bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of congenital cardiac tumours in 25,000 neonates
Authors: Sillesen A , Axelsson Raja A , Voegg R.O.B , Pihl C.A , Paerregaard M.M , Fogh K , Norsk J.B , Vejlstrup N.G , Iversen K.K , Bundgaard H 
Published: November 2020

Abstract

Background
Primary cardiac tumours in children are rare, with an estimated prevalence of 0.014% in foetuses, whereas in the paediatric population, a 100-fold difference in autopsy prevalence has been reported (0.0017% to 0.28%). In neonates, rhabdomyoma is the most common primary cardiac tumour, followed by teratoma and fibroma, all of which are benign. Cardiac rhabdomyomas are associated to tuberous sclerosis in &gt;50% of cases. The prevalence of cardiac tumours in neonates has not previously been assessed in a large population-based cohort.

Purpose
To determine the prevalence of congenital cardiac tumours by systematic echocardiography in a large, population-based, cohort of neonates.

Methods
Systematic transthoracic echocardiography (TTE), including standard sub-xiphoid, apical, left parasternal, and suprasternal views, was performed in neonates included in a population study. Cardiac tumours were defined as solid, echogenic masses, and description included location, size, and numbers (one/multiple). Information regarding subsequent diagnosis of tuberous sclerosis was collected from review of medical charts.

Results
A total of 25,537 neonates (age 12±9 days, 51.6% male) were enrolled in the study and underwent TTE. Cardiac tumours were detected in 7 neonates (4 males), corresponding to a prevalence of 0.3 [0.1; 0.6] per 1,000 live-births. Characteristics including sex, gestational age at birth, birth length and weight, APGAR 5-score, age and weight at TTE, and maternal age and pre-pregnancy BMI, did not significantly differ between the neonates with (n=7) and without (n=25,530) cardiac tumours (all p&gt;0.05). In 6 out of 7 neonates, the cardiac tumours were located in the ventricles (86%), with multiple tumours seen in five (83%) (Fig. 1A+B), and with size ranging from 2.0x1.9mm to 10.0x5.1mm. In the seventh neonate, two cardiac tumours were detected in close proximity to the aortic and pulmonary valves in the ascending aortic and main pulmonary artery wall (Fig. 1C), with sizes 5.1x4.7mm and 3.7x3.2mm, respectively. All seven neonates had otherwise structurally normal hearts and no flow obstruction. Three neonates with multiple cardiac tumours in the ventricles were subsequently diagnosed with tuberous sclerosis.

Conclusions
Systematic TTE in a population-based cohort revealed a prevalence of congenital cardiac tumours of 0.3 per 1,000 live-births. The majority of the tumours were located in the ventricles and most often multiple cardiac tumours were encountered. Detection of congenital cardiac tumours in the ventricles was associated with tuberous sclerosis in half the cases.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Danish Heart Association, Danish Children's Heart Foundation
Kynurenine-PARP 1 link mediated by microRNA 210 may be dysregulated in pulmonary hypertension
Authors: Yaylali Y.T , Akgun A.E , Secme M , Senol H , Dodurga Y 
Published: November 2020

Abstract

Background
The aims of the present study were to determine the alterations in mRNA and miR expressions and their role in signaling pathways, to correlate their levels with the severity of PH, and to investigate the relationship between those alterations and serum levels of apelin, kynurenine, and endocan in PH.

Methods
The study included 32 treatment-naive patients with precapillary PH and 55 controls. All subjects underwent RHC. Total RNA was isolated and cDNAs for mRNA and miR were synthesized. mRNA expressions of HIF-1α, HIF-2α, STAT 3, FGF-2, FGFR-1, PARP 1 and miR expressions of miR-210, miR-130a, miR-424, miR-204, and miR-223 were determined. Concentrations of kynurenine, apelin, and endocan were analyzed.

Results
HIF-2α, STAT 3, and FGF-2 were increased; miR-210 and miR-130a were increased; miR-223 and miR-204 were decreased. Apelin and kynurenine concentrations were decreased. There were positive correlations: HIF-2α-miR-424: r=0.474, p=0.011; APLN-miR-424: r=0.385, p=0.030; kynurenine-miR-210: r=0.551, p=0.004; STAT 3- PVR: r=0.478, p=0.006; miR-210- RAP: r=0.536, p=0.07; kynurenine-RAP: r=0.409, p=0.022. There were negative correlations: PARP 1-miR-210: r=−0.561, p=0.007; PARP 1- RAP: r=−0.424, p=0.27. miR-130a (OR= 1.257, p=0.016) and APLN (OR= 0.223, p=0.004) were independent risk factors for PH.

Conclusions
We report: 1) novel relationship between the kynurenine and PARP 1 signaling pathways that could be mediated by miR-210, 2) relationship between the apelin and HIF-2α signaling pathways that could be mediated by miR-424, 3) reduced levels of apelin and elevated levels of miR-130a are associated with PH, 4) elevated levels of STAT 3, miR-210, and kynurenine, and reduced levels of PARP 1 correlate with more severe hemodynamics.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Pamukkale University Scientific Research Projects Coordination Unit
Prognostic role of comorbidities in patients with pulmonary arterial hypertension
Authors: De Lorenzis A , Dardi F , Palazzini M , Zuffa E , Pasca F , Guarino D , Magnani I , Rotunno M , Ballerini A , Manes A , Galie N 
Published: November 2020

Abstract

Background
Epidemiology of pulmonary arterial hypertension (PAH) is changing and the age at diagnosis and the prevalence of comorbidities are increasing but their prognostic relevance is substantially undefined.

Purpose
To evaluate the prognostic value of comorbidities in patients with PAH and in the different clinical subgroups.

Methods
All patients with PAH referred to a single centre underwent baseline right heart catheterization, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD), WHO functional class and anamnestic comorbidities evaluation. Cox regression model was used for analysis (p-value &lt;0.1 was considered for inclusion in multivariate analysis).

Results
1311 patients were included [age 51 years; aetiology: 522 idiopathic/heritable/drug-induced (I/H/D)-PAH, 258 connective tissue disease (CTD)-associated PAH, 242 congenital heart disease (CHD)-associated PAH, 196 portal hypertension/HIV (PoHIV)-associated PAH and 93 pulmonary veno-occlusive disease (PVOD)]. 5% of patients have no comorbidities. At multivariate analysis comorbidities independently associated with prognosis are: systemic hypertension in I/H/D [HR 0.616, p=0.030], mean systemic blood pressure in CTD [HR 0.980, p=0.002] and PVOD [HR 0.962, p=0.006], dyslipidemia in CTD [HR 0.447, p=0.001] and PoHIV [HR 0.201, p=0.026], estimated glomerular filtration rate in PoHIV [HR 1.000, p&lt;0.001] and body mass index (BMI) [HR 0.966, p=0.069] in CTD. In CHD comorbidities are not independent determinants of prognosis. Other variables independently predictive of a worse prognosis are: advanced age in all PAH subgroups except PVOD; male gender in I/H/D; reduced 6MWD in I/H/D, CTD and PVOD; high BNP in I/H/D, CHD and PVOD; low cardiac index in CTD, high right atrial pressure in I/H/D and low mixed venous oxygen saturation in CHD.

Conclusion
The age at PAH diagnosis and the prevalence of comorbidities are increasing but their prognostic role seems of poor relevance as we found a protective role of these variables: high systemic blood pressure (maybe indicative of a better haemodynamic stability) in I/H/D, CTD and PVOD; dyslipidemia and high BMI (maybe indicative of a better nutritional status and a less severe autoimmune disease) in CTD; dyslipidemia and a high glomerular filtration rate (both indicative of a less severe liver disease) in PoHIV.

Funding Acknowledgement
Type of funding source: None
Impact of higher detection rate of residual pulmonary thromboemboli one-year after acute pulmonary embolism: modified CT scan imaging method with modified CT obstruction index
Authors: Nakano Y , Okumura N , Imai R , Yoshida M , Shimokata S , Adachi S , Murohara T , Kondo T 
Published: November 2020

Abstract

Background
Recently, post pulmonary embolism (PE) syndrome or chronic thromboembolic disease after acute PE, has been recognized as important long-term complications. Furthermore, patients may develop with chronic thromboembolic pulmonary hypertension.

Purpose
We aimed to evaluate the frequency of residual pulmonary thromboemboli after acute PE by using our “higher”-resolution CT scan imaging method to detect residual thromboemboli down to sub-segmental pulmonary arteries.

Methods
This study was a prospective multi-center observational study. We enrolled consecutive 34 patients with acute symptomatic PE whose informed consent was obtained, and followed up for one year. One year after the onset of acute PE, patients were referred to our hospital and multiple examination including CT scan, 6-minute walk test (6MWT), questionnaire of SF-36, echocardiography and laboratory testing were performed. Additionally, we have modified the CT obstruction index (CTOI) to quantitatively evaluate the thromboemboli down to sub-segmental pulmonary arteries.

Results
Mean age was 60.5±15.8 years, and 56% were male. No patient was categorized as low recurrent VTE risk which was caused by transient factors, one patient was associated with active cancer, and 12% had known thrombophilia. In 85% of the patients, this onset was the first obvious episode of PE. At diagnosis, elevated B-type natriuretic peptide (BNP) (≥100 pg/ml) or N-terminal (NT)-proBNP (≥500 pg/ml) was observed in 45% of the patients. Median tricuspid regurgitation peak gradient (TRPG) by echocardiography was 30.9 (19.3–50.1) mmHg. Among all, 35% of the patients received single-drug approach with DOACs. At discharge, all of the patients except two were treated with DOACs.
One year after the onset, 21% of the patient were in NYHA II and others were in NYHA I. It was notable that pulmonary thromboemboli was detected by our CT scan in 76% of the patients. Modified CTOI was median 11.9 (1.8–24.4) % as shown in the figure.
In multiple regression analysis, TRPG at diagnosis and BNP at one month were significantly associated with mCTOI (β=0.536, p=0.002 and β=−0.482, p=0.003, respectively). Additionally, lowest SpO2 during 6MWT after one year from the onset, tended to inversely associate with mCTOI (β=−0.341, p=0.052).

Conclusions
Using our modified CT scan imaging method and modified CTOI, residual pulmonary thromboemboli was able to be detected more frequently than the previous studies. Residual pulmonary thromboemboli could be one of the cause of the post PE syndrome and lead to exercise-induced desaturation.
Figures

Funding Acknowledgement
Type of funding source: None
Prognostic relevance of sleep apnea syndrome in patients with pulmonary arterial hypertension
Authors: Precek J , Vykoupil K , Kovacik F , Hutyra M 
Published: November 2020

Abstract

Introduction
Sleep disordered breathing (SDB) is a group of ventilatory disorders during sleep which includes obstructive sleep apnea (OSA), central sleep apnea (CSA), and sleep related hypoventilation. In patients with SDB, the prevalence of pulmonary hypertension (PH) ranges from 17% to 52%. While SDB is prevalent in the general population with recent estimates of 20% to 30%, in those with cardiovascular disease, particularly left ventricular failure, there is a higher reported prevalence of 47%.

Aims
The aims of this study were to determine the prevalence and prognostic relevance of sleep apnea in a cohort of patients with newly diagnosed pulmonary arterial hypertension (ESC/WHO Group 1 pulmonary hypertension).

Methods
We evaluated prospectively 76 patients with the pulmonary arterial hypertension (mean age 54±16 years; 45% male). All patients underwent right heart catheterisation, clinical assessments, sleep study, standard laboratory testing and evaluation of subjective sleepiness by the Epworth Sleepiness Scale. Sleep test was provided with an ApneaLink Plus, consisting of nasal pressure sensor, respiratory effort band, and pulse oximeter worn on the finger. Subjects previously treated for or diagnosed with SDB were excluded from the study.

Results
Sleep apnea (SA) – defined as apnea-hypopnea index (AHI) ≥5/h – was found in 59 (77.6%) of the pulmonary arterial hypertension (PAH) patients. Mean AHI in the cohort of PAH patients with SA was 26.1±16.6/h. Mean follow-up was 24 months, during which 15 (19.7%) patients died. Characteristics of parameters related to SA in groups of survivors and deceased are in table 1. From the sleep apnea-related parameters, only time with O2Sat &lt;90% – T90 was significantly associated with mortality (AUC 0.856; 95% CI 0.693 – 1.019; p&lt;0.001).

Conclusions
The presence of sleep apnea in pulmonary arterial hypertension patients is high. The prevalence of sleep apnea is higher in PAH patients than in the general population. The presence of sleep apnea in patients with PAH was not associated with worse prognosis, but noctural hypoxemia (time with O2Sat &lt;90%) was related to poor prognosis. Sleep apnea in patients with PAH should be screened for systematically.

Funding Acknowledgement
Type of funding source: None
Microvasculopathy evaluated by dual-energy computed tomography in chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension
Authors: Miwa K , Taniguchi Y , Sumimoto K , Matsuoka Y , Izawa Y , Onishi H , Tsuboi Y , Toba T , Kobayashi S , Emoto N , Hirata K 
Published: November 2020

Abstract

Background
It has been previously reported that poor subpleural perfusion (PSP) in dual-energy computed tomography (DE-CT) might suggest the microvasculopathy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unclear whether pathological findings of microvasculopathy in CTEPH and pulmonary arterial hypertension (PAH) are equivalent. The aim is to evaluate the microvasculopathy in CTEPH and PAH by using clinical parameters and DE-CT.

Methods
We retrospectively reviewed PSP (defined as subpleural spaces either not or minimally perfused in all segments) of consecutive treatment-naïve 89 CTEPH patients and 20 PAH patients who underwent DECT from Feb. 2015 to Dec. 2019.
We also evaluated hemodynamic parameters and DE-CT parameters including quantitative evaluation of pulmonary blood volume (PBV) which was calculated as the average of entire lung iodine density.

Results
PSP was observed in 49.4% of patients in CTEPH group versus 5.0% in PAH group (p&lt;0.01).
There were no significant differences in hemodynamics and lung PBV between CTEPH group and PAH group (mean pulmonary arterial pressure; 36.4±10.4mmHg vs 38.3±8.5mmHg p=0.464, pulmonary vascular resistance; 700±388dyne*sec/cm5 vs 805±440 dyne*sec/cm5 p=0.288, lung PBV; 24.9±6.4 Hounsfield Unit vs 22.0±6.6 Hounsfield Unit p=0.06, respectively), however diffusing capacity for carbon monoxide (%DLCO/VA) was significantly lower (69.5±16.8% vs 45.7±23.7% p&lt;0.01) in PAH group.

Conclusion
PSP in DE-CT, which was observed more frequently in patients with CTEPH, might suggest the different mechanism of microvasculopathy from PAH in patients with CTEPH. Microvasculopathy in CTEPH would be diffuse very distal thrombosis. DE-CT is effective modality to detect microvasculopathy of diffuse distal thrombosis in patients with CTEPH.
DECT, Poor subpleural perfusion

Funding Acknowledgement
Type of funding source: None
Cardiopulmonary exercise test could predict residual pulmonary hypertension after pulmonary endarterectomy
Authors: Coronel M.L , Flox Camacho A , Segura De La Cal T , Perez Olivares Delgado C , Cristo Ropero M.J , Nuche Berenguer J , Velazquez Martin M.T , Lopez Gude M.J , Escribano Subias P 
Published: November 2020

Abstract

Introduction
Pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombotic lesions at pulmonary arteries and arteriolar remodeling in distal regions. There is an increase in pulmonary vascular resistance that will lead to heart failure and early death without treatment. Currently, pulmonary endarterectomy (PE) is the potentially curative treatment for this condition. Cardiopulmonary exercise test (CPET) allows to quantify functional improvement after PE. Objective: To analyze changes in CPET and hemodynamic parameters after surgery in a cohort of patients with CTEPH.

Methods
502 patients with CTEPH have been evaluated until December 2018, PE was performed in 255 (51%). In 49 patients, CPET was available before and 6 months after surgery. Residual pulmonary hypertension (RPH) was defined as mean pulmonary arterial pressure ≥30 mmHg evaluated by right cardiac catheterization at 3–6 months after PE.

Results
54% were men, mean age 48±13 years. Two thirds of patients were in functional class II/III at time of diagnosis and with severe hemodynamic and functional profile. Hemodynamics and CPET parameters improved after surgery. However, in patients with RPH they did not improve significantly. Results are shown in table.

Conclusions
PE restores functional capacity in CTEPH, represented by significant improvement in CPET parameters. CPET is emerging as a non-invasive technique suitable of detecting RPH. More studies are needed to confirm this hypothesis.

Funding Acknowledgement
Type of funding source: None
Novel potential diagnostic targets revealed by plasma proteomic analysis in chronic thromboembolic pulmonary hypertension
Authors: Kriechbaum S.D , Wiedenroth C.B , Rudolph F , Peters K , Wolter J.S , Haas M , Rieth A.J , Rolf A , Hamm C.W , Mayer E , Keller T , Liebetrau C 
Published: November 2020

Abstract

Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with poor outcome if untreated, although it is a curable form of pulmonary hypertension (PH). Successful treatment requires an optimized diagnostic work-up.

Purpose
The aim of this study was to identify non-invasive biomarkers that might serve as new diagnostic parameters in the multifaceted pathophysiology of CTEPH.

Methods
The biomarker profile of 64 CTEPH patients who underwent balloon pulmonary angioplasty (BPA) was analyzed prior to and after therapy and compared with that of a healthy control group (CG1, n=25) at baseline. Proteomes were analyzed by semiquantitative screening based on a proximity extension assay of three high-throughput, multiplex immunoassay panels. Serum levels of a subset of biomarkers identified in the screening were additionally measured by immunochemical methods.

Results
Fifty protein biomarkers were found to differ between CTEPH patients and CG1. Eight biomarkers changed significantly after therapy. The overlap of these two groups revealed six targets that were all upregulated in CTEPH at baseline and modifiable by treatment. In this group of biomarkers, the levels of DCN (decorin), HGF (hepatocyte growth factor), BNP (B-type natriuretic peptide), and PAPP-A (papalysin-1) decreased after therapy, whereas SPON-1 (spondin-1) and MEPE (matrix extracellular phosphoglycoprotein) further increased at follow-up. The differences in these biomarkers in CTEPH as well as the dynamics after therapy were confirmed and quantified in enzyme-linked immunosorbent assays.

Conclusions
This study identified 6 biomarkers that might serve as new diagnostic parameters or constitute new therapeutic targets in CTEPH. Further prospective studies will be necessary to determine the specific pathophysiological role of each marker.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): SFB 1213 area CP01
Clinical course of pulmonary embolism patients treated with DOACs: comparing prognosis, recurrent thromboembolism, and major bleeding between patients with and without cancer
Authors: Nakano Y , Imai R , Yoshida M , Shimokata S , Adachi S , Murohara T , Kondo T 
Published: November 2020

Abstract

Background
Venous thromboembolism (VTE) is the third frequent acute cardiovascular syndrome in the Europe and Japan. Since direct oral anticoagulants (DOACs) are widely used now, the morbidity and mortality of pulmonary embolism (PE) patients especially associated with cancer needs to be re-evaluated.

Purpose
We evaluated the clinical course of patients with PE mainly treated with DOACs.

Methods
This retrospective observational study was conducted in a single center. The data were collected from the medical record of consecutive patients who received inpatient treatment of PE. In this study, we have compared PE patients with cancer (cancer PE) to those without cancer (non-cancer PE) and evaluated the mortality, recurrent of VTE and major bleedings.

Results
In total, 140 patients were enrolled: 94 patients were cancer-related, and 46 patients were without cancer (Table). The type of the tumor in cancer PE patients were as follows: gastric 8 (9%), esophageal 5 (5%), pancreatic 12 (13%), lung 14 (15%), lymphoma 2 (2%), gynecologic 17 (18%), renal 2 (2%), bile duct 8 (9%), colon 12 (13%), and others 17 (18%).
Kaplan-Meier curve showed that the cumulative all-cause mortality was significantly higher in the cancer PE group (35/94 (37%) vs. 2/46 (4%), P&lt;0.001 (log rank), HR 10.3 [95% CI:2.5–43.3]). The cumulative incidence of recurrent VTE was significantly higher in the cancer PE group (7/94 (7%) vs. 0/46, P=0.03 (log rank)). There was no significant difference in the cumulative incidence of major bleeding between the cancer PE group and the non-cancer PE group (8/94 (9%) vs. 5/46 (11%)).

Conclusions
The risk of recurrent VTE was still higher in cancer PE patients compared to non-cancer PE patients, although DOACs were used. Meanwhile the incidence of major bleeding was comparable in both groups, the risk of bleeding might be acceptable with using DOACs especially in cancer PE patients.
Figure 1

Funding Acknowledgement
Type of funding source: None