bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary hypertension and congenital heart disease: medical treatment and risk factors for survival
Authors: Playan Escribano J , Segura De La Cal T , Segovia Cubero J , Rueda Soriano J , Garcia Hernandez F.J , Lopez Meseguer M , Perez Penate G.M , Lara Padron A , Campo Ezquibela A , Sala Llinas E , Mombiela T , Guerra Ramos F.J , Samper G.J , Blanco I , Escribano Subias P 
Published: November 2020

Abstract

Background
Pulmonary arterial hypertension (PAH) is a common comorbidity in congenital heart disease (CHD) and significantly affects prognosis. There are four large clinical groups of CHD-related PAH: Eisenmenger syndrome, PAH associated with non-restrictive shunt, PAH associated with restrictive shunt and postoperative PAH. Our purpose was to study the clinical and prognostic differences among them.

Methods
The REHAP is a Spanish multicentre voluntary registry of patients over 14 years of age, which includes patients with CHD and PAH, starting in 2007. 664 patients were analyzed: Baseline characteristics, functional class, right catheterization data, treatment and survival were compared.

Results
664 patients were analyzed: characteristics are detailed in the table. Patients with Eisenmenger were more frequently treated with oral monotherapy as a first line therapy and received less frequently prostanoids during the follow-up. Patients with Eisenmenger had significantly better prognosis, with the best long-term survival of the 4 groups. In a cox regression model, postoperative PAH has a 1.7 hazard ratio (HR) (reference group: Eisenmenger) after adjustment for age (HR 1.02 p 0,001), functional class (HR NYHA III-IV 2.3 p&lt;0,001), sex (p 0.8) and pulmonary vascular resistance (p 0.7).

Conclusion
The clinical classification of PAH associated with CHD defines both the baseline characteristics and the prognosis of patients. Outcome relates closely to functional class and type of PAH–CHD. Eisenmenger group, which has the most severe hemodynamics, is the one with the best prognosis despite a less aggressive treatment.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Ferrer, Janssen
The role of asymmetric dimethylarginine (ADMA) in the follow-up of patients with precapillary pulmonary hypertension (PH)
Authors: Shafran I , Probst V , Campean J , Sadushi-Kolici R , Gerges C , Lang I , Skoro-Sajer N 
Published: November 2020

Abstract

Introduction
Asymmetric dimethylarginine (ADMA) interferes with L-arginine in the production of nitric oxide, a key mediator of endothelial cell function. ADMA is elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and is associated with unfavorable outcomes.

Aim
To assess the role of ADMA to monitor disease progression of PH patients treated with PAH-specific therapy.

Methods
ADMA was measured by competitive ELISA at baseline (BL) and follow-up (FU). Risk assessment including a clinical assessment, echocardiography, 6-minute walking test, NT-pro-BNP and hemodynamic assessment by right heart catheterization was performed accordingly. Risk was calculated according to the ESC/ERS 2015 guidelines by the SPHAR method.

Results
ADMA samples were collected from 113 patients treated at our institution between 2012 and 2019. 89 (79%) patients had PAH, 15 (13%) were diagnosed with CTEPH and 9 (8%) with group 3 – PH associated with lung disease. 69% were females. 15 (13.3%) patients had a low risk at baseline, 96 (85%) intermediate risk and 2 (1.8%) were high risk patients. 75% received oral medications, 31% received subcutaneous treprostinil. Median baseline ADMA was 0.738umol/l. At BL no significant difference of ADMA plasma levels was found among the different PH types (p=0.063), or between different risk categories (p=0.531).
Change in ADMA plasma levels correlated with change in risk (p=0.002, rs 0.291) and with change in mixed venous saturation (p=0.034, rs −0.205). Change in ADMA plasma levels also correlated with risk at FU (p=0.011, rs 0.240).
Patients categorized as low risk at FU had a median ADMA plasma level decrease of 22%, compared with −3 to 0% ADMA plasma level change in patients with moderate to high risk at FU (p=0.04). Patients who improved their risk category had a median decrease of ADMA plasma level of 23% vs. 2.3% in patients who did not improve (p=0.011). Decrease of ADMA plasma levels was a weak but significant discriminator for improvement of risk in ROC analysis (p=0.032, AUC 0.374).

Conclusion
ADMA plasma levels paralleled the hemodynamic and clinical benefit of PAH-specific treatments in patients with precapillary PH. ADMA could be used as a biomarker for monitoring treatment effects in precapillary PH.

Funding Acknowledgement
Type of funding source: None
Pulmonary arterial hypertension in families with hereditary hemorrhagic telangiectasia: a 13-year follow-up study
Authors: Zhou Y.-P , Jiang X , Zhang Y.-X , Sun K , Lian T.-Y , Wu T , Hua L , Xu X.-Q , Jing Z.-C 
Published: November 2020

Abstract

Background
Pulmonary arterial hypertension (PAH) can occur in families with hereditary hemorrhagic telangiectasia (HHT), but it has not been well-characterized.

Purpose
This study sought to characterize the genetic defects, clinical and hemodynamic features, and outcomes of PAH patients in HHT families.

Methods
All HHT families with at least one case of PAH investigated in our center from January 2006 to December 2018 were enrolled in the study. We did whole-exome sequencing (WES) or whole-genome sequencing (WGS) to every proband and available family members. The clinical data, hemodynamic features and outcomes of PAH patients were reviewed.

Results
A total of 64 PAH patients in 57 families were enrolled. Only 7 (12.3%) families had more than one case of PAH. Activin-receptor-like kinase 1 (ALK-1) mutation and Endoglin (ENG) mutation were confirmed in 49 (86.0%) and 3 (5.3%) families and other 5 (8.8%) had no known mutation associated with HHT or PAH. The median age when PAH diagnosis was 22 [9–33] years and female was dominant (70.3%). Most patients (84.4%) had signs of HHT and anemia was recorded in 14 (21.9%) patients. Remarkably, these patients showed severely compromised hemodynamics with elevated mean pulmonary artery pressure (62 [51, 77] mm Hg) and pulmonary vascular resistance index (17.0 [11.2, 22.8] Wood units*m2). Also, impaired exercise capacity was recorded at diagnosis with decreased six-minute walking distance (410 [342–485] meters) and over half (54.7%) were in WHO functional class III or IV. The 1-, 3-, 5- and 10-year transplantation-free survival for the overall PAH patients was 95.0%, 75.9%, 67.1% and 36.4%, respectively. Anemia (HR: 4.24 [1.32–13.65], p=0.016) and CI &lt;2.5 l/min/m2 (HR: 4.39 [1.20–16.09], p=0.026) were independent risk factors for mortality.

Conclusions
PAH in HHT families is a devastating condition characterized by a young age at PAH diagnosis, poor clinical status and outcomes mainly underlying ALK-1 mutation, which emphasizes the importance to pay attention to this group of patients.
Transplantation-free survival

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The Beijing Natural Science Foundation (7181009), the National Key Research and Development Program of China (2016YFC0901502)
A novel causative gene variant, TNFRSF13B p.Gly76Ser, in patients with pulmonary arterial hypertension
Authors: Shinya Y , Hiraide T , Kataoka M , Momoi M , Goto S , Katsumata Y , Endo J , Sano M , Kosaki K , Fukuda K 
Published: November 2020

Abstract

Background
Pulmonary artery hypertension (PAH) is a poor prognostic disease. Some causative genes were reported as the PAH-associated genes. However, the pathogenetic variants in PAH-associated genes have not been identified in majority of patients with idiopathic PAH.

Purpose
Our aim was to investigate the new causative gene variants associated with PAH.

Methods
We performed whole-exome sequencing in 272 patients with idiopathic/heritable PAH. Structural analysis simulation was performed to define how the candidate gene variant affected the structure of protein.

Results
We identified the heterozygous substitution change of c.226G&gt;A (p.Gly76Ser, rs146436713) in tumor necrotic factor receptor superfamily 13B gene (TNFRSF13B) (NM_012452.2) in 6 (2.2%) patients with idiopathic/heritable PAH, although the allele frequency of this rare variant is 0% in Integrative Japanese Genome Variation Database (control population database). Two of the six cases were blood relatives, although they did not have the known causative gene variants of PAH. One of these two relatives died of right heart failure despite the combination medical therapy, and her pathological anatomy demonstrated intimal thickening and medial hypertrophy in the pulmonary arteries, formation of plexiform lesions (Heath-Edwards classification grade V). Time-lapse images from structural analysis simulation showed the instability of N-terminal in the protein, which regulates the vascular inflammation, synthesized from TNFRSF13B p.Gly76Ser variant (Figure), suggesting that p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels.

Conclusions
TNFRSF13B p.Gly76Ser variant is a candidate of causative gene variant for PAH.
Structural analysis of proteins

Funding Acknowledgement
Type of funding source: None
Usefulness of Suita score to predict deaths from aortic aneurysm rupture and aortic dissection in general population
Authors: Otaki Y , Watanabe T.W , Konta T.K , Watanabe M.W , Asahi K.A , Yamagata K.Y , Fujimoto S.F , Tsuruya K.T , Narita I.N , Kasahara M.K , Shibagaki Y.S , Iseki K.I , Moriyama T.M , Kondo M.K , Watanabe T.W 
Published: November 2020

Abstract

Background
Deaths from aortic aneurysm rupture and aortic dissection are the major causes of sudden death in Japan. Suita score developed in Japan, as well as Framingham risk score, is reportedly associated with ischemic heart disease. However, it remains undetermined whether Suita score is associated with aortic aneurysm rupture and aortic dissection deaths in general population.

Purpose
To examine whether Suita score could predict aortic aneurysm rupture and aortic dissection deaths in general population.

Methods and results
We used a database of 534,414 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” check-up between 2008 and 2013. The univariate and multivariate Cox proportional hazard regression analyses demonstrated that Suita score was associated with both deaths from aortic aneurysm rupture and aortic dissection after adjustment for confounding risk factors. The C indices in Suita score for aortic aneurysm rupture deaths, aortic dissection deaths and ischemic heart disease deaths were 0.8295, 0.6689, and 0.7039, respectively. The C indices in Suita score to predict aortic aneurysm rupture deaths and aortic dissection deaths were significantly greater than those in Framingham risk score.

Conclusion
Suita score was superior to Framingham risk score and a feasible marker for aortic aneurysm rupture and aortic dissection deaths in general population, indicating that it could serve as an identification of high-risk subjects for aortic aneurysmal rupture and aortic dissection as well as ischemic heart disease.

Funding Acknowledgement
Type of funding source: None
Evaluation of left ventricular diastolic function in Marfan syndrome using speckle-tracking echocardiography
Authors: Garcia-Izquierdo Jaen E , Mingo Santos S , Cia Mendioroz X , Monivas Palomero V , Moreno Casado S , Navarro Rico S , Borrego Hernandez A , Torres Sanabria M , Martin Lopez C.E , Mitroi C , Gonzalez Mirelis J , Cavero Gibanel M.A , Segovia Cubero J , Forteza Gil A 
Published: November 2020

Abstract

Background/Introduction
Previous studies using conventional echocardiographic measurements have reported subclinical left diastolic dysfunction in patients with Marfan syndrome (MFS). Certain speckle-tracking echocardiography (STE) derived parameters have shown good correlation with invasive measurements of LV relaxation.

Purpose
To evaluate diastolic function in Marfan patients using STE-derived parameters along with traditional diastolic measurements and compare them with healthy controls.

Methods
We consecutively included 127 MFS patients with normal LV ejection fraction and no previous cardiovascular surgery or significant valvular regurgitation. We also studied 38 healthy controls (age and sex-matched). We performed LV and LA strain analysis using 2D STE (QLAB 10, Philips). Echocardiographic parameters recommended to assess diastolic function (according to ASE/EACVI 2016 guidelines) were also considered.

Results
Reported use of BB/ARB was 28/39% in MFS patients. According to current guidelines, all participants had normal diastolic function. MFS patients showed lower TDI e' velocities (septal and lateral) and higher average E/e' ratio compared to controls, but still within normal range. Regarding STE-derived measurements, LVGLS, EDLSR and PALS were significantly reduced in MFS. E/EDLSR ratio was higher among MFS patients, reflecting impaired LV relaxation. Interestingly, E/LVGLS was not different between both groups.

Conclusion
STE-derived parameters showed impaired LV relaxation in MFS patients compared to controls. Our results suggest that STE derived parameters can be markers of early diastolic dysfunction and provide a better insight into Marfan-related cardiomyopathy.
STE derived parameters

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Programa de Actividades de I+D de la Comunidad de Madrid
Ascending aorta: descending thoracic aorta ratio as an additional metric to early individually oriented diagnoses of abnormalities. A non-contrast enhanced cardiac CT study
Authors: Sosnowski M , Czekaj A , Brzoska J , Chromik K , Mlynarski R , Tendera M , Wojakowski W 
Published: November 2020

Abstract

Background
Coronary artery calcium (CAC) detection is the established indication for a non-contrast enhanced cardiac computed tomography (NCE-CCT). Other information, beyond CAC, can be derived from the NCE-CCT. Amongst them, data regarding thoracic aorta and its abnormalities might be of interest.

Aims
We aimed at examination whether mutual proportion of ascending aorta and descending thoracic aorta diameters (AAD:DAD ratio) could be diagnostically relevant.

Methods
This retrospective study included 4372 patients out of 5905 subjects undergoing NC-CCT during the last decade, in whom the thoracic aorta and pulmonary artery trunk were within common limits (AAD≤40mm, DAD&lt;30mm, PAD&lt;30mm). 213 persons without CVD risk factors and CAC=0 were qualified into control group (1), and 4159 patients with CVD risk factor(s) ≥1 into examined group (2) of. The range of AAD/PAD ratio normality was referenced from the group 1. In addition body mass index and CAC score were accounted for.

Results
The AAD/PAD ratio in control group was 1.35±0.22 with the normal range between 1.12 and 1.57. The 90th percentile values for AAD have been established. In patients with CAC=0, amongst those with normal BMI the increased AAD:DAD ratio (&gt;1.57), indicating high AAD, was found in 18 /43 cases with AAD&gt;90 percentile (41.2%) and in 21/498 with normal AAD (4.2%). The respective proportions in overweight patients were 23/86 (26.7%) and 12/694 (1.7%), and in obese patients 13/67 (19.4%) and 5/397 (1.3%). In patients with CAC&gt;0, and normal BMI the increased AAD:DAD ratio was found in 10/38 cases with AAD&gt;90% (26.3%) and in 14/458 with normal ascending aorta size (3.1%). Proportions in overweight patients were 23/92 (25.0%) and 15/859 (1.75%), while in obese patients were 17/107 (15.9%) and 13/579 (2.2%), resp. Normal AAD:PAD ratio in patients with established AAD increase (&gt;90 percentile), irrespective of BMI, might suggest accompanying increase in PAD. Lower AAD:PAD ratio indicated a relative increase of the DAD. Mean values of AAD and DAD in relation to BMI and CAC categories along with their ratio are presented in table 1.

Conclusions
Evaluation of thoracic aorta in NC-CCT enhanced diagnostic scope of NCE-CCT. The AAD/DAD ratio, being independent of age, gender and body constitution, does not require adjustment, should be considered as additional metric for early diagnoses of thoracic aorta abnormalities well before absolute values reach the arbitrary cut-off levels.
Table 1

Funding Acknowledgement
Type of funding source: None
'Aorta code' implementation and preliminary results of a multidisciplinary protocol for patients with acute aortic syndrome
Authors: Ferrera Duran C , Vilacosta I , Perez-Villacastin J , Busca P , Carrero A , Martin Martinez A , Martin Sanchez F.J , Dominguez Garcia M.J , Martinez I , Cobiella J , Viana Tejedor A , Cortes Martinez A , Serrano J , Bas Villalobos M , Maroto-Castellanos L 
Published: November 2020

Abstract

Background
Expediting life-saving care for patients with acute aortic syndrome (AAS) through multi-disciplinary code protocols is a potential method to improve outcomes. Other code protocols for cardiovascular emergencies, such as ST-elevation myocardial infarction and stroke have shown excellent results.

Aim
To examine the implementation and preliminary results of a code protocol “Aorta Code” for patients with AAS in a healthcare framework of a 4-hospital network in our city by reviewing the number of patients detected, patient's transference time, aortic surgery and patient's outcome during a trial period of 10 months (April 2019-January 2020). A comparison with a previous 2-year period with standard of care management of AAS was performed.

Methods
“Aorta Code” uses a specific diagnostic algorithm to improve detection of patients with AAS at the emergency room, facilitates their quick transfer to the referral hospital by activating a paging system, and places acute cardiovascular care unit, operating room and surgeons specialized in aortic pathology on standby.

Results
Compared to a previous 2-year period (2017–2018) (group I), the current implementation of “Aorta Code” in a period of 10 months (group II) in our 4-hospital network involving the healthcare of 1.100000 inhabitants resulted in the detection of more patients with AAS (group-I: n=18 patients (0.8 patients/month), group-II: n=19 patients (1.9 patients/month); p=0.013). AAS detection in secondary hospitals importantly increased (33.3% vs 63.8%, p=0.07). The “Aorta Code” achieved a significant decrease in patient's transference time to referral hospital (group-I: median 259 min (IQR 150–1911), group-II: median 129 min (IQR 95.5–167.25); p=0.035). There was a marked reduction in the number of surgeons involved in the “Aorta Code” (group-I= 7 cardiac, 6 vascular, group-II= 2 cardiac, 2 vascular). Thirty-day mortality was lower in group-II in the whole AAS cohort (group-I= 22.2%, group-II= 12.5%; p=0.660) and in type A AAS (28.6% vs 18.2%, p=0.661). Misdiagnosis rate (false-calls): 11 patients (7 of them with non-acute aortic disease).

Conclusion
“Aorta Code” facilitates detecting patients with AAS at the emergency room, speeds them to the referral hospital center, allows patients to be treated by surgeons specialized in aortic surgery and improves patient's outcome. Further prospective studies examining the utility of “Aorta Code” are warranted.

Funding Acknowledgement
Type of funding source: None
Clinical importance and configuration of collateral vessel systems in patients with Takayasu arteritis or with thymoma visualized by three-dimensional volume rendering computed tomographic angiography
Authors: Funabashi N , Kobayashi Y 
Published: November 2020

Abstract

Background
Collateral vessels form after gradual blood vessel occlusion. We speculate that in Takayasu arteritis (TA) and thymoma patients, before planning surgical procedures, a complex artery/venous system should be examined using three dimensional (3D) volume rendering computed tomographic (CT) angiography.

Purpose
To seek the clinical importance and actual complex configuration of collateral vessel systems in patients with TA or with thymoma using 3D volume rendering CT angiography with special acquisition method.

Methods
We performed 3D CT angiography in patients with Takayasu arteritis (TA) with occluded arteries (N=6) or thymoma (N=2) with occluded superior-vena-cava (SVC), respectively. For CT angiography in thymoma patients, diluted (1/4) iodinated-contrast was injected in right and left medial cubital-veins simultaneously, and images acquired 10 seconds after contrast-injection.

Results
Occluded and collateral-arteries (TA group) and occluded SVC and collateral-veins (thymoma group) were successfully visualized (Figures a-h). Collateral-arteries form from the inferior mesenteric artery (Figure a) or de novo arteries from the abdominal aorta (Figure b) after superior mesenteric artery occlusion (Figure c, d). In patients with thymoma, an SVC thymoma disrupts venous return in the neck and upper extremities; a complex venous system forms on the abdominal surface (Figure e-h).

Conclusion
In TA and thymoma patients, before planning surgical procedures, a complex artery/venous system should be examined using 3D volume rendering CT angiography. For CT in thymoma, diluted (1/4) iodinated contrast should be injected in both medial cubital veins, and images should be acquired 10 seconds after contrast-injection.
3D volume rendering CT angiography

Funding Acknowledgement
Type of funding source: None
Development of a three-dimensional prognostic score for patients with symptomatic peripheral artery disease: PAD3D score
Authors: Dopheide J.F , Adam L , Gahl B , Papac L , Kaspar M , Baumgartner I , Drexel H 
Published: November 2020

Abstract

Background
Peripheral artery disease (PAD) is a high-risk condition for cardiovascular Events, but no individual prognosis assessment exists.

Objectives
We aimed to establish an individual, clinically useful risk score based on the combined predictive value for mortality of (i) age, (ii) severity of PAD, and (iii) extent of atherosclerosis (PAD3D).

Methods
1310 patients with symptomatic PAD underwent follow-up for a mean of 50±26 months. We randomly subdivided the cohort into test and validation cohort. All-cause and cardiovascular mortality were prospectively analysed for the t PAD3D score and in combination with classical risk factors (PADRF).

Results
For test and validation cohort (n=655), all-cause and cardiovascular mortality was precisely predicted (both p&lt;0.001) by the PAD3D score (Fig. 1 A+B). The additional inclusion of classical risk factors did not increase discrimination (Fig 1 C+D) compared to PAD3D score, as AU-ROCs were similar for both scores at 12 and 24 months (Fig. 2). Thus, the addition of classical risk factors did not further improve the prognostic value. The PAD3D score provides a risk gradient of a 4.5-fold increase in all-cause and cardiovascular mortality.

Conclusions
We established a score for precise prediction of all-cause and cardiovascular mortality. The PAD3D score promises to allow for personalized goals in risk intervention.
All-cause and cardiovascular mortality

Funding Acknowledgement
Type of funding source: None