performance on data from new clinical sites and also enhancing model performance.

Abstract Figure.
E-Cigarettes and Cardiopulmonary Health
Authors: Tarran Robert , Barr R Graham , Benowitz Neal L , Bhatnagar Aruni , Chu Hong W , Dalton Pamela , Doerschuk Claire M , Drummond M Bradley , Gold Diane R , Goniewicz Maciej L , Gross Eric R , Hansel Nadia N , Hopke Philip K , Kloner Robert A , Mikheev Vladimir B , Neczypor Evan W , Pinkerton Kent E , Postow Lisa , Rahman Irfan , Samet Jonathan M , Salathe Matthias , Stoney Catherine M , Tsao Philip S , Widome Rachel , Xia Tian , Xiao DaLiao , Wold Loren E
Published: February 2021

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated. Given the recent increase in the popularity of e-cigarettes, there is an urgent need for studies to address their potential adverse health effects, particularly as many researchers have suggested that e-cigarettes may pose less of a health risk than traditional combustible cigarettes and should be used as nicotine replacements. This report is prepared for clinicians, researchers, and other health care providers to provide the current state of knowledge on how e-cigarette use might affect cardiopulmonary health, along with research gaps to be addressed in future studies.
Forward genetic screens identified mutants with defects in trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora
Authors: Huang Tsung-Yu , Lee Yi-Yun , Vidal-Diez de Ulzurrun Guillermo , Hsueh Yen-Ping
Published: February 2021

Nematode-trapping fungi (NTF) are carnivorous fungi that prey on nematodes under nutrient-poor conditions via specialized hyphae that function as traps. The molecular mechanisms involved in the interactions between NTF and their nematode prey are largely unknown. In this study, we conducted forward genetic screens to identify potential genes and pathways that are involved in trap morphogenesis and predation in the NTF Arthrobotrys oligospora. Using Ethyl methanesulfonate and UV as the mutagens, we generated 5552 randomly mutagenized A. oligospora strains and identified 15 mutants with strong defects in trap morphogenesis. Whole-genome sequencing and bioinformatic analyses revealed mutations in genes with roles in signaling, transcription or membrane transport that may contribute to the defects of trap morphogenesis in these mutants. We further conducted functional analyses on a candidate gene, YBP-1, and demonstrate that mutation of that gene was causative of the phenotypes observed in one of the mutants. The methods established in this study might provide helpful insights for establishing forward genetic screening methods for other non-model fungal species.
Veratrum Alkaloid Determination in Four Cases of Veratrum Aqua Poisonings
Authors: Melnik Elizaveta V , Belova Maria V , Potskhveriya Mikhail M , Simonova Anastasiya Yu , Tyurin Igor A , Ramenskaya Galina V
Published: February 2021

Veratrum poisonings are described in the toxicology literature as multiple Veratrum species grow in different parts of the Northern Hemisphere and are occasionally ingested by mistake. Veratrum toxicity is attributed to the steroidal alkaloids contained in all parts of the plant. In Russia, Veratrum poisonings are more common since there is an over-the-counter Veratrum lobelianum-based tincture, Veratrum Aqua (VA), which is topically used for the treatment of lice infestation. Despite its toxicity, VA is misused in traditional medicine as a remedy for alcohol use disorder. We describe four cases of VA poisoning that occurred in Moscow, Russia. Three main V. lobelianum alkaloids (jervine, protoveratrine A (proA) and protoveratrine B) were determined in patient plasma and urine samples using liquid chromatography–tandem mass spectrometry (LC–MS-MS). Here, we describe a novel validated LC–MS-MS method for jervine and proA quantification. A simple and rapid liquid–liquid extraction with methyl tert-butyl ether was utilized for analyte extraction. Chromatographic separation was achieved using a Poroshell 120 EC-C18 column, and the total run time was 14 min. The lower limit of quantification was 0.1 ng/mL for jervine and proA in both plasma and urine. Biological samples were obtained upon hospital admission and during treatment, thus enabling to get a better understanding of the alkaloid elimination profile. Upon admission, plasma concentrations of jervine (concentration range: 0.10–5.01 ng/mL) prevailed over proA (concentration range: 0–0.67 ng/mL). At this time, proA already reached maximum concentrations in urine (concentration range: 0.15–37.70 ng/mL). Maximum concentrations of jervine in urine were observed 24 h after admission (concentration range: 0.10–9.55 ng/mL). In all cases, plasma concentrations of Veratrum alkaloids correlated with condition severity. Since none of the patients confirmed VA intake, instrumental analysis was the basis for the definitive diagnosis of VA poisoning.
Pancreatic Cancer Insights: Optimization of the Diagnostic Capacity of Tumor Biomarkers
Authors: Delgado Jose Antonio , Ballesteros Maria Antonieta , Parera María Magdalena , Bauça Josep Miquel
Published: February 2021

Objective

Pancreatic cancer (PC) is one of the deadliest malignancies. The aim of this study was to determine the usefulness of the carbohydrate antigen 19.9 (CA19.9)/ carcinoembryonic antigen (CEA) ratio as a diagnostic tool.

Methods

This was a retrospective observational study (2015–2019), including laboratory requests with increased CA19.9 and CEA but no previous neoplasia. Receiver operating characteristic (ROC) curve analyses were performed for the CA19.9/CEA ratio and for CA19.9 and CEA alone for the detection of PC, and cutoff values for all strategies were selected separately and in combination.

Results

A total of 373 individuals were included. The area under the curve (AUC) for CA19.9/CEA was 0.872, whereas the AUC for CA19.9 was 0.847 and for CEA was 0.554. Cutoff values with the greatest diagnostic power were CA19.9/CEA >40, CA19.9 >1130 U/mL, and CEA > 14.5 U/mL. The combination of CA19.9/CEA > 40 with CA19.9 > 550 U/mL maximized the diagnostic accuracy for PC.

Conclusion

Our results highlight the relevance of the measurement of serum CA19.9 and CEA in the detection of PC.
The HARPS search for southern extra-solar planets – XLV. Two Neptune mass planets orbiting HD 13808: a study of stellar activity modelling’s impact on planet detection
Authors: Ahrer E , Queloz D , Rajpaul V M , Ségransan D , Bouchy F , Hall R , Handley W , Lovis C , Mayor M , Mortier A , Pepe F , Thompson S , Udry S , Unger N
Published: February 2021

We present a comprehensive analysis of 10 yr of HARPS radial velocities (RVs) of the K2V dwarf star HD 13808, which has previously been reported to host two unconfirmed planet candidates. We use the state-of-the-art nested sampling algorithm PolyChord to compare a wide variety of stellar activity models, including simple models exploiting linear correlations between RVs and stellar activity indicators, harmonic models for the activity signals, and a more sophisticated Gaussian process regression model. We show that the use of overly simplistic stellar activity models that are not well-motivated physically can lead to spurious ‘detections’ of planetary signals that are almost certainly not real. We also reveal some difficulties inherent in parameter and model inference in cases where multiple planetary signals may be present. Our study thus underlines the importance both of exploring a variety of competing models and of understanding the limitations and precision settings of one’s sampling algorithm. We also show that at least in the case of HD 13808, we always arrive at consistent conclusions about two particular signals present in the RV, regardless of the stellar activity model we adopt; these two signals correspond to the previously reported though unconfirmed planet candidate signals. Given the robustness and precision with which we can characterize these two signals, we deem them secure planet detections. In particular, we find two planets orbiting HD 13808 at distances of 0.11, 0.26 au with periods of 14.2, 53.8 d, and minimum masses of 11, 10 M⊕.
On the influence of Langmuir wave spectra on the spectra of electromagnetic waves generated in solar plasma with double plasma frequency
Authors: Kudryavtsev Igor V , Kaltman T I
Published: February 2021

In this paper, we consider the spectral dependences of transverse electromagnetic waves generated in solar plasma at the coalescence of Langmuir waves. It is shown that different spectra of Langmuir waves lead to characteristic types of transversal electromagnetic wave spectra, what makes it possible to diagnose the features of the spectra of Langmuir waves generated in solar plasma.
Multicellular “hotspots” harbor high-grade potential in lower-grade gliomas
Authors: Kirby Alastair J , Lavrador José P , Bodi Istvan , Vergani Francesco , Bhangoo Ranjeev , Ashkan Keyoumars , Finnerty Gerald T
Published: February 2021

Background

Lower-grade gliomas may be indolent for many years before developing malignant behavior. The mechanisms underlying malignant progression remain unclear.

Methods

We collected blocks of live human brain tissue donated by people undergoing glioma resection. The tissue blocks extended through the peritumoral cortex and into the glioma. The living human brain tissue was cut into ex vivo brain slices and bathed in 5-aminolevulinic acid (5-ALA). High-grade glioma cells avidly take up 5-ALA and accumulate high levels of the fluorescent metabolite, Protoporphyrin IX (PpIX). We exploited the PpIX fluorescence emitted by higher-grade glioma cells to investigate the earliest stages of malignant progression in lower-grade gliomas.

Results

We found sparsely distributed “hot-spots” of PpIX-positive cells in living lower-grade glioma tissue. Glioma cells and endothelial cells formed part of the PpIX hotspots. Glioma cells in PpIX hotspots were IDH1 mutant and expressed nestin suggesting they had acquired stem-like properties. Spatial analysis with 5-ALA-conjugated quantum dots indicated that these glioma cells replicated adjacent to blood vessels. PpIX hotspots were formed in the absence of angiogenesis.

Conclusion

Our data show that PpIX hotspots represent microdomains of cells with high-grade potential within lower-grade gliomas and identify locations where malignant progression could start.
PULMONARY NODULE DETECTION IN CHEST CT USING A DEEP LEARNING-BASED RECONSTRUCTION ALGORITHM
Authors: Franck C , Snoeckx A , Spinhoven M , El Addouli H , Nicolay S , Van Hoyweghen A , Deak P , Zanca F
Published: February 2021

This study’s aim was to assess whether deep learning image reconstruction (DLIR) techniques are non-inferior to ASIR-V for the clinical task of pulmonary nodule detection in chest computed tomography. Up to 6 (range 3–6, mean 4.2) artificial lung nodules (diameter: 3, 5, 8 mm; density: −800, −630, +100 HU) were inserted at different locations in the Kyoto Kagaku Lungman phantom. In total, 16 configurations (10 abnormal, 6 normal) were scanned at 7.6, 3, 1.6 and 0.38 mGy CTDIvol (respectively 0, 60, 80 and 95% dose reduction). Images were reconstructed using 50% ASIR-V and a deep learning-based algorithm with low (DL-L), medium (DL-M) and high (DL-H) strength. Four chest radiologists evaluated 256 series by locating and scoring nodules on a five-point scale. No statistically significant difference was found among the reconstruction algorithms (p = 0.987, average across readers AUC: 0.555, 0.561, 0.557, 0.558 for ASIR-V, DL-L, DL-M, DL-H).
Root carbon and nutrient homeostasis determines downy oak sapling survival and recovery from drought
Authors: Ouyang Sheng-Nan , Gessler Arthur , Saurer Matthias , Hagedorn Frank , Gao De-Cai , Wang Xiao-Yu , Schaub Marcus , Li Mai-He , Shen Wei-Jun , Schönbeck Leonie
Published: February 2021

The role of carbon (C) and nutrient uptake, allocation, storage and especially their interactions in survival and recovery of trees under increased frequencies and intensities of drought events is not well understood. A full factorial experiment with four soil water content regimes ranging from extreme drought to well-watered conditions and two fertilization levels was carried out. We aimed to investigate whether nutrient addition mitigates drought effects on downy oak (Quercus pubescens Willd.) and whether storage pools of non-structural carbohydrates (NSC) are modified to enhance survival after 2.5 years of drought and recovery after drought relief. Physiological traits, such as photosynthesis, predawn leaf water potential as well as tissue biomass together with pools and dynamics of NSC and nutrients at the whole-tree level were investigated. Our results showed that fertilization played a minor role in saplings’ physiological processes to cope with drought and drought relief, but reduced sapling mortality during extreme drought. Irrespective of nutrient supply, Q. pubescens showed increased soluble sugar concentration in all tissues with increasing drought intensity, mostly because of starch degradation. After 28 days of drought relief, tissue sugar concentrations decreased, reaching comparable values to those of well-watered plants. Only during the recovery process from extreme drought, root NSC concentration strongly declined, leading to an almost complete NSC depletion after 28 days of rewetting, simultaneously with new leaves flushing. These findings suggest that extreme drought can lead to root C exhaustion. After drought relief, the repair and regrowth of organs can even exacerbate the root C depletion. We concluded that under future climate conditions with repeated drought events, the insufficient and lagged C replenishment in roots might eventually lead to C starvation and further mortality.